Sistemi sa kontrolisanim otpuštanjem lekova zasnovani na mezoporoznoj silici i eritrocitnim membranama.

The main aim of this study is the development of two controlled drug delivery systems based on ordered mesoporous silica and erythrocyte membranes (in further text - ghosts) for two widely used drugs: fenofibrate and sodium diclofenac. In the first part of the study, in vitro and in vivo performance of ordered mesoporous silica (OMS) as a carrier for the poorly water soluble compound fenofibrate was evaluated. Fenofibrate was loaded into OMS via incipient wetness impregnation to obtain a 29% drug load and formulated into capsules. Two capsule dosage forms (containing 33.5 mg and 16.75 mg fenofibrate) were compared to the commercially available forms - Lipanthyl® (fenofibrate microcrystals) and Tricor® (fenofibrate nanocrystals). In vitro dissolution tests showed that the amount of fenofibrate released from Lipanthyl® and Tricor® was approximately 30%, whereas ca. 66 and 60% of the drug was released from OMS capsules containing 33.5 and 16.75 mg of fenofibrate, respectively. The in vivo study in dogs confirmed satisfying level of safety and tolerability of fenofibrate-OMS formulation (eq. 33.5 mg) with the potential to improve the absorption of fenofibrate. Though some variability in the data, this formulation was promising to be further investigated in a clinical trial setting. Subsequent clinical trial was conducted to assess the bioavailability-enhancing potential of ordered mesoporous silica in man. In this open-label, randomized, two-way cross-over study, 12 overnight fasted healthy volunteers received a single dose of fenofibrate formulated with ordered mesoporous silica or a marketed product based on micronized fenofibrate. Plasma concentrations of fenofibric acid, the pharmacologically active metabolite of fenofibrate, were monitored up to 96 hours post-dose. The rate (Cmax/dose increased by 77%; tmax reduced by 0.75 h) and extent of absorption (AUC0-24h/dose increased by 54%) of fenofibrate were significantly enhanced following administration of the ordered mesoporous silica based formulation. In the second part of the study controlled drug delivery system based on erythrocyte ghosts for amphiphilic compound sodium diclofenac was developed considering the differences between erythrocytes derived from two readily available materials - porcine slaughterhouse and outdated transfusion human blood. Starting erythrocytes, empty erythrocyte ghosts and diclofenac loaded ghosts were compared in terms of the encapsulation efficiency, drug releasing profiles, size distribution, surface charge, conductivity, surface roughness and morphology. The encapsulation of sodium diclofenac was performed by an osmosis based process - gradual hemolysis. During this process sodium diclofenac exerted mild and delayed antihemolytic effect and increased potassium efflux in porcine but not in outdated human erythrocytes. FTIR spectra revealed lack of any membrane lipid disorder and chemical reaction with sodium diclofenac in encapsulated ghosts. Localization in the suspension and spatial distribution (i. e. mapping) of residual hemoglobin in erythrocyte ghosts has been resolved by two photon excitation fluorescence microscopy. Outdated human erythrocyte ghosts with detected nanoscale damages and reduced ability to shrink had encapsulation efficiency of only 8%. On the other hand, porcine erythrocyte ghosts had encapsulation efficiency of 37% and relatively slow drug release rate. More preserved structure and functional properties of porcine erythrocytes related to their superior encapsulation and release performances, define them as more appropriate for the