The Application of Peptide Nucleic Acids (PNA) in the Inhibition of Proprotein Convertase Subtilisin/Kexin 9 (PCSK9) Gene Expression in a Cell-Free Transcription/Translation System.

Proprotein convertase subtilisin/kexin 9 (PCSK9) is a protein that plays a key role in the metabolism of low-density lipoprotein (LDL) cholesterol. The gain-of-function mutations of the PCSK9 gene lead to a reduced number of surface LDL receptors by binding to them, eventually leading to endosomal degradation. This, in turn, is the culprit of hypercholesterolemia, resulting in accelerated atherogenesis. The modern treatment for hypercholesterolemia encompasses the use of biological drugs against PCSK9, like monoclonal antibodies and gene expression modulators such as inclisiran-a short, interfering RNA (siRNA). Peptide nucleic acid (PNA) is a synthetic analog of nucleic acid that possesses a synthetic peptide skeleton instead of a phosphate-sugar one. This different structure determines the unique properties of PNA (e.g., neutral charge, enzymatic resistance, and an enormously high affinity with complementary DNA and RNA). Therefore, it might be possible to use PNA against PCSK9 in the treatment of hypercholesterolemia. We sought to explore the impact of three selected PNA oligomers on PCSK9 gene expression. Using a cell-free transcription/translation system, we showed that one of the tested PNA strands was able to reduce the PCSK9 gene expression down to 74%, 64%, and 68%, as measured by RT-real-time PCR, Western blot, and HPLC, respectively. This preliminary study shows the high applicability of a cell-free enzymatic environment as an efficient tool in the initial evaluation of biologically active PNA molecules in the field of hypercholesterolemia research. This cell-free approach allows for the omission of the hurdles associated with transmembrane PNA transportation at the early stage of PNA selection.

Holy medicine: Patron saints of wounds due to animal bites.

The cult (system of religious beliefs and rituals) of saints in Western Europe appeared in the 3rd century CE and gained momentum from the 4th to the 6th centuries. Its importance for European society in late antiquity and the early Middle Ages was undeniable; holy medicine was the only hope for sick people because the number of physicians was insufficient, and usually physicians were helpless in the face of most of the ailments that plagued society at that time. The number of saints had increased over the years, and people sought medical help from them through prayer and other religious practices. Some saints "specialized" in the treatment of various wounds, including skin diseases. Our research revealed many saints who were patrons of wounds and skin. They can be collected in three groups: patron saints against snakebites and dog bites; patron saints of the treatment of wounds, ulcers, burns, and frostbite; and patron saints against spreadable diseases such as ergotism, leprosy, and scabies. The large number of saints who were patrons against snakebites and dog bites shows the relevance and importance of the problem. In our research, we tried to find out whether the cult of saints led to the development of hospitals for the treatment of skin diseases like ergotism in the hospital of Brother St. Anthony or only in miracles of healing emphasizing the power of faith in the cure of diseases.

The history of louse-borne typhus and geomedizine.

The experience of World War I made popular the concept of medical geography (geomedicine in English, geomedizine in German), which became part of Nazism's philosophy of national welfare, safety, and solidarity. The Nazis used it to create propaganda to show some groups as rats, vermin, and Untermenschen (subhumans). In this way, more than 10 million people were killed under the Nazi regime: 6 million Jews, plus more than 5 million Gypsies, Jehovah's Witnesses, and other individuals who were not part of the German theory of "master race." The Germans' fear of typhus that spread in the Wehrmacht was so immense that during the occupation, Polish doctors used this phobia to organize a resistance movement. Contemporarily, the scope of geographic medicine encompasses the following research areas: spatial differentiation of disease incidents and the process of disease diffusion, geographic inequalities in the population's health level, and morbidity determinants among the inhabitants of developing countries. In the first half of the 19th century, it played an essential role in the activities aimed against epidemics of infectious diseases, including louse-borne typhus (epidemic typhus), cholera, and typhoid, linking these diseases to cultural determinants. Under the influence of this idea, the concept of doctor-hygienist emerged, and social medicine began to evolve.

