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Browsing by master's degree program "Utbildningsprogrammet för provisorsexamen"

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  • Viinamäki, Emilia (2023)
    Alpha-beta-hydrolase domain containing proteins (ABHD) are involved in lipid metabolism and its regulation in human and animal cells. Approximately 50 of these proteins have been identified and their physiological and pathophysiological functions are still further investigated. ABHD2, ABHD3, ABHD4, ABHD5, ABHD6, ABHD12 and ABHD16 are involved in the metabolism of glycerin esters and phospholipids, in particular lipid mediator 2-arachidonoylglycerol (2-AG) and its metabolites have a significant effect on neuroinflammation via the endocannabinoid system. ABHD12 and ABHD16A were at the center of focus in this thesis as enzymes regulating phosphatidylserine and pro-inflammatory lysophosphatidylserine. In this study, toxicity of five (5) abietane terpene derivatives was tested using mouse E15/16 prenatal cortical neurons, cultured in 96-well plates. There were totally 8 plates cultured in three different batches, 60 cell containing wells per each plate. Wells from each plate were divided into treatment groups of 17, three concentrations of every five compound, control and VEH groups. Those concentrations were 0,1 µM, 1 µM and 10 µM, and for the last two plates 1 µM, 10 µM and 100 µM. Treatment was also separated into three batches like the cell culturing. After treatment, number of living cortical neurons in each treatment groups were counted. For that, cells were treated with immunofluorescent NeuN and DAPI antigens and the fluorescence was imagined with automated microscope. CellProfiler was used to recognize and count the number of living cortical neurons. Immunofluorescent MAP2 antigens were also used but because the shape of MAP2-fluorescing cells, CellProfiler could not recognize them. Intensity of MAP2-fluorescence were measured from those imaged, so the work would not be wasted. One-way ordinary variance analyze ANOVA was carried out for the data to figure out if there were statistically significant results. For compound TAC174, there were several significant results with different concentrations but unfortunately, some results showed signs of toxicity and others improved cell-growth. Some significant results were also found with compounds TAC121, TAC147 and TAD40 showing sings of toxicity, but reliability of those results was questioned. Only one compound, TAC150 was not showing clear toxicity towards mouse cortical neurons, at least with lower concentrations. For conclusion, there were no clear or significant results if these compounds are toxic for cortical neurons. TAC150 showed the least sings of toxicity, therefore it could possibly be considered for further studies in medical field.
  • Antelo, Lauri (2023)
    African medicinal plants have been used to treat symptoms of infection successfully for thousands of years. However, no antimicrobial drugs have been developed from these plants. As antibiotic resistance is increasing rapidly, these traditional African herbal medicines can be an important solution in the fight against antibiotic resistance due to their antimicrobial properties. In this research, various extracts o the leaves of Combretum adenogonium (Combretaceae) and the fruits of Piper cubeba (Piperaceae) and Xylopia aethiopica (Annonaceae) were tested for their growth inhibitory effects against Bacillus cereus, Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli. Extracts were made with methanol, water, hexane, and chloroform. In addition, water and ethyl acetate extracts were separated from an 80 % methanol extract using solvent partition. All the studied plants are used for the treatment of infections and wounds in African traditional medicine. Water was used as extraction solvent since it is commonly used in African folk medicine. Both single solvent technique and sequential extraction were used. The antibacterial effects were screened using agar diffusion and microdilution methods. The interaction between an extract and an antibiotic was measured with a checkerboard method. Time-kill experiments were performed using microdilution and plate count methods. In this study, the chloroform extract of C. adenogonium leaves gave the best inhibitory effect of all studied plants against B. cereus (MIC 78.125 µg/ml). In general, B. cereus was the most susceptible of the selected bacteria against extracts and E. coli was the one with most resistance. Time-kill test showed that the antibacterial efficacy was fairly stable throughout the 24-hour period considered with few exceptions. According to checkerboard results, C. adenogonium chloroform extract and tetracycline appeared to inhibit each other's antibacterial activity against B. cereus. However, only one extract was studied in this study, and it is possible that C. adenogonium contains compounds that would have a potentiating effect on antimicrobials. In general, C. adenogonium extracts were effective against B. cereus. The extracts of P. Cubeba were particularly effective against S. aureus. X aethiopica extracts were equally effective for both B. cereus and S. aureus. Methanol extract X. aethiopica is the only extract studied that gave more than 90% inhibition against P. aeruginosa. Therefore, it could be concluded that X. aethiopica has the broadest activity range of the examined plants.
  • Toivonen, Laura (2021)
    Abstract Faculty: Faculty of Pharmacy Degree programme: Master of Science in Pharmacy Study track: Social pharmacy Author: Laura Toivonen Title: Deficiencies and risks related to medication use management in nursing homes identified by Regional State Administrative Agencies during their inspection visits Level: Master´s thesis Month and year: November 2021 Number of pages: 94+7 (appendice) Keywords: Medication safety, medication use process, nursing home, older adult, risk management, guidelines for safe medication practices Supervisor or supervisors: M.Sc. Pharm, PhD student Suvi Hakoinen, University of Helsinki, Keusote; Professor, PhD Marja Airaksinen, University of Helsinki Where deposited: Additional information: Abstract: Nursing home residents are often characterized by older age, multimorbidity and polypharmacy. Medication safety has become an issue as part of client/patient safety in nursing homes in Finland. Still, little is known about medication safety risks and their management in this care context. The aim of this study was to identify deficiencies and risks associated with medication use management in nursing homes using inspection visits by the Regional State Administrative Agencies (AVIs) as a data source. In addition, the aim was to evaluate what issues the AVI-authorities pay attention to in the medication use management during their inspection visits in nursing homes. The data consisted of the latest inspection reports (n = 24) prepared by the Regional State Administrative Agencies (n = 6) on the basis of their nursing home visits (nursing homes for older people). The data were analysed by deductive content analysis methods. In addition to qualitative documentary analysis, quantitative indicators were used to illustrate the frequency of the risks and deficiencies -observed in different phases in the medication use process to identify phases posing risks most commonly. Reason´s system-based risk management theory was applied as a theoretical framework for the study. A total of 372 deficiencies and risks related to medication use process were identified from the inspection reports (n = 24) of Regional State Administrative Agencies. The largest proportion (58,9 %, n = 219) of the deficiencies and risks concerned the management and quality management of the medication use process. Particularly, deficiencies and risks related to lack and competence of personnel were emphasized. Deficiencies and risks were also identified in the self- assessment guidelines for safe medication practices used in the inspected nursing homes. The second highest number of risk observations (26,9 %, n = 100) was reported for ordering, delivery and storage of medicines. In particular, the deficiencies and risks were reported for the storage and warehousing practices. Reported risk observations in other phases of the medicines use process were rare. This study showed that the medication use process in Finnish nursing homes includes deficiencies and risks endangering the safety of the older nursing home residents. In order to manage the risks, both self-assessment and inspection practices by the authorities need development. One way to improve and harmonize both self-assessment and inspection practices could be use of a comprehensive checklist covering of all the relevant issues required for the safe medication practices in nursing homes. Increasing collaboration with pharmacists could also be a way to improve medication safety in nursing homes.
