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  • Pottonen, Riitta-Liisa (2015)
    Medication safety is safety related to the use of medicines. Medication errors are drug treatment related events which can lead to medication safety incidents. Medication process is multi-professional teamwork which contains a risk of medication error on every step. It is important to identify potential safety risks in order to prevent the risk events. Medication errors can occur for example during the transfer of the prescription information in to the medication list. It is important that medication lists are accurate and up to date so that patient's medication therapy is optimal. The aim of this study was to assess whether the primary health care medication lists are up to date, accurate and easy to read. The aim was also to identify what kind of information in medication lists was open to interpretation. In one of the municipalities, the medication lists at home were compared to the medication lists at primary care to see whether both lists had identical information on the medication. The data of this study consisted of 240 medication lists from primary care units in three Finnish municipalities. The lists contained altogether 3062 medications. Most of the lists were printed from the patient information systems. Some of the lists were copied from the home medication lists. All medication lists were systematically reviewed and issues open to interpretation were documented in a structured Microsoft Excel table. The data were transferred to SPSS 20 Program for statistical analysis. Most (73%, n=174) of the medication lists (n=240) were incomplete. One-fifth (n=612) of the medications in use (n=3062) contained missing information on medicines. The total number of discrepancies was 807 (mean 3.4 discrepancies per medication list). The most common discrepancies were related to the time of administration (n=277) and dosages (n=241). Duplicate medications included a lot of confusing information. Discontinued medications were not always clearly marked. In only one of the municipalities the medication lists had a space for marking the indication. There were some differences between home medication lists (n=62) and primary care medication lists. ™ Based on this study medication lists have a lot of discrepancies and ambiguities in their information content. The medication lists do not always accurately tell the patient's current medication. Interpretation of inaccurate medication lists consumes unnecessarily doctors' and nursing staff's time. Inaccurate medication lists are a risk to patient safety. It is also important that the medication lists would be similar in all health care units. Electronic prescriptions, the National Health Archive and medication list developed by Information Management Service of Healthcare are expected to solve at least some of the problems related to medication lists.
  • Suvanto, Satu (2014)
    P-glycoprotein is an ATP-dependent efflux protein expressed in many tissues which participate in absorption, distribution and elimination of drug molecules. It can mediate clinically significant drug-drug interactions. Characteristics of P-gp have been studied widely and crystal structure of mouse P-gp has been successfully determined. P-gp binds its substrates either directly from cell membrane or from cytosol and it has at least three separate binding sites. P-gp has wide selection of substrates from many therapeutical groups. According to the latest computational models, a typical P-gp substrate can be defined with the help of molecule structural factors rather than physicochemical properties. However function of P-gp is very complex which is why drug-drug interactions should be studied for each drug pair separately. In addition expression of P-gp is regulated by nuclear receptors PXR and CAR thus P-gp induction is separate, which also complicates P-gp mediated interactions. P-gp substrates celiprolol, talinolol, aliskiren and fexofenadine have in vivo interactions with P-gp inhibitors or inducers. The objective the experimental work was to study suitability of two in vitro methods, MDCKII-cell permeability assay and MDR1-vesicle transport assay, for predicting in vivo effect of drug-drug interaction. ATP-dependent transport of substrates was determined in membrane vesicles extracted from human P-gp expressing Sf9 cells. Cell assay was used to determine efflux ratio (ER) for all the substrates alone and efflux ratio with P-gp inhibitor itraconazole for the substrates which have reported in vivo interaction with itraconazole. All compounds showed ATP dependent transport in MDR1-vesicles and celiprolol, talinolol and fexofenadine showed ER over 1 in MDCKII-MDR1 cells thus according to vesicle assay and ER-value they are P-gp substrates. However ER of talinolol and fexofenadine was not affected by inhibitor itraconazole, thus the drugs did not fulfil the inhibition criteria of FDA for P-gp substrates. The performing of interaction test was possible failed due lack of pre-incubation of the cells with the inhibitor. Talinolol had the highest ER in thus according to cell experiments talinolol has P-gp dependent transport. Aliskiren ER was not obtained because of the low recovery of the drug but it had clear ATP-dependent transport in the vesicle assay as was expected according to in vivo results. According to in vitro results and in vivo studies celiprolol is a poor P-gp substrate whereas fexofenadine showed P-gp mediated transport both in vitro and in vivo. The results suggest that significance of drug interaction is difficult to predict with the vesicle and the cell assay but they can be used to recognize P-gp substrates.
  • Hurmalainen, Virpi (2021)
    P-glycoprotein is an efflux transporter of the ABC family. It is expressed mainly in tissues that have a role in limiting the absorption and distribution of xenobiotics in the body or their elimination. P-glycoprotein is known to have an important role for example in the blood-brain barrier and in protecting the fetus from xenobiotics in the mother’s blood stream. Genetic polymorphisms in transporter proteins can cause individual differences in the pharmacokinetics of drug substances, which can lead to differences in drug efficacy or side effects. In the ABCB1 gene, which codes for p-glycoprotein, several polymorphisms have been discovered. The frequencies of these polymorphisms vary in different ethnic populations. Previous studies have shown that the effects of these polymorphisms are often substrate-dependent. Since there are several confounding factors usually present in clinical association studies, in vitro studies are needed to clarify the effects of individual polymorphisms. Polymorphisms can be studied in vitro by making intentional mutations to the gene sequence and expressing the variant gene in a suitable cell line. In this study four variant p-glycoprotein genes (c.781A>G, c.1199G>T, c.2005C>T and c.3421T>A) were created by site-directed mutagenesis, and expressed in HEK293 cells using a baculovirus recombinant protein expression method. The effects of the polymorphisms were studied by determining the expression level and the transport acitivity of the variant proteins compared to the wild-type. Western blot was used to determine the expression level and a calcein accumulation assay in HEK293 cells was used to compare the transport activities. Also a membrane vesicle transport assay with n-methyl quinidine was set up and optimized, but the variants were not yet studied with this method during this study. In this study no statistically significant differences were found in the transport activities of any of the four variants compared to the wild-type p-glycoprotein. Also the differences in protein expression level between wild-type and variant proteins were small. However, because of the previously reported substrate dependency of polymorphism effects, it would be beneficial to study the variants with at least one other substrate and one other assay method, and thus the membrane vesicle transport assay would be useful to further compare the transport activities of variant proteins to the wild-type p-glycoprotein.
