What is known and objective: Although non-steroidal anti-inflammatory drugs (NSAIDs) have been studied in randomized, controlled trials and meta-analyses in an effort to determine their cardiovascular (CV) risks, no consensus has been reached. These studies continue to raise questions, including whether cyclooxygenase-2 (COX-2) selectivity plays a role in conferring CV risk. We performed a meta-analysis of current literature to determine whether COX-2 selectivity leads to an increased CV risk. Methods: We utilized randomized, controlled trials and prospective cohort studies. We selected eight NSAIDs based on popularity and COX selectivity and conducted a search of the MEDLINE, EMBASE, and Cochrane databases. Primary endpoints included any myocardial infarction (MI), any stroke, CV death, and a combination of all three (composite CV outcomes). Twenty-six studies were found that met inclusion and exclusion criteria. Comparisons were made between all included drugs, against placebo, and against non-selective NSAIDs (nsNSAIDs). Drugs were also compared against COX-2 selective inhibitors (COXIBs) with and without inclusion of rofecoxib. Results and discussion: Incidence of MI was increased by rofecoxib in all comparison categories [all NSAIDs (OR: 1·811, 95% CI: 1·379–2·378), placebo (OR: 1·655: 95% CI: 1·029–2·661), nsNSAIDs (OR: 2·155, 95% CI: 1·146–4·053), and COXIBs (OR: 1·800, 95% CI: 1·217–2·662)], but was decreased by celecoxib and naproxen in the COXIB comparison [(OR: 0·583, 95% CI: 0·396–0·857) and (OR: 0·609, 95% CI: 0·375–0·989, respectively]. Incidence of stroke was increased by rofecoxib in comparisons with all NSAIDs and other COXIBs [(OR: 1·488, 95% CI: 1·027–2·155) and (OR: 1·933, 95% CI: 1·052–3·549), respectively]. Incidence of stroke was decreased by celecoxib when compared with all NSAIDs, nsNSAIDs, and COXIBs [(OR: 0·603, 95% CI: 0·410–0·887), (OR: 0·517, 95% CI: 0·287–0·929), and (OR: 0·509, 95% CI: 0·280–0·925), respectively]. No NSAID reached statistical significance in regard to CV death. Incidence of the composite endpoint was increased by rofecoxib when compared against all NSAIDs, placebo, and other COXIBs [(OR: 1·612, 95% CI: 1·313–1·981), (OR: 1·572, 95% CI: 1·123–2·201) and (OR: 1·838, 95% CI: 1·323–2·554), respectively]. Incidence of composite endpoint was decreased by celecoxib in the all NSAIDs and COXIBs comparisons [(OR: 0·805, 95% CI: 0·658–0·986) and (OR: 0·557, 95% CI: 0.404–0.767), respectively]. When rofecoxib was removed from the COXIBs group, no difference was found with any comparison, suggesting rofecoxib skewed the data. What is new and conclusion: This instead of the meta-analysis suggests that COX-2 selectivity may not play a role in the CV risk of NSAIDs. Rofecoxib was the only drug to demonstrate harm and skewed the data of the COX-2 selective group.

Magister Scientiae Dentium - MSc(Dent) / Background and aim: Managing orthodontic pain traditionally involves the prescription of non-steroidal anti-inflammatory drugs combined with other analgesic medication. Sugar-free chewing gum has been advocated in the control of orthodontic pain due to its mechanical and physiological effects on periodontal tissue; however, the literature is scant. The ‘placebo effect’ that conventional sugar-free chewing gum may have in the relief of orthodontic pain has not been documented. The aim of this study was to compare the effectiveness of conventional sugar-free chewing gum in reducing orthodontic pain associated with fixed appliances with a placebo (sugar-free sweets) medicament. Objectives: The objectives of the study were to determine if there were differences in pain reporting between the sugar-free chewing gum and the placebo, to ascertain whether gender influenced pain scores and to observe any differences in pain reporting between different orthodontic techniques.