usage in sodium diclofenac encapsulation process.Glavni cilj ovog rada je razvoj dva sistema sa kontrolisanim otpuštanjem lekova zasnovanih na uređenoj mezoporoznoj silici i eritrocitnim membranama (u daljem tekstu duhovima) za dva leka u širokoj upotrebi: fenofibrat i natrijum diklofenak. U prvom delu ove studije ispitivane su in vitro i in vivo performase uređene mezoporozne silike kao nosača za slabo rastvorni lek fenofibrat. Mezoporozna silika je punjena fenofibratom metodom vlažne impregnacije incipijenta dok sadržaj leka ne dostigne 29%, a potom finalno formulisana kao kapusla. Dve vrste kapsula (koje sadrže 33.5 mg i 16.75 mg fenofibrata) poređene su sa komercijalno dostupnim oblicima - Lipantil® (fenofibrat mikrokristali) i Trikor® (fenofibrat nanokristali). In vitro testovi rastvorljivosti pokazali su da je količina fenofibrata oslobođenog iz Lipantila® i Trikora® aproksimativno iznosila 30% dok je oko 66 i 60% leka oslobođeno iz kapsula sa mezoporoznom silikom koje su sadržale 33.5 i 16.75 mg fenofibrata, respektivno. In vivo studija na psima potvrdila je zadovoljavajući nivo bezbednosti i tolerantnosti formulacija sa mezoporoznom silikom i fenofibratom (33.5 mg) kao i potencijal za poboljšanje apsorpcije fenofibrata. Uprkos variabilnosti dobijenih podataka, ova formulacija je bila obećavajuća za buduća klinička ispitivanja. Sledstvena klinička studija izvedena je sa ciljem da se proceni potencijal uređene mezoporozne silike da poboljša bioraspoloživost fenofibrata kod čoveka. U ovoj otvorenoj, randomizovanoj, dvostruko ukrštenoj studiji, 12 zdravih volontera je primilo pojedinačnu dozu fenofibrata formulisanog sa uređenom mezoporoznom silikom kao i komercijalni proizvod baziran na mikroniziranom fenofibratu. Plazma koncentracije fenofibrinske kiseline, farmakološki aktivnog metabolita fenofibrata bile su praćene 96 sati nakon uzete doze. Stepen (odnos Cmax/doza bio je povećan 77%, a tmax redukovano za 0,75 h) i obim apsorpcije (PIK0-24 h je bila uvećana za 54%) fenofibrata su bili značajno povećani nakon administracije formulacije zasnovane na uređenoj mezoporoznoj silici. U drugom delu studije razvijen je sistem sa kontrolisanim otpuštanjem za amfifilni lek natrijum diklofenak uz razmatranje razlika između eritrocita izolovanih iz dva lako dostupna materijala – svinjske otpadne klanične i prestarele humane krvi. Polazni eritrociti, prazni eritrocitni duhovi kao i inkapsulirani duhovi bili su poređeni u smislu efikasnosti inkapsulacije, profila oslobađanja leka, raspodele veličine, površinskog naelektrisanja, provodljivosti, hrapavosti površine i morfologije. Inkapsulacija natrijum diklofena izvedena je procesom zasnovanim na osmozi – gradualnom hemolizom. Tokom ovog procesa natrijum diklofenak ispoljio je blag i odložen antihemolitički efekat kao i povećan efluks kalijuma kod svinjskih ali ne i kod prestarelih humanih eritrocita. FTIR spektri su otkrili odsustvo narušavanja strukture membranskih lipida kao i hemijske reakcije između natrijum diklofena i inkapsuliranih duhova. Lokalizacija rezidualnog hemoglobina u suspenziji eritrocitinih duhova i njegova prostorna distribucija određeni su primenom dvofotonske fluorescentne mikroskopije. Prestareli humani eritrocitni duhovi sa detektovanim oštećenjma na površini i smanjenom sposobnošću da se skupljaju imali su efikasnost inkapsulacije od samo 8%. Sa druge strane, svinjski eritrocitni duhovi su imali efikasnost inkapsulacije od 37% i relativno nisku brzinu oslobađanja leka. Viši stepen očuvanosti strukture i funkcije svinjskih eritrocita posmatran kroz superiornije performanse inkapsulacije i oslobađanja leka, definiše ih kao pogodniji materijal za inkapsulaciju natrijum diklofena