  • Urpelainen, Katja (2021)
    Cardiomyocyte oxygen deprivation followed by apoptosis and cardiomyocytes being replaced with fibrotic tissue can lead to heart failure. Cardiovascular diseases are the most common cause of death world-wide, contributing to 17.8 million deaths in 2017. Treatments currently available aim to maintain cardiac function but are unable to repair the damage, resulting in a poor prognosis for heart failure. Cardiomyocytes are able to proliferate but the endogenous mechanisms of cardiac repair are insufficient to replace the damaged cardiomyocytes, as only an estimated 0.3-1 % of adult cardiomyocytes are regenerated annually. It is known that before birth and up to seven days after birth mice can maintain ability to regenerate cardiomyocytes even after large damage, but this capability is lost within seven days following birth. After this, cardiomyocytes exit cell cycle and will not re-enter it sufficiently to enable cardiac repair. In adults the growth of heart muscle results mainly from hypertrophic growth meaning that the cells grow in width and length. Cardiomyocyte regeneration is an important therapeutic target to which there are no effective pharmacological therapies available yet. The aim of this study was to investigate the effect of 14 novel compounds on cardiomyocyte viability, phenotype and cell cycle activation. Novel compounds were synthesized at the Faculty of Pharmacy, Division of Pharmaceutical Chemistry and Technology, University of Helsinki in Finland. Initial toxicity and cell viability screening was conducted with lactate dehydrogenase assay (LDH assay) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay (MTT assay) using COS-1 cells. Based on these assays tolerable concentrations of compounds were determined. Activity analysis was conducted using human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) and immunocytochemistry staining in conjunction with high-content analysis (HCA). Stress response was measured by imaging and analyzing expression of pro-B-type natriuretic peptide (proBNP) and cell cycle activation was imaged and analyzed by using 5- bromo-2’-deoxyuridine (BrdU) as a marker of active cell cycle. In addition, the DNA content of the cardiomyocytes was measured using 4’,6-diamidino-2-phenylindole (DAPI) staining as well as cardiomyocyte morphology investigated with cardiac troponin T (cTnT) staining. One of the compounds, K6, decreased proBNP expression, which can be considered as a sign of decreased stress response. However, K6 also decreased the number of BrdU positive cardiomyocytes that can be considered as a sign of decreased cell cycle activity. Together these markers indicate that the decreased activity may not be due to a stress response caused by the compound. Another compound, K12, increased proBNP expression in all tested concentrations and it also decreased the number of BrdU positive cardiomyocytes. Together these could be considered as an indication of cardiotoxicity. The rest of the compounds did not exhibit remarkable biological activity or there was too great variance between the results of the independent experiments (n=3) to draw definite conclusions. Compounds for this study were chosen for the sole reason of not been tested for biological effects before. Using a defined compound library or screening a larger number of compounds could deliver more predictable results. Early toxicity and viability screenings were a good approach allowing to define toxic compounds and concentrations before continuing with further studies. Pharmacological therapies to induce cardiac regeneration will continue to be an important area of interest in cardiovascular drug research. Phenotypic screening in conjunction with high-content analysis offers variable and statistically significant data on cardiomyocyte proliferation and stress response. The results of the screening could be improved with careful selections of test molecules based on their structure and biological activity. Early toxicity and viability screening further improve the predictability of results. As a result of this study a compound that would induce cardiomyocyte proliferation was not found, however, one compound that seemed to decrease cardiomyocyte stress response was detected and this compound could be of interest for further studies.
  • Tseloev, Idris (2018)
    An ultra-high-pressure liquid chromatography method was used for simultaneous detection of 25 small peptide hormones and their metabolites in urine after solid-phase extraction. This method is first screening step in anti-doping analysis of urine samples. It should be fast, generic and able to detect any sample that may contain a prohibited substance while avoiding false negatives and reducing false positive results. Detection was achieved using quadrupole time-of-flight mass spectrometry coupled with electrospray ionization source in positive mode. Analytes included growth hormone secretagogues, gonadotropin releasing factors, anti-diuretic hormones and their metabolites which are all covered by the list of prohibited substances of the World Anti-Doping Agency (WADA). The practical part of investigation was done in United Medix Laboratories and the aim of study was to expand current screening method by adding new compounds. Optimal experimental conditions were stablished after investigation of different parameters concerning sample preparation and instrumental analysis. The extraction procedure was done by using weak cation exchange SPE with two washing steps (Milli-Q water and methanol), and elution with 5 % formic acid in methanol. The procedure was validated in terms of recovery, specificity, limits of detection, stability and robustness. Recovery was evaluated with 10 ng/ml concentration of analytes and the rest of validation procedures were done at half of minimum required performance level set by WADA (1 ng/ml). Recoveries ranged from 2,6 to 85 % with LODs from 0,01 to 1,76 ng/ml. The suitability of the method was assessed by analyzing different spiked urine specimens containing target substances.
  • Silén, Sanna-Mari (2012)
    Individually tailored smoking cessation, SC, service provided by community pharmacies is a chargeable special service for customers motivated to quit smoking. The service is based on the PAS service model developed in Great Britain and it has been provided by Finnish community pharmacies since 2006. It includes 4-6 meetings with a specially trained pharmacist, who provides counselling, support, SC plan and follow-up. In this pilot study, the service was investigated from customers' viewpoint, assessing their SC outcomes and experiences. The pilot study was a cooperation project of Division of Social Pharmacy and Association of Finnish Pharmacies. It was a part of a larger SC project co-ordinated by Pulmonary Association Heli and financed by Ministry of Social Affairs and Health. This pilot study assessed the feasibility of the service from customer's viewpoint. It assessed weather the service could increase customers' ability to stay abstinent in different phases of the service. Customers' experiences in relation to SC service and SC itself were also assessed. 14 voluntary pharmacies in different geographical locations in Finland participated in this intervention study and they recruited altogether 36 customers. Before customer recruitment pharmacies received education and introduction of the SC service provided by the Association of Finnish Pharmacies. As part of study protocol, the pharmacies informed local healthcare professionals about the pilot study and asked them to send suitable customers to the service. Pharmacies were paid an expert reward for each customer and they were able to provide SC service to the customers either free or with a low charge. Customers' smoking status and experiences about SC service were assessed with two enquiry forms, which they had filled at the beginning of the service and after three months they had started the service. Their background information was collected with specific background forms during the first meeting and their progress in SC service was investigated by service progress forms. 20 of the 28 customers who returned the first enquiry form and 13 of the 17 customers who returned the second enquiry form were abstinent (55,6 % and 36,1 % of all customers, respectively). All the quitters used some pharmaceutical treatment. Customers who quitted assessed their ability to stay abstinent higher than those who were unable to quit, at the outset and during the service. The customers considered service useful and support of the pharmacist was found important. The customers also considered it significant for pharmacies to provide the SC service. Approximately 32 % of the customers who returned the first enquiry form and 41 % who returned the second enquiry form would pay for the service. They would pay 45 € on average (10-100 €). Multidisciplinary service model was not working as expected, since only a small number of customers were recruited by other healthcare professionals. As a result some of the pharmacies recruited customers also from the pharmacy counter without any contact to other healthcare. 36 % of the 36 customers were abstinent at three months. The control group, planned for the pilot study, failed in recruitment and thus we can only compare our findings to other international studies of the SC service, which have provided similar results. Individually tailored SC service provided by pharmacies is suitable SC support for motivated customers. Customers considered service important and useful, but poor willingness to pay creates challenges for pharmacies to provide this kind of service.
