Cílené mutace lidského histaminového H4 receptoru: Postavení Arg-341 za vzájemného působení H4R agonistů cyanoguanidinového typu

Univerzita Karlova v Praze Farmaceutická fakulta v Hradci Králové Katedra biochemických věd Kandidát: Kateřina Ládová Školitel: Prof. Dr. Armin Buschauer Doc. RNDr. Lenka Skálová, Ph.D. Název diplomové práce: Cílené mutace lidského histaminového H4 receptoru: Postavení Arg-341 za vzájemného působení H4R agonistů cyanoguanidinového typu Lidský histaminový H4 receptor (hH4R) byl objeven v roce 2000. Předpokládá se, že H4R zaujímá postavení v imunologických pochodech a může tak být potenciálním cílem vývoje nových léků v terapii zánětlivých onemocnění. Naklonování a exprese hH4Ru odstartovaly hledání selektivních agonistů a antagonistů. Nedávno byl v sérii agonistů cyanoguanidinového typu identifikován vysoce účinný a receptorově selektivní H4R agonista, UR-PI376, (2-cyano-1-[4-(1-H-imidazol-4-yl)butyl]-3-[(2-fenylthio)ethyl] guanidin), s jasnými preferencemi k hH4Ru před H4Rem myšovitých (mH4R). Dle molekulárních modelových studií, UR-PI376 tvoří dvě vodíkové vazby mezi cyanoguanidinovým zbytkem a argininem 341 hH4Ru, což vedlo k doměnce, že Arg-341 je důvodem, proč je UR-PI376 selektivnější k hH4Ru než k lidskému histaminovému H3 receptoru (hH3R) a proč upřednostňuje hH4R před mH4Rem. Abychom objasnili roli této aminokyseliny ve vzájemné interakci s cyanoguanidiny, vytvořili jsme tři mutanty:...Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Kateřina Ládová Consultant: Prof. Dr. Armin Buschauer Doc. RNDr. Lenka Skálová, Ph.D. Title of diploma thesis: Site-directed mutagenesis of the human histamine H4 receptor: The role of Arg-341 in the interaction with cyanoguanidine-type H4R agonists The human histamine H4 receptor (hH4R) was discovered in 2000. The H4R is supposed to be involved in immunological processes and is considered a potential drug target, e. g., for the treatment of inflammatory diseases. Cloning and expression of the hH4R inspired to the search for selective agonists and antagonists. Recently, UR-PI376 (2-cyano-1-[4-(1H- imidazol-4-yl)butyl]-3-[(2-phenylthio)ethyl]guanidine) was identified within a series of cyanoguanidines as a highly potent and subtype-selective H4R agonist with pronounced preference for the human over the murine H4R (mH4R). According to molecular modelling studies, the cyanoguanidine moiety of UR-PI376 forms charge-assisted hydrogen bonds with Arg-341 of the hH4R, suggesting this amino acid brings about selectivity for the hH4R over the hH3R and is the reason for the preference of UR-PI376 for hH4R over mH4R as well. To elucidate the role of this amino acid in the interaction with...Department of Biochemical SciencesKatedra biochemických vědFaculty of Pharmacy in Hradec KrálovéFarmaceutická fakulta v Hradci Králov

The Importance of Self-Reported Medication Adherence in the Evaluation of the Effectiveness of Pharmacotherapy