The theoretical part shortly describes chirality with focus on chiral pharmaceuticals. The processes of their absorption, distribution, metabolism and elimination in human body are discussed. These points are very important to understand possible fate of chiral drugs in the environment as there is only little data concerning their environmental behaviour. The occurrence and enantioselective toxicity of chiral drugs is also discussed here. One of the chapters describes non-steroidal anti-inflammatory drugs, as they are analyzed in the wastewater in the experimental part, and their occurrence in the environment. The experimental part describes optimization of the enantioselective HPLC method using Chiralpak AD as column for ibuprofen and ketoprofen. Reproducible separation of enantiomers wasn’t achieved for naproxen. Optimized methods were then applied for analysis of samples from municipal wastewater treatment plant in Brno-Modřice.

What is known and objective: Although non-steroidal anti-inflammatory drugs (NSAIDs) have been studied in randomized, controlled trials and meta-analyses in an effort to determine their cardiovascular (CV) risks, no consensus has been reached. These studies continue to raise questions, including whether cyclooxygenase-2 (COX-2) selectivity plays a role in conferring CV risk. We performed a meta-analysis of current literature to determine whether COX-2 selectivity leads to an increased CV risk. Methods: We utilized randomized, controlled trials and prospective cohort studies. We selected eight NSAIDs based on popularity and COX selectivity and conducted a search of the MEDLINE, EMBASE, and Cochrane databases. Primary endpoints included any myocardial infarction (MI), any stroke, CV death, and a combination of all three (composite CV outcomes). Twenty-six studies were found that met inclusion and exclusion criteria. Comparisons were made between all included drugs, against placebo, and against non-selective NSAIDs (nsNSAIDs). Drugs were also compared against COX-2 selective inhibitors (COXIBs) with and without inclusion of rofecoxib. Results and discussion: Incidence of MI was increased by rofecoxib in all comparison categories [all NSAIDs (OR: 1·811, 95% CI: 1·379-2·378), placebo (OR: 1·655: 95% CI: 1·029-2·661), nsNSAIDs (OR: 2·155, 95% CI: 1·146-4·053), and COXIBs (OR: 1·800, 95% CI: 1·217-2·662)], but was decreased by celecoxib and naproxen in the COXIB comparison [(OR: 0·583, 95% CI: 0·396-0·857) and (OR: 0·609, 95% CI: 0·375-0·989, respectively]. Incidence of stroke was increased by rofecoxib in comparisons with all NSAIDs and other COXIBs [(OR: 1·488, 95% CI: 1·027-2·155) and (OR: 1·933, 95% CI: 1·052-3·549), respectively]. Incidence of stroke was decreased by celecoxib when compared with all NSAIDs, nsNSAIDs, and COXIBs [(OR: 0·603, 95% CI: 0·410-0·887), (OR: 0·517, 95% CI: 0·287-0·929), and (OR: 0·509, 95% CI: 0·280-0·925), respectively]. No NSAID reached statistical significance in regard to CV death. Incidence of the composite endpoint was increased by rofecoxib when compared against all NSAIDs, placebo, and other COXIBs [(OR: 1·612, 95% CI: 1·313-1·981), (OR: 1·572, 95% CI: 1·123-2·201) and (OR: 1·838, 95% CI: 1·323-2·554), respectively]. Incidence of composite endpoint was decreased by celecoxib in the all NSAIDs and COXIBs comparisons [(OR: 0·805, 95% CI: 0·658-0·986) and (OR: 0·557, 95% CI: 0.404-0.767), respectively]. When rofecoxib was removed from the COXIBs group, no difference was found with any comparison, suggesting rofecoxib skewed the data. What is new and conclusion: This instead of the meta-analysis suggests that COX-2 selectivity may not play a role in the CV risk of NSAIDs. Rofecoxib was the only drug to demonstrate harm and skewed the data of the COX-2 selective group.

No description available.