  • Kilpiö, Tommi (2021)
    Plant cell culture can be used for the production of valuable secondary metabolites. Inspired by the previous studies focusing on capsaicinoid production, this study aimed for establishing plant cell cultures of Capsicum chinense to produce capsinoids. Capsinoids are non-pungent capsaicinoid analogues with potential health benefits. Another aim of this study was to determine the α-solanine content in Capsicum plants and cell cultures to ensure that no toxic amounts are formed during the cell culture. Cell cultures of non-pungent Capsicum chinense cultivars, Trinidad Pimento and Aji Dulce strain 2, were established, and the cultures were fed with intermediates, vanillin and vanillyl alcohol, to enhance the production. In addition, cell cultures of extremely pungent Trinidad Scorpion cultivar were established and they were fed with vanillyl alcohol to study if this would result in formation of capsinoids instead of capsaicinoids. A high-performance liquid chromatography (HPLC) method with UV detection was validated for determining the capsiate contents of the cell culture samples and fruit samples for comparison. To analyze the α-solanine content of the cell culture samples and leaves and flowers of three cultivars belonging to three different Capsicum species, an HPLC-UV method was validated for this purpose as well. Despite validating a sensitive and specific method for capsiate analysis, no detectable amounts of capsiate were detected in any of the cell culture samples. Cell cultures of pungent cultivars did not produce detectable amounts of capsaicinoids either. Results from analyzing the real fruit samples were in accordance with previous literature reports, and Aji Dulce fruits were found to contain higher amounts of capsiate compared to Trinidad Pimento, although having only one indoor grown Aji Dulce fruit analyzed limits the reliability. The analytical method for determining α-solanine content had problems with internal standard and specificity. This method could be used for making rough estimates about the possible α-solanine content. No hazardous amounts were detected in any of the cell culture samples. Only one sample consisting of Aji Dulce young leaves could contain α-solanine slightly above the limits set for commercial potatoes. Results with flowers of Rocoto San Pedro Orange (C. pubescens) and Aji Omnicolor (C. baccatum) were inconclusive and it couldn’t be ruled out that they might contain large amounts of α-solanine. The reason why capsinoids, or even capsaicinoids, were not detected in the cell culture samples remains unsolved, but it could be speculated that capsinoids might degrade in the cell culture environment or that selection of cultivar or cell line is critical. This study gave further proof to the previous assumptions that chili leaves are safe and should not contain notable amounts of α-solanine.
  • Vidjeskog, Katarina (2021)
    Solunulkoiset vesikkelit eli EV:t ovat nanokokoisia solujen tuottamia lipidikaksoiskalvon peittämiä kalvorakkuloita. Solut vapauttavat EV:itä solunulkoiseen tilaan ja niitä on kaikissa kehon nesteissä. Aiemmin niiden uskottiin olevan vain solujen tapa päästä eroon tarpeettomasta materiaalista, mutta nykyisin tiedetään, että EV:illä on tärkeä merkitys solujenvälisessä viestinnässä. Sitä mukaa kun ymmärrys EV:iden merkityksestä on kasvanut, on kasvanut myös kiinnostus niiden tutkimiseen. EV:itä voidaan eristää lähes kaikista kehon nesteistä, mutta veressä niitä on erityisen runsaasti. Plasman EV:t ovat pääosin peräisin punasoluista ja verihiutaleista. Kun nanopartikkelit ovat kosketuksissa veren kaltaisten biologisten nesteiden kanssa, niiden ympärille muodostuu proteiinirakenne, jota kutsutaan proteiinikoronaksi. Proteiinikoronan koostumus vaikuttaa nanopartikkeleiden pintaominaisuuksiin. Se voi vaikuttaa myös esimerkiksi niiden soluinteraktioihin ja signalointiominaisuuksiin. Tämän pro gradutyön tarkoituksena oli tutkia punasolujen ja niistä tuotettujen nanoerytrosomien EV tyypin proteiinikoronan määrää ja vertailla näitä määriä toisiinsa. Mittaukset suoritettiin ihmisen veri plasmasta, joka oli pitoisuudeltaan 100 %:sta, 50 %:sta sekä 25 %:sta. Verestä peräisin olevien EV:iden etu sekä mahdollisina lääkekuljettimina, että tutkimuskäytössä on se, että ne ovat myrkyttömiä, heikosti immunogeenisiä, helposti saatavissa olevia, helppokäyttöisiä sekä varastoitavia. Tutkimustulosten perusteella proteiinikoronan määrä on EryEV:illä ja NanoEry:illä samaa suuruusluokkaa. Havaittavaa eroa ei ainakaan näin pienellä otoskoolla ollut havaittavissa.
