Consciousness of the consequences of smoking cigarettes and the prevalence of cigarette smoking among medical students

Cigarettes are composed of toxic substances that result in the development of chronic obstructive pulmonary disease (COPD) and cardiovascular diseases. Smoking is also a risk factor of many cancers. Among the billions of smokers in the world, many of them are doctors and medical students - people who realize the importance of negative consequences of this addiction. We made an anonymous questionnaire, which contained 28 original questions and was published on the Internet to find out how many students of Medical Universities in Poland are addicted to tobacco and if they are aware of the consequences of their addiction. Papierosy składają się z wielu toksycznych substancji, powodują rozwój POChP, chorób sercowo-naczyniowych, a także są predykatorami wielu nowotworów. Wśród miliardów palaczy na świecie są lekarze, studenci medycyny, ludzie, którzy zdają sobie sprawę z wagi komplikacji tego uzależnienia. Przeprowadzono anonimową ankietę, która zawierała 28 oryginalnych pytań i została opublikowana w internecie, aby sprawdzić, ilu studentów uniwersytetów medycznych w Polsce jest uzależnionych od tytoniu i czy są oni świadomi konsekwencji uzależnienia

Stress among medical students in Poland

There is no doubt that stress is bonded with daily routine of students. Medical colleges are one of these environments, which are associated with negative impact of stress on many fields of life like physical health, academic feedback and physiological mood of student`s. Aim of study is to analyse the incidence of stress among students from different fields of study in Medical Universities in Poland. In that case we perform anonymous questionnaire, which contained 23 original questions and was widespreaded via Internet. Stress is a common problem among students from medical faculties. There is no doubt that stress is an inseparable companion during not only studies, but also after degree while working as a professional. For that reason it is necessary to encourage young people to find their own effective manner to cope with stress

Amanita Phalloides intoxication - methods of treatment and epidemiology in Lublin voivodeship in last 5 years

Introduction: In Poland, mushrooms poisonings, are still quite often, especially in autumn. Each year, in our country 500-1000 cases of mushrooms poisoning are registered, from which 70% are adults, and 30% children. Amanita Phalloides, also known as a ‘death cap’ is one of the most poisonous mushrooms in our climatic zone, and is responsible for ca. 90-95 % of all deadly mushroom poisonings. Aim of the study: is to present an epidemiology of Amanita poisonings in a Lublin voivodeship in a last 5 years, as well as the up to date methods of managing this kind of poisonings. Materials and methods: Data comes from the database of the Department of the Toxicology of Medical University of Lublin. To present the methods of treatment, the analysis of the available publications was made. Results: In years 2013-2018 in a Clinical Department of Toxicology of the Medical University in Lublin, 78 patients were hospitalized because of the mushroom intoxication. 37 (47.5%) of them were male and 41 (52,5%) - women. In 27 patients (34%), the poisoning with Amanita Phalloides was confirmed. The most mushrooms poisonings occurred in 2017 (21). Mushroom poisoning is the most common in summer and autumn - the most cases occured in August, September and October. Discussion: First steps in case of suspecting amatoxins intoxication is to take the clinical history of the patient and start stabilizing measures. To confirm Amanita poisoning, a test that allows to detect α-amanitine in urine can be made. Several drug treatments have been applied in intoxications by amatoxins, from which the biggest role plays sylibin and N-acetylcystein

RIPK4 downregulation impairs Wnt3A-stimulated invasiveness via Wnt/β\beta-catenin signaling in melanoma cells and tumor growth in vivo

Purpose The role of Wnt signaling in oncogenesis and drug resistance is well known. Receptor-interacting protein kinase (RIPK4) contributing to the increased activity of many signaling pathways, including Wnt/$\beta$-catenin, may be an important target for designing new drugs for metastatic melanoma, but its role in melanoma is not fully understood. Methods We tested the effect of genetic manipulation of RIPK4 (CRISPR/Cas9) on xenograft growth. In addition, immunohistochemistry was used to detect active $\beta$-catenin, Ki67 and necrosis in xenografts. Wnt signaling pathway activity was examined using Western blot and Top-Flash. The effect of RIPK4 knockout on melanoma cells in vitro stimulated Wnt3A on wound overgrowth, migration and invasion ability was then evaluated. Results Our study showed that CRISPR/Cas9-mediated RIPK4 knockout (KO) significantly reduced tumor growth in a mouse model of melanoma, particularly of WM266.4 cells. RIPK4 KO tumors exhibited lower percentages of $Ki67^{+}$ cells as well as reduced necrotic area and decreased levels of active $\beta$-catenin. In addition, we observed that RIPK4 knockout impaired Wnt3A-induced activation of LRP6 and $\beta$-catenin, as manifested by a decrease in the transcriptional activity of $\beta$-catenin in Top-Flash in both tested melanoma cell lines, A375 and WM266.4. Prolonged incubation (48 h) with Wnt3A showed reduced level of MMP9, C-myc, and increased SOX10, proteins whose transcription is also dependent on $\beta$-catenin activity. Moreover, RIPK4 knockout led to the inhibition of scratch overgrowth, migration and invasion of these cells compared to their controls. Conclusion RIPK4 knockdown inhibits melanoma tumor growth and Wnt3A stimulated migration and invasion indicating that RIPK4 might be a potential target for melanoma therapy

