Loh Shwu Chun. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (leaves [109]-120). / Abstracts in English and Chinese; appendix also in Chinese. / Acknowledgements --- p.i / Abstract --- p.ii / Abstract (in Chinese) --- p.iv / List of Abbreviations --- p.v / List of Tables --- p.vii / List of Figures --- p.ix / Table of Contents / Chapter Chapter One: --- Introduction and Study Objectives / Chapter 1. --- Introduction --- p.1 / Chapter 1.1 --- Definition and diagnostic criteria of the metabolic syndrome --- p.2 / Chapter 1.2 --- Clinical states of the metabolic syndrome --- p.5 / Chapter 1.2.1 --- Impaired Glucose Tolerance (IGT) and Impaired Fasting Glucose (IFG) --- p.6 / Chapter 1.2.2 --- The metabolic syndrome and type 2 diabetes mellitus --- p.7 / Chapter 1.2.3 --- Dyslipidaemia --- p.8 / Chapter 1.2.4 --- Hypertension --- p.10 / Chapter 1.2.5 --- Obesity --- p.11 / Chapter 1.3 --- Effects of weight loss on the metabolic syndrome --- p.13 / Chapter 1.4 --- Ethnic differences in the prevalence of the metabolic syndrome --- p.15 / Chapter 1.5 --- Treatment of the metabolic syndrome --- p.16 / Chapter 1.6 --- Oral Hypoglycaemic agents and their failure in the metabolic syndrome --- p.17 / Chapter 1.6.1 --- Sulphonylureas --- p.17 / Chapter 1.6.2 --- Biguanides --- p.18 / Chapter 1.6.3 --- Alpha-glucosidase Inhibitors --- p.20 / Chapter 1.6.4 --- Peroxisome Proliferator-Activated Receptors (PPARs) --- p.21 / Chapter 1.6.4.1 --- Thiazolinedinediones --- p.22 / Chapter 1.6.4.1.1 --- Rosiglitazone --- p.24 / Chapter 1.6.4.1.1.1 --- Mode of Action --- p.24 / Chapter 1.6.4.1.1.2 --- Adverse events and current status --- p.26 / Chapter 1.7 --- Orlistat --- p.27 / Chapter 1.7.1 --- Mode of Action --- p.28 / Chapter 1.7.2 --- Adverse events and current status --- p.28 / Chapter 1.7.3 --- Therapeutic Potential in the Metabolic Syndrome --- p.29 / Chapter 1.8 --- Study Hypothesis --- p.30 / Chapter 1.9 --- Study Objectives --- p.30 / Chapter Chapter Two: --- Research Design and Methods / Chapter 2 --- Study Protocol --- p.31 / Chapter 2.1 --- Overall Design --- p.31 / Chapter 2.1.1 --- Patients Selection Criteria --- p.31 / Chapter 2.1.1.1 --- Inclusion Criteria --- p.31 / Chapter 2.1.1.2 --- Exclusion Criteria --- p.33 / Chapter 2.1.2 --- Recruitment Period --- p.34 / Chapter 2.1.2.1 --- Screening Period --- p.34 / Chapter 2.1.2.2 --- Run- In Period (Visit 0) --- p.35 / Chapter 2.1.2.3 --- Randomisation --- p.35 / Chapter 2.1.2.4 --- Evaluation Periods (Visit 2 to 4) --- p.37 / Chapter 2.2 --- Investigations --- p.37 / Chapter 2.2.1 --- Oral Glucose Tolerance Test (OGTT) --- p.38 / Chapter 2.2.2 --- Anthropometric measurements --- p.38 / Chapter 2.3 --- Analytical Methods --- p.39 / Chapter 2.3.1 --- Determinations of insulin levels in plasma samples --- p.39 / Chapter 2.3.1.1 --- Principle of the Insulin assay --- p.40 / Chapter 2.3.2 --- Determinations of glucose concentrations in samples --- p.42 / Chapter 2.3.2.1. --- Principle of the glucose assay --- p.42 / Chapter 2.4 --- Calculations --- p.43 / Chapter 2.4.1 --- Insulin (hepatic) sensitivity (HOMA) --- p.43 / Chapter 2.4.2 --- Area Under the Curves --- p.44 / Chapter 2.4.3 --- Sample Size Calculations --- p.45 / Chapter 2.5 --- Statistical Analysis --- p.46 / Chapter Chapter Three: --- Results / Chapter 3.1 --- Study Population --- p.48 / Chapter 3.2 --- Randomisation --- p.49 / Chapter 3.3 --- Study Results --- p.50 / Chapter 3.3.1 --- Indices of Glycaemic Control --- p.54 / Chapter 3.3.1.1 --- HbAlc --- p.54 / Chapter 3.3.1.2 --- Fasting Plasma Glucose --- p.58 / Chapter 3.3.1.3 --- Fasting Insulin --- p.58 / Chapter 3.3.1.4 --- 75g Oral Glucose Tolerance Test --- p.59 / Chapter 3.3.1.4.1 --- Glucose --- p.59 / Chapter 3.3.1.4.1.1 --- 2hr-Glucose --- p.61 / Chapter 3.3.1.4.1.2 --- GlucoseAuc --- p.62 / Chapter 3.3.1.4.2 --- Insulin --- p.63 / Chapter 3.3.1.4.2.1 --- 2-hr insulin --- p.63 / Chapter 3.3.1.4.2.2 --- InsulinAuc --- p.65 / Chapter 3.3.1.5 --- HOMA score --- p.67 / Chapter 3.3.2 --- Clinical Determinants --- p.69 / Chapter 3.3.2.1 --- Lipid Profiles --- p.69 / Chapter 3.3.2.1.1. --- Total Cholesterol --- p.69 / Chapter 3.3.2.1.2 --- HDL-Cholesterol --- p.70 / Chapter 3.3.2.1.3 --- LDL-Cholesterol --- p.71 / Chapter 3.3.2.1.4 --- Triglycerides --- p.72 / Chapter 3.3.2.2 --- Anthropometric Evaluations --- p.74 / Chapter 3.3.2.2.1 --- Body Weight --- p.74 / Chapter 3.3.2.2.2 --- Waist Circumference Difference --- p.75 / Chapter 3.3.2.2.3 --- Hip --- p.76 / Chapter 3.3.2.2.4 --- Body Fat --- p.78 / Chapter 3.3.2.2.5 --- BMI --- p.78 / Chapter 3.3.2.3 --- Blood Pressure --- p.79 / Chapter 3.3.2.4 --- RCCA and LCCA --- p.79 / Chapter 3.3.2.5 --- Other outstanding measurements --- p.82 / Chapter 3.4 --- Side Effects experienced --- p.82 / Chapter Chapter Four: --- Discussion and Conclusion / Chapter 4.1 --- Summary of the results --- p.83 / Chapter 4.1.1 --- Effects of Diet and Lifestyle Changes --- p.83 / Chapter 4.1.2 --- Effects of Orlistat --- p.84 / Chapter 4.1.3 --- Effects of Rosiglitazone --- p.35 / Chapter 4.2 --- Implications for therapy --- p.86 / Chapter 4.2.1 --- Management of metabolic syndrome --- p.87 / Chapter 4.2.2 --- Early Diagnosis --- p.88 / Chapter 4.2.3 --- Lifestyle Modification --- p.89 / Chapter 4.2.4 --- Pharmacological Targets --- p.92 / Chapter 4.2.4.1 --- Statins --- p.92 / Chapter 4.2.4.2 --- Fibrates --- p.93 / Chapter 4.2.4.3 --- ACE Inhibitors --- p.93 / Chapter 4.2.4.4 --- Thiazolidinediones --- p.94 / Chapter 4.2.4.4.1 --- Economic Evaluations of Thiazolidinediones --- p.97 / Chapter 4.2.4.5 --- Orlistat --- p.98 / Chapter 4.2.4.5.1 --- Economic Evaluations of Orlistat --- p.102 / Chapter 4.3 --- Limitations of the study --- p.104 / Chapter 4.3.1 --- Small sample size --- p.104 / Chapter 4.3.2 --- Short period of study --- p.105 / Chapter 4.3.3 --- Adherence to lifestyle modifications --- p.105 / Chapter 4.3.4 --- Analytical assays --- p.106 / Chapter 4.3.5 --- Follow up end of study --- p.106 / Chapter 4.3.6 --- Ultrasound measurement of the common carotid arteries --- p.106 / Chapter 4.3.7 --- Availability of thiazolinediones --- p.107 / Chapter 4.4 --- Conclusion and Implications for future studies --- p.107 / References --- p.110 / Appendix I --- p.121 / Appendix II --- p.122 / Appendix III --- p.125

Diss. (sammanfattning) Linköping : Univ., 2005. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 4 uppsatser.