Introdução: Os antiinflamatórios não esteróides (AINEs), incluindo a aspirina, são drogas largamente utilizadas para tratamento das doenças inflamatórias e da dor, e que podem causar efeitos colaterais sérios, causando considerável morbidade e mortalidade, relacionadas á doença ulcerosa, duodenal e gástrica, particularmente ao sangramento gastrointestinal. O risco relativo global de complicações gastroduodenais é de três a dez vezes, maior nos usuários de AINEs, quando comparado com indivíduos sadios. Cerca de 25% dos usuários crônicos dos antiinflamatórios não esteroides (AINEs) deverão desenvolver doença ulcerosa, e de 2 a 4% deverão apresentar sangramento ou perfuração. Mais de 17.000.000 de norte americanos utilizam vários tipos de drogas antiinflamatórios não esteróides (AINEs) diariamente e que provocam mais de 100.000 hospitalizações e cerca de 7000 a 10.000 mortes por ano nos Estados Unidos da América do Norte, fazendo desta família de drogas uma das mais comumente usadas em todo planeta. Cerca de 50% das lesões observadas em endoscopias de controle, ocorrem sem que o paciente tenha qualquer tipo de sintoma. Acredita-se que houve recrudescimento da prevalência de lesões digestivas pela substituição dos antiinflamatórios COX-2 pelos antiinflamatórios tradicionais, principalmente pela ausência de cuidados na prevenção deste tipo de ocorrência, em populações consideradas de risco. Objetivos: a) avaliar a prevalência de lesões e complicações digestivas secundárias ao uso de AINEs; b) qual é o perfil clínico deste paciente atendido em razão de queixas digestivas e a relação destas com os achados endoscópicos. Materiais e métodos: estudo aberto, prospectivo, multicêntrico avaliando consecutivamente 1.231 pacientes submetidos a exame de endoscopia digestiva alta em virtude de queixas digestivas, única ou associadas, como: 1) pirose; 2) dor epigástrica; 3) dor abdominal; 4) náusea; 5) vômito. Antes da realização do exame de endoscopia digestiva alta, os pacientes respondiam a questionário cujo objetivo era avaliar o início e o tipo de queixa clínica, o uso de medicamentos e possíveis complicações associadas como sangramento digestivo. Os critérios de inclusão foram: pacientes de ambos os sexos com idade mínima de 18 anos e que tivessem sintomas prévios iniciados, no máximo, há 14 dias antes da realização do exame de endoscopia digestiva alta. Os critérios de exclusão foram os de pacientes que se recusaram a participar do estudo e/ou de assinar o Termo de Consentimento Livre e Esclarecido, os incapazes de responder ao questionário, os com idade inferior aos 18 anos, os pacientes que já haviam realizado cirurgia gástrica e pacientes portadores de insuficiência renal ou hepática. Resultados: Foram avaliados 1.213 pacientes de 18 a 82 anos sendo que 65% destes eram do sexo feminino, 13,1% eram fumantes e 15,6% referiam ingestão de bebidas alcoólicas. A utilização de AINEs foi mais frequente no sexo feminino, porém número de complicações foi maior nos pacientes do sexo masculino (sangramentos foi duas vezes maior; p=0,045 e a ocorrência de úlcera quase 1,5 vezes maior; p=0,041). Os principais sinais e sintomas relatados foram epigastralgia e pirose (67% e 62%, respectivamente). Os 1.213 pacientes foram alocados em dois grupos: Grupo I - AINE composto por 228 (18,8%) e o Grupo II - Não AINEs (NAINEs) por 985 (81,2%) pacientes.. O exame de endoscopia digestiva alta foi normal em 3,9% dos pacientes do grupo I e em 10,7% dos do grupo II (p< 0,001). A probabilidade de um paciente que não utiliza AINE ter endoscopia digestiva alta normal é 2,5 vezes maior quando comparado aos que utilizaram AINEs (p=0,001). As presenças de lesões erosivas ou ulceradas no estômago e duodeno também foram mais frequentes nos pacientes do Grupo I quando comparado aos do Grupo II. Observa-se que é maior a incidência de lesões, tanto erosivas quanto ulceradas no estômago quando comparadas ao duodeno (erosões: 49,12% vs 13,60 respectivamente, p=0,001; úlceras: 14,04% vs 11,84% respectivamente, p= 0,05). O risco de hemorragia digestiva, 12 vezes maior (6,14% vs 0,51%) nos pacientes que fizeram uso de AINEs sendo o estômago o sítio de maior prevalência de sangramento. Não se observou diferença