  • Seppälä, Katariina (2024)
    General anaesthetics are pharmaceutical agents used to induce general anaesthesia, a reversible state of unconsciousness. Caenorhabditis elegans, a nematode species, has been successfully used as a model organism in the study of gaseous anaesthetics due to its amenability to genetic modification, fully mapped nervous system connectome and high evolutionary conservation. However, C. elegans is less well characterised as a model organism in the study of non-gaseous anaesthetics. The primary aim of the study was to study the potential of ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, and urethane, a nonselective modulator of various neurotransmitter-gated ion channels, to immobilise C. elegans without activating antioxidant response signalling by transcription factor SKN-1, the nematode orthologue of the mammalian Nrf/CNC proteins. The transparent body of C. elegans enables microscopic imaging of cellular processes, but high-quality imaging requires the immobilisation of the worm. A commonly used chemical immobilising agent, sodium azide, causes SKN-1 activation in C. elegans, which may limit the use of sodium azide in studies on SKN-1 promoters. A secondary aim of this study was to study the impact of ketamine, an activator of mTOR (mechanistic target of rapamycin) signalling, on the lifespan of C. elegans. The lifespan of C. elegans has been found to increase with inhibition of the mTOR homologue pathway in previous studies. Ketamine and urethane were administered to wild-type C. elegans in aqueous media in 96-well plates. Behavioural endpoints of immobility and uncoordination were assessed manually via microscopic observation and video recordings. SKN-1 activation was studied by measuring drug-induced fluorescence in mutant strain CL2166, which carries a green fluorescent protein reporter of SKN-1 downstream target GST-4 (glutathione-S-transferase). A lifespan assay was performed with sterile C. elegans strain SS104 by incorporating ketamine in the worm maintenance agar. In this study, urethane did not appear to be a potent immobilisation agent. Ketamine was found to cause reversible weak immobilisation at a similar concentration at which sodium azide fully paralyses wild-type C. elegans. At lower doses ketamine caused uncoordinated locomotion. Short-term exposure to an immobility-inducing dose of ketamine was not found to significantly activate SKN-1. In the lifespan assay, ketamine unexpectedly appeared to significantly increase the nematode lifespan compared to control treatment.
  • Pykälämäki, Matias (2023)
    Parkinson’s disease (PD) is a progressive neurodegenerative disease characterized by the death of nigrostriatal dopaminergic neurons and formation of intraneuronal protein aggregates called Lewy bodies and Lewy neurites. These inclusions consist of a protein called α-synuclein (aSyn) but also of other proteins, lipids and cell organelles. Progressive cell death leads to nonmotor and motor symptoms. Current therapies for PD are symptomatic and do not modify the disease progression. Therefore, there is a need for the development of therapies attenuating the neurodegeneration. The pre-formed fibrils (PFF) model enables studying of aSyn aggregation and mechanisms behind inclusion formation. The PFF model is based on the exogenous aSyn fibrils’ tendency to result in formation of Lewy body -like inclusions when added in cell culture or in animals. Primary neuronal cultures of mice and rats have typically been used to model aSyn aggregation in vitro with the PFF model. Primary neuronal cultures provide practicality and are able to depict relevant features of dopaminergic neurons. To gain insight about the composition of E13.5 primary embryonic mouse midbrain culture and to enable adaptation of an existing protocol to study other cell types, this study identified and quantified several relevant cellular phenotypes in the micro island culture. The cells were fixed on day in vitro (DIV) 8 or DIV 22 and analysis was conducted using fluorescent immunocytochemistry combined with automated image analysis software, CellProfiler. On DIV 8, tyrosine hydroxylase -positive dopaminergic neurons represented 5 % of the total cells in the culture. Neuronal nuclear antigen -positive neurons resulted representing 30 % of the total cells. Gabaergic neurons were identified to be abundant in the culture and certain dopaminergic neurons were identified as immunoreactive for GABA. Choline acetyltransferase -positive cholinergic neurons were also identified to be present in the culture. The number of oligodendrocyte precursors (OPCs) was observed to be significantly smaller than the number of dopaminergic neurons. OPCs represented around 1 % of the culture on DIV 8. Glutaminergic neurons, parvalbumin-positive interneurons, microglia or astrocytes were not identified in the culture on DIV 8. The number of astrocytes was observed to increase as the incubation time was prolonged to DIV 22. Overall these findings provide valuable insights of the composition of cell phenotypes in E13.5 mouse midbrain culture. The results also provide additional validation for suitability of the original protocol to robustly produce midbrain dopaminergic cultures with minimal number of glial cells. Understanding more about the relevance and interplay of different cell phenotypes in PD pathophysiology can provide valuable insight for the development of potential therapeutic strategies.
