Low levels of vitamin D in population exposed to significant environmental pollution.

In recent years, monitoring of vitamin D levels and possible use of supplementation is gaining attention. Numerous studies showed low levels of vitamin D in winter months followed by improvement during summer. These changes are mostly dependent on the level of sun exposure, but also on geographical location, genetic factors, social-economic status, quality of nutrition and environmental pollution. In this observation we found significant decrease in vitamin D levels in populations exposed to extreme environmental pollution in area of central Europe. This region is known for extreme burden from microparticles originating in chemical industry, surface coal mining and cold-based power stations. Vitamin D levels in all patients was determined by ELISA. Using 540 patients in our department of clinical immunology and allergology we measured the levels of vitamin D in 2016 to 2021 period. In only 4 patients (0.74 %) we found vitamin D levels higher than 30 ng/ml. The curve of observed values does not reflect dependency on sun exposure and does not change during the year. We discuss the effect of environmental contaminants, lifestyle and economic and social factors. From our observations, we propose to directly supplement population with vitamin D, particularly children and seniors. From our observations, we propose to directly supplement population with vitamin D, particularly children and seniors.

Trained Immunity as an Adaptive Branch of Innate Immunity.

The concept of trained immunity has become one of the most interesting and potentially commercially and clinically relevant ideas of current immunology. Trained immunity is realized by the epigenetic reprogramming of non-immunocompetent cells, primarily monocytes/macrophages and natural killer (NK) cells, and is less specific than adaptive immunity; therefore, it may cross-protect against other infectious agents. It remains possible, however, that some of the observed changes are simply caused by increased levels of immune reactions resulting from supplementation with immunomodulators, such as glucan. In addition, the question of whether we can talk about trained immunity in cells with a life span of only few days is still unresolved.

ß-glucan as a new tool in vaccine development.

Vaccination constitutes one of the major breakthroughs in human medicine. At the same time, development of more immunogenic vaccine alternatives to using aluminium-based adjuvants is one of the most important phases of vaccination development. Among different sources of carbohydrate polymers, including plants, microbes and synthetic sources tested, glucans were found to be the most promising vaccine adjuvant, as they alone stimulate various immune reactions including antibody production without any negative side effects. The use of glucan particles as a delivery system is a viable option based on the documented efficient antigen loading and receptor-targeted uptake in antigen-presenting cells. In addition to particles, soluble glucans can be used as novel hydrogels or as direct immunocyte-targeting delivery systems employing novel complexes with oligodeoxynucleotides. This review focuses on recent advances in glucan-based vaccine development from glucan-based conjugates to a glucan-based delivery and adjuvant platform.

Development of Fish Immunity and the Role of ß-Glucan in Immune Responses.

Administration of ß-glucans through various routes, including immersion, dietary inclusion, or injection, have been found to stimulate various facets of immune responses, such as resistance to infections and resistance to environmental stress. ß-Glucans used as an immunomodulatory food supplement have been found beneficial in eliciting immunity in commercial aquaculture. Despite extensive research involving more than 3000 published studies, knowledge of the receptors involved in recognition of ß-glucans, their downstream signaling, and overall mechanisms of action is still lacking. The aim of this review is to summarize and discuss what is currently known about of the use of ß-glucans in fish.

Current possibilities of wound dressing with regard to pathophysiology of healing.

Optimization of chronic wound treatment has been constantly a subject of research. Understanding the physiological healing of wounds, permanent development of new dressing materials and correct observance of antiseptic guidelines have led to new approaches in the care of chronic wounds. The primary objective in treatment and care of chronic wounds is rapid wound closure with a functional and aesthetically acceptable scar. Though primary healing wounds is simple, many problems occur in chronic wounds, especially in the elderly and in patients with associated comorbidities. The wound should be maintained in conditions ensuring physiological healing. The condition of each wound must be properly evaluated; the wound must be carefully cleaned and then treated individually according to the current stage of healing. Many of the formerly used therapeutic procedures are outdated today. At present we have numerous modern materials including bioactive dressings which should be used in treatment of chronic wounds. New findings in molecular and cellular biology have improved our knowledge of the physiological healing of wounds and the approach to wound treatment.