Made available in DSpace on 2014-08-13T14:50:42Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-07-30Bitstream added on 2014-08-13T18:00:56Z : No. of bitstreams: 1 000750041.pdf: 2177704 bytes, checksum: 3b2c1f34dc67cf43d4c50a885f043499 (MD5) / O termo Diabetes mellitus (DM) descreve uma desordem metabólica caracterizada por hiperglicemia crônica que leva a alterações no metabolismo de carboidratos, lipídeos e proteínas resultante de defeitos na ação, secreção de insulina, ou ambos. Tais alterações levam a sérias consequências no individuo diabético, como perda de peso, aumento dos níveis de lipídeos no sangue podendo levar ao aumento da incidência de doenças cardiovasculares como aterosclerose e infarto. Além disso, pode causar doenças renais e danos à visão, e em casos mais graves, óbito. A incidência de pessoas diabéticas tem aumentado a cada ano, e pesquisas realizadas recentemente apontam que esse é um número que só tende a aumentar nos próximos anos, principalmente devido aos péssimos hábitos alimentares e estilo de vida sedentário. O tratamento para o DM inclui insulinoterapia e o uso de hipoglicemiantes orais. No entanto, sabe-se que esses medicamentos possuem efeitos adversos, como ganho de peso, desconfortos abdominais e diarreias. Partindo dessas informações, a busca de novas alternativas para o tratamento de DM tem crescido muito nos últimos anos. O uso de plantas medicinais no tratamento de diversas doenças, como o diabetes, é feito desde os primórdios da humanidade. Diante disso, a pesquisa envolvendo plantas medicinais com propriedades hipoglicemiantes tem sido alvo dos pesquisadores nos últimos anos, principalmente para comprovação da sua eficácia e verificação da toxicidade das mesmas. A família Fabaceae possui aproximadamente 300 espécies, popularmente conhecidas como pata-de-vaca ou unhade- boi, devido ao formato de suas folhas e são amplamente utilizadas como analgésicos, antiinflamatórios e no tratamento de diabetes. O gênero Bauhinia, pertencente a essa família possui muitas espécies que são utilizadas no tratamento do diabetes. Diante disso, o objetivo desse trabalho foi avaliar a atividade hipoglicemiante do ... / The term Diabetes mellitus (DM) defines a metabolic disorder characterized by cnronic hyperglycemia, which leads to alterations in carbohydrate, proteins and lipids metabolism resultant of defects in insulin action andJor secretion. Those alterations lead to serious consequences to diabetic people as weight loss, increase incidence of cardiovascular diseases, renal and optical diseases, and in some cases, death. The incidence of diabetic people is increasing every year and recent1y researches showed that this number will increase on next years, mainly due to bad eating habits and sedentary life style. The treatment of DM inc1udes insulin therapy and the use of oral hypoglycemic agents. However, those medicaments have many collateral effects as weight gain, abdominal discomforts and diarrheas. Based on this information, studies involving new altematives for the treatment of DM are growing in the last years. The use of medicinal plants in the treatment of diverse diseases like diabetes has been done since the beginning of humanity. Due to this, the studies involving medicinal plants with hypoglycemic properties have been the target of researches in the last years, mainly to verify its effectiveness and toxicity. The family Fabaceae has approximately 300 species, which are popular1y called cow's foot and nail ox, due the format of theirs leafs and are largely used as analgesic, anti-inflammatory and hypoglycemic. The genus Bauhinia, belonging to this family has many species, which are used in diabetes treatment, and it has been researches target showing promising results. Because of that, the objective of this work was to evaluate the hypoglycemic activity of crude extract of Bauhinia holophylla, a species very used in traditional medicine. There are no studies that prove its effectiveness in the diabetes treatment. Swiss mice diabetic (STZSAL and STZEXT) and normoglycemic (CTLSAL and CTLEXT) received treatment for 15 days with the crude ...