The Role of Toll-like Receptor 2 (TLR2) in the Development and Progression of Hashimoto's Disease (HD): A Case Study on Female Patients in Poland.

Chronic lymphocytic thyroiditis, commonly known as HD, is one of the most common thyroid disorders. Due to the diverse factors affecting the etiopathogenesis of this disease (hormonal disorders and genetic and environmental factors), as well as the direct involvement of the immune system, scientists are increasingly willing to undertake research aimed at explaining the impact of the loss of immune tolerance and reactivity of autoantigens on the development of the disease. One of the directions of research in recent years is the role of the innate immune response, particularly Toll-like receptors (TLRs), in the pathogenesis of HD. The purpose of this study was to determine the importance of Toll-like receptor 2 (TLR2) expression on selected populations of immune cells, namely, monocytes (MONs) and dendritic cells (DCs), in the course of HD. Particular attention was paid to the analysis of TLR2's correlation with clinical parameters and the possibility its use as a potential biomarker molecule in the diagnostic process. Based on the obtained results, we found a statistically significant increase in the percentage of all analyzed populations of immune cells, i.e., mDC BDCA-1+CD19-, pDC BDCA-1+CD123, classical MONs CD14+CD16-, and non-classical MONs CD14+CD16+ showing on their surface TLR2 expression in patients diagnosed with HD compared to the healthy volunteers. Moreover, in the study group, we noted a more than 6-fold increase in the concentration of the soluble form of TLR2 in plasma compared to healthy patients. In addition, the correlation analysis showed significant positive correlations between the level of TLR2 expression on selected subpopulations of immune cells and biochemical indicators of thyroid function. Based on the obtained results, we can assume that TLR2 may be involved in the immunopathogenesis of HD.

Current Status of Cell-Based Therapies for Vitiligo.

Vitiligo is a chronic pigmentary disease with complex etiology, the signs of which are caused by the destruction of melanocytes in the epidermis, leading to the lack of melanin pigment responsible for skin coloration. The treatment of vitiligo, which aims at repigmentation, depends both on the clinical characteristics of the disease as well as on molecular markers that may predict the response to treatment. The aim of this review is to provide an overview of the clinical evidence for vitiligo cell-based therapies taking into account the required procedures and equipment necessary to carry them out as well as their effectiveness in repigmentation, assessed using the percentage of repigmentation of the treated area. This review was conducted by assessing 55 primary clinical studies published in PubMed and ClinicalTrails.gov between 2000 and 2022. This review concludes that the extent of repigmentation, regardless of the treatment method, is highest in stable localized vitiligo patients. Moreover, therapies that combine more than one cell type, such as melanocytes and keratinocytes, or more than one method of treatment, such as the addition of NV-UVB to another treatment, increase the chances of >90% repigmentation. Lastly, this review concludes that various body parts respond differently to all treatments.

Effect of Epstein-Barr Virus Infection on Selected Immunological Parameters in Children with Type 1 Diabetes.

