Exercise-induced hematuria exacerbated by improper hydration, low RBC MCV and dapagliflozin use.

BACKGROUND: Dapagliflozin is a reversible, highly potent, and selective Sodium-Glucose Co-Transporter-2 inhibitor indicated for the treatment of type 2 diabetes. It is generally well tolerated, with a low risk of hypoglycaemia and diabetic ketoacidosis. CASE PRESENTATION: We report a new adverse effect of dapagliflozin in a form of a transient hematuria, presenting in a 54-years-old male patient with type 2 diabetes after exercise and insufficient hydration. The process of hematuria in the patient is strongly linked with initial period of treatment. CONCLUSION: Dapagliflozin appears to have a rare adverse effect in the form of transient hematuria. Exercise, insufficient hydration, and low RBC MCV may play a role in such episodes.

Reports analysis of psychotropic drugs related adverse reactions in Australia and Poland during the COVID 19 pandemic.

BACKGROUND: The COVID-19 pandemic has caused significant changes to the global health care system AIMS: It is unknown whether the COVID-19 pandemic influenced the occurrence of adverse drug reactions (ADR) of antidepressive agents, benzodiazepines, and antipsychotics plus mood stabilizers (AaMS). The study was designed in order to compare the incidence of ADR during the COVID-19 pandemic with the period preceding the pandemic in Poland and Australia, different in terms of their COVID-19 prevention strategy. METHOD: We analysed ADR from the three surveyed pharmacological groups of drugs observed in Poland and Australia in the period prior to, and during the COVID-19 pandemic RESULTS: In Poland, a noticeable increase in the reported ADR of the assessed drug groups was observed during the COVID-19 pandemic. The highest was for antidepressive agents, but the reporting of ADR for benzodiazepines and AaMS drugs also increased significantly. In the case of ADR in Australian patients, the increase in the number of reported ADR for antidepressive agents was modest compared to that seen in Poland, but still noticeable, and there was a significant increase in ADR for benzodiazepines CONCLUSIONS: This study showed that the COVID-19 pandemic has had an impact on the incidence of ADR reported among both Polish and Australian patients but the modality of this was different.

Muscle pain and muscle weakness in COVID19 patients: Cross-talk with statins - Preliminary results.

BACKGROUND: Muscle pain and muscle weakness, common symptoms among statin-treated patients, may worsen with COVID-19 infection. AIMS: The aim of the paper was to find out if concomitant COVID-19 infections increase the frequency of specific side effects of statins such as muscle pain and muscle weakness. METHOD: A total of 66 patients diagnosed with COVID-19 without comorbidities participated in the study. The patients were divided into two groups: statin-users who had not experienced adverse effects of statins in the past (statin group (SG)) and patients who had not used any drugs in the past six months (control group (CG)). The severity of muscle pain and creatinine kinase (CK) activity was evaluated in each patient, and muscle weakness was confirmed by a dynamometer test (grip strength on both hands). RESULTS: In SG, muscle pain was more common and it was characterized by a high level of intensity. Muscle weakness occurred more frequently in the SG and it was more frequent compared to CG. The CK parameter was observed to be higher in the SG compared to the CG and was often associated with the severity of muscle pain in the range of moderate to severe. CONCLUSIONS: Our study indicates that COVID-19 is associated with the higher risk of occurrence of typical statin-related side effects, especially with more advanced age, which should be considered in future trials and treatments.

A retrospective analysis of the "Neverending Trip" after administration of a potent full agonist of 5-HT2A receptor - 25I-NBOMe.