  • Leinoluoto, Otto (2023)
    Diseases of the posterior eye segment, such as age-related macular degeneration (AMD), diabetic retinopathy, diabetic macular edema and glaucoma are the leading cause of blindness worldwide. Current therapy to treat these vision-threatening diseases relies on intravitreal injections to maintain a desired therapeutic drug concentration in the back of the eye. Frequent intravitreal injections are uncomfortable with poor patient compliance and causes major burden to the healthcare systems as well as to the patients. Small molecule drugs have shorter half-life in the vitreous and are eliminated rapidly. This requires frequent intravitreal dosing intervals that are not feasible in the clinical settings. Also, intravitreally injected small molecule drugs are often poorly and non-specifically distributed to the ocular tissues causing adverse effects. To address these issues, controlled and sustained drug delivery systems in the form of drug conjugates are desirable. Conjugating small molecule drugs with enzymatically cleavable peptide linkers increases the residence time in the vitreous. The peptide linker gets cleaved by vitreal enzyme and the released drug reaches the target in retina and choroid. Aim of this thesis was to screen a library of 25 peptide linkers for cleavage in the presence of porcine vitreal enzymes. The peptide linkers were chemically synthesized and the in vitro stability of the peptide linkers were studied in freshly isolated porcine vitreous. Ten time point samples were collected over a period of 45 days and the peptide cleavage in porcine vitreous was assessed by LC-MS method. A TQ-S liquid chromatography-mass spectrometer was used to study the linker cleavage. LC-MS method development for the peptide library was carried out using IntelliStart wizard function. Out of the 25 peptide linker in the library, stability of eight linkers were not included in the LC-MS analysis as a mass method could not be developed. Out of 17 peptide linkers studied, 14 were categorized as fast cleaving linkers (>90% of the linker cleaved in porcine vitreous after 5 h). Three linker peptides; P4, P5 and P25 were categorized as slow cleaving linkers. Conjugating slow cleaving peptide linkers to small molecule drugs will increase the half-life and enhance the duration of drug action upon intravitreal injection. In this study, linkers that are hydrolyzed by specific enzymes present in vitreous or ocular tissues are exploited to investigate their potential for delivering small molecule drugs.
  • Eronen, Sini-Tuulia (2022)
    Introduction: When people age, the composition of sleep changes and sleep becomes more sensitive to external disturbances, making insomnia also more common. Medication is not the first-line treatment option for insomnia. Benzodiazepines or benzodiazepine receptor agonists for the treatment of insomnia have been in the focus of past studies. The content of the dosing instructions for the supplied medicines has not been studied. The dosing instructions should provide clear instructions on how to dose the medicine prescribed to the patient. The aim of this study was to investigate the content and quality of dosing instructions prescribed for the treatment of insomnia for Finns aged ≥75 years in 2020 based on the prospective reimbursement register data by the Social Insurance Institution of Finland (Kela). Materials and methods: The reimbursed purchases of all medicines by persons aged ≥75 years from 1.1.2020 to 31.12.2020 were selected by ATC code from the medicines data according to the Insomnia: Current Care guidelines. The data was gathered from Kela’s dispensations reimbursed under the National Health Insurance scheme. The dataset consisted of 1,080,843 delivery lines, which were screened, and 328,285 lines were included in the analyses. Dosage instructions were reviewed according to the following predetermined five categories: frequency of use, dose, timing, warnings or remarks, and inappropriate instructions. In addition, 1000 dosing instructions were randomly derived to study the phrasing and appropriateness of the dosing instructions in more detail. Results: In 2020, an average of 3.8 reimbursed hypnotic drug deliveries were made per elderly person. Of the deliveries, 68% were for women. 52% of drug deliveries were partially made later and not by original prescription. In the hypnotic dataset, the three most administered drugs were zopiclone (41%), mirtazapine (34%) and zolpidem (12%). The dosage was prescribed in 98–99% of the dosage instructions. Dosing schedule was reported in 83% of dosing instructions and regularity of use was reported in 57% of them. Only 3-6% of the dosing instructions had comments or warnings. 1–2% of the dosing instructions were vague. The duration or regularity of use was clearly indicated in 5% of the dosing instructions. Only 0.1% of dosage instructions contained instructions for discontinuation or reduction. Discussion: The dose and timing of administration were well reported, but the frequency of use was reported in only about half of the dosing instructions. Only few dosing instructions contained remarks or warnings even though hypnotics are at risk for the elderly. Among the three most administered drugs for the treatment of insomnia were two benzodiazepine receptor agonists, zopiclone and zolpidem. However, they may not be suitable for the elderly according to Beers criteria and their use should be avoided. During 2020, an average of four drug deliveries were made per elderly person for the treatment of insomnia, which may indicate prolonged hypnotics use. In addition, more than half of the deliveries were partially made later and not by original prescription. Thus, several drug packages are prescribed for prescriptions, although the drug-based treatment of insomnia should only be short-lived. Conclusions: There are significant deficiencies in the contents and quality in the dosing instructions for drugs delivered to the elderly for insomnia. Minimum information on dose, timing and duration of use was not found in all dosing instructions in this study. Understandable dosing instructions and the reduction in the amount of medication in the prescription could have a further effect on reducing the long-term use of hypnotics, also increasing the safety of medicine use in the elderly.
  • Hämäläinen, Klaus (2022)
    Multiple Sclerosis (MS) is an incurable autoimmune demyelinating disease affecting the central nervous system (CNS). Although the detailed pathogenesis remains unclear, recent research has highlighted the involvement of B cells. For decades, however, MS research was based on T cell-focused animal models of autoimmune encephalomyelitis (EAE), which do not reflect the involvement of B cells in the pathogenesis. Therefore, B cell-dependent EAE models are hypothesized to allow a better understanding of MS immunohistopathology and may therefore lead to the development of efficient treatments. In our spontaneous relapsing-remitting (RR) EAE model, B cells are recruited from the endogenous repertoire by transgenic myelin oligodendrocyte glycoprotein (MOG) -reactive T cells, causing the development of EAE in 3–4-month-old mice. Interestingly, MOG-specific antibodies are present long before actual onset of clinical disease and can be detected already in 5-week-old RR mice and disease development in RR mice is dependent both on the presence of (presumably MOG-specific) B cells as well as on stimuli provided by intestinal microbiota. Firstly, we evaluated the broader usability of induced germinal center cell (iGB) culture as a model for B cell repertoire studies. Then, by using iGB culture, we studied whether MOG-specific B cells are present in secondary lymphoid organs of younger than 4-week-old and germ-free RR mice. Finally, this study aimed to investigate whether the repertoire of MOG-specific B cells undergoes significant qualitative changes from young healthy mice to older acutely sick RR mice, and whether at the time of disease onset the recruited MOG-specific B cells expand and mature in the cervical nodes (cLN) or in the CNS. To do so, following the hosting-lab’s previous single-cell RNA sequencing (scRNA-seq) of B cells derived from cLN of 5-week-old RR mice, we performed the scRNA-seq of B cells from CNS, spleen, and cLN of acutely sick RR EAE mice. We demonstrated that iGB culture is an unsuitable tool to expand pre-activated B cells, and hence, in our hands it was inappropriate for repertoire studies. However, iGB culture proved to be useful for screening different organs for MOG-specific B lymphocytes, and we found that anti-MOG antibodies were firstly detected in 3-4-week-old RR mice, and MOG-specific B cells were present also in germ-free RR mice. Our scRNA-seq results revealed many highly expanded MOG-specific B cell clonotypes in acutely sick RR mice. Moreover, the B cell repertoire of sick RR mice was more diverse, including IgG1, IgM, IgG2b, IgG2c, and IgG3 isotypes, compared to healthy 5-week-old RR mice that had only IgG1 or IgM isotypes. Two-thirds of the expanded clonotypes were primarily detected in the CNS in sick RR mice, indicating that clonotypes develop further and continue isotype switching within the CNS. We also detected more somatic mutation in the variable region of expanded clones of sick RR mice compared to 5-week-old RR mice. The results of this study clearly show an antigen-driven evolution of the MOG-specific B cell repertoire from healthy young to acutely sick RR mice, which seems to occur mainly in CNS itself. In contrast, cLN are the major initial priming site of MOG-specific B cells in healthy RR mice, even under germ-free conditions. This suggests that commensal microbiota is not required for initial recruitment of MOG-specific B cells, but for the development of EAE. To further validate our encouraging scRNA-Seq results, it is necessary, in future experiments, to confirm the MOG-specificity of expanded clonotypes.