Vemurafenib and dabrafenib downregulates RIPK4 level

Vemurafenib and dabrafenib are BRAF kinase inhibitors (BRAFi) used for the treatment of patients with melanoma carrying the V600E BRAF mutation. However, melanoma cells develop resistance to both drugs when used as monotherapy. Therefore, mechanisms of drug resistance are investigated, and new molecular targets are sought that could completely inhibit melanoma progression. Since receptor-interacting protein kinase (RIPK4) probably functions as an oncogene in melanoma and its structure is similar to the BRAF protein, we analyzed the impact of vemurafenib and dabrafenib on RIPK4 in melanomas. The in silico study confirmed the high similarity of BRAF kinase domains to the RIPK4 protein at both the sequence and structural levels and suggests that BRAFi could directly bind to RIPK4 even more strongly than to ATP. Furthermore, BRAFi inhibited ERK1/2 activity and lowered RIPK4 protein levels in BRAF-mutated melanoma cells (A375 and WM266.4), while in wild-type BRAF cells (BLM and LoVo), both inhibitors decreased the level of RIPK4 and enhanced ERK1/2 activity. The phosphorylation of phosphatidylethanolamine binding protein 1 (PEBP1) - a suppressor of the BRAF/MEK/ERK pathway - via RIPK4 observed in pancreatic cancer did not occur in melanoma. Neither downregulation nor upregulation of RIPK4 in BRAF- mutated cells affected PEBP1 levels or the BRAF/MEK/ERK pathway. The downregulation of RIPK4 inhibited cell proliferation and the FAK/AKT pathway, and increased BRAFi efficiency in WM266.4 cells. However, the silencing of RIPK4 did not induce apoptosis or necroptosis. Our study suggests that RIPK4 may be an off-target for BRAF inhibitors

Deciphering the functional role of RIPK4 in melanoma

The receptor-interacting protein kinase 4 (RIPK4) plays an important role in the development and maintenance of various tissues including skin, but its role in melanoma has not been reported. Using patient-derived cell lines and clinical samples, we show that RIPK4 is expressed in melanomas at different levels. This heterogenous expression, together with very low level of RIPK4 in melanocytes, indicates that the role of this kinase in melanoma is context-dependent. While the analysis of microarray data has revealed no straightforward correlation between the stage of melanoma progression and RIPK4 expression in vivo, relatively high levels of RIPK4 are in metastatic melanoma cell lines. RIPK4 down-regulation by siRNA resulted in the attenuation of invasive potential as assessed by time-lapse video microscopy, wound-healing and transmigration assays. These effects were accompanied by reduced level of pro-invasive proteins such as MMP9, MMP2, and N-cadherin. Incubation of melanoma cells with phorbol ester (PMA) increased PKC-$1\beta$ level and hyperphosphorylation of RIPK4 resulting in degradation of RIPK4. Interestingly, incubation of cells with PMA for short and long durations revealed that cell migration is controlled by the NF-$\kappa$ signaling in a RIPK4-dependent ($RIPK4^{high}$) or independent ($RIPK4^{low}$) manner depending on cell origin (distant or lymph node metastasis) or phenotype (mesenchymal or epithelial)

Melanogenesis is directly affected by metabolites of melatonin in human melanoma cells