Diabetes mellitus is a group of metabolic disorders with different etiologies, pathogeneses and clinical pictures, characterized by chronic hyperglycemia due to abnormal insulin secretion or action. Type 1 diabetes mellitus is the most common type of diabetes mellitus in children and adolescents, accounting for about 90% of diabetes in the population under the age of 18. The etiopathogenesis of type 1 diabetes is multifactorial. The disease occurs as a result of the interaction of three factors: genetic predisposition, environmental factors and the immune response. Research in recent years has focused on the involvement of Epstein-Barr virus (EBV) in the pathogenesis of type I diabetes. The goals of treating type 1 diabetes include maintaining blood-glucose, fructosamine and glycated hemoglobin (HbA1c) levels; therefore, the main purpose of this study was to evaluate the effect of EBV infection on the activation of selected immune cells, fructosamine levels and HbA1c levels in children with type I diabetes. Based on our study, we found a lower percentage of CD8+ T lymphocytes with expression of the CD69 molecule in patients with anti-VCA antibodies in the IgG class, and a lower percentage of CD8+ T lymphocytes with expression of the CD25+ molecule in patients with anti-EBNA-1 antibodies in the IgG class, which may indicate limited control of the immune system during EBV infection in patients. There was a lower percentage of CD3+CD4+ T lymphocytes secreting IL-4 in the study group, indicating that a deficiency in IL-4 production may be related to the development of type 1 diabetes. There was an increase in the percentage of CD4+CD3+IL-10 lymphocytes in the study group with anti-VCA antibodies present in the IgG class and anti-EBNA-1 antibodies in the IgG class compared to the patients without antibodies. In addition, there was a significant increase in fructosamine levels and higher glycated hemoglobin levels in the study group with antibodies to EBV antigens. In addition, an increase in the percentage of T lymphocytes with a CD4+CD3+IL-17+ phenotype in the patients with anti-VCA IgG antibodies was confirmed, and higher HbA1c levels may suggest that EBV infection is accompanied by an increase in IL-17 secretion.

From Alpha to Delta-Genetic Epidemiology of SARS-CoV-2 (hCoV-19) in Southern Poland.

In Poland, the first case of SARS-CoV-2 infection was confirmed in March 2020. Since then, many circulating virus lineages fueled rapid pandemic waves which inflicted a severe burden on the Polish healthcare system. Some of these lineages were associated with increased transmissibility and immune escape. Mutations in the viral spike protein, which is responsible for host cell recognition and serves as the primary target for neutralizing antibodies, are of particular importance. We investigated the molecular epidemiology of the SARS-CoV-2 clades circulating in Southern Poland from February 2021 to August 2021. The 921 whole-genome sequences were used for variant identification, spike mutation, and phylogenetic analyses. The Pango B.1.1.7 was the dominant variant (n = 730, 89.68%) from March 2021 to July 2021. In July 2021, the B.1.1.7 was displaced by the B.1.617.2 lineage with 66.66% in July 2021 and 92.3% in August 2021 frequencies, respectively. Moreover, our results were compared with the sequencing available on the GISAID platform for other regions of Poland, the Czech Republic, and Slovakia. The analysis showed that the dominant variant in the analyzed period was B.1.1.7 in all countries and Southern Poland (Silesia). Interestingly, B.1.1.7 was replaced by B.1.617.2 earlier in Southern Poland than in the rest of the country. Moreover, in the Czech Republic and Slovakia, AY lineages were predominant at that time, contrary to the Silesia region.

Typhus works of Rudolf Weigl, PhD, Ludwik Fleck, MD, and Eugeniusz Lazowski, MD, against the Nazis.

Typhus has been present in Central Europe and Russia since the 19th century, but it was not until 1918 that it became an epidemic problem in Poland. Poverty, general devastation, unsanitary living conditions, and the extensive spread of the disease forced the Polish government to organize effective measures to improve the population's health. One such measure was the establishment of a typhus research center in Lviv. The center was led by Rudolf Weigl, who in the 1930s succeeded in elaborating a clinically effective vaccine. In September 1939, when the Germans invaded Poland, the problem of typhus returned, primarily due to the ghettos where the Nazis confined Jews in poor, crowded, and unsanitary conditions. Later, in 1941 when Nazis tried to invade the Soviet Union (where typhus was endemic), the typhus vaccine-the work of Weigl and Ludwik Fleck (also an employee of the Lviv institute)-was in high demand. The Germans feared typhus due to its persistence and speed of spread. The Nazi typhus phobia was also used by some Polish doctors who took advantage of this disease to protect their patients from being deported or located in camps. An example of such a doctor was Eugeniusz Lazowski, who even organized a "false pandemic" to save the local population.

Ergotism and Saint Anthony's fire.