estatística quando analisada a presença de esofagite erosiva nos dois grupos. Conclusões: Evidenciamos frequência maior de úlcera gástrica, úlcera duodenal e sangramento digestivo nos pacientes que utilizaram AINEs. Não foram encontradas relações entre os achados endoscópicos e os sintomas dispépticos. Não observamos influência dos AINEs no aparecimento de esofagite erosiva / Introduction: The non steroidal anti-inflammatory drugs (NSAID), including aspirin, are drugs widely used in the treatment of inflammatory diseases and pain. This use may cause serious side-effects, leading to considerable morbidity and mortality related to ulcer, duodenal and gastric disease, especially gastrointestinal bleeding. The overall relative risk of gastroduodenal complications is three to ten times higher in users of NSAID, compared to healthy individuals. Around 25% of the chronic users of non steroidal anti-inflammatory drugs (NSAID) will develop ulcer disease, and 2 to 4% will present bleeding or perforation. More than 17,000,000 North Americans use several kinds of non steroidal anti-inflammatory drugs (NSAID) on a daily basis. This causes more than 100,000 hospitalizations and from 7,000 to 10,000 deaths every year in the USA, which makes this drug one of the most commonly used on the planet. About 50% of the lesions observed in endoscopies occur without any kind of symptom. It is believed that there was an increase in the prevalence of digestive lesions due to the replacement of COX-2 anti-inflammatory drugs with traditional anti-inflammatory drugs, especially because of the lack of preventive care of this kind of occurrence in at-risk populations. Goals: a) Evaluate the prevalence of lesions and digestive complications, secondary to the use of NSAID; b) Evaluate the clinical profile of the patient seen for digestive complaints and the relation of these complaints with the endoscopic findings. Materials and Methods: Prospective, multi-centric, open study, evaluating consecutively 1,231 patients who underwent upper gastrointestinal endoscopy exam due to digestive complaints in isolation or associated, such as: 1) pyrosis; 2) epigastric pain; 3) abdominal pain; 4) nausea; 5) vomiting. Before performing the exam of upper gastrointestinal endoscopy, patients answered a questionnaire whose goal was to evaluate the onset and kind of clinical complaint, the use of medication and possible complications associated to digestive bleeding. The inclusion criteria were: Patients of both sexes with the minimum age of 18 and whose symptoms had begun up to 14 days before undergoing the upper gastrointestinal endoscopy. Exclusion criteria: patients who refused to participate in the study and/ or who refused to sign the Informed Consent Term, the ones who were unable to respond to the questionnaire, the ones who were under 18 years old, patients who had undergone a previous gastric surgery and patients with kidney or hepatic failure. Results: 1,213 patients with ages ranging from 18-82 were evaluated, 65% of which were female and 13,1% were smokers, 15,6% mentioned they ingested alcoholic beverages. The use of NSAID was more frequent among females. However, the number of complications was higher among males (bleeding occurred twice as much; p=0,045 and the occurrence of ulcer was almost 1,5 times higher; p=0,041). The main signs and symptoms reported were epigastralgia and pyrosis (67% and 62%). The 1,213 patients were divided into two groups: Group I- NSAID, made up by 228 (18,8%) and Group II- Non NSAID, made up by 985 patients (81,2%). The upper gastrointestinal endoscopy was normal in 3,9% of the patients in Group I and in 10,7% of the patients in Group II (p<0,001). A patient who does not use NSAID will be 2,5 times more likely to have normal upper gastrointestinal endoscopy than the one who used NSAID (p=0,001). The presence of erosive or ulcer lesions in the stomach and duodenum was more frequent in Group I patients when compared to those of Group II. It is observed that the incidence of lesions in the stomach, both erosive and ulcer is higher when compared to the duodenum (erosions: 49,12% vs. 13,60, p=0,001; ulcers: 14,04% vs. 11,84, p= 0,05). The risk of digestive bleeding is 12 times higher (6,14% vs. 0,51%) in patients who used NSAID, and the stomach is the site with higher prevalence of bleeding. No statistic difference was observed when the presence of erosive esophagitis in both groups was analyzed. Conclusions: We observed that the frequency of gastric ulcer, duodenal ulcer and digestive bleeding was higher in patients who used NSAID. Relations between the endoscopic findings and the dyspeptic symptoms were not found. The influence of NSAIDs on the appearance of erosive esophagitis was not observed