Pemberantasan Tindak Pidana Perbankan Di Indonesia Menurut Undang-undang Nomor 10 Tahun 1998

Tujuan dilakukannya penelitian ini adalah untuk mengetahui bagaimana cara memberantas tindak pidana perbankan di Indonesia dan bagaimana bentuk-bentuk tindak pidana perbankan menurut Undang-Undang Nomor 10 Tahun 1998. Dengan menggunakan metode penelitian yuridis normatif disimpulkan: 1. Pengawasan sebagai sarana dalam memberantas tindak pidana perbankan. pengawasan yang dilakukan terdiri dari pengawasan eksternal yang dilakukan oleh regulator dalam hal ini Bank Indonesia; pengawasan internal meliputi penerapan tata kelola Perusahaan, prinsip know your employee dan kepatutan; pengawasan masyarakat yang dilakukan dengan menerapkan prinsip keterbukaan. Tindak pidana perbankan yang dilakukan oleh orang dalam sangat erat kaitannya dengan dominasi terhadap kebijakan dan administrasi oleh seorang atau beberapa orang, dan lemahnya pengawasan bank baik pengawasan yang dilakukan oleh pengawas internal maupun pengawas eksternal. 2. Bentuk-bentuk Tindak Pidana Perbankan menurut undang-Undang Nomor 10 Tahun 1998 tentang Perbankan yaitu Tindak Pidana yang berkaitan dengan perizinan, Tindak Pidana yang berkaitan dengan rahasia bank, Tindak Pidana yang berkaitan dengan pengawasan dan pembinaan, Tindak Pidana yang berkaitan dengan USAha bank, dan tindak pidana yang berkaitan dengan sikap dan/atau tindakan yang dilakukan oleh pengurus bank, pegawai bank, pihak terafiliasi, dan pemegang saham bank

Evidence of increasing incidence of type 1 diabetes and ketoacidosis among children in the Republic of Srpska in period 2017–2022 with special focus on COVID-19 global pandemic years

Background and objectivesPrimary focus of the research was to determine the incidence of type 1 diabetes mellitus in the period from 2017 to 2022, and whether COVID-19 had an impact on the increase in the number of newly diagnosed children with diabetes type 1 under the age of 15 in the Republic of Srpska (Bosnia and Herzegovina). In the period 2001–2016 the incidence of type 1 diabetes mellitus was 11/100,000, with an annual increasing rate of 14.2%.MethodsAvailable data from pediatric endocrinology clinics, in the Republic of Srpska, on the number of newly diagnosed patients with diabetes mellitus in the period from January 1, 2017 until December 31, 2022 were used. A retrospective analysis was performed, and the capture-recapture method was used for the final assessment, and the obtained result corresponds to about 99% of the population.ResultsThe total number of children in the group of 0–14 years of age diagnosed with type 1 diabetes mellitus in this period was 183, of which 96 (52.46%) were boys, and 87 (47.54%) were girls. The average age at which diabetes mellitus was diagnosed was 8.3 ± 3.9 years. Average incidence of diabetes in the period 2017–2022 was 19/100,000 (95% CI 13.1–25.0). The highest incidence was 28.7/100,000 in 2020, the first year of the global COVID-19 pandemic. Out of a total of 183 newly diagnosed cases in the period 2017–2022, 73 (39.9%) were diagnosed with ketoacidosis upon admission. The largest number of newly diagnosed children was recorded in the group of children aged 10–14 years.ConclusionIn the last 6 years, there has been a significant increase in the incidence of type 1 diabetes mellitus in children under the age of 15. With an incidence of 19.4/100,000 in the Republic of Srpska, we entered the group of countries with high-risk for diabetes. Further steps must focus on the education of the entire society in order to recognize the symptoms of the disease in time and prevent the occurrence of ketoacidosis, which could significantly reduce the burden on health systems, especially in times of global pandemics, such as the COVID-19 pandemic

Applicability of Ottawa ankle rules in predicting the need for radiography in ankle and midfoot injuries in Rwanda

Objective: To assess the applicability of Ottawa Ankle Rules in predicting the need for the radiography in ankle and midfoot injuries in Rwanda.Design: This was a prospective multicenter cross-sectional study carried over a 6 month duration, from May 2018 to October 2018.Setting: University Teaching Hospital of Kigali (UTH-Kigali), Rwanda Military Hospital (RMH) and King Faisal Hospital, Kigali, Rwanda (KFH-K).Patients and methods: Adult patients presenting with acute ankle and midfoot injuries at the emergencies of three referral hospitals in Kigali. Patients were examined using OARs and underwent radiography to rule out the presence or absence of the fracture.Results: A total of 196 patients from three referral hospitals in Kigali were enrolled in the study. The sensitivity and specificity of the OARs were 97.9% and 35.8% respectively.Conclusion: In this study, Ottawa Ankle Rules have high sensitivity and low specificity; however, it showed high false positive values due to high sensitivity of the test. When properly applied, Ottawa Ankle Rules can decrease the number of unnecessary ankle or midfoot radiographs and limiting the waiting time in acute settings in Rwanda. Key words: Ottawa ankle rules, Radiography, Applicability, Validatio