  • Toppari, Antti (2011)
    Nowadays growing number of new active pharmaceutical ingredients (API) have large molecular weight and are hydrophobic. The energy of their crystal lattice is bigger and polarity has decreased. This leads to weakened solubility and dissolution rate of the drug. These properties can be enhanced for example by amorphization. Amorphous form has the best dissolution rate in the solid state. In the amorphous form drug molecules are randomly arranged, so the energy required to dissolve molecules is lower compared to the crystalline counterpart. The disadvantage of amorphous form is that it is unstable. Amorphous form tends to crystallize. Stability of amorphous form can be enhanced by adding an adjuvant to drug product. Adjuvant is usually a polymer. Polymers prevent crystallization both by forming bonds with API molecules and by steric hindrance. The key thing in stabilizing amorphous form is good miscibility between API and polymer. They have to be mixed in a molecular level so that the polymer is able to prevent crystallization. The aim of this work was to study miscibility of drug and polymer and stability of their dispersion with different analytical methods. Amorphous dispersions were made by rotary evaporator and freeze dryer. Amorphicity was confirmed with X-ray powder diffraction (XRPD) right after preparation. Itraconazole and theophylline were the chosen molecules to be stabilized. Itraconazole was expected to be easier and theophylline more difficult to stabilize. Itraconazole was stabilized with HPMC and theophylline was stabilized with PVP. Miscibility was studied with XRPD and differential scanning calorimetry (DSC). In addition it was studied with polarized light microscope if miscibility was possible to see visually. Dispersions were kept in stressed conditions and the crystallization was analyzed with XRPD. Stability was also examined with isothermal microcalorimetry (IMC). The dispersion of itraconazole and theophylline 40/60 (w/w) was completely miscible. It was proved by linear combination of XRPD results and single glass transition temperature in DSC. Homogenic well mixed film was observed with light microscope. Phase separation was observed with other compositions. Dispersions of theophylline and PVP mixed only partly. Stability of itraconazole dispersions were better than theophylline dispersions which were mixed poorer. So miscibility was important thing considering stability. The results from isothermal microcalorimetry were similar to results from conventional stability studies. Complementary analytical methods should be used when studying miscibility so that the results are more reliable. Light microscope is one method in addition to mostly used XRPD and DSC. Analyzing light microscope photos is quite subjective but it gives an idea of miscibility. Isothermal microcalorimetry can be one option for conventional stability studies. If right conditions can be made where the crystallization is not too fast, it may be possible to predict stability with isothermal microcalorimetry.
  • Rahikainen, Otto (2023)
    Ramansironta on sähkömagneettisen säteilyn ilmiö, jonka avulla voidaan havaita molekyylivärähdyksiä niistä sironneen valon avulla. Kun sähkömagneettinen säteily kohtaa molekyylin se voi häiritä elektronipilveä ytimen ympärillä ja prosessin lopputuloksena energiaa vapautuu sironneen säteilyn muodossa. Tätä kutsutaan epäelastiseksi sironnaksi. Mikäli sironnassa ei tapahdu fotonin energiassa muutosta kyseessä on elastinen siroaminen. Mikäli näytteeseen menevän ja sironneen fotonin välillä havaitaan energian muutos, käytetään ilmiöstä nimeä epäelastinen Raman sironta. Energian muutosta voidaan mitata, ja saatu spektri antaa tietoa kohdemolekyylistä. Tämän työn tarkoituksena oli tutkia eri Raman-spektroskopiatekniikoiden, lähinnä spontaani-Raman spektroskopian sekä koherentti anti-Stokes Ramanspektroskopian ja mikroskopian soveltuvuutta lääkemolekyylien havaitsemiseen sekä nanopartikkeleiden karakterisoinnissa ja nanopartikkeleiden ja solujen välisten interaktioiden tutkimisessa. Tekniikan vahvuuksiin kuuluu käytön suhteellinen helppous ja CARS-mikroskopian nopeus sekä korkea erotuskyky, mahdollisuus havainnoida solunäytteitä, ja epätodennäköisyys vaurioittaa tutkittavaa kohdetta. Haasteisiin lukeutuu fluoresenssin taipumus häiritä signaalia, spontaani-Raman mikroskopian heikompi erottelukyky, analyysin hitaus sekä tarve valikoida molekyyli, jonka rakenne antaisi vahvan Raman-signaalin. Tutkimuksen alatavoitteina oli sopivan lääkemolekyylin valitseminen nanopartikkeliformulaatioon, nanopartikkeleiden formulointi, niiden karakterisointi Raman-spektroskopiatekniikoilla, ja lopulta tutkia Raman spektroskopian soveltuvuutta nanopartikkeleiden ja lääkeaineen sekä solujen interaktioiden tutkimisessa ja lääkeaineen havaitsemisessa solujen sisältä. Tutkimuksessa uutta on se, että ensimmäistä kertaa polymeerinanopartikkeleiden ja niihin ladattujen lääkeaineiden soluunkulkeutumisen tutkiminen pelkällä Raman-spektroskopialla ilman esim. fluoresoivia merkkiaineita. Tutkimuksen tavoitteen pääasiallisesti täyttyivät. Valitsimme kohdemolekyyliksi klorotaloniilin, fungisidin joka on edullinen ja antaa selvästi tunnistettavan Raman-signaalin. Klorotaloniilille suoritettiin normaalit sytotoksisuuskokeet sekä vapaana lääkeaineena että formuloituina nanopartikkeleina. Nanopartikkelien formulointi onnistui ja molemmat Raman-spektroskopiatekniikat näyttivät selvästi sekä lääkemolekyylin että polymeerin kemikaalispesifiset Raman signaalit. Lääkemolekyylin havaitsemin solujen sisältä onnistui. Polymeerimolekyylit eivät missään vaiheessa kulkeutuneet solujen sisälle. Tämä oli ehkä yllättävää koska käytimme makrofageja, mutta toisaalta myös johdonmukainen muiden tutkimusten kanssa. Raman-tekniikat osoittautuivat hyviksi tutkimusmenetelmiksi, ja erityisesti CARS-mikroskoopin suuri erotuskyky osoittautui hyödylliseksi soluunkulkeutumisen kuvantamisessa.
  • Berg, Staffan (2013)
    The usage of polymer conjugation to modulate the biopharmaceutical behavior of both protein drugs as well as small molecule drugs is discussed. Emphasis has been given to polyethylene glycol (PEG) and poly[N-(2-hydroxypropyl)methacrylamide] (PHPMA) but also other polymers are looked into. Drug products on the market as well as drug candidates in clinical trials are used as examples when reviewing different polymers. The material is looked upon from a biopharmaceutical point of view. In the experimental part a polymer-drug conjugate for the treatment of ovarian cancer is synthesized and characterized. The conjugate has a HPMA polymer backbone with the anticancer drug gemcitabine attached through enzymatically labile Gly-Phe-Leu-Gly linkers. The conjugate is expected to target passively and actively to cancer tissue. The enhanced permeation and retention effect is responsible for the passive targeting, while Fab' fragments of OV-TL16 monoclonal antibodies provide the active targeting of the copolymer conjugate. In vitro cytotoxicity studies of a PHPMA-gemcitabine conjugate (without active targeting) was carried out on two ovarian cancer cell lines, A2780S and A2780AD. The IC50 values of the conjugate was shown to be 50.6 nM and 14.3 nM for A2780S and A2780AD, respectively. The corresponding IC50 values for free gemcitabine were 7.0 nM for the A2780S cell line and 3.9 nM for A2780AD cells. A preliminary in vivo efficacy study in mice with subcutaneous A2780AD tumor xenografts showed that a PHMA-gemcitabine conjugate given at a dose of 15 mg/kg (gemcitabine equivalence) was able to shrink the tumor volume by 50 % while only inducing minor body weight loss.
