Seasonal and Treatment-Related Variation in 25-Hydroxy Vitamin D Concentration in Patients with Rheumatoid Arthritis.

Background/Objectives: 25-hydroxy vitamin D (25-OH-D) is a fat-soluble compound that plays many essential functions, including bone formation, neuromuscular functions, and prevention of osteoporosis and inflammation. Recent data indicate that its metabolites are associated with rheumatoid arthritis (RA) progression and neuropathic pain in RA patients. We aimed to assess the effect of RA pharmacotherapy and seasonal variation on serum levels of 25-OH-D in RA patients who received treatment with methotrexate (MTX) or leflunomide (LEF) for at least one year. Methods: This study is a retrospective analysis of data collected from 101 patients with RA who received treatment for at least one year. All of them have supplemented 25-OH-D (2000 IU daily) for at least one year. Results: We observed a significant seasonal variation in 25-OH-D concentration (p = 0.004). Moreover, there were significant differences (p = 0.03) between LEF (50.63 ± 17.73 ng/mL) and MTX (34.73 ± 14.04 ng/mL) treatment groups, but only for the summer population. A correlation was observed between 25-OH-D and RA duration-once again, in the summer population (the whole group-r = -0.64; treatment subgroups-r = -0.82 for LEF and -0.61 for MTX). Deficiency of 25-OH-D (below 20 ng/mL) was confirmed in 28.7% of patients, while 18.8% had suboptimal 25-OH-D levels (20-30 ng/mL). Conclusions: Our results showed that both RA pharmacotherapy and seasonal variation affect the serum levels of 25-OH-D in patients with active RA.

Axitinib Trough Concentration and its Influence on the Efficacy and Toxicity of Second-line Renal Cell Carcinoma Treatment.

INTRODUCTION: There are known correlations between axitinib exposure and treatment response. The aim of the article was to study relationships between the axitinib steady-state trough concentration and the treatment efficacy and toxicity. PATIENTS AND METHODS: 35 patients (24 men and 11 women), treated or initiating treatment with axitinib, were included in the study over the period 2016-2019. Blood samples were collected following 2 weeks of treatment (in patients who initiated the therapy) and at the end of Cycles 1, 2, and 3 thereafter (in the entire study population). For concentration measurements, high-performance liquid chromatography - mass spectrometry (HPLC-MS) was applied. Treatment efficacy was assessed according to the RECIST 1.1 criteria. Therapy toxicity was evaluated according to the CTCAE criteria. RESULTS: A statistically significant relationship between the first measured axitinib trough concentration (Ctrough first) value and treatment response (P = .004) as well as the median progression-free survival (mPFS) (P = .003) was observed. The association between axitinib Ctrough first and the median overall survival (mOS) was not statistically significant (P = .142). A statistically significant relationship was observed between the mean trough concentration from 3-month observation (Ctrough 1-3m) and treatment response (P = .008) as well as mPFS (P = .001), without a significant relationship for mOS (P = .097). At least grade 3 adverse reactions were meaningfully associated with Ctrough first (P = .012) and Ctrough 1-3m (P = .003). CONCLUSION: There are significant relationships between axitinib Ctrough and treatment response, PFS, and grade ≥ 3 toxicity. The data collected may be used to determine indications for axitinib therapy monitoring based on Ctrough measurements.

Pancreatic Injury after COVID-19 Vaccine-A Case Report.

The COVID-19 pandemic has caused more than 3 million deaths worldwide. Recently developed genetically engineered vaccines are the most critical solution for controlling the pandemic. Clinical trials on a large number of participants confirmed their safety and efficacy. However, with the growing number of vaccinated people, new infrequent adverse effects have been reported, not described in the medicinal product characteristics. We would like to report a case of acute pancreatic injury that occurred shortly after administering Pfizer BioNTech COVID-19 mRNA vaccine (Comirnaty). The report points out the potential need for close monitoring of patients reporting abdominal pain after vaccination (unresponsive to standard oral painkillers) because such symptom can be associated with acute pancreatitis.

Efficacy of coenzyme Q10 in supportive therapy of the cardiovascular diseases and in the prevention of cardiotoxicity caused by chemotherapy.