Effect of use of insulin pump with low glucose suspend feature on metabolic control in children with type 1diabetes

Introduction. The automatic suspension of the insulin pump and discontinuationof insulin delivery in case of hypoglycemia is one of the features ofVeo insulin pump when it is connected with the sensor used for continuousmonitoring of glycemia (CGM). This type of therapy is currently consideredto be the best one for achieving a good metabolic control in children withtype 1 diabetes mellitus. The objective of the study was to check whetherthe use of an option for automatic suspension in case of hypoglycemia andcombined bolus affects the metabolic control in children with type 1 diabetesmellitus using the insulin pump for a three-month period.Methods. The study included 25 participants (13 girls and 12 boys), aged7 to 15 years with average age 11.88 ± 3.15 years and average diabetes durationof 6.12 ± 2.5 years. On average, the participants have already beenusing the insulin pump Paradigm Veo TM MMT-754 for 3.08 ± 1.73 years.The measurements of HbA1c were done at the beginning of the study, thenafter three and six months.Results. The percentage of glucose serum levels above 7.8 mmol/L insignificantlyincreased, while the percentage of glucose serum levels below3.9 mmol/L decreased during the three-month period of CGM wearing.The initial HbA1c was 7.53 ± 0.87%. After three months of wearing, CGMHbA1c showed a slight decrease to 7.48 ± 0.73%, while at the follow-up afteranother three months without CGM HbA1c increased to 7.57 ± 0.98%.Conclusion. This study shows that the use of an insulin pump with the optionof automatic suspension in case of hypoglycemia and combined bolusis only associated with a certain improvement in the metabolic controlafter three months of continuous wearing without increasing the risk ofhypoglycemia

Comparative studies on osmosis based encapsulation of sodium diclofenac in porcine and outdated human erythrocyte ghosts

The objective of our study was to develop controlled drug delivery system based on erythrocyte ghosts for amphiphilic compound sodium diclofenac considering the differences between erythrocytes derived from two readily available materials - porcine slaughterhouse and outdated transfusion human blood. Starting erythrocytes, empty erythrocyte ghosts and diclofenac loaded ghosts were compared in terms of the encapsulation efficiency, drug releasing profiles, size distribution, surface charge, conductivity, surface roughness and morphology. The encapsulation of sodium diclofenac was performed by an osmosis based process - gradual hemolysis. During this process sodium diclofenac exerted mild and delayed antihemolytic effect and increased potassium efflux in porcine but not in outdated human erythrocytes. FTIR spectra revealed lack of any membrane lipid disorder and chemical reaction with sodium diclofenac in encapsulated ghosts. Outdated human erythrocyte ghosts with detected nanoscale damages and reduced ability to shrink had encapsulation efficiency of only 8%. On the other hand, porcine erythrocyte ghosts had encapsulation efficiency of 37% and relatively slow drug release rate. More preserved structure and functional properties of porcine erythrocytes related to their superior encapsulation and release performances, define them as more appropriate for the usage in sodium diclofenac encapsulation process