Orientador: José Roberto Bosqueiro / Banca: Luiz Otávio Regasini / Banca: Débora Cristina Damasceno / Resumo: O termo Diabetes mellitus (DM) descreve uma desordem metabólica caracterizada por hiperglicemia crônica que leva a alterações no metabolismo de carboidratos, lipídeos e proteínas resultante de defeitos na ação, secreção de insulina, ou ambos. Tais alterações levam a sérias consequências no individuo diabético, como perda de peso, aumento dos níveis de lipídeos no sangue podendo levar ao aumento da incidência de doenças cardiovasculares como aterosclerose e infarto. Além disso, pode causar doenças renais e danos à visão, e em casos mais graves, óbito. A incidência de pessoas diabéticas tem aumentado a cada ano, e pesquisas realizadas recentemente apontam que esse é um número que só tende a aumentar nos próximos anos, principalmente devido aos péssimos hábitos alimentares e estilo de vida sedentário. O tratamento para o DM inclui insulinoterapia e o uso de hipoglicemiantes orais. No entanto, sabe-se que esses medicamentos possuem efeitos adversos, como ganho de peso, desconfortos abdominais e diarreias. Partindo dessas informações, a busca de novas alternativas para o tratamento de DM tem crescido muito nos últimos anos. O uso de plantas medicinais no tratamento de diversas doenças, como o diabetes, é feito desde os primórdios da humanidade. Diante disso, a pesquisa envolvendo plantas medicinais com propriedades hipoglicemiantes tem sido alvo dos pesquisadores nos últimos anos, principalmente para comprovação da sua eficácia e verificação da toxicidade das mesmas. A família Fabaceae possui aproximadamente 300 espécies, popularmente conhecidas como pata-de-vaca ou unhade- boi, devido ao formato de suas folhas e são amplamente utilizadas como analgésicos, antiinflamatórios e no tratamento de diabetes. O gênero Bauhinia, pertencente a essa família possui muitas espécies que são utilizadas no tratamento do diabetes. Diante disso, o objetivo desse trabalho foi avaliar a atividade hipoglicemiante do ... / Abstract: The term Diabetes mellitus (DM) defines a metabolic disorder characterized by cnronic hyperglycemia, which leads to alterations in carbohydrate, proteins and lipids metabolism resultant of defects in insulin action andJor secretion. Those alterations lead to serious consequences to diabetic people as weight loss, increase incidence of cardiovascular diseases, renal and optical diseases, and in some cases, death. The incidence of diabetic people is increasing every year and recent1y researches showed that this number will increase on next years, mainly due to bad eating habits and sedentary life style. The treatment of DM inc1udes insulin therapy and the use of oral hypoglycemic agents. However, those medicaments have many collateral effects as weight gain, abdominal discomforts and diarrheas. Based on this information, studies involving new altematives for the treatment of DM are growing in the last years. The use of medicinal plants in the treatment of diverse diseases like diabetes has been done since the beginning of humanity. Due to this, the studies involving medicinal plants with hypoglycemic properties have been the target of researches in the last years, mainly to verify its effectiveness and toxicity. The family Fabaceae has approximately 300 species, which are popular1y called cow's foot and nail ox, due the format of theirs leafs and are largely used as analgesic, anti-inflammatory and hypoglycemic. The genus Bauhinia, belonging to this family has many species, which are used in diabetes treatment, and it has been researches target showing promising results. Because of that, the objective of this work was to evaluate the hypoglycemic activity of crude extract of Bauhinia holophylla, a species very used in traditional medicine. There are no studies that prove its effectiveness in the diabetes treatment. Swiss mice diabetic (STZSAL and STZEXT) and normoglycemic (CTLSAL and CTLEXT) received treatment for 15 days with the crude ... / Mestre