Cardiovascular diseases are the most common cause of death in Poland and in the world. People with cardiovascular disease or high cardiovascular risk require early detection and pharmacotherapy. New methods of prevention and treatment are needed. Coenzyme Q10 (CoQ10) is an essential component of the human body. CoQ10 plays an important role in the biosynthesis of adenosine-5'-triphosphate (ATP) and has antioxidant activity. More and more evidence indicates that CoQ10 is closely related to cardiovascular disorders. Its supplementation may be beneficial in various chronic and acute disorders. Coenzyme Q10 used in heart failure reduces mortality and improves exercise capacity. CoQ10 can reduce the values of systolic blood pressure (SBP) and diastolic blood pressure (DBP) in hypertensive patients. CoQ10 supplementation prevents electrocardiographic (ECG) changes in patients taking doxorubicin and has a positive effect on heart function during anthracycline chemotherapy. The review article was based on available literature found in the Medline database and includes preclinical and clinical research. Further research related to CoQ10 can contribute to significant progress in the prevention and treatment of cardiovascular diseases but may also be the basis for increasing the range of indications for this drug.

The influence of tobacco smoke exposure on selected markers of oxidative stress, kidneys and liver function in the serum of rats with streptozotocin-induced diabetes.

BACKGROUND: The significance of the free radicals is emphasized in the pathophysiology of diabetes and the progression of chronic diabetic complications. Smoking cigarettes increases the risk of developing type II diabetes and intensifies pathophysiological processes during the development of type I diabetes. Tobacco smoke is also additional source of free radicals. Moreover, smoking causes variety of adverse effects on organs, that have no direct contact with the tobacco smoke itself. The objective of the study was to examine the effects of tobacco smoke on the serum concentrations of relevant oxidative stress markers such as total protein (TP), reduced glutathione (GSH), glutathione S-transferase (GST) and thiobarbituric acid reactive substances (TBARS), as well as renal (creatinine, urea) and liver function (alkaline phosphatase, ALP; alanine aminotransferase, ALT; aspartate aminotransferase, AST) among animals with induced diabetes after administration of a single dose of streptozotocin (65 mg/kg, ip). METHODS: The markers of oxidative stress and biochemical parameters were determined using spectrophotometric methods. As a biomarker of exposure to tobacco smoke, cotinine was determined using high-performance liquid chromatography with diode array detection (HPLC-DAD). RESULTS: Tobacco smoke exposure of diabetic rats was manifested by significantly elevated liver enzymes activity - ALT (p < 0.05) and ALP (p < 0.01), higher creatinine and urea concentration (p < 0.01), lower GSH amount (p < 0.05), and higher GST activity (p < 0.05). CONCLUSIONS: Tobacco smoking induce liver and renal damage through the mechanisms including increased oxidative stress.

Photosensitivity reactions in the elderly population: questionnaire-based survey and literature review.

PURPOSE: Older people are at risk of developing adverse drug reactions, including photosensitivity reactions. Therefore, the aim of the study was to assess the use of potentially photosensitizing medications and photoprotection in the elderly population. PATIENTS AND METHODS: Three hundred and fifty-six respondents (223 [63%] women and 133 [37%] men) aged ≥65 years filled in the original questionnaire concerning photosensitivity reactions to drugs. The diagnosis of drug-induced photosensitivity was based on medical history and clinical examination. RESULTS AND CONCLUSION: We found that drugs potentially causing phototoxic/photoallergic reactions comprised more than one fifth of all drugs used by the participants. The most numerous group was patients treated with 3-5 drugs potentially causing phototoxic/photoallergic reactions simultaneously. Of all drugs, ketoprofen was found to cause the highest number of photosensitivity reactions. Cutaneous adverse reactions were also observed for hydrochlorothiazide, atorvastatin, simvastatin, telmisartan, and metformin. Moreover, it was found that the incidence of photosensitivity reactions can be significantly reduced by using proper photoprotection.

Is it possible to prevent chemotherapy-induced heart failure with cardiovascular drugs - the review of the current clinical evidence.