Introdução: Os antiinflamatórios não esteróides (AINEs), incluindo a aspirina, são drogas largamente utilizadas para tratamento das doenças inflamatórias e da dor, e que podem causar efeitos colaterais sérios, causando considerável morbidade e mortalidade, relacionadas á doença ulcerosa, duodenal e gástrica, particularmente ao sangramento gastrointestinal. O risco relativo global de complicações gastroduodenais é de três a dez vezes, maior nos usuários de AINEs, quando comparado com indivíduos sadios. Cerca de 25% dos usuários crônicos dos antiinflamatórios não esteroides (AINEs) deverão desenvolver doença ulcerosa, e de 2 a 4% deverão apresentar sangramento ou perfuração. Mais de 17.000.000 de norte americanos utilizam vários tipos de drogas antiinflamatórios não esteróides (AINEs) diariamente e que provocam mais de 100.000 hospitalizações e cerca de 7000 a 10.000 mortes por ano nos Estados Unidos da América do Norte, fazendo desta família de drogas uma das mais comumente usadas em todo planeta. Cerca de 50% das lesões observadas em endoscopias de controle, ocorrem sem que o paciente tenha qualquer tipo de sintoma. Acredita-se que houve recrudescimento da prevalência de lesões digestivas pela substituição dos antiinflamatórios COX-2 pelos antiinflamatórios tradicionais, principalmente pela ausência de cuidados na prevenção deste tipo de ocorrência, em populações consideradas de risco. Objetivos: a) avaliar a prevalência de lesões e complicações digestivas secundárias ao uso de AINEs; b) qual é o perfil clínico deste paciente atendido em razão de queixas digestivas e a relação destas com os achados endoscópicos. Materiais e métodos: estudo aberto, prospectivo, multicêntrico avaliando consecutivamente 1.231 pacientes submetidos a exame de endoscopia digestiva alta em virtude de queixas digestivas, única ou associadas, como: 1) pirose; 2) dor epigástrica; 3) dor abdominal; 4) náusea; 5) vômito. Antes da realização do exame de endoscopia digestiva alta, os pacientes respondiam a questionário cujo objetivo era avaliar o início e o tipo de queixa clínica, o uso de medicamentos e possíveis complicações associadas como sangramento digestivo. Os critérios de inclusão foram: pacientes de ambos os sexos com idade mínima de 18 anos e que tivessem sintomas prévios iniciados, no máximo, há 14 dias antes da realização do exame de endoscopia digestiva alta. Os critérios de exclusão foram os de pacientes que se recusaram a participar do estudo e/ou de assinar o Termo de Consentimento Livre e Esclarecido, os incapazes de responder ao questionário, os com idade inferior aos 18 anos, os pacientes que já haviam realizado cirurgia gástrica e pacientes portadores de insuficiência renal ou hepática. Resultados: Foram avaliados 1.213 pacientes de 18 a 82 anos sendo que 65% destes eram do sexo feminino, 13,1% eram fumantes e 15,6% referiam ingestão de bebidas alcoólicas. A utilização de AINEs foi mais frequente no sexo feminino, porém número de complicações foi maior nos pacientes do sexo masculino (sangramentos foi duas vezes maior; p=0,045 e a ocorrência de úlcera quase 1,5 vezes maior; p=0,041). Os principais sinais e sintomas relatados foram epigastralgia e pirose (67% e 62%, respectivamente). Os 1.213 pacientes foram alocados em dois grupos: Grupo I - AINE composto por 228 (18,8%) e o Grupo II - Não AINEs (NAINEs) por 985 (81,2%) pacientes.. O exame de endoscopia digestiva alta foi normal em 3,9% dos pacientes do grupo I e em 10,7% dos do grupo II (p< 0,001). A probabilidade de um paciente que não utiliza AINE ter endoscopia digestiva alta normal é 2,5 vezes maior quando comparado aos que utilizaram AINEs (p=0,001). As presenças de lesões erosivas ou ulceradas