  • Mönkkönen, Iina (2024)
    Lääkityspoikkeamat aiheuttavat maailmanlaajuisesti eniten vältettävissä olevia potilashaittoja terveydenhuollossa. Vaaratapahtumista raportoiminen on tärkeää lääkitysturvallisuuden edistämiseksi, sillä raportoinnin avulla saadaan tietoa lääkehoitoprosessin riskikohdista, jota voidaan puolestaan hyödyntää kehitettäessä lääkehoitoprosessien suojauksia. Tutkimuksen tavoitteena oli selvittää, millaisia sosiaali- ja terveydenhuollossa tapahtuneita lääkehoidon vaaratapahtumia apteekeissa on havaittu ja estetty sekä millaisiin kehittämistoimenpiteisiin apteekkien vaaratapahtumailmoitukset johtivat tapahtumayksiköissä. Tutkimus toteutettiin retrospektiivisenä rekisteripohjaisena tutkimuksena avoapteekkien sosiaali- ja terveydenhuollon yksiköihin lähettämistä HaiPro-vaaratapahtumailmoituksista sekä tapahtumayksiköiden seurantalomakkeista. Tutkimusaineisto oli kerätty Pohjanmaan, Kanta-Hämeen ja Keski-Uudenmaan hyvinvointialueilla 1.2.2022-31.12.2023. Alkuperäinen aineisto sisälsi 457 vaaratapahtumailmoitusta. Aineiston esikäsittelyssä poistettiin ilmoitukset, jotka eivät olleet sosiaali- ja terveydenhuollossa tapahtuneita vaaratapahtumia (n=11). Ilmoitukset, jotka koskivat useampaa kuin yhtä lääkeainetta tai potilasta (n=15) jaettiin erillisiksi tapauksiksi. Strukturoitujen kohtien valintojen oikeellisuus tarkistettiin tapahtumakuvausten perusteella ja tarvittaessa valinta korjattiin. Lopulliselle tutkimusaineistolle (n=461) suoritettiin kuvaileva määrällinen analyysi (frekvenssit ja prosenttiosuudet) Microsoft Excel ohjelmistolla. Aineistosta laskettiin vaaratapahtumien määrä, luonne, havaitsija, tyyppi sekä asiakkaalle ja apteekille aiheutuneet seuraukset, yleisimmin esiintyneet lääkeaineet, lääkeaineryhmät sekä suuren riskin lääkkeiden osuus. Terveydenhuollon yksiköiden kehittämistoimenpiteille suoritettiin laadullinen sisällönanalyysi aineistolähtöisesti sekä tarkasteltiin kehittämistoimenpiteiden jakautumista yksilö- ja järjestelmänäkökulmiin. Lähes kaikki (94 %) aineiston vaaratapahtumista (n=461) oli apteekin havaitsemia. Valtaosa tapauksista oli läheltä piti -tapahtumia (71 %). Vaaratapahtumat olivat lähes aina lääkehoitoon liittyviä (98 %). Yleisimmin kyseessä oli määräyspoikkeama (93 %), jossa oli väärä annos tai vahvuus (26 %), epäselvä tai puutteellinen annosohje (13 %) tai SIC-merkintä puuttui (11 %). Eniten vaaratapahtumailmoituksia oli hermostoon vaikuttavista lääkeaineista (23 %) sekä systeemisesti vaikuttavista infektiolääkkeistä (19 %). Suurin osa sosiaali- ja terveydenhuollossa ehdotetuista kehittämistoimenpiteistä (n=470) oli tapahtuman käsittelyä ja siitä keskustelua (63 %). Yleisimmin ehdotettiin asian käsittelyä tai siitä keskustelua ylilääkärin ja lääkäreiden kanssa (15 %) tai moniammatillisessa palaverissa (14 %). Tämä tutkimus osoittaa apteekin roolin keskeisen merkityksen sosiaali- ja terveydenhuollon toimijana ja lääkitysturvallisuuden varmistajana. Tutkimuksen perusteella apteekkien vaaratapahtumailmoittaminen voi tukea muun sosiaali- ja terveydenhuollon lääkehoitoprosessien turvallisuuden kehittämistä, mutta kehittämistoimien vaikuttavuutta lääkehoidon vaaratapahtumien ilmaantumiseen tulisi tutkia lisää.