Chan Siu-Wah. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (leaves 173-200). / Abstracts in English and Chinese; appendix in Chinese. / Table of Contents --- p.i / Abstract --- p.v / 論文摘要 --- p.ix / Acknowledgments --- p.xii / Table of Figures --- p.xiii / Table of Tables --- p.xvii / Chapter Chapter 1. --- Introduction --- p.1 / Chapter Chapter 2. --- Literature Review --- p.3 / Chapter 2.1 --- Diabetes Mellitus (DM)： Overview --- p.3 / Chapter 2.1.1 --- Diagnosis and Diagnostic Criteria --- p.4 / Chapter 2.1.2 --- Classifications of Diabetes Mellitus --- p.8 / Chapter 2.1.3 --- Management of Type 2 Diabetes Mellitus --- p.15 / Chapter 2.2 --- Diabetes Mellitus Complications： Overview --- p.25 / Chapter 2.2.1 --- Microvascular Complications --- p.26 / Chapter 2.2.2 --- Macrovascular Complications --- p.31 / Chapter 2.3 --- Type 2 Diabetes Mellitus - A Rising Global Burden --- p.32 / Chapter 2.3.1 --- Prevalence of Type 2 Diabetes Mellitus --- p.32 / Chapter 2.3.2 --- Prevalence of Type 2 Diabetes Mellitus in Hong Kong --- p.36 / Chapter 2.3.3 --- Mortality and Morbidity of Type 2 Diabetes Mellitus in Hong Kong --- p.40 / Chapter 2.4 --- cost of Type 2 Diabetes Mellitus - Under-explored Area in Hong Kong and Asia --- p.46 / Chapter 2.4.1 --- Cost of Type 2 Diabetes Mellitus in the USA --- p.48 / Chapter 2.4.2 --- Cost of Type 2 Diabetes Mellitus in Europe --- p.57 / Chapter 2.4.3 --- Cost of Type 2 Diabetes Mellitus in Asia-Pacific --- p.61 / Chapter 2.5 --- Hong Kong Healthcare System --- p.65 / Chapter 2.5.1 --- Hospital Authority in Hong Kong (Public Healthcare Sector) --- p.67 / Chapter 2.5.2 --- Hong Kong Healthcare Financing System --- p.73 / Chapter 2.6 --- New Emerging Drug Treatment for Type 2 DM in Hong Kong Chinese - Rosiglitazone --- p.77 / Chapter 2.6.1 --- Clinical Efficacy and Tolerability of Rosiglitazone --- p.77 / Chapter 2.6.2 --- Cost-effectiveness of Rosiglitazone --- p.78 / Chapter Chapter 3. --- Hypothesis and Objectives --- p.81 / Chapter 3.1 --- Cost of Type 2 Diabetes Mellitus in Hong Kong Chinese --- p.81 / Chapter 3.1.1 --- Hypothesis --- p.81 / Chapter 3.1.2 --- Objectives --- p.81 / Chapter 3.2 --- Cost-effectiveness Analysis of Metformin + Rosiglitazone vs. Metformin + Glibenclamide for Type 2 DM Patient Whose Diabetes is not Adequately Controlled by Metformin Alone from a Payer's Perspective --- p.82 / Chapter 3.2.1 --- Hypothesis --- p.82 / Chapter 3.2.2 --- Objectives --- p.83 / Chapter Chapter 4. --- Cost of Type 2 Diabetes Mellitus in Hong Kong Chinese --- p.84 / Chapter 4.1 --- Subjects and Methods --- p.84 / Chapter 4.1.1 --- Subjects --- p.84 / Chapter 4.1.2 --- Methods --- p.85 / Chapter 4.1.3 --- Validity and Reliability of the Chinese Questionnaire --- p.96 / Chapter 4.2 --- Results --- p.96 / Chapter 4.2.1 --- Subjects' Characteristics --- p.96 / Chapter 4.2.3 --- Comorbidity --- p.102 / Chapter 4.2.4 --- Complications --- p.102 / Chapter 4.2.5 --- Costs of Type 2 DM --- p.104 / Chapter 4.3 --- Discussions --- p.123 / Chapter Chapter 5 --- Cost-effectiveness Analysis of Metformin + Rosiglitazone vs. Metformin + Glibenclamide for Type 2 DM Patient Whose Diabetes is not Adequately Controlled by Metformin Alone from a Payer's Perspective --- p.134 / Chapter 5.1 --- Methods --- p.134 / Chapter 5.1.1 --- Model Overview --- p.134 / Chapter 5.1.2 --- "Success, Failure and Discontinuation Rates" --- p.138 / Chapter 5.1.3 --- Resources Use and Costs --- p.142 / Chapter 5.1.4 --- Health-Related Quality of Life (HRQOL) --- p.148 / Chapter 5.1.5 --- Base Case Analysis --- p.149 / Chapter 5.1.6 --- Sensitivity Analyses --- p.149 / Chapter 5.2 --- Results --- p.150 / Chapter 5.2.1 --- Base Case Model - CE Analysis: cost per controlled Type 2 DM patient --- p.150 / Chapter 5.2.2 --- Sensitivity Analysis- CE Analysis: cost per controlled Type 2 DM patient --- p.151 / Chapter 5.2.3 --- Base Case Model - CE Analysis: cost per EQ5D utility score --- p.154 / Chapter 5.2.4 --- Sensitivity Analysis- CE Analysis: cost per EQ5D utility score --- p.155 / Chapter 5.3 --- Discussions --- p.158 / Chapter Chapter 6. --- Conclusions --- p.163 / Appendix --- p.165 / References

<p>Gliklazid je jedan od najče&scaron;će kori&scaron;ćenih lekova u terapiji dijabetes melitusa tip 2. U poslednje vreme, utvrđeno je da gliklazid ispoljava i druge pozitivne farmakolo&scaron;ke efekte kao &scaron;to su imunomodulatorni i anti-koagulacioni efekti, ukazujući na njegovu potencijalnu primenu u terapiji dijabetes melitusa tip 1. Gliklazid se odlikuje varijabilnim stepenom apsorpcije nakon peroralne primene i iz tog razloga pretpostavlja se da bi tehnike njegove ciljane isporuke, kao &scaron;to je mikroinkapsulacija, mogle da dovedu do pobolj&scaron;anja njegove apsorpcije i njegove potencijalne primene u terapiji T1DM. Pokazano je da različite žučne kiseline, uključujući i holnu, imaju stabilizacione efekte u domenu primene mikrovezikula i kontrolisanog osobađanja lekova, te je moguće da bi njihov dodatak u mikrovezikularnu formulaciju