no estômago e duodeno também foram mais frequentes nos pacientes do Grupo I quando comparado aos do Grupo II. Observa-se que é maior a incidência de lesões, tanto erosivas quanto ulceradas no estômago quando comparadas ao duodeno (erosões: 49,12% vs 13,60 respectivamente, p=0,001; úlceras: 14,04% vs 11,84% respectivamente, p= 0,05). O risco de hemorragia digestiva, 12 vezes maior (6,14% vs 0,51%) nos pacientes que fizeram uso de AINEs sendo o estômago o sítio de maior prevalência de sangramento. Não se observou diferença estatística quando analisada a presença de esofagite erosiva nos dois grupos. Conclusões: Evidenciamos frequência maior de úlcera gástrica, úlcera duodenal e sangramento digestivo nos pacientes que utilizaram AINEs. Não foram encontradas relações entre os achados endoscópicos e os sintomas dispépticos. Não observamos influência dos AINEs no aparecimento de esofagite erosiva / Introduction: The non steroidal anti-inflammatory drugs (NSAID), including aspirin, are drugs widely used in the treatment of inflammatory diseases and pain. This use may cause serious side-effects, leading to considerable morbidity and mortality related to ulcer, duodenal and gastric disease, especially gastrointestinal bleeding. The overall relative risk of gastroduodenal complications is three to ten times higher in users of NSAID, compared to healthy individuals. Around 25% of the chronic users of non steroidal anti-inflammatory drugs (NSAID) will develop ulcer disease, and 2 to 4% will present bleeding or perforation. More than 17,000,000 North Americans use several kinds of non steroidal anti-inflammatory drugs (NSAID) on a daily basis. This causes more than 100,000 hospitalizations and from 7,000 to 10,000 deaths every year in the USA, which makes this drug one of the most commonly used on the planet. About 50% of the lesions observed in endoscopies occur without any kind of symptom. It is believed that there was an increase in the prevalence of digestive lesions due to the replacement of COX-2 anti-inflammatory drugs with traditional anti-inflammatory drugs, especially because of the lack of preventive care of this kind of occurrence in at-risk populations. Goals: a) Evaluate the prevalence of lesions and digestive complications, secondary to the use of NSAID; b) Evaluate the clinical profile of the patient seen for digestive complaints and the relation of these complaints with the endoscopic findings. Materials and Methods: Prospective, multi-centric, open study, evaluating consecutively 1,231 patients who underwent upper gastrointestinal endoscopy exam due to digestive complaints in isolation or associated, such as: 1) pyrosis; 2) epigastric pain; 3) abdominal pain; 4) nausea; 5) vomiting. Before performing the exam of upper gastrointestinal endoscopy, patients answered a questionnaire whose goal was to evaluate the onset and kind of clinical complaint, the use of medication and possible complications associated to digestive bleeding. The inclusion criteria were: Patients of both sexes with the minimum age of 18 and whose symptoms had begun up to 14 days before undergoing the upper gastrointestinal endoscopy. Exclusion criteria: patients who refused to participate in the study and/ or who refused to sign the Informed Consent Term, the ones who were unable to respond to the questionnaire, the ones who were under 18 years old, patients who had undergone a previous gastric surgery and patients with kidney or hepatic failure. Results: 1,213 patients with ages ranging from 18-82 were evaluated, 65% of which were female and 13,1% were smokers, 15,6% mentioned they ingested alcoholic beverages. The use of NSAID was more frequent among females. However, the number of complications was higher among males (bleeding occurred twice as much; p=0,045 and the occurrence of ulcer was almost 1,5 times higher; p=0,041). The main signs and symptoms reported were epigastralgia and pyrosis (67% and 62%). The 1,213 patients were divided into two groups: Group I- NSAID, made up by 228 (18,8%) and Group II- Non NSAID, made up by 985 patients (81,2%). The upper gastrointestinal endoscopy was normal in 3,9% of the patients in Group I and in 10,7% of the patients in Group II (p<0,001). A