  • Mannermaa, Siiri (2023)
    Medication safety is an important target of development in health and social services systems internationally. Medication errors are one of the biggest risk factors in medication safety. Majority of the medication incidents could be avoided by improving the medication treatment process. Patient safety incident reporting systems enable health and social services to collect systematic data from risk factors within the medication treatment process. This study was conducted as a retrospective registry-based study where medication incidents that occurred in health and social care units reported by community pharmacies to the incident reporting system HaiPro from 21st of September 2021 to 31st of October 2022 were analysed. Cases that did not meet the criteria for this study (n=55) were removed from the original data (n=3841). If needed, the nature and type of the reported error were corrected. A descriptive quantitative analysis was conducted for the final data (n=3786) using Microsoft Excel. The number, natures, types, observers, and prescription types of medication errors were investigated from the data. In addition, the most common groups of medicinal substance and high risk medicines were identified. A qualitive content analysis was performed to near miss cases involving high-risk medications (n=446) using the Atlas.ti program. Interventions, measures following the interventions and risks prevented by the measures were identified from the open description in the incident reports. The qualitative analysis was performed as an abductive content analysis. Of the medication errors included in the study (n=3786) 91% were detected by community pharmacies and the majority (68%) of the reported incidents were near misses. Most (96%) of the safety incidents (n=3786) were associated with the patient’s medication treatment and had occurred mostly during the prescribing process (92%). As a result from the prescribing errors, patients were most commonly prescribed wrong dose or strength of the medicine (26%) or the prescription lacked SIC marking (26%). High-risk medications occurred in 16% (n=591) of the incidents (n=3786). Most frequently detected high-risk medications were opioids (35 %). Three quarters (76 %) of safety incidents associated with high-risk medications were near misses (n=446). The majority (92 %) of interventions (n=471) made to prevent safety incidents associated with high-risk medications were made by community pharmacies. The most frequent intervention was community pharmacies contacting the doctor. Based on the HaiPro incident reports made about medication errors in health and social care units reported by community pharmacies, it can be concluded that community pharmacies are a central barrier in primary care medication treatment process. Community pharmacies detect and report medication errors that have occurred in other health and social care units. Safety incidents reported by pharmacies systematically accumulate important information that can be used in the development of medication safety in primary care at a unit, wellbeing services county and national levels.
  • Laakso, Johanna (2022)
    The operation of community pharmacies has developed extensively over the past decades, with special emphasis on medication counselling services. In addition to dispensing, pharmacies can offer various kinds of clinical pharmacy services, such as medication reviews, automated dose dispensing and other services to support rational use of medicines. All this activity requires patient information, which is currently available in pharmacies only from prescriptions, reimbursement information, and by asking the customer. Because of this, a need to increase the availability of patient information in pharmacies has come up. The aim of this study was to determine what kind of patient information should be available in community pharmacies for 1) the statutory dispensing of medicines, the medication counselling and treatment monitoring, and 2) other services related to promotion of health and well-being and prevention of diseases. Furthermore, the study investigated experts' experiences of the sufficiency of patient information in pharmacies, as well as in what form and from what period the information should be available in pharmacies. The study was conducted as a 3-round Delphi study with an expert panel consisting of 20 pharmacists specialized in clinical pharmacy. Consensus was formed with the help of a preliminary patient information list which had been compiled based on the literature and the expertise of the research group (a total of 39 patient data items). The limit of the experts' consensus was set to ≥80%. The Delphi-rounds were conducted as electronic surveys during the spring and summer of 2022. The responses were analysed using quantitative and qualitative methods. Most of the expert panellists (n=20) perceived that the patient information available in community pharmacies was insufficient. This study reached a strong consensus that pharmacies should have quite a large set of patient information available both for dispensing medicines and medication counselling, and for providing services supporting rational use of medicines. Of the patient data items, nine reached the consensus line concerning dispensing of medicines and 31 measures concerning other services. From both points of view, information about the client's diagnoses, blood pressure, and the GFR value indicating kidney function were rated as the most important to be available in community pharmacies. However, the panellists also reported challenges to overcome in the access and utilization of the patient information, for example, related to current legislation, resources, and competences of pharmacists. These aspects should be considered in the development of community pharmacy practice and electronic patient information (e.g., Kanta services).
  • Pihlajakoski, Marjo (2022)
    Operations of pharmaceutical supply chain and medication management practices will be evaluated as part of the ongoing social and health services reform in Finland. One of the goals is to develop digital medication management tools and services to meet the needs of both healthcare professionals and medicine users. The aim of this study was to examine population's willingness to use on new digital services by community pharmacies to promote rational pharmacotherapy and to support cooperation between those involved in the medication use process. The material for this study consisted of the national population survey conducted in 2020 for the VN TEAS report “Activation of price competition for pharmaceutical products and the population's expectations for pharmacy operations” (online survey for 18–79-year-old adults, n = 1650). The survey respondents represented well the target population expect those with higher educational level were over-represented. The current study focused on questions related to digital medication management services provided by community pharmacies, which were divided into the following 4 topics to form sum variables: 1) purchasing and dispensing process of medicines (4 items), 2) customer`s communication with pharmacy and health care personnel (2 items), 3) pharmacy and healthcare personnel`s communication with the customer (4 items) and 4) support services for medication self-management (12 items). The associations of the background variables to the sum variables were calculated using cross-tabulation and the Chi-Square test. Frequencies and percentages were used to present. The majority (85–90%) of the respondents were in favor of the possibility of sending messages electronically between the customer, the community pharmacy and other healthcare personnel by using a shared communication channel, such as My Kanta to update medication information online. Multimorbidity, medication use, and higher medication costs increased the respondent’s positive attitude towards the electronic communication channel. Three-quarters (76%) of respondents were willing to use electronic medicine purchasing and dispensing services. Younger respondents (18–34 years) were more interested in these services than older ones. The electronic medication self-management support services had more discrete opinions among respondents. More than half of the respondents indicated their strong willingness to use at least one of the medication self-management support online services listed in the survey instrument. Those aged 18–34 years (69%), those with higher education (62%), those living in the Province of Southern Finland (60%) and those living in the Helsinki Metropolitan Area (67%) were more positive than others. Of the respondents who opted for pharmacy's remote online services, 55% were willing to seek advice for reconciling their medication list. According to the survey, Finnish adults are willing to use new electronic services by community pharmacies. In particular, they were willing to use a shared electronic communication channel between the customer, the pharmacy and other healthcare personnel, such as MyKanta to update information related to their medication. The willingness to have support self-care support for medication self-management primarily from the pharmacy's online services was lower than the willingness to use online purchasing and dispensing services. Of the remote medication self-management services medication reconciliation had the highest demand. Future research should focus on enhancing use of electronic medication self-management services provided by community pharmacies. Further research should also be targeted to understand medicine user needs for support as it may vary between patient groups, requiring segmentation of services.