Beta Glucan: Supplement or Drug? From Laboratory to Clinical Trials.

Glucans are part of a group of biologically active natural molecules and are steadily gaining strong attention not only as an important food supplement, but also as an immunostimulant and potential drug. This paper represents an up-to-date review of glucans (ß-1,3-glucans) and their role in various immune reactions and the treatment of cancer. With more than 80 clinical trials evaluating their biological effects, the question is not if glucans will move from food supplement to widely accepted drug, but how soon.

A horizontal transmission of genetic information and its importance for development of antibiotics resistance.

Genetic information is transmitted among organisms through two pathways - vertically from generation to generation (from parents to progeny) and horizontally (laterally) by direct exchange of genetic material across species barriers. These are primarily prokaryotes, in which the exchange of genes or whole gene segments by horizontal transmission is quite common. They can dynamically and in a relatively short time generate highly diverse genomes, which does not allow the vertical transmission. As a result, prokaryotes can rapidly acquire new properties such as virulence and pathogenicity as well as resistance to toxins, including antibiotics, by which they increase their adaptability. Therefore, reinfection-resistant microorganisms are always more difficult to treat than infections caused by non-resistant bacteria. Antibiotic resistance today is a global problem of health care service. Not only does the number of diseases caused by resistant pathogenic strains of bacteria increase, but also the cost of treatment increases disproportionately, the length of hospitalization is prolonged, and mortality is often rising. Therefore, when indicating antibiotic therapy, it is important to keep in mind that both overuse and abuse of antibiotics contribute to the spread of antibiotic resistance genes. This is equally true for antibiotic applications in veterinary medicine, agriculture, including aquacultures, or in the food industry. Keywords: horizontal transmission of genetic information, endosymbiosis, antibiotic resistance, risks of the emergence and spread of antibiotic resistance, prevention of antibiotic resistance.

(Anti)mutagenic and immunomodulatory properties of quercetin glycosides.

BACKGROUND: Quercetin-3-O-ß-D-glucopyranoside (isoquercitrin) and quercetin-3-O-rutinoside (rutin) are common components of a normal human diet and are increasingly used in food supplements. Here their effect on mutagenesis and immunity is shown. RESULTS: The in vitro (anti)mutagenic potential was compared with that of quercetin using the Ames test in Salmonella typhimurium His(-) strains TA100, TA98 and TA102. Isoquercitrin only slightly increased the number of revertants, while rutin was totally non-mutagenic. On the other hand, all compounds displayed dose-dependent protective activity against H2O2 - and tert-butyl hydroperoxide-induced oxidative damage to the TA102 strain and at 75 µmol L(-1) inhibited H2O2/Fe(2+)-induced formation of the open circular and linear forms of the DNA plasmid pBSIISK(-). In mice, none of the flavonols (0.86 µmol day(-1), 34 days) induced harmful effects. In immunized animals, all compounds enhanced ex vivo B cell proliferation; quercetin stimulated lymphocyte basal proliferation and increased the number of IgM-producing lymphocytes. Rutin promoted NK cytotoxic activity, supported T cells and enhanced gut epithelium renewal. No effect on IgG-forming cells was found. CONCLUSION: Isoquercitrin displayed negligible and rutin no mutagenicity, but both showed significant antimutagenic and DNA-protective effects against oxidative damage. In vivo, they supported the readiness of the immune system for specific humoral immune response.

Leg Ulcer Therapy by Local Injection of Autologous Growth Factors: Results of a Pilot Study.