BACKGROUND: 5-HT2A receptor (e.g. 25I-NBOMe) agonists not only pose risks of acute intoxication but also long-term effects and significant adverse reactions, e.g. hallucinogen persisting perception disorder (HPPD), derealization, and depersonalization. AIMS: We evaluated the risk associated with single and repeated use of 25I-NBOMe. We aimed to identify factors that may increase the risk of HPPD, increase its severity and determine the time when the first symptoms appear. Herein, we report the first extensive evaluation of 25I-NBOMe-induced HPPD. METHOD: We assessed all reports (58) collected by The Pomeranian Pharmacovigilance Centre (PPC) from 2013 to 2020. RESULTS: The study included a total of 58 reports of adverse reactions caused by 25I-NBOMe. In the case of 15 reports (in patients aged 19-26 years), symptoms persisted many months after the discontinuation of 25I-NBOMe. The most common were: pseudohallucinations, bizarre delusions, derealizations and in some cases development or worsening of depression has been diagnosed. HPPD-like symptoms were most common in patients who took the drug regularly (i.e., several times a month). The risk of HPPD-like symptoms is higher in patients who have severe visual pseudohallucinations, severe bizarre delusions, derealization and/or depersonalization onset immediately after taking the drug. Recurrence of HPPD symptoms may be provoked by many factors, however, there is some cases there is no apparent reason. HPPD after 25I-NBOMe use can last from 2 months up to 2 years. In some patients, pharmacological treatment was necessary due to 25I-NBOMe-induced HPPD and depression. CONCLUSIONS: The study showed long-lasting effects after 25I-NBOMe administration and allowed for the determination of HPPD risk factors.

CD56bright cells respond to stimulation until very advanced age revealing increased expression of cellular protective proteins SIRT1, HSP70 and SOD2.

BACKGROUND: NK cells are cytotoxic lymphocytes of innate immunity composed of: cytotoxic CD56dim and immunoregulatory CD56bright cells. The study aimed to analyze the expression of cellular protective proteins: sirtuin 1 (SIRT1), heat shock protein 70 (HSP70) and manganese superoxide dismutase (SOD2) in CD56dim and CD56bright NK cells of the young, seniors aged under 85 ('the old') and seniors aged over 85 ('the oldest'). We studied both non-stimulated NK cells and cells stimulated by IL-2, LPS or PMA with ionomycin. The expression level of proinflammatory cytokines TNF and IFN-γ was also assessed in NK cell subsets and some relationships between the studied parameters were analyzed. RESULTS: CD56bright cells showed sensitivity to most of the applied stimulatory agents until very advanced age in regards to the expression of SIRT1 and intracellular HSP70. On the contrary, CD56dim cells, sensitive to stimulation by most of the stimulatory agents in the young and the old, in the oldest lost this sensitivity and presented rather high, constant expression of SIRT1 and HSP70, resistant to further stimulation. With reference to SOD2 expression, CD56dim cells were insensitive to stimulation in the young, but their sensitivity increased with ageing. CD56bright cells were sensitive to most of the applied agents in the young and the old but in the oldest they responded to all of the stimulatory agents used in the study. Similarly, both NK cell subsets were sensitive to stimulation until very advanced age in regards to the expression of TNF and IFN-γ. CONCLUSIONS: CD56bright cells maintained sensitivity to stimulation until very advanced age presenting also an increased expression of SIRT1 and HSP70. CD56dim cells showed a constantly increased expression of these cellular protective proteins in the oldest, insensitive for further stimulation. The oldest, however, did not reveal an increased level of SOD2 expression, but it was significantly elevated in both NK cell subsets after stimulation.The pattern of expression of the studied cellular protective proteins in ageing process revealed the adaptation of NK cells to stress response in the oldest seniors which might accompany the immunosenescence and contribute to the long lifespan of this group of the elderly.

NK cells of the oldest seniors represent constant and resistant to stimulation high expression of cellular protective proteins SIRT1 and HSP70.