Cardiovascular diseases and cancer are the most common death causes in the USA and Europe. Moreover, many patients suffer from both of these conditions - a situation which may result from cardiotoxicity of anticancer treatment. In order to reduce the severity of this adverse effect, various methods have been proposed, including the usage of new drug forms and less toxic analogs, omitting the combinations of potentially cardiotoxic drugs and introducing potential cardioprotective agents to the therapy. However, prevention of cardiotoxicity still seems to be insufficient. The article reviews the results of current studies on the use of cardiovascular drugs in the prevention of cardiotoxicity. Based on this knowledge, the most promising cardioprotective drugs seem to be carvedilol, nebivolol, enalapril, and candesartan, as they prevent heart remodeling and correct elevated resting heart rate, which directly affects mortality. Alternatively, in case of adverse reactions, statins might be considered.

ANGIOEDEMA AFTER ANGIOTENSIN-CONVERTING ENZYME INHIBITORS.

Angiotensin-converting enzyme inhibitors (ACEI) are one of the most frequently used drugs in the therapy of cardiovascular diseases. Beneficial therapeutic effects may be accompanied by different adverse reactions including angioedema. Recently published data suggest that ACEI-induced angioedema can be life-threatening without emergent intervention, for example due to the respiratory arrest. Monitoring this adverse Jreaction may be especially important for elderly patients who probably receive many different medicines and supplements and thus might be particularly at risk of adverse drug reactions. In the paper we describe two cases of ACEI-induced angioedema in older patients.

Coenzyme Q10 - A new player in the treatment of heart failure?

Coenzyme Q10 is the only endogenously synthesized lipid with a redox function which exhibits broad tissue and intracellular distribution in mammals. Beneficial effects of Coenzyme Q10 supplementation were observed in several age-related diseases including heart failure. CoQ10 (coenzyme Q10) level is significantly decreased in patients with this disease, which correlates with severity of clinical symptoms. Supplementation with various pharmaceutical formulations of CoQ10 improves impaired cardiac function and clinical course of heart failure. Current data from clinical trials indicate that CoQ10 can significantly reduce morbidity and mortality of heart failure patients in addition to guideline recommended pharmacotherapy.

Reimbursement of biosimilars in Poland: is there a link to health technology assessment?

INTRODUCTION: Due to their complex structures, biosimilars are not generics. The differences between them are considered during market authorization processes but remain unclear during reimbursement decision-making. METHODS: We analyzed the reimbursement of biopharmaceuticals in Poland with an emphasis on biosimilars and compared the health technology assessment (HTA) process with that defined in other countries. Recommendations provided by the Polish HTA organization and those in other countries were included as source documents. The period of interest covered January 2012 to December 2014. RESULTS: The reimbursement process for biosimilars in Poland is the same as that for generics. In contrast to other countries, a HTA is not involved in decision-making in Poland. DISCUSSION: The short administrative procedure for reimbursement of biosimilars in Poland accelerates the decision-making process; therefore, therapies can be made available to patients more quickly. However, this procedure can potentially lead to underestimation of aspects concerning the effectiveness and safety of biosimilars.

[Addiction to benzodiazepines - analysis of patients of Independent Public Hospital for Mental Diseases Patients in Miedzyrzecz].

Benzodiazepines (BZD) are substances with proven anxiolytic, sedative, hypnotic, muscle relaxant, and anticonvulsant effect whose activity targets a macromolecular complex comprising GABAA receptors, benzodiazepine receptors and chloride channels. Broad spectrum of action of benzodiazepines affects their more and more frequent consumption by the patients, despite the reports on their addictive potential. The aim of the study was to analyze patients addicted to benzodiazepines, taking into account factors that may increase the risk of addiction. Material and Methods: The study was based on medical records of 52 patients (27 women, 25 men) of Independent Public Hospital for Mental Diseases Patients in Miedzyrzecz from January 2013 to June 2015. The initial diagnosis of admitted patients included psychiatric and behavioral disorders due to taking hypnotics and sedatives (substance withdrawal). We analyzed the amount and time of use of benzodiazepines, alcohol consumption, as well as previous therapies due to alcohol abuse or alcohol dependence. Results: Among the 52 patients (27 women, 25 men aged 26 to 68 years), the majority of city dwellers was working with secondary education Average time of benzodiazepine use was 16 years, 60% of the patients were addicted to 1 benzodiazepine, 20% to two, 10% to three, and nearly 10% to 4. Clonazepam, alprazolam and diazepam were among the most frequently abused benzodiazepines. Conclusions: More and more often observed too long term treatment with benzodiazepines poses the risk of dependence on this group of drugs.