  • Lindevall, Mari (2021)
    The purpose of this systematic review is to investigate the usage of artificial intelligence in the pharmaceutical industry in the fields of pharmaceutical manufacturing, product development, and quality control. Today, developing and getting a new drug on the market is time-consuming, ineffective, and expensive. Artificial intelligence is seen as one possible solution to the problems of the pharmaceutical industry. From 734 articles 77 academic study articles were included. Included articles showed artificial neural networks to be the most used artificial intelligence method between 1991 and 2021. The search was conducted from three databases with the following inclusion criteria: studies using AI in either pharmaceutical manufacturing, product development or quality control, English as the language, and Western medicine-based pharmacy as a branch of science. This systematic literature review has three main limitations: the possibility of an important search word missing from the search algorithm, the selection of articles according to one person's assessment, and the possible narrow picture of the used artificial intelligence methods in the pharmaceutical industry, as pharmaceutical companies also research the subject. The use of artificial intelligence in product development has been studied the most, while its use in quality control has been studied the least. In the studies, tablets were a popular drug form, while biological drugs were underrepresented. In total, the number of studies published increased over three decades. However, most of the articles were published in 2020. Nearly half of the articles had some connection to a pharmaceutical company, indicating the interest of both the academy and pharmaceutical companies in the use of artificial intelligence in manufacturing, product development, and quality control. In the future, the efficacy of artificial intelligence, as well as its limitations as a method, should be investigated to conclude its potential to play a key role in reforming the pharmaceutical industry. The results of the study show that a wave of artificial intelligence has arrived in the pharmaceutical industry, however, its real benefits will only be seen with future research.
  • Alho, Eerika (2024)
    Biological medicines are used, for example, in the treatment of diabetes, cancer, and autoimmune diseases. Biological medicines cause a significant part of the costs of prescription drugs in outpatient care. In Finland, automatic substitution of biological medicines will be introduced in 2024–2025 to promote the use of biosimilars and to increase price competition. When substituting biological medicines, pharmacists are required to counsel the customer and ensure proper use of the new administration device. The objective of this study was to study Finnish community pharmacists’ knowledge about biological medicines and biosimilars and the need for further training. Data was collected with an electronic questionnaire and analyzed using frequencies and percentages. Associations between background variables and readiness for automatic substitution were analyzed using crosstabulation and chi-squared test. Differences in drug-specific knowledge were compared using sum variables. Most pharmacists (n=899) answered that they understood at least the basics of what biological medicines and biosimilars are. The important role of biosimilars in reducing society's drug costs seemed to be well understood, but only one in four (25.0%) felt that they were ready for automatic substitution. Master’s degree in pharmacy, graduating as a pharmacist (BSc) between 2010 and 2022, and working in community pharmacy for less than 10 years after graduating as pharmacist (BSc) increased the experience of readiness for automatic substitution. Previous work in the pharmaceutical industry or wholesale trade, in official positions or in research and teaching positions also increased the experience of readiness for automatic substitution, as well as clinical expertise or additional training in the field of pharmacy. Drug-specific knowledge seemed to be best about enoxaparin and insulins. Further training was needed especially on the differences of administration devices and giving injection advice. The strength of this study was a representative sample of pharmaceutical personnel working in Finnish community pharmacies, although low response rate weakens generalizability of the results. The results give an indication of how Finnish community pharmacists assessed their knowledge about biological medicines and biosimilars before the introduction of automatic substitution in Finland. Further research is needed to monitor the development of knowledge about biological medicines and to examine customers’ experience on the quality of medication counselling related to biological medicines at pharmacies.
  • Vuorela, Arja (2024)
    Adoptive cell therapy utilizes the patient's own immunological system in the treatment of cancer. T cells expressing the chimeric antigen receptor (CAR) are produced from the patient's own T-cells. The CAR gene is introduced into the T cells by a gene transfer vector, which results in the T cells expressing the CAR molecule that recognizes the antigen on the surface of the cancer cell. When CAR-T cells are returned to the body, they recognize the cancer cell with the CAR molecule and destroy it. CAR-T cell therapy has shown promising results in the treatment of malignant hematological cancers. The white blood cells used as starting material for CAR-T cells are collected from the patient using a specially designed leukapheresis device. The collected leukapheresis product is transported to the CAR-T cell manufacturing site as soon as possible, either fresh or frozen. The aim of this stability study of leukapheresis products was to determine the effect of storage time and temperature on the quality of fresh cell products regarding cell number, viability and composition. In addition, the goal was to determine the optimal storage temperature and the shelf life of leukapheresis product to ensure high quality cell starting material for CAR-T cell production. The study was performed by dividing the leukapheresis products into two cell bags immediately after collection, one stored at +15–25 °C and the other at +2–8 °C for five days. The leukapheresis products were examined at five different time points (0, 25, 49, 73 and 121 h) for white blood cell count, viability, apoptosis and white blood cell composition. The microbiological purity of the cell products was examined after leukapheresis. The leukocyte composition was stable, viability and cell yield over 80 % for at least 72 hours at +2–8 °C storage temperature. Although small proportions of cells were apoptotic after the 48 hours of storage +2–8 °C, the leukapheresis products contained more than 80 % viable leukocytes after 72 hours and over 70 % after 120 hours. Leukapheresis products remained stable for 48 hours at +15–25 °C, after which their leukocyte composition changed, leukocyte viabilities and yields decreased. The viabilities of the leucocytes were above 90 % for 48 hours at +15–25 °C, but at the 73 h time point, only half of the cells were viable. The optimum storage temperature for leukapheresis products was +2–8 °C, at which white blood cells remained in good quality for 72 hours. These results can be used to set quality requirements for the cell source material of CAR-T cell product and to plan the transport from the collection site of the leukapheresis to the CAR-T cell production site.