  • Jokinen, Birgitta (2010)
    Angiogenesis may be regarded as one of the most important phenomena involved in basic physiology as well as in numerous pathological conditions. Angiogenesis is a multistep process involving the balance of pro- and con-angiogenic factors. Several studies have suggested that angiogenesis is regulated in vitro and in vivo by peptides thymosin ȕ4 (Tȕ4) and tetrapeptide Ac-SDKP (N-acetyl-seryl-aspartyl-lysyl-proline). There are also studies supporting the view that Ac-SDKP, a peptide fragment is released from the proline-containing C-terminus of Tȕ4 (43-mer) by hydrolyzing prolyl oligopeptidase (POP). POP is a widely existing serine protease cleaving oligopeptides of no longer than 30 amino acids. Thus, Tȕ4 should first be cleaved into a shorter peptide by some other, yet unknown peptidase. POP has been mostly studied in memory and learning disorders as well as in neurodegenerative diseases. The true physiological character of POP is still unresolved. In this Master's thesis, the associations of the factors involved in angiogenesis are reviewed in the literature part as well as the character, presence and function of the angiogenic molecules 7ȕ4, Ac-SDKP and POP. In the experimental part attempts were made to find whether POP and Tȕ4 increase Ac-SDKP formation and capillary tube network and consequently, whether the POP activity, tetrapeptide and capillary formation could be inhibited by the proline-spesific POP inhibitor KYP-2047. The study had two phases. The first phase included POP activity and Ac-SDKP measurements(time period 0-180 min) with Wistar rat kidney homogenates. Study groups were 0,1 and 0,5 µM KYP-2047 (+2 µM Tȕ4), 1:20 (0.625 µM) human recombinant POP (+ 2 µM Tȕ4), 2 µM 7ȕ4 (pos. control) and raw homogenate (neg. control). The second phase involved the study of capillary formation (time period 0-180 min) with primary endothelial HUVECs on a 48-well plate seeded with 50 000 cells/well on an extracellular membrane mimicking MatrigelTM Matrix dissolved in DMEM. Study groups treated with fetal bovine serum and antibiotics were 5 and 10 µM KYP-2047 (+4 µM Tȕ4), 1:20 (0.625 µM) human recombinant POP (+4 µM Tȕ4)4 µM Tȕ4 (pos. control) and DMEM (neg. control). The wells were cultured and capillary formation photographed with a light microscope using a digital camera. All experiments were repeated four times, and each study group in wells was measured in triplicate. Enclosed capillaries were counted manually and statistical tests were performed. 7ȕ4 along with POP participated in the formation of AC-SDKP in the kidney homogenates. Cultures of primary endothelial cells on Matrigel resulted in clear capillary formation in Tȕ4 and POP groups. KYP-2047 had a strong POP-inhibitory activity on antiangiogenesis throughout the study resulting. Obviously, underlying mechanisms of angiogenesis and the function of the interaction between POP, Tȕ4 and Ac-SDKP in capillary formation require further studies.
  • Neittaanmäki, Eerika (2015)
    Actinic keratoses are premalignant skin lesions caused by sun UV-radiation. A small portion of these lesions progress into invasive squamous cell carcinoma over the years. Actinic keratoses are a growing problem in the healthcare around the world. P53 mutations are found in actinic keratosis and adjacent areas. Treatment options include surgical removal, cryotherapy, local treatment creams such as immunomodulators, and photodynamic therapy (PDT). Aminolevulenic acid (ALA) is an endogenous light-sensitizer used in PDT and methylaminolevulinate (MAL) and hexylaminolevulinate (HAL) are its esters. Either artificial light or daylight can be used as a light source in PDT. In PDT light activates the photosensitizer, which initiates a photochemical reaction and target cell destruction. The most common side effects of PDT are erythema and pain during treatment. The benefits of PDT are good cosmetic outcome and the possibility to treat large areas. In the present study 3 light-sensitizers (BF-200 ALA, MAL, HAL 0,2 % and 2 %) were tested on healthy volunteers to compare the skin irritation, pain and fluorescence caused by the treatment. Fluorescence intensity reflects PpIX production capacity. The second part of the present study was a clinical study comparing BF-200 ALA and MAL in treatment of actinic keratoses with daylight-PDT. Each patient received both light-sensitizers on opposite sides of the head and the results were evaluated 3 months after treatment. On healthy skin BF-200 ALA, MAL and HAL 2 % caused more irritation compared to HAL 0,2 %. HAL 2 % didn't differ from ALA and MAL-groups in severity of reactions, erythema or fluorescence photobleaching. In HAL-treated areas pain was smaller than in ALA- and MAL-groups. However, in lesional skin there might be differences in absorption, distribution and PpIX formation. Both BF-200 ALA and MAL were effective in daylight-PDT and there were no significant differences between the groups in either efficacy or pain caused by the treatment. Long-term follow up is still required to confirm if the results sustain.