BACKGROUND: Natural killer cells (NK cells) are cytotoxic lymphocytes of innate immunity that reveal some immunoregulatory properties, however, their role in the process of ageing is not completely understood. The study aimed to analyze the expression of proteins involved in cellular stress response: sirtuin 1 (SIRT1), heat shock protein 70 (HSP70) and manganese superoxide dismutase (SOD2) in human NK cells with reference to the process of ageing. Non-stimulated and stimulated with IL-2, LPS or PMA with ionomycin cells originated from peripheral blood samples of: seniors aged over 85 ('the oldest'; n = 25; 88.5 ± 0.5 years, mean ± SEM), seniors aged under 85 ('the old'; n = 30; 75.6 ± 0.9 years) and the young (n = 31; 20.9 ± 0.3 years). The relationships between the levels of expression of cellular protective proteins in the studied population were also analyzed. The concentrations of carbonyl groups and 8-isoprostanes, markers of oxidative stress, in both stimulated and non-stimulated cultured NK cells were measured to assess the level of the oxidative stress in the cells. RESULTS: The oldest seniors varied from the other age groups by significantly higher expression of SIRT1 and HSP70 both in non-stimulated and stimulated NK cells. These cells also appeared to be resistant to further stimulations with IL-2, LPS or PMA with ionomycin. Highly positive correlations between SIRT1 and intracellular HSP70 in both stimulated and non-stimulated NK cells were observed. SOD2 presented low expression in non-stimulated cells, whereas its sensitivity to stimulation increased with age of donors. High positive correlations between SOD2 and surface HSP70 were observed. We found that the markers of oxidative stress in NK cells did not change with ageing. CONCLUSIONS: The oldest seniors revealed well developed adaptive stress response in NK cells with increased, constant levels of SIRT1 and intracellular HSP70. They presented also very high positive correlations between expression of these cellular protective proteins both in stimulated and non-stimulated cells. These phenomena may contribute to the long lifespan of this group of elderly. Interestingly, in NK cells SOD2 revealed a distinct role in cellular stress response since it showed sensitivity to stimulation increasing with age of participants. These observations provide novel data concerning the role of NK cells in the process of ageing.

NKT-like cells reveal higher than T lymphocytes expression of cellular protective proteins HSP70 and SOD2 and comparably increased expression of SIRT1 in the oldest seniors.

INTRODUCTION: NKT-like cells are "non-classical", "CD1d-independent" NKT cells which represent highly differentiated, conventional T lymphocytes coexpressing several NK (natural killer) associated receptors. They are effector lymphocytes of both innate and adaptive immunity and simultaneously regulatory cells of the adaptive immune system. They reveal large granular lymphocyte morphology and can mediate both MHC-restricted and MHC-unrestricted cytotoxicity, secrete many cytokines and modulate Th1 immune responses. The aim of our study was to analyze the expression of proteins involved in cellular stress response: sirtuin 1 (SIRT1), heat shock protein 70 (HSP70) and manganese superoxide dismutase (SOD2) in NKT-like cells compared to T lymphocytes during ageing. MATERIAL AND METHODS: The study involved three groups of participants: the oldest seniors (n = 25; aged over 85; mean age 88 ± 0.5 ys), the old (n = 30; aged under 85; mean age 76 ± 0.9 ys) and the young (n = 32; mean age 21 ± 0.3 ys). Whole blood samples were analyzed by flow cytometry to assess the NKT-like (CD3+CD56+) and T (CD3+) cell populations. RESULTS: The group of the oldest seniors differed from the other age groups by much higher percentage of both NKT-like cells and T lymphocytes expressing SIRT1, HSP70 and SOD2. The expression of these proteins correlated positively with the age of the participants. Interestingly, the significantly higher expression of the studied protective proteins; i.e. HSP70 and SOD2 was found in CD3+CD56+ cells compared to CD3+ lymphocytes and this phenomenon concerned all the studied age groups. These differences were not significant regarding the expression of SIRT1; however, the same tendency was noticeable. CONCLUSIONS: The analysis of CD3+ and CD3+CD56+ lymphocytes showed the increase in the number of NKT-like cells and decreased number of T cells in the process of ageing. The increased expression of cellular protective proteins SIRT1, HSP70 and SOD2 in NKT-like and T-lymphocytes of the oldest seniors seems to correspond to longevity and the observed correlations may suggest the involvement of these proteins in establishing cellular homeostasis specific for healthy ageing. Furthermore, the higher expression of the protective proteins in NKT-like cells compared to T lymphocytes may indicate their particular role in the interplay between innate and adaptive immunity responses during the process of ageing.

Hyperventilation with Maintenance of Isocapnia. An "Old New" Method in Carbon Monoxide Intoxication.