The effect of L-arginine and ascorbic acid on the visceral fat and the concentrations of metalloproteinases 2 and 9 in high-fat-diet rats.

INTRODUCTION: L-arginine (L-arg) and vitamin C supplementation may decrease fat accumulation and have a favourable effect on carbohydrate metabolism. This is partly caused by matrix metalloproteinases (MMPs), which are involved in adipocyte development and remodelling. Our study evaluated the effects of L-arg and vitamin C supplementation on the content of visceral fat (VF%), activity of MMPs, and insulin resistance (IR) in rats fed a high-fat diet (HFD). MATERIAL AND METHODS: The experiment was performed using 48 Wistar rats divided into four groups: Group 1 was fed a standard diet, Group 2 a HFD, Group 3 a HFD supplemented with L-arg (A), and Group 4 a HFD supplemented with L-arg and vitamin C (AC). The animals were euthanized after six weeks. The concentrations of serum glucose, insulin, MMP-2, and MMP-9, as well as IR by Homeostatic Model Assessment (HOMA) and VF% were measured. RESULTS: Statistically significant increases in VF%, MMP-2, MMP-9, insulin, and HOMA-IR levels were observed in the HFD group when compared to the control group. A smaller increase in VF%, insulin, and HOMA-IR was seen in Group 3 (A) and 4 (AC). L-arg supplementation protected against increases in MMP-2 and MMP-9 in Group 3 (A) and 4 (AC). CONCLUSIONS: L-arginine could protect from an increase in visceral fat through a change in the activity of MMPs and amelioration of insulin sensitivity in rats fed a HFD. The addition of vitamin C did not improve the effects of L-arginine supplementation.

Current approach for detection of sub-clinical left ventricular dysfunction associated with chemotherapy.

The article describes the current knowledge concerning approaches for detection of sub-clinical left ventricular dysfunction associated with chemotherapy. The authors focused on the problem of defining cardiotoxicity as well as diagnostic methods, which may be useful in predicting the occurrence of such complications. Currently, cardiac biomarkers measurement (troponin, NT-proBNP), tissue Doppler-based strain imaging and peak systolic longitudinal strain rate are most useful for detection of early myocardial changes during therapy, whereas speckle tracking echocardiography (STE) and peak systolic global longitudinal strain (GLS) appear to be the best measure. The problem of cardiotoxicity requires close cooperation between oncologists and cardiologists, particularly in light of the growing number of cancer cases.

Effect of L-arginine supplementation on insulin resistance and serum adiponectin concentration in rats with fat diet.

OBJECT: The purpose of this study was to determine whether supplementation with L-arginine, a substrate used in the production of nitric oxide, had an effect on adiponectin concentration in rats fed a high-fat diet. The influence of L-arginine on insulin resistance was also evaluated. MATERIALS AND METHODS: The experiment was performed using 36 Wistar rats divided into three groups: group 1 was fed a standard diet, group 2 a high-fat (HF) diet, group 3 a HF diet supplemented with L-arginine. After 42 days, serum levels of lipids, glucose, insulin, NO, and adiponectin were measured. Insulin resistance (IR) was estimated by the Homeostasis Model Assessment (HOMA). RESULTS: Body mass was equal in all 3 groups, at the beginning as well as at the end of the study, however, in group 2 the amount of visceral fat was greater after 42 days. In group 3, there was a tendency for visceral fat to decrease. An increase in cholesterol, triglycerides, insulin and HOMA-IR, as well as a decrease in NO and adiponectin were seen in group 2, while in group 3, L-arginine supplementation ameliorated these disturbances. CONCLUSIONS: Our study shows that L-arginine supplementation in rats fed a HF diet is associated with an increase in insulin sensitivity. Our findings suggest that the underlying mechanism could be at least partially related to an increase in adiponectin concentration.