  • Lähteenmäki, Ida (2024)
    Alzheimer's disease is a progressive neurodegenerative disease of the central nervous system, in which accumulation of amyloid β plaques and hyperphosphorylated tau proteins cause neuronal death, loss of synapses, and impaired neurotransmission. Alzheimer's disease's main symptoms are memory dysfunction (dementia) and decline in cognition. One of the most significant factors believed to cause dementia in Alzheimer's disease is the destruction of dendritic spines. Dendritic spines are small protrusions of dendrites where most of the glutamatergic synapses are located and where mainly excitatory synaptic functions occur. Loss of dendritic spines is directly correlated to the loss of synaptic function, which then causes memory dysfunction and impaired cognition. Also, the morphology of dendritic spines is important for their stability and strength. The spine head's size is correlated to the number of postsynaptic receptors. Cerebral dopamine neurotrophic factor (CDNF) and mesencephalic astrocyte-derived neurotrophic factor (MANF) are unconventional neurotrophic factors, which have neuroprotective and -restorative effects via regulating endoplasmic reticulum (ER) stress and unfolded protein response (UPR). Accumulation of unfolded and/or misfolded proteins in the lumen of ER causes ER stress, which then activates UPR, which again maintains protein homeostasis by reducing the amount of unfolded/misfolded proteins. In this study, we injected CDNF, MANF or PBS into the hippocampus of C57BL/6 mice to analyze whether they increase dendritic spine density and improve their morphology, especially by increasing the density of mature spines. This study shows that MANF increases dendritic spine density and CDNF does not. MANF increases the density of most of the mature and immature spines but interestingly decreases the density of mature stubby spines. These results are very promising and MANF's effect on dendritic spine formation should be studied further. In another separate study, we investigated whether CDNF and MANF activate the ERK1/2 pathway on organotypic hippocampal slices. This pathway is important for memory formation, and another neurotrophic factor, brain-derived neurotrophic factor (BDNF), has been shown to increase dendritic spine density by stimulating the ERK1/2 pathway. CDNF and MANF activate UPR, but there is some evidence that UPR might also activate ERK1/2, which could then explain CDNF's and MANF's mechanism of action. CDNF and MANF-treated hippocampal slices had visually thicker and darker bands in ERK1/2 antibody staining but any conclusion cannot be made because of the sample sizes being too small.
  • Autzen Virtanen, Anja (2023)
    Poorly water-soluble drugs are challenging to formulate as solid oral dosage forms because of their inadequate solubility in the gastro-intestinal tract. Amorphous solid dispersions (ASDs) are a proven method of increasing the oral bioavailability of poorly water-soluble drugs through drug supersaturation. Downstream processing of ASDs into oral tablets has gained academic interest in recent years. However, minitablets, which are tablets smaller than 4 mm in size, have not received the same level of attention. Minitablets have been cited as a promising dosage form for children, the elderly and in veterinary use because of their good compliance, flexible dosing, and ease of swallowing. In this work, 15 different blends of microcrystalline cellulose and lactose have been characterized for their suitability in the formulation of an ASD of spray-dried poorly soluble indomethacin in PVP K 29-32 or HPMCAS MF as minitablets. Minitablets were compressed at the compression forces ~1000 N and ~1500 N. The flowability of the blends were evaluated based on the Carr’s indices, Hausner ratios and angles of repose. From the most promising blends, 3.0 mm placebo minitablets were manufactured. A mixing test using colored beetroot powder was used to determine the optimal mixing time. The finished tablets were tested for their uniformity of mass, crushing strength, height, and disintegration. Based on their Carr’s indices and Hausner ratios, Vivapur 105, Vivapur 200, Pharmatose 200M and Pharmatose 80M had the best flowabilities. Placebo minitablets were successfully manufactured from blends of these excipients except for the 1:1 ratio of Vivapur 105/Pharmatose 80M. The mixing test indicated that the optimal mixing time is 20 to 25 minutes. The mass variation for all placebo batches except the 1:3 ratio of Vivapur 105/Pharmatose 80M was less than 10 percent from the average mass and most batches therefore fulfilled the uniformity of mass requirement of the European Pharmacopoeia. For five of the batches, the variation was within 2.80 percent. The average crushing strengths were between 32.4 N and 79.7 N and increased with increasing compression force. All batches of placebo minitablets disintegrated within 6 to 19 seconds on average except the 1:3 ratio of Vivapur 105/Pharmatose 80M which took 90 seconds to disintegrate. Minitablets filled in capsules disintegrated within 124 to 167 seconds on average except for the previously mentioned slower disintegrating batch which disintegrated in 477 seconds. All placebo minitablets, individual or loaded into capsules disintegrated within 15 minutes thereby fulfilling the requirement of the European Pharmacopeia. When considering the results obtained for placebo minitablets, the 3:1 ratio blend of Vivapur 200/Pharmatose 200M with 0.5 % (w/w) magnesium stearate was found to be the most promising candidate for ASD formulation. This formulation was subsequently used as the basis for the manufacture of 3.0 mm minitablets containing 6.22 % (w/w) of a spray-dried dispersion of indomethacin and PVP K 29-32. Except for one outlier, the mass variation of these minitablets fell within 2.37 % of the average mass, thereby fulfilling the requirement of the European Pharmacopoeia. Single indomethacin-PVP minitablets disintegrated within 6 minutes and 38 seconds, and capsules containing twelve minitablets disintegrated within 10 minutes and 37 seconds, which also is accordance with the pharmacopoeia. At 80.3 to 80.4 N the crushing strength was at the upper end of the targeted range, but still adequate. Thus, the formulation developed in this study appears promising for the manufacture of minitablets containing 6.22 % of an amorphous indomethacin-PVP dispersion. This study demonstrated that minitablets could be manufactured from a spray-dried solid dispersion despite its poor flowability.
  • Lahtinen, Katja (2024)
    Cardiac fibrosis (CF) is a physiological response to various stress factors encountered by the heart, with the aim of maintaining proper functioning of this vital pump in an altered situation such as increased mechanical stress or sudden injury in heart muscle. CF is characterized by excessive production of extracellular matrix (ECM) components and stress fibers in cardiac tissue, accompanied by morphological changes of the heart muscle. The responsible cells behind these changes are fibroblasts (FBs) that undergo phenotypic change by transdifferentiating into myofibroblasts (myoFBs). Although being initially a supportive response, CF can lead to deterioration of the heart performance and even heart failure, if prolonged. Given the lack of effective enough therapies against CF, and the strong involvement of CF in cardiovascular diseases (CVDs) that are associated with high mortality rate, the need for new effective therapies is urgent. Indeed, a diversity of approaches to fight CF have been proposed, among them protein kinase C (PKC) and its signaling cascades. PKC has been shown to play a role in fibrosis and many studies suggest antifibrotic properties of PKC, yet the results are challenged by the opposite findings. Despite the dichotomous results, new small molecules that function as partial agonist of PKC seemed to be a promising strategy for the treatment of fibrosis. To further explore the role of PKC activation in CF, the aim of this study was to first develop and characterize a human cardiac fibroblast (HCF)-based CF model, in which the effects of seven new PKC modulators on HCFs could then be evaluated. To create the CF model and provoke a fibrotic response, HCFs were treated with either transforming growth factor β1 (TGF-β1), Angiotensin II (Ang-II), endothelin-1 (ET-1), or combination of treatments, followed by determination of HCF proliferation activity and α-smooth muscle actin expression (α-SMA), a marker of myoFBs. After the treatments, the original goal was to continue in compound testing phase by exposing the HCFs to the PKC-modulators to see whether any differences could be determined in α-SMA expression or proliferation activity. However, no considerable effects of fibrosis-inducing treatments on the activation of HCFs were observed, thus preventing this progression. Nevertheless, toxicity tests were performed on the compounds and the results indicated relatively low overall toxicity for the lower concentration: six out of seven compounds yielded over 70% HCF viability at 3 μM concentration with three of them reaching even over 80% viability, while the corresponding value for the previously published PKC agonist HMI-1a3 was 54%. Although these results are promising for the lower concentrations of PKC-modulators, it is obvious that more in-depth studies are required prior to drawing any unambiguous conclusions.