INTRODUCTION: Exposure to carbon monoxide (CO) is among the most common causes of acute and chronic poisonings worldwide. The crucial point of treatment of such acute poisonings is to eliminate CO from the body as fast as possible. There are currently two approaches to the management of the CO intoxication: hyperbaric oxygen therapy (HOT) and normobaric oxygen therapy (NOT). HOT is highly effective and capable of achieving the CO elimination half-time (T½) as low as 15 minutes. Unfortunately this method is expensive and not always readily available. The elimination of CO with the use of NOT (T½~70 min) is slower, but treatment can be started even on the site of the exposure and continued while the patient is transported to a hospital. The aim of the study was to evaluate the effectiveness of a method using therapeutic hyperventilation with maintenance of isocapnia (IH) in the elimination of CO in volunteers exposed to CO and to compare selected gasometric and respiratory parameters during IH with the values obtained during hyperventilation with pure oxygen ("non-isocapnic hyperventilation"-NIH). MATERIAL AND METHODS: The study involved 13 healthy, chronically-smoking volunteers. Each of them participated in two independent hyperventilation tests: IH and NIH. The levels of carboxyhemoglobin (COHb) and selected gasometric, cardiac and respiratory parameters were measured at 0, 10 and 20 minutes during both tests. Among 13 volunteers (8 women and 5 men) the initial COHb level was 5.0±1.5% (mean±SD) before the IH tests and 5.1±1.9% before the NIH tests (p>0.05). After 20 minutes of the procedures the mean COHb level was 2.9±0.9% for IH and 3.6±1.2% for NIH (p<0.01). The T½ of COHb was 29.6±12.2 min and 47.3±19.2 min respectively (p<0.01). After 10 minutes of NIH respiratory alkalosis was noted in 11 participants (84.6%). Such problem was not seen during the IH procedures. No serious adverse effects were recorded during either IH or NIH. Mild symptoms such as: dyspnea, headache and paresthesias were reported by 6 volunteers (46%) during both IH and NIH tests. It is worth noting that paresthesias were only reported during NIH, by 2 participants (15.4%). CONCLUSIONS: The elimination T½ of CO during IH was comparable with the values reported during HOT, and lower than can be achieved with NOT or NIH. No serious adverse effects were reported during IH procedures. Further studies, especially direct comparisons with NOT and HOT, are necessary to evaluate the effectiveness of IH in the treatment of acute CO poisoning.

Expression of cellular protective proteins SIRT1, HSP70 and SOD2 correlates with age and is significantly higher in NK cells of the oldest seniors.

BACKGROUND: NK cells are key effector lymphocytes of innate immunity provided with constitutive cytolytic activity, however, their role in human ageing is not entirely understood. The study aimed to analyze the expression of proteins involved in cellular stress response sirtuin 1 (SIRT1), heat shock protein 70 (HSP70) and manganese superoxide dismutase (SOD2) in non-stimulated NK cells of the oldest seniors (n = 25; aged over 85; mean age 88 years) and compare with NK cells of the old (n = 30; aged under 85; mean age 76 years) and the young (n = 32; mean age 21 years) to find potential relationships between the level of expression of these proteins in NK cells and longevity. The concentration of carbonyl groups and 8-isoprostanes in NK cell lysates reflecting the level of oxidative stress was also measured. RESULTS: The group of the oldest seniors differed from the other age groups by significantly higher percentage of NK cells expressing SIRT1, HSP70 and SOD2. The concentration of both carbonyl groups and 8-isoprostanes in NK cell extracts remained within the normal range in all age groups. The percentage of NK cells with the expression of, respectively, SIRT1, HSP70 and SOD2 correlated positively with age. Some correlations between expression levels of particular protective proteins SIRT1, HSP70 and SOD2 were observed in the study population. CONCLUSIONS: The increased expression of cellular protective proteins SIRT1, HSP70 and SOD2 in NK cells of the oldest seniors seems to correspond to longevity and the observed correlations may suggest the involvement of these proteins in establishing NK cell homeostasis specific for healthy ageing process.

Drinking "Vodka" or vodka - This is a question.

"Vodka" i.e. 2-methyl-2-butanol (2M2B) is growing in popularity as a substance of abuse, especially among East European youngsters. At present, there is not much data regarding its toxicity both in humans and animals. The direct effect of 2M2B on human tissue was evaluated and compared to that of two other alcohols (ethanol, 3-methyl-1-butanol). The used concentrations corresponded to those obtained from consumers of 2M2B. The experiments were carried out on HEK293 cell line with the use of the following techniques: MTT test, phase contrast and fluorescent microscopy. The MTT test indicated that the toxicity of 2M2B was comparable to that of ethanol, but it was much lower than that observed after 3-methyl-1-butanol (3M1B). The high toxicity of the latter alcohol was confirmed by the microscopy techniques. On the other hand, the toxicity of 2M2B - expressed by the reduction of the number of survived cells - was slightly higher compared to one induced by ethanol. Also, the values of pIC50 for each alcohol reflect its level of toxicity described above. On the basis of the literature data it is possible to argue that the toxicity of the tested alcohols results primarily from membrane damage induced by their solvent properties.