  • Hannula, Mirva (2010)
    Prolyl oligopeptidase (POP, prolyl endopeptidase, EC 3.4.21.26) is a serine-type peptidase (family S9 of clan SC) hydrolyzing peptides shorter than 30 amino acids. POP has been found in various mammalian and bacterial sources and it is widely distributed throughout different organisms. In human and rat, POP enzyme activity has been detected in most tissues, with the highest activity found mostly in the brain. POP has gained scientific interest as being involved in the hydrolyzis of many bioactive peptides connected with learning and memory functions, and also with neurodegenerative disorders. In drug or lesion induced amnesia models and in aged rodents, POP inhibitors have been able to revert memory loss. POP may have a fuction in IP3 signaling and it may be a possible target of mood stabilizing substances. POP may also have a role in protein trafficking, sorting and secretion. The role of POP during ontogeny has not yet been resolved. POP enzyme activity and expression have shown fluctuation during development. Specially high enzyme activities have been measured in the brain during early development. Reduced neuronal proliferation and differentation in presence of POP inhibitor have been reported. Nuclear POP has been observed in proliferating peripheral tissues and in cell cultures at the early stage of development. Also, POP coding mRNA is abundantly expressed during brain ontogeny and the highest levels of expression are associated with proliferative germinal matrices. This observation indicates a special role for POP in the regulation of neurogenesis during development. For the experimental part, the study was undertaken to investigate the expression and distribution of POP protein and enzymatic activity of POP in developing rat brain (from embryonic day 14 to post natal day 7) using immunohistochemistry, POP enzyme activity measurements and western blot-analysis. The aim was also to find in vivo confirmation of the nuclear colocalization of POP during early brain ontogeny. For immunohistochemistry, cryosections from the brains of the fetuses/rats were made and stained using specific antibody for POP and fluorescent markers for POP and nuclei. The enzyme activity assay was based on the fluorescence of 7- amino-4-methylcoumarin (AMC) generated from the fluorogenic substrate succinyl-glycyl-prolyl-7-amino-4-methylcoumarin (Suc-Gly-Pro-AMC) by POP. The amounts of POP protein and the specifity of POP antibody in rat embryos was confirmed by western blot analysis. We observed that enzymatic activity of POP is highest at embryonic day 18 while the protein amounts reach their peak at birth. POP was widely present throughout the developmental stages from embryonic day 14 to parturition day, although the POP-immunoreactivity varied abundantly. At embryonic days 14 and 18 notably amounts of POP was distributed at proliferative germinal zones. Furthermore, POP was located in the nucleus early in the development but is transferred to cytosol before birth. At P0 and P7 the POP-immunoreactivity was also widely observed, but the amount of POP was notably reduced at P7. POP was present in cytosol and in intercellular space, but no nuclear POP was observed. These findings support the idea of POP being involved in specific brain functions, such as neuronal proliferation and differentation. Our results in vivo confirm the previous cell culture results supporting the role of POP in neurogenesis. Moreover, an inconsistency of POP protein amounts and enzymatic activity late in the development suggests a strong regulation of POP activity and a possible non-hydrolytic role at that stage.
  • Puranen, Pinja (2023)
    Medical devices play a crucial role in healthcare, yet their importance is underscored by the potential for adverse events that can lead to serious consequences for patients and users. As a result, manufacturers of medical devices are required to actively monitor the safety and performance of their devices after placing them on the market. In response to incidents involving medical devices and their safety, the European Union Medical Device Regulation (MDR) came into force in May 2021, bringing more emphasis to the post-market surveillance (PMS) of medical devices. In this study, the current state of the post-market surveillance system of medical device manufacturers in Finland was investigated by conducting an online questionnaire in 2023. A total of 30 medical device companies participated in the questionnaire for a return rate of 17%. The dataset included manufacturers of different sizes, producing medical devices of all risk classes. To identify differences in the use of post-market surveillance data sources between different types of companies, the two-sided non-parametric Kruskal-Wallis-Test was used. The rest of the data was analysed using descriptive analysis. The post-market surveillance data sources with the highest reported intensity of use included customer complaints and feedback, production monitoring, and regulatory intelligence monitoring, while Post Market Clinical Follow-up and health services research were used significantly less. Significant differences between manufacturers of different device risk classes were identified for three data sources; manufacturers of higher risk class devices were found to utilize these data sources to a higher extent than manufacturers of low-risk devices. The manufacturers of medical devices seem to utilise reactive post-market surveillance data consistently to a high extent. On the other hand, the results suggest that proactive post-market surveillance methods remain underutilised despite the introduction of the MDR. Medical device manufacturers also use post-market surveillance data sources to different extents, in particular with respect to the medical device risk class. Overall, the results indicate that the MDR is bringing more emphasis on post-market surveillance, which in turn has increased the workload of medical device manufacturers.
  • Pylkkänen, Sarita (2013)
    Harmful drug effects are common among older medicine users. Potentially harmful drugs for older people have been defined by different criteria. Potentially inappropriate medications (PIMs) defined by Beers criteria have been associated with adverse effects, increased costs, need of hospital care and disabilities. Drugs with anticholinergic properties (DAPs) are associated with anticholinergic side effects, cognitive decline and delirium. Psychotropic drugs have been associated with increased risk of falls and mortality. Concurrent use (≥3) of psychotropic drugs has been considered harmful for older people by the Swedish National Board of Health and Welfare. The aim of this study was to examine the prevalence of potentially harmful drug (PHD) use (DAPs, PIMs, or concurrent use of ≥3 psychotropic drugs) and the accumulation of PHDs in aged people living in nursing homes and assisted living facilities. The objective was also to investigate which patient characteristics are associated with PHD use or accumulation of these drugs. The cross-sectional data was collected in 2011-2012 as a part of a larger study "Reducing inappropriate, anticholinergic and psychotropic drug use among older residents in institutional care". The study population (N=326) consisted of ≥ 65-aged residents living in nursing homes or assisted living facilities in Helsinki (n=227) and Kouvola (n=99). The mean age was 83.5 years, 70.0 % were women and mean Charlson comorbidity index was 2.6. Residents were divided into four groups: aged using 1) DAPs, 2) PIMs defined by Beers criteria, 3) concurrent use of ≥3 psychotropic drugs and 4) no PHDs in use. Both those fulfilling any of these criteria and those fulfilling all the three criteria (accumulation of PHD) are described. Users in these groups were compared to the non-users. A majority of the residents, 78,8 % (95 % CI: 74,4 - 83,3) used ≥1 PHDs: 67,8 % (95 % CI: 62,7- 72,9) used ≥1 DAPs, 32,2 % (95 % CI: 27,1- 37,3) ≥1 PIMs and 32,2 % (95 % CI: 27,1-37,3) used ≥3 psychotropics concurrently. Of the residents, 41 (12.6 %) had a medication treatment that fulfilled all the three criteria of PHD use. These residents used significantly more PHDs than others (average mean 4,8 [range 3-7] vs. 1,6 [range 0-6]). The residents having the PHD accumulation were more often males and used more drugs than others. There were no statistical differences among the other characteristics of these groups. The most common PHDs were mirtazapine (n=66), lorazepam (n=64), oxazepam (n=62), ketiapine (n=58) and stimulant laxatives without opioids (n=58). Use of DAPs was associated with multimorbidity, use of PIMs with weaker health related quality of life, and use of psychotropics with younger age. High number of drugs was associated with all these criteria. Use and accumulation of potentially harmful drugs is common among the aged living in nursing homes and assisted living facilities. New means are needed to optimize drug treatments and to educate professionals taking care of these patients. Special attention should be paid on the use of antipsychotics, benzodiazepines, mirtazapine and stimulant laxatives.