gliklazida mogao dodatno da pobolj&scaron;a oslobađanje gliklazida, njegovu apsorpciju i antidijabetičke efekte. S tim u vezi, cilj ovog istraživanja je da se ispita hipoglikemijski efekat gliklazida primenjenog u obliku alginatnih mikrovezikula, sa ili bez dodatka holne kiseline na T1DM modelu pacova. Trideset &scaron;est pacova obolelih od T1DM indukovanog aloksanom i odgovarajuće zdrave kontrolne životinje su nasumično raspoređene u &scaron;est grupa (n=6) i tretirane jednokratnom dozom fiziolo&scaron;kog rastvora, suspenzijom gliklazida, gliklazidom u obliku alginatnih mikrovezikula, samo holnom kiselinom, i mikrovezikulama gliklazida sa ili baz dodatka holne kiseline. Uzorkovana je krv tokom 10 h nakon unete doze i merena je koncentracija glukoze u krvi I koncentracija gliklazida u serumu kori&scaron;ćenjem HPLC metode. Mikrovezikule gliklazida su ispoljile hipo-glikemijski efekat kod pacova obolelih od dijabetesa, uprkos njegovim smanjenim koncentracijama u serumu, dok je dodatak holne kiseline u mikrovezikularnu formulaciju smanjio hipoglikemijski efekat gliklazida. Ovo potvrđuje izostanak sinergističkog efekta između gliklazida i holne kiseline. Takođe, ni proces mikroinkapsulacije niti dodatak holne kiseline nisu doprineli pobolj&scaron;anju apsorpcije gliklazida, &scaron;to ukazuje na činjenicu da su njegovi hipoglikemijski efekti nezavisni od njegove apsorpcije i koncentracije u serumu. Stoga se može pretpostaviti da su hipoglikemijski efekti gliklazida pre pod uticajem crevno-metaboličke aktivacije nego ciljanog oslobađanja u digestivnom traktu sistemske apsorpcije. Mikrovezikule gliklazida ispoljavaju hipoglikemijski efekat kod pacova obolelih od T1DM nezavisno od insulina, te mogu imati potencijalnu primenu u terapiji T1DM. Ovaj rad su podržali: HORIZON 2020 MEDLEM projekat broj 690876; Projekat Sekretarijata naučnog i tehnolo&scaron;kog razvoja Vojvodine broj . 114-451-2072-/2016-02; Projekat Ministarstva obrazovanja, nauke i tehnolo&scaron;kog razvoja Republike Srbije broja 41012.</p> / <p><!--[if gte mso 9]><xml> <o:DocumentProperties> <o:Author>mladen</o:Author> <o:Version>16.00</o:Version> </o:DocumentProperties> <o:OfficeDocumentSettings> <o:AllowPNG/> </o:OfficeDocumentSettings></xml><![endif]--><!--[if gte mso 9]><xml> <w:WordDocument> <w:View>Normal</w:View> <w:Zoom>0</w:Zoom> <w:TrackMoves/> <w:TrackFormatting/> <w:PunctuationKerning/> <w:ValidateAgainstSchemas/> <w:SaveIfXMLInvalid>false</w:SaveIfXMLInvalid> <w:IgnoreMixedContent>false</w:IgnoreMixedContent> <w:AlwaysShowPlaceholderText>false</w:AlwaysShowPlaceholderText> <w:DoNotPromoteQF/> <w:LidThemeOther>EN-US</w:LidThemeOther> <w:LidThemeAsian>X-NONE</w:LidThemeAsian> <w:LidThemeComplexScript>X-NONE</w:LidThemeComplexScript> 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<p>Iako je dijabetes melitus (DM) tip 2 je hronično oboljenje čija se stopa značajno povećala poslednjih decenija, podaci o odnosu pacijenta prema leku i lečenju dijabetes melitusa su retki i odnose se na pojedine aspekte terapije. Glavni kamen spoticanja u lečenju dijabetesa jeste nepridržavanje pacijenata propisanim lekovima, &scaron;to otežava održavanje normalne glikoregulacije i doprinosi razvoju te&scaron;kih komplikacija koje značajno utiču na kvalitet života pacijenata sa DM. Raspolaganje tačnim podacima o upotrebi antidijabetičnim lekova, kao i uvidom u realno stanje o odnosu pacijenata prema leku u lečenju DM tipa 2, omogućava pobolj&scaron;anje farmakoterapijske prakse i kreiranje intervencije za pobolj&scaron;anje adherencije pacijenata Ciljevi ovog istraživanja bili su: 1) analiza obima potro&scaron;nje i strukture antidijabetičnih lekova na teritoriji Republike Srpske i njihovo poređenje sa upotrebom i strukturom propisivanja u okolnim zemljama kao i državama sa razvijenom farmakoterapijskom praksom; 2) analiza obima potro&scaron;nje i strukture antidijabetičnih lekova u op&scaron;tini Foča i poređenje sa savremenim farmakoterapijskim smernicama; 3) određivanje procenta pokrivenosti antidijabetičnom terapijom pacijenata sa DM tip 2 tokom jedne godine u op&scaron;tini Foča; 4) određivanje adherencije pacijenata sa DM tipa 2 prema antidijabetičnoj terapiji metodom brojanja tableta/doza insulina i putem validiranog upitnika; 5) određivanje kvaliteta života povezanog sa zdravljem pacijenata sa DM tipa 2 u op&scaron;tini Foča primenom validiranog upitnika SF-36v2; 6) određivanje prediktora neadherenije kod primene obe metode merenja adherencije u odnosu na karakteristike i kvalitet života pacijenata