It has been widely accepted that ergot is a fungal disease caused by infection with the parasitic Claviceps purpurea leading to the development of typical black kernels n the plant. Ingestion of infected rye grains containing ergot alkaloids-usually in the form of contaminated rye bread-causes poisoning, also known as ergotism. The negative impacts of ergot contamination of grain on the health of humans and animals were first documented in ancient times. The history of ergotism shows the influence of food on human health. Although ergot has been known for ages, until the 18th century, its nature was not recognized. It was a part of the rye plant and it was used in traditional medicine. The diet was based was mostly on rye that led to neurologic disorders and gangrene. In the Middle Ages, in regions where rye was a dietary staple, many cases of a peculiar epidemic were recorded. Two names are usually used to describe it: "Saint Anthony's fire" and "holy fire," although there are many more appellations. The history of ergotism is a very important part of history of dermatology. The saint who people prayed to for protection against the disease was Anthony the Great (251-356). Monks of the Order of Saint Anthony played a particular role in treating ergotism by natural methods and specialized in treating skin diseases. Ergot alkaloids still pose a risk to human and animal safety if they appear in food.

Vitamin D, calcium and phosphorus status in children with short stature - effect of growth hormone therapy.

OBJECTIVE: The aim of the study was to assess the level of calcium, phosphorus and vitamin D in the blood of patients treated for short stature (SS). MATERIAL AND METHODS: The study encompassed 110 children treated for somatotropin hypopituitarism (SHP) in the Department of Paediatric Endocrinology and Diabetology at the Medical University of Lublin. The levels of calcium, phosphorus and vitamin D were marked for both groups in the peripheral blood collected on a routine basis for diagnostic examinations. The parameters were compared within the group of children with SHP, both the patients who were about to start the therapy and those in the course of the therapy as well as between the research group (110 children) and the control group. RESULTS: The results obtained were compared with the results in the control group that comprised 41 children with a general good health status, although with nasal septum deviation treated in the Department of Paediatric Otolaryngology at the Medical University of Lublin. CONCLUSIONS: On the basis of the research performed, the following conclusions were drawn: 1) children with SHP were characterised with calcium-phosphorus imbalance. The level of calcium, phosphorus and vitamin D was diminished. The values did not change due to a several-year hormone growth treatment (HGT). 2) the level of calcium and phosphorus was appropriate in the control group children, but the vitamin D level was considerably lowered. This shows the necessity for vitamin D control and supplementation, not only in children with SS.

Impaired Innate Immunity in Pediatric Patients Type 1 Diabetes-Focus on Toll-like Receptors Expression.

Type 1 diabetes (DM1) is classified as an autoimmune disease. An uncontrolled response of B and T lymphocytes to the body's own tissues develops in the absence of immune tolerance. The main aim of the study was to evaluate the effect of the duration of type 1 diabetes in children on the expression of TLR receptors and the relationship with the parameters of glycemic control in patients. As a result, we showed significant differences in the level of TLR2, TLR4 and TLR9 expression in patients with DM1 in the early stage of the disease and treated chronically compared to the healthy group. Additionally, in this study, we found that the numbers of CD19+ B cells, CD3+ CD4+, CD3+ CD8+ T cells and NK cells are different for newly diagnosed DM1 individuals, patients receiving chronic treatment and for healthy controls, indicating an important role of these cells in killing pancreatic beta cells. Moreover, higher levels of IL-10 in patients with newly diagnosed DM1 have also been found, confirming the reports found in the literature.

Wanda Blenska and the program of leprosy treatment in Uganda.

Wanda Blenska (1911-2014), a Polish physician, established a leprosy treatment center in the village of Buluba in Uganda in 1951, which lasted until 1993. Through her efforts, the village for lepers in Buluba, established in 1934, which had previously been a place of isolation conducted by the Little Sisters of St. Francis in Uganda, became such an important leprosy treatment and research center that eventually the facility was able to cooperate with similar centers in India and South Africa. It then became affiliated with research institutes in London and Amsterdam; the Borstel Research Institute near Hamburg, Germany; and the World Health Organization. Blenska developed a working relationship with the government of Uganda and contributed to changes in the government provision of health care for lepers by creating a network of leprosy treatment stations throughout the country. Through her efforts, public health education and leprosy prophylaxis became available for thousands of people, effectively changing the national attitude toward this disease. In 1994, one of the buildings of the St. Francis hospital complex in Buluba was named in her honor (The Wanda Blenska Training Centre).

