Diabetes mellitus är en av Sveriges största folksjukdomar och beräknas drabba omkring 5% av Sveriges befolkning där 85–90 % av de drabbade utgörs av typ-2 diabetes. Globalt beräknas de drabbade svara upp mot 500 miljoner och siffran fortsätter att stiga. Diabetes delas främst i typ 1 och typ 2-diabetes där typ 1 innebär förstörda betaceller och avtagen insulinproduktion medan typ 2 innebär nedsatt insulinkänslighet med avtagande betacellsfunktion. Orsak till diabetes mellitus tros vara genetisk dock finns det tydliga kopplingar mellan typ 2-diabetes och livsstil. Gemensamt för båda typerna är hyperglykemi. Typ 2 är direkt kopplat till hjärt-och kärlsjukdomar och behovet att ett glukossänkande preparat med skyddande effekt på hjärta och kärl är eftertraktat. Livsstilsförändring är alltid första steget i behandling av typ 2-diabetes och vid otillräcklig effekt tillkommer farmakologisk behandling där metformin alltid är förstahandspreparatet. Vid otillräcklig effekt med metformin eller kontraindikation ges natrium-glukos-kotransportör-2-hämmare, sulfonureider, glitazoner och/eller inkretinbaserade preparat som dipeptidylpeptidas 4-hämmare och/eller insulin. Denna studies syfte är att undersöka om dipeptidylpeptidas 4-hämmare vildagliptin har en skyddande effekt mot utveckling av kardiovaskulära komplikationer hos patienter med typ 2-diabetes. För att besvara frågeställning valdes 5 olika studier i databasen PubMed där vildagliptin jämfördes med andra plasmaglukossänkande agenter. Studiens slutsats är att vildagliptin inte har en uttalad effekt på kardiovaskulära komplikationer hos typ 2-diabetikerna även då den har en dämpande effekt på de inflammatoriska och glykemiska markörerna hsCRP, TNF-1, IL -1 och SDF-1. Vildagliptin i kombinationsterapi har en sänkande effekt på HOMA-IR, HOMA-, MAGE, FPPr och kan rekommenderas som behandling till typ 2- diabetiker med fokus på glukoskontroll. Association mellan blodglukos, insulin och inflammation är direkt relaterad till diabetes och kardiovaskulära komplikationer och intresset för vidare undersökning av dess association är stor.

Under 2017 var det 6,6 miljoner av Sveriges befolkning som hämtade ut minst ett läkemedel från apotek. Idag blir det allt vanligare med läkemedelsbehandling både inom hemmet och inom sjukvården. Patienter som har 5 läkemedel eller fler har en ökad risk för bristande följsamhet i sin läkemedelsbehandling. Syftet med denna studie var att undersöka vilket informationsunderlag patienterna använder sig utav för att hålla reda på sin läkemedelsbehandling samt i vilken utsträckning använder sig patienterna av receptlistan ”Mina sparade recept på apoteket”. Sex farmaceutstudenter genomförde patientintervjuer på 8 olika apotek i Sundsvall, Fränsta, Härnösand och Stockholm. Till studien rekryterades slutgiltigt 167 kunder och 55 % använde sig av ”Mina sparade recept på apotek”. 13% använde sig av läkemedelslistan ”Mina aktuella läkemedel” . 98% kände till listan ”Mina sparade recept på apotek”. Vid varje apoteksbesök så hade 57 apotekskunder fått listan utskriven från apoteket. Läkemedelslistan ”Mina aktuella läkemedel” användes av 13% och Läkemedelsförteckningen användes av 2%. Utfallet för de 167 kunder som deltog i studien var att 26% upplevde att det fanns svårigheter att hålla ordning på sin läkemedelsbehandling. Att använda receptlistan ”Mina sparade recept på apotek” som sitt underlag är inte det optimala då inaktuella recept kan finnas, samt att recept kan saknas som är aktuella då receptgiltighetstiden är 12 månader och därefter makuleras och återfinns bland inaktuella recept. Det optimala underlaget bör vara läkemedelslistan ”Mina aktuella läkemedel” som varje enskild förskrivare borde uppdatera till den aktuella och att även skriva ut den till sin patient vid varje besök för att minska riskerna för felmedicinering. / In 2017, there were 6.6 million of Sweden's population that retrieved at least one drug from the pharmacy. Today, drug treatment is becoming increasingly common both in the home and in the healthcare sector. Patients who have 5 drugs or more have an increased risk of lack of compliance in their drug therapy. The purpose of this study was to investigate which information base the patients use to keep track of their drug treatment and to what extent patients use the prescription list "My saved prescriptions at the pharmacy". Six pharmaceutical students conducted patient interviews at eight different pharmacies in Sundsvall, Fränsta, Härnösand and Stockholm. For the study, 167 patients were finally recruited and 55% used the "My saved prescriptions at the pharmacy". 13% used the drug list “My current medicines". 98% knew the list ""My saved prescriptions at the pharmacy ". At each pharmacy visit, 57 pharmacy customers had received the list printed from the pharmacy. The drug list "My current medicines" was used by 13% and the pharmaceutical list was used by 2%. The outcome for the 167 customers who participated in the study was that 26% felt that there were difficulties in keeping track of their drug treatment. Using the prescription list "My saved prescriptions at the pharmacy" as their basis is not the optimum when outdated prescriptions can be found, and that recipes can be missing which are current since the prescription validity is 12 months and then canceled and found among outdated prescriptions. The optimal basis should be the drug list "My current medicines" that each individual prescriber should update to the current version and also print it to their patient at each visit to reduce the risk of error medication.