Univerzita Karlova v Praze, Farmaceutická fakulta v Hradci Králové Katedra sociální a klinické farmacie Kandidát: Mgr. Kateřina Ládová Školitel: PharmDr. Petra Matoulková, Ph.D.; PharmDr. Magda Vytřísalová, Ph.D. (konzultant) Název disertační práce: Význam hodnocení adherence k léčbě pomocí výpovědi pacienta v posouzení účinnosti farmakoterapie Úvod a cíle: Adherence k léčbě je velmi variabilním faktorem, který může ovlivnit terapeutickou hodnotu léčiva. Především u chronických onemocnění představuje non-adherence problém, který může mít zdravotní, sociální, ale i ekonomické následky. V měření adherence je často využívána metoda výpovědi pacienta (VP), která je mimo jiné snadno aplikovatelná do výzkumu i do každodenní klinické praxe. Sledování adherence pomocí VP může přispět nejen k maximalizaci terapeutické účinnosti, ale i k minimalizaci rizika selhání terapie. Standardizace procesu měření je však nezbytná. Navíc, některé obtížně monitorovatelné faktory typu healthy adherer effect (HAE) odrážející tendenci pacientů pečovat o své zdraví mohou mít příznivý vliv na výstupy léčby. Tyto výsledky pak mohou být nesprávně přisouzeny analyzované terapii. Hlavními cíli této dizertační práce proto bylo: 1) zhodnotit literární doklady o významu HAE při hodnocení adherence k léčbě a výsledků...Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Social and Clinical Pharmacy Candidate: Mgr. Kateřina Ládová Supervisor: PharmDr. Petra Matoulková, Ph.D.; PharmDr. Magda Vytřísalová, Ph.D. (Consultant) Title of Doctoral Thesis: The Importance of Self-Reported Medication Adherence in the Evaluation of the Effectiveness of Pharmacotherapy Introduction and Objective: Medication adherence (MA) is a highly variable factor affecting the response to the therapy. Especially in chronic disease, non-adherence presents a problem that may have health, social, and even economic consequences. Measuring MA is the most often performed by self-reported surveys which enables, among others, their simple application in research as well as in every day clinical practices. Self-reported MA monitoring may contribute to maximizing the effectiveness of pharmacotherapy and minimizing the risk of therapy failure, however, standardization of measuring process is needed. Moreover, some factors such as healthy adherer effect (HAE), which reflect patient health seeking behaviour but cannot be easily monitored, can favourably affect health outcomes. Acquired results may then be incorrectly attributed to drug therapy examined in the study. Hence, the main aims of this doctoral thesis were: 1) to...Katedra sociální a klinické farmacieDepartment of Social and Clinical PharmacyFarmaceutická fakulta v Hradci KrálovéFaculty of Pharmacy in Hradec Králov

The Importance of Self-Reported Medication Adherence in the Evaluation of the Effectiveness of Pharmacotherapy

Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Social and Clinical Pharmacy Candidate: Mgr. Kateřina Ládová Supervisor: PharmDr. Petra Matoulková, Ph.D.; PharmDr. Magda Vytřísalová, Ph.D. (Consultant) Title of Doctoral Thesis: The Importance of Self-Reported Medication Adherence in the Evaluation of the Effectiveness of Pharmacotherapy Introduction and Objective: Medication adherence (MA) is a highly variable factor affecting the response to the therapy. Especially in chronic disease, non-adherence presents a problem that may have health, social, and even economic consequences. Measuring MA is the most often performed by self-reported surveys which enables, among others, their simple application in research as well as in every day clinical practices. Self-reported MA monitoring may contribute to maximizing the effectiveness of pharmacotherapy and minimizing the risk of therapy failure, however, standardization of measuring process is needed. Moreover, some factors such as healthy adherer effect (HAE), which reflect patient health seeking behaviour but cannot be easily monitored, can favourably affect health outcomes. Acquired results may then be incorrectly attributed to drug therapy examined in the study. Hence, the main aims of this doctoral thesis were: 1) to..

Site-directed mutagenesis of the human histamin H4 receptor: The role of Arg-341 in the interaction with cyanoguanidine - type H4R agonists

Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Kateřina Ládová Consultant: Prof. Dr. Armin Buschauer Doc. RNDr. Lenka Skálová, Ph.D. Title of diploma thesis: Site-directed mutagenesis of the human histamine H4 receptor: The role of Arg-341 in the interaction with cyanoguanidine-type H4R agonists The human histamine H4 receptor (hH4R) was discovered in 2000. The H4R is supposed to be involved in immunological processes and is considered a potential drug target, e. g., for the treatment of inflammatory diseases. Cloning and expression of the hH4R inspired to the search for selective agonists and antagonists. Recently, UR-PI376 (2-cyano-1-[4-(1H- imidazol-4-yl)butyl]-3-[(2-phenylthio)ethyl]guanidine) was identified within a series of cyanoguanidines as a highly potent and subtype-selective H4R agonist with pronounced preference for the human over the murine H4R (mH4R). According to molecular modelling studies, the cyanoguanidine moiety of UR-PI376 forms charge-assisted hydrogen bonds with Arg-341 of the hH4R, suggesting this amino acid brings about selectivity for the hH4R over the hH3R and is the reason for the preference of UR-PI376 for hH4R over mH4R as well. To elucidate the role of this amino acid in the interaction with..