Toll-Like Receptors-2 and -4 in Graves' Disease-Key Players or Bystanders?

Graves' disease (GD) is an autoimmune disease that affects the thyroid. The development of autoimmunity is associated with innate immune responses where the prominent role plays Toll-like receptors (TLRs). The aim of our study was to assess the relationship between the expression levels of TLR-2 and TLR-4 on CD4+ and CD8+ T as well as CD19+ B lymphocytes in patients with GD and selected clinical parameters. The study group consisted of 32 women with GD, the control group consisted of 20 healthy women. Immunophenotyping was performed using the flow cytometry and cytokines concentrations were assessed using ELISA assay. The mean percentage of CD4+/TLR-2+ and CD8+/TLR-2+ T cells in patients with GD was higher than in the control group (p < 0.0001). After obtaining euthyroidism, the mean percentage of CD4+/TLR-2+ T cells in patients with GD decreased (p < 0.0001). The expression level of TLR-2 on CD4+ T lymphocytes correlated with serum FT3 concentration in patients with GD (r = 0.47, p = 0.007). The mean percentage of CD8+/TLR-2+ T cells in patients with GD before treatment compared to patients with GD after obtaining euthyroidism was higher (p = 0.0163). Similar findings were found for TLR-4. Thus the TLR-2 and TLR-4 can be a prognostic marker for Graves' disease.

Influence of Resveratrol on Sphingolipid Metabolism in Hepatocellular Carcinoma Cells in Lipid Overload State.

BACKGROUND: Obesity is characterized by increased long chain fatty acids (LCFA) uptake and impaired lipid metabolism in hepatocytes. Consequently, an enhanced intracellular lipid content, including sphingolipids, may lead to lipotoxicity. It is believed that resveratrol (RSV), one of the most extensively studied plant-derived polyphenols, and its interaction with sphingolipid metabolism may constitute one of the major therapeutic targets for cancer and metabolic diseases treatment. OBJECTIVE: The aim of this study was to ascertain, whether resveratrol may affect sphingolipid metabolic pathways, enzymes and transporters in a lipid overload state. METHODS: The experiments were conducted on hepatocellular carcinoma cells (HepG2) incubated with RSV and/or Palmitic Acid (PA) at the concentration of 0.5 mM and 50 µM, respectively for 16h. Intra- and extracellular sphingolipid concentrations were assessed by high-performance liquid chromatography and gas liquid chromatography. Moreover, the expression of caspase 3, selected fatty acid transporters and sphingolipid metabolism pathway proteins were estimated by Western Blot. RESULTS: RSV alone and together with PA significantly increased the intracellular concentration of ceramide, sphinganine and sphingosine as well as the expression of enzymes related to de novo ceramide synthesis pathway. Moreover, in our study, we observed augmented ceramide and sphingomyelin efflux into the incubation media in these groups. In addition, RSV substantially reduced intracellular triacylglycerols accumulation in lipid overload conditions. CONCLUSION: The above-mentioned findings suggest that RSV, at least partially, demonstrates a potential protective effect on HepG2 cells in a lipid overload state.

Fatty acid amide hydrolase inhibitor (URB597) as a regulator of myocardial lipid metabolism in spontaneously hypertensive rats.