[Analysis of the problem of addiction in the elderly]. / Analiza problemu uzaleznien w grupie osób w wieku podeszlym.

Demographic changes observed in recent decades around the world lead to the aging of societies at a rapid rate. The increasing number of elder people is a result of extending the average length of human life. Elder people are struggling with many problems--loneli- ness, disability or financial problems. The problem can also be addiction, usually suspected in young people. The aim of the study was to evaluate the prevalence of addiction--smoking, drinking alcohol, use of medicines and drugs, watching television or using the Internet--in the elderly. Additional objective was to assess the problem of sleep disorders and the purchase of OTC drugs, dietary supplements and vitamin preparations in this population. Examined group consisted of 104 people aged over 65 years, of whom only 23 were smokers and 86 were consumers of various alcohols. None of the respondents confirmed any contact with drugs and the use of addiction treatment. Only 4 respondents did not watch any TV programs and 37 did not use the Internet (nor themselves nor with the help of others). 94 respondents used drugs and non-prescription preparations. 57 responders did not experienced sleep disorders.

[Efficacy of alcohol withdrawal syndrome therapy in patients from Independent Public Hospital for Mental Diseases in Miedzyrzecz]. / Skutecznosc leczenia alkoholowego zespofu abstynencyjnego u pacjentów Samodzielnego Publicznego Szpitala dla Nerwowo i Psychicznie Chorych w Miedzyrzeczu.

Consumption of alcohol is a serious social problem. Research on alcohol addicts prove that its consumption affects the physical and mental health of drinking person, his/her family and the social dimension (eg. crime, unemployment, poverty). The aim of this study was to evaluate the effectiveness of the treatment of alcohol withdrawal syndrome (AW) in patients of 2417 Unit of Treatment of Alcohol Withdrawal Syndromes of Independent Public Hospital for Mental Diseases (SPSNPCH) in Miedzyrzecz. The study was conducted in 122 of 24/7 Unit of Treatment of Alcohol Withdrawal Syndromes (SPSNPCH) treated from January to March 2015. Patients during hospitalization were subjected to intensive pharmacotherapy of AW (Stage I) and cognitive-behavioral therapy (Stage II). Of the group of 122 people starting treatment Stage I was completed by 112 patients (90%); 10 patients (8%) have been discharged at their own request. The participation in Stage II was consented only by 54 patients, of which 6 (4%) withdrew from this form of therapy. Full two-stage treatment consisting of pharmacotherapy of AWS and then psychotherapy was completed only by 48 (39%) patients.

Changes in mineral status are associated with improvements in insulin sensitivity in obese patients following L-arginine supplementation.

PURPOSE: The aim of this study is to evaluate the long-term influence of L-arginine intake on mineral concentration in patients with obesity and to assess the changes in lipid serum levels, fat content, and insulin resistance that result. METHODS: A randomized double-blind placebo-controlled study was conducted. 88 obese patients were randomly assigned to receive either 9 g of L-arginine or placebo daily, for 6 months. At baseline and after 6 months, selected anthropometrical measurements and blood biochemical analyses were performed and mineral levels were assessed. To assess insulin sensitivity, the gold-standard euglycemic clamp methodology was used. RESULTS: We found that 6 months of L-arginine supplementation resulted in significant increases in insulin sensitivity (Δ1.1 mg/kg/min, P < 0.01) and zinc levels (Δ1.5 µmol/L, P < 0.001). Moreover, a positive correlation between the change in zinc concentration in serum and the change in insulin sensitivity was observed (R = 0.80, P < 0.01). In the group of patients treated with L-arginine, a negative correlation between the change in zinc concentration in serum and the change in body fat content was noted (R = -0.38, P < 0.05). CONCLUSIONS: L-Arginine supplementation affects zinc status in obese patients. One beneficial influence is related to the improvements in insulin sensitivity.

The effects of L-arginine, alone and combined with vitamin C, on mineral status in relation to its antidiabetic, anti-inflammatory, and antioxidant properties in male rats on a high-fat diet.