INTRODUCTION: Population ageing has led to an increase in the prevalence of many chronic diseases that occur in elderly patients including chronic wounds of various aetiologies, especially leg ulcers. The treatment of these wounds is lengthy and associated with health, economic and social problems. The aim of our study was to compare the outcomes of local injections of autologous growth factors with standard dressings for leg ulcer treatment. METHODS: The study included 25 patients with leg ulcers treated with autologous growth factors, and 15 patients treated with standard wet dressings only. The area and depth of ulcers were measured on days 0, 5, 28, 84 and 168, and statistically processed using the chi-square test, the Fischer exact test, the Wilcoxon two-sample test, the non-parametric paired Wilcoxon test and the Friedman analysis of variance (ANOVA) test at a significance level of 5%. RESULTS: Area and depth did not significantly differ between the two groups before initiation of the treatment (p = 0.472 and p = 0.242, respectively). During the study period, the average leg ulcer area decreased in both the study and control groups by 72% and 40%, respectively. The paired Wilcoxon test showed that this decrease was significant in the study group (p < 0.001), but not in the control group (p = 0.075). CONCLUSION: Leg ulcers heal better when treated with autologous growth factor injections than when treated with standard dressings alone. A further study with a larger number of patients is needed to confirm the presented results. However, this method seems to be a promising way to treat ulcers of the lower extremities.

Glucans as New Anticancer Agents.

For decades, glucans have been studied for their biological and immunological activities. The scientific community has mainly focused on immune reactions, but other areas, such as cholesterol levels and diabetic retinopathy, have shown the positive effects of glucan supplementation. However, the majority of studies focused on possible cancer suppression, where glucans showed clear and significant effects on numerous types of cancers, leading not only to clinical trials, but to approval as an official drug. The aim of this review is to describe the current knowledge of this field.

Immunity in cancer and atherosclerosis.

Cancer and cardiovascular diseases have been classified as non-communicable diseases for decades. Both diseases have characteristics of immune reactions, which are principally identical, but differing in important aspects. The aim of this communication is to highlight new approaches to immune processes involved in both types of diseases.

Atherosclerosis as autoimmune disease.

No attention is usually focused on the possible involvement of immune mechanisms, particularly of autoimmunity, on the development and progress of atherosclerosis. The pioneering work occurring almost 50 years ago was overlooked, and the idea of atherosclerosis as an autoimmune disease only started gaining traction about 10 years ago. Our review discusses the recent findings and offers insights into the possibility that alterations of the immune system play a significant role in the development of atherosclerosis.

ß-glucans and cholesterol (Review).

Hypercholesterolemia is one of primary risk factors of cardiovascular disease, together with metabolic syndrome, hypertension and diabetes. Although progress has been made, the search for novel methods of preventing and treating dyslipidemia is ongoing and current therapies for cardiovascular disease induce various side effects. ß­glucans are linear unbranched polysaccharides found in various natural sources, such as mushrooms. Due to their structure they are able to interact with innate immunity receptors, however they also act as dietary fibers in the digestive tract. As there are two forms of ß­glucans, insoluble and soluble forms, they are able to interact with lipids and biliary salts in the bowel and consequently reduce cholesterol levels. Therefore, they may be developed as a suitable therapeutic option to treat patients with dyslipidemia, as they are natural molecules that do not induce any significant side effects. The current review discusses the evidence supporting the effects of ß­glucans on cholesterol levels.

Orally administered marine (1-->3)-beta-D-glucan Phycarine stimulates both humoral and cellular immunity.

(1-->3)-beta-D-Glucans represent highly conserved structural components of cell walls in yeast, fungi, or seaweed. However, it is still unknown how they mediate their effects. The aim of this study was to evaluate both intraperitoneal and oral application of seaweed-derived (1-->3)-beta-D-glucan Phycarine. Phycarine showed significant stimulation of phagocytosis by peripheral blood cells. In addition, the efficiency of chemotherapy of Lewis lung carcinoma with cyclophosphamide was potentiated by Phycarine administration. Phycarine also strongly shortened the recovery of leucopenia caused either by chemotherapy or irradiation. Besides the role in stimulation of cellular immunity, we also found a significant increase of antibody formation. Using a suckling rat model for evaluation of the absorption and tissues distribution of enterally administered (125)I-Phycarine, we found that the majority of Phycarine was detected in the stomach and duodenum 5 min after the administration. This amount sharply decreased during first 30 min. A significant amount of Phycarine entered proximal intestine in a shortly after the gavage. Its transit through proximal intestine was decreasing with time and simultaneously increasing in the ileum. Systemic blood levels were very low (less than 0.5%). Taken together, these observations suggest that Phycarine is similarly effective both after i.p. and oral application, has very strong stimulating effects on three types of experimentally induced leucopenia and stimulates both humoral and cellular branch of immune reactions. The majority of Phycarine can be detected throughout the gastrointestinal tract, supporting the feasibility of enteral administration of Phycarine in the treatment of gastrointestinal diseases.