sa DM tip 2 u op&scaron;tini Foča. Ispitivanje se sastojalo iz dva dela. U prvom delu sprovedeno je retrospektivno farmakoepidemiolo&scaron;ko praćenje upotrebe antidijabetičnih lekova kao i određivanje strukture ovih lekova na teritoriji Republike Srpske u periodu od 01.01.2013. do 31.12.2013.godine i izvr&scaron;eno je poređenje sa upotrebom i strukturom propisivanja u okolnim zemljama kao i državama sa razvijenom farmakoterapijskom praksom. U drugom delu ispitivanja sprovedeno je farmakoepidemiolo&scaron;ko ispitivanje primene antidijabetičnih lekova na nivou same op&scaron;tine Foča u okviru koje je pored analize obima potro&scaron;nje i strukture antidijabetičnih lekova u istom periodu kao i na teritoriji Republike Srpske i poređenja sa savremenim farmakoterapijskim smernicama, određivan i procenta pokrivenosti antidijabetičnom terapijom mereno redovno&scaron;ću ponovnih popunjavanja recepata od strane lekara op&scaron;te prakse tokom jednogodi&scaron;njeg perioda. Takođe je sprovedeno i ispitivanje adherencije prema antidijabetičnim lekovima primenom dve različite metode merenja kao i kvalitet života pacijenata sa DM tip 2 između 01.01.2015. i 31.12.2015.godine. Ukupna upotreba antidijabetika za lečenje dijabetesa tip 1 i tip 2 na teritoriji Republike Srpske iznosila je 38,29 DDD/1000st/dan. Upotreba insulina i analoga iznosila je 11,28 DDD/1000st/dan. Ukupna upotreba oralnih lekova koji snižavaju glukozu i krvi, isključujući insuline iznosila je 27,01 DDD/1000st/dan, a metformin je najče&scaron;će kori&scaron;ćeni predstavnik. Sličan obim i struktura upotrebe antidijabetičnih lekova utvrđena je i u op&scaron;tini Foča. Procenat pokrivenosti antidijabetičnom terapijom pacijenata sa DM tip 2 tokom jedne godine u op&scaron;tini Foča iznosio je vi&scaron;e od 94,91%. Adherencija određivana metodom brojanja tableta/doza insulina iznosila je 52,3%, a merena primenom validiranog upitnikom iznosila je svega 44,9%. Statistički značajni prediktori neadherencije određivane primenom metode brojanja tableta/doza insulina su doplata cena leka kao i niži skor dimenzije mentalnog zdravlja kada je u pitanju kvalitet života. Prediktori neadherencije merene primenom validiranog upitnikom bili su mu&scaron;ki pol, kao i niži skor dimenzije mentalnog kao i fizičkog zdravlja kada je u pitanju kvalitet života. Na osnovu ovih saznanja, intervencije za pobolj&scaron;anje adherencije pacijenata bi bile usmerene na edukaciju pacijenata mu&scaron;kog pola, zatim na smanjivanje izdataka pacijenata za lekove, &scaron;to će doprineti i boljem kvalitetu života ovih pacijenata.</p> / <p>Although diabetes mellitus (DM) type 2 is a chronic disease whose rate has increased significantly in recent decades, data on the patient&#39;s attitudes towards the medicine and the treatment of diabetes mellitus are rare and relate to individual aspects of the therapy. The main stumbling block in the treatment of diabetes is not taking prescribed drugs regularly, which makes it difficult to maintain normal glycoregulation and contribute to the development of severe complications that significantly affect the quality of life of patients with DM. The disposition of accurate data on the use of antidiabeticdrugs, as well as the insight into the real state of the patient&#39;s relationship with the medication in the treatment of DM type 2, enables the improvement of pharmacotherapeutic practice and the creation of an intervention to improve patient adherence.<br />The objectives of this research were:<br />1) analysis of the volume of consumption and structure of anti-diabetic medicines on the territory of the Republic of Srpska and their comparison with the use and structure of prescribing in the surrounding countries as well as countries with developed pharmacotherapeutic practice;<br />2) analysis of the volume of consumption and structure of antidiabetic drugs in the municipality of Foča and comparison with modern pharmacotherapeutic guidelines;<br />3) determining the percentage of coverage with antidiabetic therapy of patients with DM type 2 during one year in the municipality of Foča;<br />4) determining the adherence of patients with DM type 2 in antidiabetic therapy by the method of pill counts /volume of insulin and by validated questionnaire;<br />5) determining the quality of life associated with the health of patients with DM type 2 in the municipality of Foča using the validated questionnaire SF-36v2;<br />6) determination of the predictor of nonadherence in the application of both methods of adherence measurement in relation to the characteristics and quality of life of patients with DM type 2 in the municipality of Foča.