The aim of this project is to assess the versatility of the Sloppymerase by performing stable transfection in NIH/3T3 cells and decide whether this cell line can be a candidate for further research on the Sloppymerase as a cancer model. The American cancer society predicts 1,806,590 new cancer cases in the US in 2020. To understand and by extension prevent the disease progress of cancer, proper cancer modeling is essential. The Sloppymerase is a 2-subunit fusion polymerase that has been designed by Ola Söderberg group. The Sloppymerase gene is carried by an inducible expression vector and consists of the 5’ to 3’ exonuclease subunit from Polymerase 1 and the translesion synthesis polymerase (TLS) Polymerase η. The Sloppymerase has a low fidelity and can insert mismatching nucleotides which can lead to mutations that eventually can lead to cancer. NIH/3T3 cells were grown on cell culture plates and an antibiotic kill curve was established to determine the optimal concentration of the selection antibiotics. Transfected cells were selected with Geneticin to create a stable cell line and the gene expression of the Sloppymerase was induced with Doxycycline. The RNA was extracted from cell lysate from the induced cells and was thereafter purified followed by RT-q-PCR. The protein expression was examined with Western blotting. Transcription of the Sloppymerase gene was confirmed with RT-q-PCR and stable transfection was thereby verified. No bands were seen in the Western blot and therefore protein expression has not yet been validated. Further studies are needed to examine the theoretical cancerous effects of the Sloppymerase.

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Background: It is well known that patients' adherence to chronic drug treatment is low and in developed countries it is estimated to be 50 percent. In other European countries, pharmaceutical services are already offered but this is not done in Sweden yet. The pharmaceutical services are aimed at specific patient groups to improve drug utilization and adherence in patients with chronic drug treatment.  Aim: The aim of this study was to investigate whether it was feasible to develop and conduct pharmaceutical counselling through a videoconference call since pharmaceutical services have not been offered through videoconference calls before.Method: Material for the intervention was developed by the researcher. The study was conducted during October and November 2021, customers were recruited from two pharmacies in Uppsala. The intervention was evaluated based on how the pharmacist and customers used the material developed for the pharmaceutical service. Additionally, semi-structured interviews were conducted to evaluate customers experience of the pharmaceutical service  Results: The five customers who participated in the study were satisfied with the experience of the pharmaceutical service and thought the technology worked well. However, customers had different experiences of how useful the material developed for the service was. Conclusion: It was feasible to offer pharmaceutical counselling as a videoconference call. However, the study population was small and had little diversity. Further studies are needed to evaluate the effectiveness of the pharmaceutical service in terms of improved adherence and drug utilization.

Background: Pharmaceuticals are a big part of healthcare expenditures. Advancements such as the sequencing of the human genome and technical methods has led to the development of more advanced drugs. Aim: The aim of this study was to explore the trends in new drug development areas and the costs of drugs in different therapy areas. Method: To do this, data from the Swedish Medical Products Agency, e-Hälsomyndigheten and the 20 biggest pharmaceutical companies regarding new approved drugs during a 20-year period, costs and new chemical entities in late development stage has been analyzed. Results: Each year, between 20 and 60 new drugs are approved. New chemical entities are most prevalent in the ATC-group L, which includes oncology and immunomodulating drugs. Innovation is also seen in group J, antiinfectives. The cost of drugs has increased during the study period, especially for oncology drugs. In the coming years, we can expect the introduction of even more oncology drugs, as mostdrugs in later development phases are expected to be classified in this group. Conclusion: Over the studied period, the most innovative therapeutic group has not changed but rather grown. The cost of drugs has also grown, possibly because of more new drugs introduced but also due to expanded indications and larger patient groups. It is hard to see a future where oncology drugs are not the biggest cost since in the coming years, many of the expected new drugs will fall into the same category.

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Cromolyn sodium (CS) is a mast cell stabilizer administered to treat allergic diseases. A topical system would sustain its delivery and may be designed for treatment of atopic dermatitis. Established HPLC protocols for detection of CS are time consuming and intensive, indicating the need for a more streamlined method. This study aimed at developing and validating a sensitive and selective LC-MS method for quantifying CS in skin permeation studies that was less time and resource demanding. The optimized method involved an isocratic mobile phase (10 mM NHHCO, pH 8.0, 90% and ACN, 10%) at a flow rate of 0.25 mL/min. Detection involved direct MS/MS channels with m/z 467.0255 (precursor) and / 379.0517 (fragment) using argon as the collision gas. CS calibrants were prepared in PBS, pH 7.4, and methanol for validation (0.1-2.5 g/mL). To ensure no skin interference, dermatomed porcine skin was mounted on Franz diffusion cells that were analyzed after 24 h. The skin layers were also separated, extracted in methanol, and analyzed using the developed method. Retention time was 1.9 min and 4.1 min in methanol and buffer, respectively. No interfering peaks were observed from the receptor and skin extracts, and linearity was established between 0.1 and 2.5 g/mL. Interday and intraday accuracy and precision were within the acceptable limit of ±20% at the LLOQ and ±15% at other concentrations. Overall, the simplified, validated method showed sensitivity in detecting CS in skin without interference and was applied to demonstrate quantification of drug in skin following 4% cromolyn sodium gel exposure.