Pressure overload, which is typical of hypertension, is known to evoke alterations not only in the morphology of the heart but also in the preference of myocardial energetic substrates usage. Nowadays, the endocannabinoid system (ECS) serves as a potential therapeutic target for cardiovascular disorders and, simultaneously, affects whole body metabolism homeostasis. Therefore, an open question is whether ECS, apart from decreasing blood pressure, also affects cardiac muscle metabolism in hypertensive conditions. All experiments were conducted on a genetic model of primary hypertension i.e. spontaneously hypertensive rats (SHRs) and Wistar Kyoto rats (WKY) served as a normotensive control. ECS was chronically activated by 2-weeks intraperitoneal injections of fatty acid amide hydrolase (FAAH) inhibitor - URB597. Lipid analyses in the left ventricle and serum were based on ex vivo heart perfusion in Langendorff perfusion system, thin layer chromatography, and gas liquid chromatography. The total expression of selected proteins was determined using Western blot as well as immunohistochemical techniques. As expected, URB597 markedly reduced systolic as well as mean blood pressures in SHRs. Moreover, prolonged FAAH inhibition resulted in stimulation of 3H-palmitate uptake and incorporation into different lipid fractions in cardiomyocytes in the hypertensive as well as normotensive conditions. An increase in fatty acid oxidation caused by URB597 treatment was observed only in WKY rats, but not SHRs, and was accompanied by an elevation in peroxisome proliferator-activated receptor alpha (PPARα) and ß-hydroxyacyl-CoA dehydrogenase (ß-HAD) expressions. Chronic activation of ECS significantly upregulates palmitate uptake and its esterification but not oxidation in the SHR's myocardium.

The Endocannabinoid System Affects Myocardial Glucose Metabolism in the DOCA-Salt Model of Hypertension.

BACKGROUND/AIMS: Recent interest in the use of cannabinoids as therapeutic agents has revealed the involvement of the endogenous cannabinoid system (ECS) in the regulation of the cardiovascular system in hypertension. Abnormalities in glucose metabolism and insulin action are commonly detected in hypertensive animals. Thus, potential antihypertensive drugs should be investigated with respect to modulation of glucose homeostasis. Therefore, the aim of the present study was to evaluate the effects of the ECS activation after chronic fatty acid amide hydrolase inhibitor (URB597) administration on plasma glucose and insulin concentrations as well as parameters of myocardial glucose metabolism in the deoxycorticosterone acetate (DOCA)-salt hypertensive rats, an animal model of secondary hypertension. METHODS: Hypertension was induced by DOCA (25mg/kg) injections and addition of 1% NaCl in the drinking water for six weeks. Chronic activation of the ECS was performed by URB597 (1mg/kg) injections for two weeks. We examined fasting plasma levels of insulin (ELISA), glucose and intramyocardial glycogen (colorimetric method). Expressions of glucose transporters (GLUT1, 4) and selected proteins engaged in GLUT translocation as well as glucose metabolism were determined using Western blotting. RESULTS: Hypertension induced hypoinsulinemia with concomitant lack of significant changes in glycemia, reduced intramyocardial glycogen content and increased pyruvate dehydrogenase (PDH) expression in the cardiac muscle. Importantly, chronic URB597 administration in the hypertensive rats increased insulin concentration, elevated plasmalemmal GLUT1 and GLUT4 expression and concomitantly improved myocardial glycogen storage. CONCLUSION: Chronic administration of fatty acid amide hydrolase (FAAH) inhibitor has potential protective properties on myocardial glucose metabolism in hypertension.

The effects of chronic FAAH inhibition on myocardial lipid metabolism in normotensive and DOCA-salt hypertensive rats.