patient who does not use NSAID will be 2,5 times more likely to have normal upper gastrointestinal endoscopy than the one who used NSAID (p=0,001). The presence of erosive or ulcer lesions in the stomach and duodenum was more frequent in Group I patients when compared to those of Group II. It is observed that the incidence of lesions in the stomach, both erosive and ulcer is higher when compared to the duodenum (erosions: 49,12% vs. 13,60, p=0,001; ulcers: 14,04% vs. 11,84, p= 0,05). The risk of digestive bleeding is 12 times higher (6,14% vs. 0,51%) in patients who used NSAID, and the stomach is the site with higher prevalence of bleeding. No statistic difference was observed when the presence of erosive esophagitis in both groups was analyzed. Conclusions: We observed that the frequency of gastric ulcer, duodenal ulcer and digestive bleeding was higher in patients who used NSAID. Relations between the endoscopic findings and the dyspeptic symptoms were not found. The influence of NSAIDs on the appearance of erosive esophagitis was not observed

L'objectiu principal d'aquestaTesi Doctoral és el desenvolupament de diferents estratègies per disminuir els límits de detecció de l’electroforesicapil•lar per a la determinació de compostos farmacèutics i els productes de cura personal. Aquestes estratègies es basen en les tècniques de preconcentració electroforètiques i cromatogràfiques, i l'ús de l’espectrometria de masses com a sistema de detecció. Com a tècniques de preconcentració electroforètiques s'han estudiat les tècniques de samplestacking i sweeping, i com a tècnica de preconcentració cromatogràficas’ha avaluat l'acoblament en línia entre l'extracció en fase sòlida i l'electroforesicapil•lar (In-line SPE-CE). Entre elsPPCPs, aquesta tesi doctoral es centra específicament en els antiinflamatoris no esteroïdals(AINE), els parabens i els filtres ultraviolats. Un altre dels objectius d'aquestaTesi Doctoral és estudiarl’aplicabilitat de les metodologies desenvolupades per a l'anàlisi de mostres ambientals per determinar PPCP. / The main objective of this Doctoral Thesis is the development of different strategies to decrease the detection limits of capillary electrophoresis for the determination of pharmaceutical and personal care products. These strategies are based on electrophoretic and chromatographic preconcentration techniques, and the use of mass spectrometry as a detection system. The electrophoretic preconcentration techniques studied included sample stacking techniques and sweeping while the chromatographic preconcentration technique evaluated was in-line coupling between solid phase extraction and capillary electrophoresis. With respect to PPCPs, this Doctoral Thesis focuses specifically on non-steroidal anti-inflammatory drugs (NSAIDs), parabens and UV-filters. Another objective of this Doctoral Thesis is to study the suitability of the developed methodologies for the determination of PPCPs in environmental samples.

Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Eliška Holinská Supervisor: Prof. MUDr. Radomír Hrdina, CSc. Title of diploma thesis: Pharmacoteraphy of headache in adults Headache is one of the most common health problem that encounters almost everyone during the life. Depending on the cause, headaches can be divided on the primary headaches, which are the subject of the diploma thesis, and secondary headaches, which are caused by other diseases. The primary headaches are migraine, tension-type headache, cluster headache and primary chronic daily headache. Headache is not a life-threating condition but it can significantly reduce the quality of life, particularly the chronic forms of headache. The determination of the right diagnosis is essential for the choice of appropriate therapy. For primary headache are typical negative test results, there are no structural lesions or signs of organic brain damage. Diagnostics is comlicated and it is primarily based on a carefully processed medical history. In the therapy of primary headache are used both pharmacological and non-pharmacological methods, optimaly in combination. Pharmacological treatment consists of preventive and acute therapy. The preventive treatment is given to reduce the...