Background: Multi-dose drug dispensing (MDD) is an alternative to assist patients with difficulties in administering and handling their medications. In 2019 the primary care units at Region Gotland reported a high number of discrepancies, regarding patients with MDD discharged from the Hospital of Visby. Due to the high proportion of discrepancies between the patient's medication list in TakeCare and the prescription list of MDD the clinical pharmacists at the hospital began to check all patients marked for discharge in order to discover and prevent eventual discrepancies. Aim: To identify discrepancies between the patient’s medication list and the prescription for MDD when discharged from the Hospital of Visby and investigate whether there has been a decrease since 2019. Method: A quantitative cross-sectional study was performed. Medication lists from each patient’s journal and their prescribing record from the prescription system for MDD were reviewed to identify discrepancies, which then were noted and discussed with the physician in charge. Identified discrepancies were rated into pre-defined categories and compared with data from previous years. A chi-square test was performed to investigate the significant difference of discrepancies between the units. The results from the intervention were summarized into figures and tables. Results: Medication lists from 144 patients with a mean age of 83 years were included. Discrepancies were identified in 34% of the patients and a total of 98 discrepancies were noted, which proves a significant decrease since 2019 when the number of discrepancies was 70%. Totally 79% of the discrepancies were estimated to have occurred during the patient's hospital stay. The highest number of discrepancies were found in the medical department and the difference between all inpatient care departments was significant (p <0.0001). Conclusion: The results indicate a decrease in discrepancies since 2019. Further research is necessary to clarify the reason behind the discrepancies.

Bakgrund: Paracetamol är ett av de mest kända och använda läkemedlet över hela världen för analgetisk och antipyretisk effekt. Paracetamol är ett receptbelagt läkemedel men säljs även receptfritt. Läkemedlet anses vara säkert under graviditet och därför kan den användas så länge den rekommenderade dosen inte överskrids. Hur paracetamol verkar är det inte klarlagt än idag däremot finns det en del hypoteser och teorier Syfte: Syftet med litteraturstudien är att, med hjälp av djurstudier, undersöka hur en tidig exponering av paracetamol ger neurologiska negativa effekter under hjärnutvecklingen.  Metod: Artikelsökning till litteraturstudien gjordes i databasen Pubmed genom sex sökningar där 12 artiklar kunde besvara studiens frågeställning. Sökningen följde exkluktions kriterierna: humana studier, paracetamol har antingen en positiv eller ingen påverkan på hjärnutvecklingen, paracetamols påverkande på framtida sexuella samt reproduktionsbeteende som ses i vuxen ålder. Artiklarna som inkluderades var från och med år 2016–2022, ett undantag gjordes dock vid sökning 5 och 6 där artiklar inkluderades från 2014–2022. Resultat: Paracetamol exponering under tidig hjärnutveckling har visat minskade koncentrationsnivåer av monoaminer, dess metaboliter och aminosyror i olika hjärnregioner. Dessa förändringar har kopplats till neurofysiologisk och kognitiv försämring som försämrad minne och inlärningsförmåga. Även oxidativ stressindex har ökat efter paracetamol exponeringen vilket associerades med inducerad oxidativ stress. Antioxidanterna superoxiddistumas och glutation minskade också vilket ökade de skadliga radikalerna i kroppen vilket ökade den oxidativa stressen. Slutsats: Slutligen kan en slutsats dras om en tidig paracetamol exponering. Läkemedlet har visat neurotoxiska effekter under tidig hjärnutveckling vilket har i in vivo studier visat ökad oxidativ stress, abnormitet i kognitiva funktioner och risk för neuropsykiatriska dysfunktioner. Därmed bör försiktighetsåtgärder och rekommendationerna kring paracetamol användningen under graviditet iakttas och nödvändigt utvärderas av läkare som farmaceuter och läkemedelsverket.

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No description available.