The aim of this study was to evaluate the influence of the intake of L-arginine alone and of L-arginine with vitamin C on mineral concentration in rats fed with a high-fat diet, and to assess the lipid glucose, insulin, and total antioxidant status (TAS) and tumor necrosis factor (TNF) alpha serum levels that result. Wistar rats were assigned to groups fed with either a standard control diet (C), a diet high in fat (FD), a diet high in fat with L-arginine, or a diet high in fat with L-arginine and vitamin C. After 6 weeks, the length and weight of the rats were measured, and the animals were euthanized. The liver, spleen, kidneys, pancreas, heart, and gonads were collected, as were blood samples. The total serum cholesterol, triglyceride, fasting glucose, insulin, TAS, and TNF alpha levels were measured. The tissue calcium, magnesium, iron, zinc, and copper concentrations were determined. It was found that L-arginine supplementation diminished the effect of the modified diet on the concentration of iron in the liver and spleen and of copper in heart. At the same time, it was observed that L-arginine supplementation reduced the effect of the high-fat diet on insulin, TNF alpha, and TAS. The combination of L-arginine and vitamin C produced a similar effect on the mineral levels in the tissues as did L-arginine used alone. Moreover, positive correlations between serum insulin and iron in the liver, between TNF alpha and iron in the liver, and between TNF alpha and copper in the heart were observed. The level of TAS in serum was inversely correlated with the copper level in the heart and the iron level in the liver. We concluded that the beneficial influence of L-arginine on insulin, TAS, and TNF alpha serum level is associated with changes in the iron and copper status in rats fed with a high-fat diet. No synergistic effect of L-arginine and vitamin C in the biochemical parameters or in the mineral status in rats fed with the modified diet was observed.

[Safety of nicotine addiction treatment]. / Bezpieczenstwo terapii uzaleznien od nikotyny.

Not all smoking addicts can succeed in quitting smoking with willpower only. These people may use nicotine replacement therapy (patches, gums, lozenges, sublingual tablets, inhalers), medicines (bupropion, varenicline and cytisine) and psychological aid. Each drug, besides its therapeutic effect, creates the risk of adverse reactions which number and severity is not always accepted by the patient. The aim of the study was to analyze adverse effects of bupropion, varenicline and cytisine formulations reported by patients. From July 2011 to June 2013 Regional Centre for Monitoring Adverse Drug Reactions (Department of Clinical Pharmacology, Department of Cardiology, Poznan University of Medical Sciences) recorded 32 suspected adverse reactions to the use of drugs for the treatment of nicotine addiction (12 after the preparation of cytisine and varenicline, 8 after preparations of bupropion). High determination caused that none of the patients withdrew from the therapy because of adverse effects.

Green tea extract reduces blood pressure, inflammatory biomarkers, and oxidative stress and improves parameters associated with insulin resistance in obese, hypertensive patients.

Green tea (GT) consumption is known to be associated with enhanced cardiovascular and metabolic health. The purpose of this study is to examine the hypothesis that supplementation with GT alters insulin resistance and associated cardiovascular risk factors in obese, hypertensive patients. In a double-blind, placebo-controlled trial, 56 obese, hypertensive subjects were randomized to receive a daily supplement of 1 capsule that contained either 379 mg of GT extract (GTE) or a matching placebo, for 3 months. At baseline and after 3 months of treatment, the anthropometric parameters, blood pressure, plasma lipid levels, glucose levels, creatinine levels, tumor necrosis factor α levels, C-reactive protein levels, total antioxidant status, and insulin levels were assessed. Insulin resistance was evaluated according to the homeostasis model assessment-insulin resistance protocol. After 3 months of supplementation, both systolic and diastolic blood pressures had significantly decreased in the GTE group as compared with the placebo group (P < .01). Considerable (P < .01) reductions in fasting serum glucose and insulin levels and insulin resistance were observed in the GTE group when compared with the placebo group. Serum tumor necrosis factor α and C-reactive protein were significantly lower, whereas total antioxidant status increased in the GTE group compared with the placebo (P < .05). Supplementation also contributed to significant (P < .05) decreases in the total and low-density lipoprotein cholesterol and triglycerides, but an increase in high-density lipoprotein cholesterol. In conclusion, daily supplementation with 379 mg of GTE favorably influences blood pressure, insulin resistance, inflammation and oxidative stress, and lipid profile in patients with obesity-related hypertension.