Pharmacovigilance and toxicovigilance system in Pomeranian province in 2015.

In Pomeranian Centre of Toxicology (PCT) pharmacovigilance (PhV) system is organized simultaneously with toxicovigilance system (ToxV). The purpose of the study was to explore the effectiveness and usefulness of the adverse reactions monitoring system in which PhV and ToxV are organized according to a common scheme. We evaluated the effectiveness of our PhV and ToxV system and investigated the frequency and the nature of adverse reactions after drugs and other chemical substances administration. All ADRs were designated as "A-type reactions" or "B-type reactions" according to their nature. The study has shown also some limitations of the standard form for ADRs monitoring (known as "yellow card") in case of reporting of adverse drug reactions after drug intoxication.

[Methemoglobinemia as a result of acute accidental "poppres" poisoning ­ a case report].

Recently we observe an increase in the number of intoxications due to xenobiotics that may induce acute methemoglobinemia. Our study showed a case of acute methemoglobinemia (MetHb 55..2%) in 25 ­ year old man. Clinical symptoms were caused by ingestion of "poppers" which was used by patient as "aphrodisiac". Summary: Conclusions: 1. Oral intake of alkyl nitrites, including isobutyl nitrite, is burdened with the risk of life-threatening methemoglobinemia . 2. In the case of poisonings running with normal pO2, reduced level of oxygen saturation, clinical signs of cyanosis does not react to oxygen therapy, and "chocolate" tinge of blood methemoglobinemia should be suspected. 3. In every case of MetHb the use of antidote, which is methylene blue, should be considered. 4. The severity of cyanosis correlates with the level of methemoglobin.

[Analysis of intoxication with novel psychoactive substance (NPS) in Pomeranian region, from January to July 2015]. / Analiza zatruc nowymi substancjami psychoaktywnymi (NPS) w województwie pomorskim, w okresie od stycznia do lipca 2015 r.

INTRODUCTION: During initial months of the year 2015 we observed the increase number of patients intoxicated with NPS in Poland. In our work we analysed the scale of this phenomenon in Pomeranian region. MATERIALS AND METHODS: Study was carried out on period from 1 January 2015 to 31 July 2015. Analysis was based on records derived from Electronic Poison Information Database developed and used on a daily basis on Pomeranian Centre of Toxicology (PCT), data obtained from Centre for Monitoring of Adverse Effects of Medicaments and Chemical Substances based in PCT and on information gathered from patients treated in Pomeranian Centre of Toxicology for NPS intoxication. RESULTS: Our study has shown slow, continuous rise in the number of intoxications with NPS in analysed period. The most frequent cause of intoxication were synthetic compounds. 99 cases needed treatment in Clinical Toxicology Unit due to their severe state. The youngest exposed person was 13 y.o., while the oldest was 53 y.o. Mean age was 22.5 y.o. with median 20 years. Majority of intoxications were among males (80.54%). 61.53% of all patients came from Tricity agglomeration. Ethanol was the prevalent coingestant. The most commonly used substance was generic NPS (70.59% of cases), followed by unknowns psychoactive substance (16.29% of cases), herbal mixture (16.29% of cases) and dextrometorphan (5.88% of cases). The study did not find one drug name that would be prevalent over others, with the most frequent commercial name being "Mocarz", found in 4 cases. Most dangerous substances found in NPS were PMA, PMMA, 25C-NBOMe and 251-NBOMe. There were no deaths of patients treated in PCT because of acute intoxication with NPS.

[Physician attitudes toward the reporting of adverse drug reactions on the Pomeranian region]. / Postawy pomorskich lekarzy wobec obowiazku raportowania niepozadanych dzialan produktów leczniczych.