AIMS: There is significant evidence that the endocannabinoid system (ECS) takes part in the regulation of the cardiovascular system in hypertension. It is quite well established that hypertension causes several changes in the heart metabolism, but it is still unknown whether the ECS affects this process. Therefore, we investigated the influence of prolonged ECS activation on myocardial lipid metabolism in deoxycorticosterone acetate (DOCA)-salt hypertensive rats by chronic fatty acid amide hydrolase (FAAH) inhibition. MATERIALS AND METHODS: We examined the uptake and oxidation of palmitic acid during the heart perfusion as well as intramyocardial and plasma lipid contents using gas liquid chromatography. Total, plasmalemmal and intracellular expressions of selected proteins were estimated by the Western blot technique. Moreover, the left ventricle's morphology, including myocardial vessels density, was measured using immunohistochemistry. KEY FINDINGS: We demonstrated that hypertension induced cardiomyocytes and myocardial blood vessels hypertrophy, followed by a reduction in myocardial palmitate oxidation. Interestingly, prolonged activation of the ECS in the normotensive rats induced cardiomyocyte enlargement and intensified fatty acids metabolism. We have also shown that FAAH inhibition improved morphology of coronary blood vessels and only partially maintained its effect on lipid metabolism in the DOCA-salt hearts (i.e. elevated plasma and intramyocardial TAG contents as well as plasmalemmal FAT/CD36 and total FATP1 expressions). SIGNIFICANCE: This study revealed that chronic FAAH inhibition has no protective effects on the heart lipid metabolism in hypertension.

SHORT syndrome in a two-year-old girl - case report.

BACKGROUND: SHORT syndrome is a rare genetic congenital defects condition. The frequency of the disease still remains unknown. CASE PRESENTATION: We report the two-year-four-month old female with SHORT syndrome who present growth retardation and dysmorphic features (triangular-shaped face, prominent forehead, ocular depression, lipodystrophy at the lumbar region and around elbows), consistent with the phenotype described for this syndrome. The molecular analysis showed the presence of heterozygous variant c.1956dupT (p.Lys653*) in exon 15 of PIK3R1. CONCLUSIONS: The frequency of the disease still remains unknown; solely several dozen cases have been described worldwide.

Effects of activation of endocannabinoid system on myocardial metabolism.

Endocannabinoids exert their effect on the regulation of energy homeostasis via activation of specific receptors. They control food intake, secretion of insulin, lipids and glucose metabolism, lipid storage. Long chain fatty acids are the main myocardial energy substrate. However, the heart exerts enormous metabolic flexibility emphasized by its ability to utilzation not only fatty acids, but also glucose, lactate and ketone bodies. Endocannabinoids can directly act on the cardiomyocytes through the CB1 and CB2 receptors present in cardiomyocytes. It appears that direct activation of CB1 receptors promotes increased lipogenesis, pericardial steatosis and bioelectrical dysfunction of the heart. In contrast, stimulation of CB2 receptors exhibits cardioprotective properties, helping to maintain appropriate amount of ATP in cardiomyocytes. Furthermore, the effects of endocannabinoids at both the central nervous system and peripheral tissues, such as liver, pancreas, or adipose tissue, resulting indirectly in plasma availability of energy substrates and affects myocardial metabolism. To date, there is little evidence that describes effects of activation of the endocannabinoid system in the cardiovascular system under physiological conditions. In the present paper the impact of metabolic diseases, i. e. obesity and diabetes, as well as the cardiovascular diseases - hypertension, myocardial ischemia and myocardial infarction on the deregulation of the endocannabinoid system and its effect on the metabolism are described.

Zygmunt Kramsztyk (1849-1920) - the most outstanding medical philosopher among Polish ophthalmologists of the 19th and 20th centuries.

Zygmunt Kramsztyk (1849-1920) was a Polish ophthalmologist of Jewish origin, the founder of the ,,Medical Critique" magazine. He studied medicine at the Main School of Warsaw and Imperial University of Warsaw, graduating in 1 872, and completed his PhD in 1879 submitting the dissertation entitled "On changes perceived in eyes of leukaemic patients". From 1880 to 1904 he was the head of the Ophthalmic Ward at the Orthodox Jew Hospital in Warsaw. In 1898 he was appointed the chief physician in that hospital, remaining in this role for the next 4 years. Zygmunt Kramsztyk wrote critiques, essays and popular science articles. He penned many works on ophthalmology. He also wrote a textbook entitled "Clinical symptoms of eye diseases".