INTENZIVNO LIJEČENJE SUICIDALNIH BOLESNIKA

Ciljevi istraživanja: Utvrditi ukupni broj bolesnika koji su pokušali učiniti suicid i koji su liječeni u jedinicama intenzivnoga liječenja KBC Rijeka u razdoblju od 1. siječnja 2010. godine do 31. prosinca 2014. godine, odrediti distribuciju dobi i spola suicidalnih bolesnika, utvrditi metode kojim su bolesnici pokušali učiniti suicid, analizirati broj suicidalnih bolesnika koji su liječeni strojnom ventilacijom i odrediti trajanje strojne ventilacije, utvrditi trajanje boravka i ishod liječenja u Jedinici intenzivnog liječenja, ustanoviti prisutnost psihičkih poremećaja kao važnog čimbenika rizika. Ispitanici i postupci: Ova petogodišnja studija obuhvatila je 139 bolesnika koji su pokušali učiniti suicida i koji su liječeni u Jedinicama intenzivnog liječenja KBC Rijeka. Podaci su prikupljeni uvidom u medicinsku dokumentaciju ispitanika. Upisani su i obrađeni u računalnom programu Microsoft Excel te su prikazani u obliku tablica i grafikona s objašnjenjem rezultata. Rezultati: Prosječna dob bolesnika je bila 47,5 godina, četvrtina bolesnika bila je u dobi od 51 do 60 godina, bilo je 16% više žena nego muškaraca. Samootrovanje je bila najčešća metoda pokušaja samoubojstva s udjelom od 82%. Ventilacijska potpora primijenjena je u 47% bolesnika. Prisutnost psihičkog poremećaja utvrđena je u 47% bolesnika. 9% bolesnika je preminulo. Zaključak: Bolesnici koji su pokušali suicid su akutno ugroženi bolesnici, ali uz pravodobno provedene mjere suvremenoga intenzivnoga liječenja 87% bolesnika se oporavi unutar 5 dana.Aims: To establish the total number of patients who had tried to commit suicide and were treated in the ICU Hospital Rijeka in the period from January the 1st of 2010 to December the 31st of 2014, to determine the distribution of age and gender suicidal patients, to determine the method by which the patients tried to suicide, analyze the number of suicidal patients treated with mechanical ventilation and determine the duration of ventilation hardware, determine the duration of stay and treatment outcome in the Intensive Care Unit. To establish the presence of mental disorders as an important risk factor. Material and Methods: This five-year study included 139 patients who attempt suicide and who were treated in the Intensive Care Unit of Hospital Rijeka. Data were collected by examining the medical records of patients. Subscribed and analyzed in a computer program Microsoft Excel, and they are presented in the form of tables and charts explaining the results. Results: The average age of patients was 47.5 years, a quarter of the patients were aged from 51 to 60 years, there were 16% more women than men. Self poisoning was the most common method with a share of 82%. Ventilation support was applied in 47% of patients. The presence of mental disorder was found in 47% of patients. 9% of the patients died. Conclusion: Patients who have attempted suicide are acutely severely compromised patients, with intensive treatment 87% of patients recover within 5 days

INTENZIVNO LIJEČENJE SUICIDALNIH BOLESNIKA

Ciljevi istraživanja: Utvrditi ukupni broj bolesnika koji su pokušali učiniti suicid i koji su liječeni u jedinicama intenzivnoga liječenja KBC Rijeka u razdoblju od 1. siječnja 2010. godine do 31. prosinca 2014. godine, odrediti distribuciju dobi i spola suicidalnih bolesnika, utvrditi metode kojim su bolesnici pokušali učiniti suicid, analizirati broj suicidalnih bolesnika koji su liječeni strojnom ventilacijom i odrediti trajanje strojne ventilacije, utvrditi trajanje boravka i ishod liječenja u Jedinici intenzivnog liječenja, ustanoviti prisutnost psihičkih poremećaja kao važnog čimbenika rizika. Ispitanici i postupci: Ova petogodišnja studija obuhvatila je 139 bolesnika koji su pokušali učiniti suicida i koji su liječeni u Jedinicama intenzivnog liječenja KBC Rijeka. Podaci su prikupljeni uvidom u medicinsku dokumentaciju ispitanika. Upisani su i obrađeni u računalnom programu Microsoft Excel te su prikazani u obliku tablica i grafikona s objašnjenjem rezultata. Rezultati: Prosječna dob bolesnika je bila 47,5 godina, četvrtina bolesnika bila je u dobi od 51 do 60 godina, bilo je 16% više žena nego muškaraca. Samootrovanje je bila najčešća metoda pokušaja samoubojstva s udjelom od 82%. Ventilacijska potpora primijenjena je u 47% bolesnika. Prisutnost psihičkog poremećaja utvrđena je u 47% bolesnika. 9% bolesnika je preminulo. Zaključak: Bolesnici koji su pokušali suicid su akutno ugroženi bolesnici, ali uz pravodobno provedene mjere suvremenoga intenzivnoga liječenja 87% bolesnika se oporavi unutar 5 dana.Aims: To establish the total number of patients who had tried to commit suicide and were treated in the ICU Hospital Rijeka in the period from January the 1st of 2010 to December the 31st of 2014, to determine the distribution of age and gender suicidal patients, to determine the method by which the patients tried to suicide, analyze the number of suicidal patients treated with mechanical ventilation and determine the duration of ventilation hardware, determine the duration of stay and treatment outcome in the Intensive Care Unit. To establish the presence of mental disorders as an important risk factor. Material and Methods: This five-year study included 139 patients who attempt suicide and who were treated in the Intensive Care Unit of Hospital Rijeka. Data were collected by examining the medical records of patients. Subscribed and analyzed in a computer program Microsoft Excel, and they are presented in the form of tables and charts explaining the results. Results: The average age of patients was 47.5 years, a quarter of the patients were aged from 51 to 60 years, there were 16% more women than men. Self poisoning was the most common method with a share of 82%. Ventilation support was applied in 47% of patients. The presence of mental disorder was found in 47% of patients. 9% of the patients died. Conclusion: Patients who have attempted suicide are acutely severely compromised patients, with intensive treatment 87% of patients recover within 5 days