  • Manninen, Kalle (2023)
    Oncolytic adenoviruses are a new cancer treatment platform which aims to eliminate cancer through direct lysis of cancer cells by viral replication and the activation of the immune system by the release of tumor antigens upon oncolysis. In the PeptiCRAd technology, the activation of an anti-cancer immune response is enhanced by the addition of poly-lysine modified cancer peptides, where the antigen presentation to the immune system is improved in comparison to plain oncolytic viruses. PeptiCRAd complexes have been assumed to form solely by electrostatic interactions, but the thermodynamic profiles and mechanisms involved in the complexation have not been previously addressed. Thus, by adding isothermal titration calorimetry as part of the analysis repertoire provides valuable information of the characteristics of PeptiCRAd complexes. In this study, the applicability of isothermal titration calorimetry in PeptiCRAd complexation analyses was evaluated based on initial peptide-to-virus and virus-to-peptide titrations, and a method of analysis was created for the thermodynamics of the interactions of the complex. Optimization of the experimental method (i.e., titration protocol) and the data analysis (i.e., calculation models) remains inconclusive for quantitative analysis as data obtained from the measurements was mainly of bad quality, thus requiring further optimization to obtain reliable data. However, using surface plasmon resonance as an already established method for poly-lysine peptide-virus interaction studies gave robust data and can be used as a base or guideline to further develop isothermal titration calorimetry analyses for characterizing PeptiCRAd complexes. Although isothermal titration calorimetry measurements were unsuccessful for quantification purposes, it was possible to qualitate the mechanisms of PeptiCRAd complexation for four different peptides with fair confidence. The peptides showed low heats of binding, and positive and negative cooperative binding in ionic and non-ionic solutions, respectively. Based on this, the binding of peptides in PeptiCRAd complexes was determined to be driven by hydrophobic inter-peptide interactions on the virus surface, although an electrostatic attraction is indeed present at the virus-peptide interface, initiating the binding event. Also, improvements to the titration protocol for PeptiCRAd analyses with isothermal titration calorimetry are suggested for further optimizations in the future to conclusively determine the applicability of the isothermal titration calorimetry technique for characterizing peptide-virus interactions of PeptiCRAd complexes.
  • Kylkilahti, Sanni (2022)
    Chilit ovat Capsicum-sukuun kuuluvia yleensä korkean kapsaisiinipitoisuuden omaavia paprikalajeja. Niitä käytetään mausteena. Lisäksi chilien sisältämillä kapsaisinoideilla on todettu olevan useita farmakologisia ominaisuuksia, kuten analgeettisia ja antioksidanttisia vaikutuksia. Niiden antimikrobisia ominaisuuksia on myös hieman tutkittu, mutta tutkimuksia on vielä verrattain vähän. Tämän työn tarkoituksena oli selvittää muutamien eri chililajikkeista valmistettujen uutteiden antimikrobisia vaikutuksia Escherichia colia ja Staphylococcus aureusta vastaan. Uutteet testattiin dimetyylisulfoksidiin (DMSO) ja veteen liuotettuina. Lisäksi testattiin myös kahden puhdasaineen, kapsiaatin ja solaniinin, vaikutuksia kyseisiä bakteereita vastaan. Antimikrobiakokeet suoritettiin 96-kuoppalevyllä noudattaen aseptisia työtapoja. Testattuja chiliuutteita oli 19. Uutteita valmistettiin eri chililajikkeiden versoista (1 kpl) siemenistä (3 kpl), lehdistä (10 kpl) ja hedelmistä (5 kpl). Dimetyylisulfoksidiin liuotetut uutteet testattiin pitoisuuksilla 2,0 mg/ml ja 4,0 mg/ml. Veteen liuotetut uutteet testattiin pitoisuudella 4,0 mg/ml. Solaniini- ja kapsiaattiuutteet testattiin kahdeksalla eri pitoisuudella (0,001172–0,15 μg/ml). Tutkimuksen tuloksena on, että testatut chiliuutteet eikä solaniini- ja kapsiaattiuutteet estäneet E. colin tai S. aureuksen kasvua. DMSO:iin liuotetuista uutteista korkeimmat estoprosentit kumpaakin bakteeria vastaan saatiin nuorilla Pimento-lehdillä. Veteen liuotetuista uutteista korkein estoprosentti E. colia vastaan saatiin Dulcen versoilla (30 % esto) ja S. aureusta vastaan Dulcen hedelmillä (50 % esto). Aiemmat tutkimustulokset chilien antimikrobisista vaikutuksista ovat ristiriitaisia, joten yhteneviä johtopäätöksiä chilien vaikutuksista bakteereihin ei voida tehdä. Johtopäätöksenä voidaan todeta, että chileillä on lukuisia terveysvaikutuksia. Antimikrobisen tehon varmistamiseksi tarvittaisi kuitenkin lisää tutkimuksia. Antibioottiresistenssi on maailmanlaajuinen ongelma, koska yhä useammat bakteerit ovat resistenttejä käytetyille antibiooteille. Tulevaisuudessa onkin erittäin tärkeää löytää uusia yhdisteitä bakteerien tappamiseksi, joten tutkimuksia uusien antimikrobisten aineiden löytämiseksi tarvitaan jatkuvasti lisää