<br />The investigation consisted of two parts.<br />In the first part, a retrospective pharmacoepidemiological monitoring of the use of antidiabetic drugs was carried out, as well as determining the structure of these drugs in the territory of the Republic of Srpska in the period from January, 1st 2013 until December, 31st 2013, and a comparison was made with the use and prescription structure in neighboring countries as well as countries with developed pharmacotherapeutic practices. In the second part of the study, a pharmacoepidemiological study was carried out on the use of antidiabetic drugs at the level of the municipality of Foča itself, in which, besides analyzing the volume of consumption and structure of anti-diabetic drugs in the same period as in the territory of the Republic of Srpska and comparison with modern pharmacotherapeutic guidelines, the percentage of coverage by antidiabetic therapy was measured by the regularity of the prescription prescribed by the general practitioner over a one-year period. Medication adherence to antidiabetic drugs was also carried out using two different methods of measurement as well as the quality of life of patients with DM type 2 between January, 1st 2015 and December, 31st 2015. The total use of antidiabetic for the treatment of type 1 diabetes and type 2 in the territory of the Republic of Srpska was 38.29 DDD / 1000st / day. The use of insulin and analogs was 11.28 DDD / 1000st / day. The total use of blood glucose lowering drugs , excluding insulins, was 27.01 DDD / 1000st / day, and metformin is the most commonly used representative. A similar volume and structure of the use of anti-diabetic drugs was also determined in the municipality of Foča. The percentage of coverage of antidiabetic therapy of patients with DM type 2 during one year in the municipality of Foca amounted to more than 94.91%. Adherence determined by the pill counts and the volume of insulin method was 52.3%, and measured by applying the validated questionnaire was only 44.9%. Statistically significant predictors of nonadherence determined by the method of pill counts/volume of insulin are copayment, a fix fee for prescription made by patients as well as the lower score of the mental health dimension when it comes to quality of life. The non-adherence predictors measured using the validated questionnaire were the male sex, as well as a lower score of the mental dimension as well as physical health when it comes to quality of life. Based on these findings, interventions to improve patient adherence would focus on health education of male patients, and policy changes regarding availability of antidiabetic medication through copayment reductions , which will contribute to a better quality of life for these patients.</p>

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No / Hyperphosphorylated tau plays an important role in the formation of neurofibrillary tangles in brains of patients with Alzheimer's disease (AD) and related tauopathies and is a crucial factor in the pathogenesis of these disorders. Though diverse kinases have been implicated in tau phosphorylation, protein phosphatase 2A (PP2A) seems to be the major tau phosphatase. Using murine primary neurons from wild-type and human tau transgenic mice, we show that the antidiabetic drug metformin induces PP2A activity and reduces tau phosphorylation at PP2A-dependent epitopes in vitro and in vivo. This tau dephosphorylating potency can be blocked entirely by the PP2A inhibitors okadaic acid and fostriecin, confirming that PP2A is an important mediator of the observed effects. Surprisingly, metformin effects on PP2A activity and tau phosphorylation seem to be independent of AMPK activation, because in our experiments (i) metformin induces PP2A activity before and at lower levels than AMPK activity and (ii) the AMPK activator AICAR does not influence the phosphorylation of tau at the sites analyzed. Affinity chromatography and immunoprecipitation experiments together with PP2A activity assays indicate that metformin interferes with the association of the catalytic subunit of PP2A (PP2Ac) to the so-called MID1-alpha4 protein complex, which regulates the degradation of PP2Ac and thereby influences PP2A activity. In summary, our data suggest a potential beneficial role of biguanides such as metformin in the prophylaxis and/or therapy of AD.