  • Lindholm, Anni (2023)
    Biologisten lääkkeiden käyttö on merkittävästi lisääntynyt 2000-luvulla, mikä on hoidollisten hyötyjen ohella lisännyt lääkekustannuksia. Vaihtokelpoisten ja halvempien biosimilaarien käyttöä on edistetty koulutuksella, lääkemääräyskäytäntöjen ohjauksella ja lainsäädännöllä. Vuosina 2024–2025 useat avoterveydenhuollossa käytettävät biologiset lääkkeet tulevat apteekissa tapahtuvan lääkevaihdon (apteekkivaihdon) piiriin. Potilaiden näkemykset biologisista lääkkeistä ovat tärkeä tutkimusaihe hoitotulosten, lääkevaihdon, rationaalisen lääkehoidon edistämisen ja lääkepolitiikan kehittämisen näkökulmista. Tutkimuksen tavoitteena oli tutkia potilaiden näkemyksiä biologisten lääkkeiden hinnoista, kustannuksista ja niiden merkityksestä. Tavoitteiden mukaiset tutkimuskysymykset liittyivät: 1) potilaiden preferenssiin lääkkeiden hoidollisesta arvosta lääkkeen hintaan verrattuna (ensisijainen tutkimuskysymys) ja yhteiskunnan lääkesäästöistä, 2) lääkkeiden hinnan merkitykseen lääkevaihdossa (potilaiden taloudellisten taustatekijöiden vaikutus ja euro-määräinen hyväksymis/maksuhalukkuus lääkevaihdossa) ja 3) potilaan oman lääkehoidon kustannettavuuteen. Tutkimus perustui Yliopiston Apteekin (YA) ja Helsingin yliopiston (HY) tammikuussa 2021 toteuttaman kyselytutkimuksen aineistoon. Kyselyyn vastasivat YA:n kanta-asiakkaat sekä Reumaliiton ja IBD- ja muut suolistosairaudet ry:n viestinnän kautta tavoitetut henkilöt. Kysely oli kohdistettu reuma-, IBD- (tulehduksellinen suolistosairaus) ja ihopsoriasispotilaille, jotka käyttivät alkuperäistä biologista lääkettä (BA), biosimilaaria (BS) tai perinteisiä pienimolekyylisiä lääkeitä (PL). Vastaajia oli yhteensä 1338 (BA-käyttäjiä 226, BS-käyttäjiä 71 ja PL-käyttäjiä 1041). Tulosmuuttujina käytettiin yksittäisiä kysymyksiä ja summamuuttujia. Lääkekäyttäjäryhmän ja muiden taustamuuttujien yhteyttä tulosmuuttujiin tutkittiin kaksi- ja monimuuttuja-analyyseillä. Suurin osa (83 %) potilaista oli sitä mieltä, että lääkkeen hinta ei saisi vaikuttaa lääkkeen valintaan biologista lääkettä määrättäessä, ja 62 %:n mielestä biosimilaarien käyttö auttaisi säästämään terveydenhuollon lääkekustannuksissa ja mahdollistaisi suuremman potilasmäärän hoidon biologisilla lääkkeillä. Potilaan taloudelliset taustatekijät eivät olleet monimuuttuja-analyysin perusteella yhteydessä näkemyksiin biologisten lääkkeiden lääkevaihdosta tai kiinnostukseen lääkevaihdosta. Jos biologisen lääkkeen hypoteettinen omavastuuhinta potilaalle olisi 600 euroa vuodessa, 14 % alkuperäisvalmisteen käyttäjistä olisi valmis vaihtamaan biosimilaariin, jos sen kustannus olisi hänelle 30 % nykyistä pienempi. Biosimilaarien käyttäjistä 38 % olisi valmis maksamaan lisää saadakseen alkuperäisvalmisteen. Biologisten lääkkeiden käyttäjillä (BA 36 % ja BS 44 %) oli ollut enemmän taloudellisia ongelmia lääkkeiden ostossa kuin perinteisten lääkkeiden käyttäjillä (25 %) (p <0,001). Potilaat suhtautuivat yleisesti myönteisesti biosimilaarien käyttöön lääkekustannusten hillitsemiseksi, mutta pitivät hoidollisia perusteita hintaa tärkeämpänä. Potilaan taloudelliset tekijät eivät olleet yhteydessä näkemyksiin lääkevaihdosta tai vaihtohalukkuuteen. Merkittävä osa potilaista on kiinnostunut vaihdosta edullisempaan biosimilaariin. Tulokset korostavat biologisiin lääkkeisiin ja lääkevaihtoon liittyvän lääkeinformaation merkitystä.
  • Kiviluoto, Katrimari (2014)
    In a pharmacotherapy process prescriber, provider, administrator and evaluator of the effects of medication cooperate in a coordinated way to ensure optimum outcomes of the patient's medications. This requires that all professionals involved in the pharmacotherapy process know their functions and responsibilities in an interprofessional team. No previous studies have explored legislative facilitators and barriers that have impact on the interprofessional pharmacotherapy process even though interprofessional collaboration for assuring safe and effective pharmacotherapy is one of the main objectives of Medicines Policy 2020 in Finland (Ministry of Social Affairs and Health 2011). The aim of this study was to examine how legislation prevents or facilitates the interprofessional pharmacotherapy process. The data consisted acts, decrees, regulations and directives concerning pharmacotherapy process in the healthcare. Changes in the Finnish legislation from 1990 until present were studied, taking also into account the European Union legislation since 1995 when Finland became a member. Research method was qualitative content analysis. A modified form of the causal diagram of the impact of law and legal practices on public health system performance by Burris et al (2012) was used as a theoretical framework. Interprofessional collaboration applicable to pharmacotherapy process has been taken into account in the main enactments. These enactments concern rights and duties of healthcare professional, patient’s rights, resources required in healthcare, communication and information transfer, and pharmacotherapy process. Enactments that complicate the interprofessional pharmacotherapy process relate especially to communicational barriers. Facilitating enactments include guidelines ensuring coordinated clinical practice for effective and safe medication use and improved communication, collaboration and patient-centeredness as well as accessibility of cross-border healthcare. A trend was observed that the legislation enacted on the 21st Century put more emphasis on interprofessional collaboration, development of technology and mobility of citizens. According to this study there are more facilitators than barriers for interprofessional pharmacotherapy process. Recent enactments even emphasize more interprofessional cooperation in health care than did those enacted before the 21st Century. Still, enactments are general: they should be made more detailed to give a better understanding of interprofessional cooperation, also related to the pharmacotherapy process for safe, effective and evidence-based medication use.