The Importance of Self-Reported Medication Adherence in the Evaluation of the Effectiveness of Pharmacotherapy

Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Social and Clinical Pharmacy Candidate: Mgr. Kateřina Ládová Supervisor: PharmDr. Petra Matoulková, Ph.D.; PharmDr. Magda Vytřísalová, Ph.D. (Consultant) Title of Doctoral Thesis: The Importance of Self-Reported Medication Adherence in the Evaluation of the Effectiveness of Pharmacotherapy Introduction and Objective: Medication adherence (MA) is a highly variable factor affecting the response to the therapy. Especially in chronic disease, non-adherence presents a problem that may have health, social, and even economic consequences. Measuring MA is the most often performed by self-reported surveys which enables, among others, their simple application in research as well as in every day clinical practices. Self-reported MA monitoring may contribute to maximizing the effectiveness of pharmacotherapy and minimizing the risk of therapy failure, however, standardization of measuring process is needed. Moreover, some factors such as healthy adherer effect (HAE), which reflect patient health seeking behaviour but cannot be easily monitored, can favourably affect health outcomes. Acquired results may then be incorrectly attributed to drug therapy examined in the study. Hence, the main aims of this doctoral thesis were: 1) to..

Vitamin D: sources, physiological role, biokinetics, deficiency, therapeutic use, toxicity, and overview of analytical methods for detection of vitamin D and its metabolites

Vitamin D has a well-known role in the calcium homeostasis associated with the maintenance of healthy bones. It increases the efficiency of the intestinal absorption of dietary calcium, reduces calcium losses in urine, and mobilizes calcium stored in the skeleton. However, vitamin D receptors are present ubiquitously in the human body and indeed, vitamin D has a plethora of non-calcemic functions. In contrast to most vitamins, sufficient vitamin D can be synthesized in human skin. However, its production can be markedly decreased due to factors such as clothing, sunscreens, intentional avoidance of the direct sunlight, or the high latitude of the residence. Indeed, more than one billion people worldwide are vitamin D deficient, and the deficiency is frequently undiagnosed. The chronic deficiency is not only associated with rickets/osteomalacia/osteoporosis but it is also linked to a higher risk of hypertension, type 1 diabetes, multiple sclerosis, or cancer. Supplementation of vitamin D may be hence beneficial, but the intake of vitamin D should be under the supervision of health professionals because overdosing leads to intoxication with severe health consequences. For monitoring vitamin D, several analytical methods are employed, and their advantages and disadvantages are discussed in detail in this review

Self-reported medication administration errors in clinical practice of nurses: a descriptive correlation study

Background Medication administration errors (MAE) are a worldwide issue affecting the safety of hospitalized patients. Through the early identification of potential causes, it is possible to increase the safety of medication administration (MA) in clinical nursing. The study aimed to identify potential risk factors affecting drug administration in inpatient wards in the Czech Republic. Material and Methods A descriptive correlation study through a non-standardized questionnaire was used. Data were collected from September 29 to October 15, 2021, from nurses in the Czech Republic. For statistical analysis, the authors used SPSS vers. 28 (IBM Corp., Armonk, NY, USA). Results The research sample consisted of 1205 nurses. The authors found that there was a statistically significant relationship between nurse education (p = 0.05), interruptions, preparation of medicines outside the patient rooms (p < 0.001), inadequate patient identification (p < 0.01), large numbers of patients assigned per nurse (p < 0.001), use of team nursing care and administration of generic substitution and an MAE. Conclusions The results of the study point to the weaknesses of medication administration in selected clinical departments in hospitals. The authors found that several factors, such as high patient ratio per nurse, lack of patient identification, and interruption during medication preparation of nurses, can increase the prevalence of MAE. Nurses who have completed MSc and PhD education have a lower incidence of MAE. More research is needed to identify other causes of medication administration errors. Improving the safety culture is the most critical challenge for today’s healthcare industry. Education for nurses can be an effective way to reduce MAEs by enhancing their knowledge and skills, mainly focusing on increasing adherence to safe medication preparation and administration and a better understanding of medication pharmacodynamics. Med Pr. 2023;74(2):85–9