Conselho Nacional de Desenvolvimento Científico e Tecnológico / Studies on the topical use of diclofenac in horses deal mostly with pharmacokinetics and the clinical effect of the medication, few studies addressed its tolerability or its oral use. The aim of this study was to obtain data related to pharmacokinetics and distribution of diclofenac sodium in synovial fluid after oral or topical administration in healthy ponies as well as to evaluate the tolerability of oral and topical diclofenac sodium administered on a frequency similar to a treatment period. Healthy ponies were divided into three groups and treated with topical (group I, n = 6) or oral (group II, n = 6) diclofenac at a dose of 2.5 mg kg-1 and oral phenylbutazone (group III, n = 3) at a dose of 2.2 mg kg-1. To evaluate the bioavailability blood samples were collected at different times, from 30 minutes to 144 hours and synovial fluid samples 6, 12 and 24 hours, after starting treatment. Blood samples collected 24 hours before and until 144 hours after starting treatment were used for CBC, WBC, biochemical and coagulation profiles. A significant difference was found between group I and group II on prothrombin time, activated partial thromboplastin time, fibrinogen, hematocrit, hemoglobin, erythrocytes, total leukocytes, neutrophils, band cells, lymphocytes, eosinophils, and alkaline phosphatase. Similar results were found between group II and group III, however, the activated partial thromboplastin time did not differ. Even though the plasma concentration of diclofenac sodium was higher in group II than in group I, the synovial concentration tended to be higher in group I. The diclofenac bioavailability and tolerability data obtained in ponies showed that the topic administration delivered therapeutic concentrations of diclofenac and proved to be safer, as the oral administration resulted in blood changes. / Os estudos sobre a utilização tópica do diclofenaco conduzidos na espécie equina abordam em sua maioria a farmacocinética e o efeito clínico desta medicação. A tolerabilidade frente ao diclofenaco e a utilização deste medicamento por via oral têm sido pouco estudadas. Nossos objetivos foram obter dados relacionados à farmacocinética sanguínea e distribuição do diclofenaco de sódio no líquido sinovial, após a administração oral e tópica em pôneis sadios, bem como avaliar a tolerabilidade do diclofenaco de sódio administrado por via oral e tópica, usando uma frequência de administração semelhante a um período de tratamento. Pôneis clinicamente sadios foram divididos em três grupos e tratados com diclofenaco por via tópica (grupo I, n=6) e oral (grupo II, n=6), na dose de 2,5 mg kg-1 e fenilbutazona oral (grupo III, n=3) na dose de 2,2 mg kg-1. Para avaliar a biodisponibilidade foram coletadas amostras de sangue em diferentes momentos, desde 30 minutos até 144 horas após início do tratamento e amostras de líquido sinovial as 6, 12 e 24 horas, após o início do tratamento. Amostras de sangue foram coletadas a cada 24 horas até 144 horas após início do tratamento para hemograma, leucograma, bioquímico e coagulograma. Diferenças significativas foram encontradas entre o grupo I e o grupo II em determinados tempos no tempo de protrombina, tempo de tromboplastina parcial ativado, fibrinogênio, hematócrito, hemoglobina, hemácias, leucócitos totais, segmentados, bastonetes, linfócitos, eosinófilos e fosfatase alcalina. Resultados semelhantes foram observados entre o grupo II e o grupo III, no entanto o tempo de tromboplastina parcial ativado não apresentou diferença. Embora a concentração plasmática do diclofenaco de sódio no grupo II tenha sido mais elevada que no grupo I, a concentração sinovial foi maior no grupo I. Os dados obtidos sobre a biodisponibilidade e tolerabilidade do diclofenaco em pôneis mostram que a aplicação tópica é superior à oral por resultar em concentrações sinoviais mais elevadas do fármaco, além de ser mais segura, pois não alterou significativamente os parâmetros avaliados.