INTENZIVNO LIJEČENJE SUICIDALNIH BOLESNIKA

Ciljevi istraživanja: Utvrditi ukupni broj bolesnika koji su pokušali učiniti suicid i koji su liječeni u jedinicama intenzivnoga liječenja KBC Rijeka u razdoblju od 1. siječnja 2010. godine do 31. prosinca 2014. godine, odrediti distribuciju dobi i spola suicidalnih bolesnika, utvrditi metode kojim su bolesnici pokušali učiniti suicid, analizirati broj suicidalnih bolesnika koji su liječeni strojnom ventilacijom i odrediti trajanje strojne ventilacije, utvrditi trajanje boravka i ishod liječenja u Jedinici intenzivnog liječenja, ustanoviti prisutnost psihičkih poremećaja kao važnog čimbenika rizika. Ispitanici i postupci: Ova petogodišnja studija obuhvatila je 139 bolesnika koji su pokušali učiniti suicida i koji su liječeni u Jedinicama intenzivnog liječenja KBC Rijeka. Podaci su prikupljeni uvidom u medicinsku dokumentaciju ispitanika. Upisani su i obrađeni u računalnom programu Microsoft Excel te su prikazani u obliku tablica i grafikona s objašnjenjem rezultata. Rezultati: Prosječna dob bolesnika je bila 47,5 godina, četvrtina bolesnika bila je u dobi od 51 do 60 godina, bilo je 16% više žena nego muškaraca. Samootrovanje je bila najčešća metoda pokušaja samoubojstva s udjelom od 82%. Ventilacijska potpora primijenjena je u 47% bolesnika. Prisutnost psihičkog poremećaja utvrđena je u 47% bolesnika. 9% bolesnika je preminulo. Zaključak: Bolesnici koji su pokušali suicid su akutno ugroženi bolesnici, ali uz pravodobno provedene mjere suvremenoga intenzivnoga liječenja 87% bolesnika se oporavi unutar 5 dana.Aims: To establish the total number of patients who had tried to commit suicide and were treated in the ICU Hospital Rijeka in the period from January the 1st of 2010 to December the 31st of 2014, to determine the distribution of age and gender suicidal patients, to determine the method by which the patients tried to suicide, analyze the number of suicidal patients treated with mechanical ventilation and determine the duration of ventilation hardware, determine the duration of stay and treatment outcome in the Intensive Care Unit. To establish the presence of mental disorders as an important risk factor. Material and Methods: This five-year study included 139 patients who attempt suicide and who were treated in the Intensive Care Unit of Hospital Rijeka. Data were collected by examining the medical records of patients. Subscribed and analyzed in a computer program Microsoft Excel, and they are presented in the form of tables and charts explaining the results. Results: The average age of patients was 47.5 years, a quarter of the patients were aged from 51 to 60 years, there were 16% more women than men. Self poisoning was the most common method with a share of 82%. Ventilation support was applied in 47% of patients. The presence of mental disorder was found in 47% of patients. 9% of the patients died. Conclusion: Patients who have attempted suicide are acutely severely compromised patients, with intensive treatment 87% of patients recover within 5 days