Melatonin (N-acetyl-5-methoxytryptamine, MEL), its kynurenic ($N^{1}$-acetyl-$N^{2}$-formyl-5-methoxykynurenine, AFMK) and indolic derivatives (6-hydroxymelatonin, 6(OH)MEL and 5-methoxytryptamine, 5-MT) are endogenously produced in human epidermis. Melatonin, produced by the pineal gland, brain and peripheral organs, displays a diversity of physiological functions including anti-inflammatory, immunomodulatory, and anti-tumor capacities. Herein, we assessed their regulatory effect on melanogenesis using amelanotic (A375, Sk-Mel-28) and highly pigmented (MNT-1, melanotic) human melanoma cell lines. We discovered that subjected compounds decrease the downstream pathway of melanin synthesis by causing a significant drop of cyclic adenosine monophosphate (cAMP) level, the microphthalmia-associated transcription factor (MITF) and resultant collapse of tyrosinase (TYR) activity, and melanin content comparatively to N-phenylthiourea (PTU, a positive control). We observed a reduction in pigment in melanosomes visualized by the transmission electron microscopy. Finally, we assessed the role of G-protein-coupled seven-transmembrane-domain receptors. Obtained results revealed that nonselective MT1 and MT2 receptor antagonist (luzindole) or selective MT2 receptor antagonist (4-P-PDOT) did not affect dysregulation of the melanin pathway indicating a receptor-independent mechanism. Our findings, together with the current state of the art, provide a convenient experimental model to study the complex relationship between metabolites of melatonin and the control of pigmentation serving as a future and rationale strategy for targeted therapies of melanoma-affected patients

Vitamin D endocrine system in breast cancer

Vitamin D is a steroid hormone of great importance in the human body. It is produced in the skin from 7-dehydrocholesterol, upon UV radiation. In order to exert its functions, vitamin D has to be hydroxylated (via CYP27A1 and CYP27B1 hydroxylases), which is followed by its interaction with the vitamin D receptor (VDR) or retinoic acid-related orphan receptors a or gamma (ROR alpha and ROR gamma). By binding with the vitamin D response elements (VDRE) located in the promoter regions, the vitamin D ligand-receptor complex may regulate vitamin D-related genes. Recently, vitamin D has acquired a great interest for its plausible association with cancer development. This review discusses the potential role of vitamin D, its analogues, and enzymes involved in its metabolism with breast cancer incidence and outcome. According to the literature, alterations in the vitamin D endocrine system, both at the mRNA and protein level, have an impact on breast cancer incidence and prognosis. Moreover, specific enzymes participating in vitamin D metabolism may serve as therapeutic targets. Notably, treatment with vitamin D analogues also gives promising results in experimental research. However, given the fact that breast cancer is heterogenous disease, further studies are needed to thoroughly elucidate the potential of vitamin D and enzymes involved in its metabolism in breast cancer development, progression and therapy. Therefore, plausible effects of vitamin D in cancer therapy or prevention have been the principal aim of numerous studies

Comparison of two suicide attempts with long-acting insulin – The rare way to commit suicide

Introduction. In previous years, the number of suicide attempts has increased in Europe. Intoxication with hypoglycemic drugs, including insulin is a rare a tool for attempting suicide that may lead to a severe patient status. Aim. The aim of the study was to assess the severity of insulin poisoning with examples of two patients. Methods. The analysis of clinical history of patients and review of available literature. Results. A 22-year-old patient was hospitalized in the Department of Toxicology and Cardiology due to a suicide attempt in the way of insulin poisoning; time of poisoning was unknown, and the level of glucose was indeterminable. The patient was treated with intensive specific pharmacotherapy. After hospitalization, which lasted 5 months, the patient’s condition had been stabilized but with no verbal contact and quadriplegic paralysis. Another patient was a 41-year-old woman hospitalized two times in the Department of Toxicology and Cardiology due to the insulin poisonings. In each case of hospitalization of this woman, severe recurrent hypoglycemia was observed up to 25 mg% until the fifth day of hospitalization and the treatment used improved the patient’s condition and there was no development of serious complications. Conclusion. Normally effective treatment at the right time can recover the patient completel

Fatal pesticide intoxication - case report of a 2 patients

Pesticides is a collective term for a group of chemicals used predominantly in agriculture and against vectors in vectorborne diseases such as malaria, filariasis, etc. Organophosphates (OP) have become nowadays the most widely used pesticides among the world. However, they are very highly toxic to humans. Poisoning with OP is a life - threatening condition. It is responsible for the symptoms due to a cholinergic effects. The Acetylcholinesterase (ACHE) enzyme inhibition leads to an acetylcholine accumulation, which causes symptoms such as diarrhea, sweating, vomiting, small pupils, muscle tremors, increased saliva and tears production and confusion. Other type of pesticides are also common used in agriculture. Glyphosate is a broad‐spectrum systemic herbicide used to kill weeds. It is promoted by the manufacturer as having no risks to human health. We present two patients with a fatal pesticide poisoning. First patient drank OP agent, which was decanted in a non-original bottle. Despite the intensive treatment, including high doses of atropine, and toxogonine, patient died after 6 days due to acute respiratory failure. The second one, tried to commit suicide by drinking 2 glasses of a pesticide called ‘Roundap’ (glyphosate). Short time after admission to a hospital, a myocardial infarction occurred. The patient died the same day, due to a cardiac arrest