  • Kaukovuori, Jouni (2021)
    Johdanto: Terveydenhuollon tietojärjestelmiin potilaista kertyvää tieto on hyvä esimerkki massadatasta. Se muodostuu lukuisista yksittäisistä, irrallisista tapahtumista. Potilastiedon toissijaisella hyödyntämisellä tarkoitetaan tiedon käsittelyä muuta tarkoitusta kuin potilaan terveyden edistämistä ja hoitamista varten. Toisiokäytölle on tyypillistä, että pääasiallisena kiinnostuksen kohteena ei ole yksilötason tiedon hyödyntäminen, vaan isommasta potilasjoukosta saatava summatieto, josta yksilön tunnistetiedot on poistettu. Toisiokäyttö mahdollistaa potilastiedon hyödyntämisen esimerkiksi tieteellisessä tutkimuksessa ja tietojohtamisessa. Tavoite: Tutkimuksessa selvitettiin HUSin tietoaltaasta louhitun aineiston avulla, onko tietoaltaaseen tallennetun aineiston avulla mahdollista tutkia lääkehoidon turvallisuutta ja rationaalisuutta sekä selvittää, millaisessa muodossa tietoaltaan data saadaan käyttöön ja millaisia toimenpiteitä datalle tulee tehdä, jotta sitä voidaan hyödyntää potilastiedon analysoinnissa. Aineisto ja menetelmät: Massadatan hyödyntämistä pilotoitiin rekisteritutkimuksessa, jossa esimerkkinä käytettiin opioideja. Rationaalisen lääkehoidon toteutumisen tutkimiseksi määriteltiin lääkeindikaattorit eli tunnusluvut, jotka oli tarkoitettu opioidien lääkehoidon kokonaiskuvan tarkasteluun. Indikaattoreiden avulla luotiin pohja hakuparametreille ja lausekkeille, joita tietoallashaussa käytettiin. Aineisto louhittiin tietoaltaasta maaliskuussa 2020 ja se muodostui opioideja koskevista lääkemääräysmerkinnöistä, jotka oli kirjattu potilastietojärjestelmään 1.1.2015-31.12.2019. Tulokset: Tietoallashausta saatiin 321 000 potilaan opioidimääräysdataa yhteensä noin 1,73 miljoonaa riviä. Kotiutumisen yhteydessä annetut opioidireseptit rajattiin jatkoanalyysin ulkopuolelle, sillä niitä koskeva tieto ei ollut rakenteisessa muodossa. Sairaalassa annettuja säännöllisiä opioidilääkemääräyksiä koskeva aineisto oli noin 258 000 riviä. Dataa siivottiin, järjesteltiin ja validoitiin data-analyysiä varten. Toimenpiteistä huolimatta data ei soveltunut indikaattorien laskentaan. Johtopäätökset: Tietoallasaineiston käytön mahdollisuudet rationaalisen ja turvallisen lääkehoidon tutkimukseen olivat tämän tutkimuksen perusteella rajalliset. Massadata-aineiston saattaminen tutkimuksellisesti hyödynnettävään muotoon vaatii menetelmän, joka pitää sisällään useita työvaiheita ja niiden kehittäminen vaatii tietoteknistä erityisasiantuntemusta. Vaikka dataa saatiin paljon, yksittäisen potilaan opioidilääkehoidosta ei saatu kokonaiskuvaa, koska merkittävä osa datasta oli rakenteettomassa muodossa. Potilastiedon toissijaisen hyödyntämisen kannalta aineiston rakenteisen osan merkittävimmät käytön esteet liittyivät datan laatuun ja luotettavuuteen. Jotta tietoaltaasta saatava aineisto soveltuisi toisiokäyttöön tai tieteelliseen tutkimukseen, pitää sekä potilastietojärjestelmän merkintä- ja kirjaamistapoja yhtenäistää sekä data tulisi tallentaa tietoaltaaseen yhä rakenteisemmassa muodossa.
  • Virolainen, Jenni (2012)
    Patient safety is a part of quality and safety of care. Patient safety is defined as freedom for a patient from unnecessary harm or potential harm associated with healthcare. Patient safety covers safety of care, medication safety and safety of devices. Different authorities have promoted patient safety in Finland. The Ministry of Social Affairs and Health set up the Steering Group for the Promotion of Patient Safety for a term extending from 1 November 2006 to 31 October 2009 to coordinate the work for promoting patient safety and to evaluate related development needs at the national level. It has published a national Patient Safety Strategy for the years 2009-2013. Patient safety is also included in the Health Care Act. The National Institute for Welfare and Health (THL) has a Finnish national programme on patient safety: Patient Safety with Skills. Other authorities promoting patient safety in Finland are Finnish Medicines Agency (Fimea) and National Supervisory Authority for Welfare and Health (Valvira). Many studies are related to Patient Safety. In the Seminar of Patient Safety Research 2011 studies were separated to following categories: Patient Safety Culture as a Challenge for Organisations, Medication Safety, Safeguard of Care, Preparation for Patient Safety, Learning of Patient Safety, Control of Patient Documents and Financing of Patient Safety. The aim of this study is to explore Finnish patient safety studies. This study was conducted by using an electronic survey. The survey was sent to members of Finnish Patient Safety Society and a mailing list of Patient Safety Network. The survey was also sent to attendees of the Seminar of Patient Safety Research 2011. Altogether 81 responses were obtained. A patient safety research had been done in 60 per cent of organizations. A patient safety research will be done in 62 per cent of organizations. 10 per cent of the researches were meant for the internal use of the organization but were also published in Finland and abroad. 21 per cent of the researches were published in Finland and abroad. 18 per cent of the researches were published only in Finland and 12 per cent only abroad. 25 per cent of the researches were meant only for the internal use of organization. 14 per cent of the respondents left this question unanswered. A personal grant from a foundation was the most common way of financing for patient safety research. Many different kinds of sponsors were also mentioned. There was co-operation between organizations in 58 per cent of researches. 86 per cent of respondents were interested in a network of patient safety researchers. Using of Reporting System for Safety Incidents in Health Care Organizations (HaiPro) was asked as a detail of this study. HaiPro was used in 65 per cent of organizations. 89 per cent of respondents said that their organization takes advantage of HaiPro but the level of use varied between respondents.