Leukemia inhibitory factor gene mutations in the population of infertile women are not restricted to nulligravid patients.

OBJECTIVE: Leukemia inhibitory factor (LIF) is one of the key cytokines in the embryo implantation regulation. We investigated the prevalence of the LIF gene mutations in the population of infertile women that consisted of nulligravid and secondary infertile patients. STUDY DESIGN: We designed a LIF gene mutation screening method that is based on the Temperature Gradient Gel Electrophoresis (TGGE). The population to screen consisted of 176 infertile women including group A of 147 nulligravid women and group B of 29 women with secondary infertility that had a history of either miscarriage or an ectopic pregnancy but no live births. The control population was comprised of 75 healthy fertile subjects. The groups of fertile controls and infertile patients were compared for statistically significant differences using the t-test. RESULTS: Six potentially functional LIF gene mutations, the G to A transitions at the position 3400 leading to the valin to methionin exchange at codon 64 (V64M) in the AB loop region of the LIF protein, were detected. All of the six positive women were infertile. Four of them were nulligravid and two of them had history of spontaneous conception followed by early miscarriage. No positive TGGE samples were identified in the control group, which means that the frequency of functionally relevant mutations of the LIF gene in infertile women is significantly enhanced in comparison with controls (P<0.05, t-test). CONCLUSION: The results suggest that the LIF gene mutations affect fertility. Even though they occur infrequently, their impact on molecular events during early phases of pregnancy should be further established.

Stimulation of ileal epithelium growth and regeneration by dietary nucleotide extracts.

The gastrointestinal tract epithelium plays an important role not only in digestion and absorption of nutrients, but also in antigen and pathogen signal translocation toward the gut associated lymphoid tissue. Malnutrition in various degrees is recognized as the most common cause of the immune system dysfunction. Research done in the past several years has revealed that dietary nucleotides (dNT) represent an essential compound of nutrition because of their importance in metabolic pathways, energetic processes and nucleic acid synthesis during tissue renewal. Much evidence accumulated suggests that dNT are essential for the growth and maturation of the gut epithelia. In previous experiments we have documented immunoregulative properties of dNT-containing extracts. In this study Balb/c female mice were fed (1) standard diet, (2) dNT-supplemented diet, and (3) dNT-supplemented water for 4 weeks. The supplement in dose of 100 mg/kg/l comprised original extract (Imuregen, Uniregen Ltd., Náchod, Czech Republic). Samples of terminal ileum in each dietary group were removed for histological examination. The length of villi was evaluated by computer morphometry. The highest growth of intestinal villi was observed in group administered dNT-supplemented water. We have found no pathological changes of intestinal epithelium in any experimental group.

Effects of glucan on bone marrow.

Bone marrow damage represents a significant problem in cancer treatment. Therefore, it is clear that the pharmacologic protection against bone marrow damage is of considerable interest, since the development of novel and effective medical approaches to combat radiation or cytotoxic damage are of major importance not only to the medical field but also to several industries and the military. This review represents a summary of our knowledge of the effects of various glucans on bone marrow protection.

The Effects of ß-Glucan on Pig Growth and Immunity.

With increasing amounts of data showing significant immunostimulating effects of glucan, it is not surprising that attention is also focused on commercially farmed animals. Despite marked progress, development of more efficient uses of glucan in pig farming still needs substantial additional research.

The Effects of ß - Glucan on Fish Immunity.

Administration of glucans through immersion, dietary inclusion or injection has been found to enhance many types of immune responses, resistance to bacterial and viral infections and to environmental stress in many fish species. Although the efficacy of the glucan varies with types and administration, glucan used as an immunomodulatory and mostly immunostimulatory additive has been found satisfactory in eliciting immunity in commercial aquaculture. Development of more efficient administration methods will facilitate the routine and prophylactic use of glucans as natural immunostimulants of fish. Using a PubMed search, this review has an extensive literature on glucan in fish immunity.