INTRODUCTION: The purpose of the study was to explore the attitudes and knowledge about Pharmacovigilance (PhV) and determine the frequency of ADRs reporting by physicians. MATERIALS AND METHODS: This was a questionnaire based survey filled in by 62 physicians. RESULTS: The study has shown the lack of awareness of doctors about important role of adverse drug reporting in drug safety. Moreover, the majority of physicians who are aware how important is the PhV admitted, that they have never reported such reactions in the past. According to physicians, the main factors that discouraged them from reporting such reactions were unclear "yellow card", and a lack of confidence, whether the reaction was indeed caused by a drug. CONCLUSIONS: In order to improve the safety of the drugs there is a need to show important role of adverse reactions reporting for public safety and make clear and easy procedures to report ADRs.

[Intoxication of female patient with generalised cancer in hospital--a case report]. / Zatrucie pacjentki z uogólniona choroba nowotworowa w szpitalu--opis przypadku.

Medical errors are crucial factors influencing hospital mortality. We present a case of 79-year-old female, who was admitted to the hospital due to complications associated with advanced cancer disease. After several days of hospitalization, the woman died as a result of cancer as well as severe drugs intoxication. The investigation showed extremely high concentrations of chlorprothixen and tramadol in the. blood of the patient. This paper describes a number of medical errors made by hospital staff, of which the most significant was an inappropriate drugs policy.

[Drug interaction in 63-year-old male sportsman--a case report]. / Interakcje Ieków u 63-letniego sportowca--opis przypadku.

UNLABELLED: We present a case of 63-year-old male with hypertension and hyperlipidaemia, who was an athlete in the "masters category". Because of interaction between amlodipine and simvastatin, in combination with physical activity, the patient reported: muscle pain, weakness of the muscles, dizziness, and confusion. After amlodipine and simvastatin discontinuation, all symptoms resolved rapidly. CONCLUSIONS: (1) Concomitant use of several drugs by elderly individual patients, the risk of drug--physical activity interactions may occur.

Acute intoxication due to tert-amyl alcohol--a case report.

We presented a case of 28 year-old male, who was found in a deep coma complicated with acute respiratory failure because of recreational intoxication with tert-amyl alcohol (TAA). The TAA blood level at the admission was 83 µg/mL determined by gas chromatography-mass spectrometry (GC-MS). In the last few months popularity of TAA among alcohol and drug addicted people in Europe is still growing. The main reasons of these are: self-healing of addiction, low price of this xenobiotic compare to alcohol, and problem to detect this xenobiotic in generally used screening tests.

[Age and gender trends of inpatient recreational acute dextromethorphan intoxication hospitalized in Pomeranian Center of Toxicology between 2009-2011]. / Struktura wieku i plci pacjentów hospitalizowanych w Pomorskim Centrum Toksykologii, w latach 2009 - 2011, z powodu rekreacyjnych zatruc dekstrometorfanem.

Dextromethorphan (DXM) is a derivative of codeine with an antitussive properties. Acute poisonings with this drug are related to serious, often life-threatening clinical symptoms. In the last decade the number of DXM poisonings increased and the problem was particularly noticeable among adolescents. The aim of this study was to analyze selected demographic and clinical parameters of patients who were hospitalized due to DXM poisoning in Pomeranian Centre of Toxicology between 2009-2011. The study included 170 individuals which was 2.7% of all admissions in this period. In 2009 and 2010, the proportion of patients poisoned with DXM did not exceed 1.5%, while in the years 2011- 2013 it tripled and reached up to 3.5%. The age of patients ranged from 12 to 42 (mean 18) years. Women were more frequently hospitalized. The dose of ingested DXM ranged from 150 to 2700 (mean 588.7) mg. The analysis revealed that the dose of ingested DXM was increasing with the age of patients.

[Neurological disturbances in patient who ingested high doses of simvastatin]. / Zaburzenia neurologiczne u pacjenta przyjmujacego wysokie dawki simwastatyny.

We presented a case of 54-year old man, with dyslipidemia who, during his work, was exposed to prolonged electromagnetic radiation. Because of his concerns about the development of atherosclerosis, higher doses of simvastatin than recommended by the doctor, were used by him. After five weeks of such therapy the central nervous system symptoms such as: memory loss, cognitive disorders, sleeplessness, nervousness were presented. It is probable that the mentioned above symptoms were caused by high doses of drug took by the patient, and increased in blood-brain barrier permeability caused by electromagnetic radiation which lasted for about eight years.