Prescription of tablets is one of most common means for treatments of patients within the healthcare sector. Not seldom, drug manufacturers supply a limited number of tablet strengths, or physicians unnecessary prescribes a to high tablet strengths. This results in the situation where patients end up splitting tablets.  Another reason for splitting tablets is that they are voluminous, and thereby hard to swallow. Upon dividing tablets, fragments can become unequal in size, and parts of the tablets can crumble, leaving a tablet dose sometimes not compliant with government issued regulation, stated in different Pharmacopeias. Major parts of split tablets are prescribed to elderly people, who require lower dosages.  Some tablets are hard and small and elderly people have difficulties in dividing them, due to e.g. trembling and insufficient muscle strength in hands. The aim of this study was to investigate, pros and cons with splitting tablets, and how it´s practically done by the patient. What advice are given from staff in pharmacies to customers, in order to get it right. During two weeks, in March 2018, structured interviews were conducted on patients who had prescriptions on divided tablets. Among 7677 customers in eight pharmacies in Sweden 188 (2, 4 %) presented a prescription with split tablets. Of them, 171 accepted to participate in a survey to find an answer to the aim of this study. Out of the 171 customers 153 (89 %) divided their tablets. 74 (49 %) broke the tablets with their hands, 47 (31 %) with a knife and 22 (14 % ) use a device for dividing tablets.  The rest had recently received a prescription on a divided tablet.  Most common split tablets were within the ATC-codes C and N, cardiovascular and psychotropic drugs. They were split by 139 (81 %) of the customers. Within ATC-code N05 benzodiazepines 53 (31 %), C09 antidepressant 23 (13 %), N06 RAS 19 (11 %) and C07 betablocker 16 (9 %) divided tablets. Among the costumers who divided their tablets, 47 (28 %) said that the tablet size was not ideal to divide. About 36 (21 %) reported that they had difficulties dividing tablets; the number was highest among women. About 50 % of the customers had been given instructions by the pharmacist about how to split a tablet. The result of this study shows a need of lower strengths of some tablets, and that prescribers should be more aware and not unnecessary prescribe split tablets, since there are many especially elderly people that have difficulties in dividing them in equal parts.

Pharmaceuticals have been developed as long as humanity has suffered from diseases. It is something today’s people take for granted and is associated with strict rules as well as social initiatives. The purpose of pharmacies has developed from being an authoritarian part in healthcare to focusing on the customer and their needs. This particular role for pharmacies is one of the main focuses in this candidate thesis. A survey was performed at seven different pharmacies located at seven different sites in Sweden. The survey illuminates relevant questions around the dialogue between the customer and pharmacist. The communication between pharmacist and customer is an important aspect in the process of a purchase, because medicine has become more advanced and precise. The communication is a complicated procedure that requires to be mastered by pharmacists and also by customers at a specific point in time and place. This interplay creates customer satisfaction. The result showed that customers were generally reassured with the treatment of their medicine. The pharmacist gave relevant and enough information according to the answers on the survey. It showed that doctors still have the most trust amongst customers regarding the medicine information, thereafter the pharmacist. Possibly the reason for this depends on the relations between doctors and patients compared to pharmacists and customers. Even though pharmacists today have a major role when it comes to medical treatment and customers are satisfied, it is still common that they search for information in other ways. Digitalisation will probably affect this subject.

No description available.

The tumor microenvironment is important for tumor growth and progression, where the cancer associated fibroblast (CAF) is one central cell type. The CpG island methylator phenotype (CIMP) divides colorectal cancer (CRC) into three subgroups and in this study we investigate how the different CIMP-groups and adjacent fibroblasts affect each other. This was done with the aim of finding CIMP-specific markers and to see if different tumor-fibroblast interactions result in differently invasive tumors. Here we report that CIMP-negative tumors have increased expression of fibronectin, while CIMP-high tumors have reduced expression of E-cadherin, findings that were seen in both tumor tissue samples and tumor cell lines. We also show that CIMP-negative and CIMP-high cancer cells induce an alignment of the fibronectin fibers produced by the fibroblasts and that CIMP-high cancer cells migrate with directionality on these matrices. These findings indicate that the different tumor subgroups in fact induce different phenotypes in CAFs, resulting in CIMP-specific markers. They also indicate that CIMP-negative and CIMP-high tumors may induce an alignment of fibronectin in order to promote cancer cell migration and thereby also tumor invasion.

Colorectal cancer (CRC) has either an infiltrative or pushing growth pattern, and patients in the former group have a worse prognosis. Infiltrative tumours are linked to epithelial-mesenchymal transition, which in turn is associated with increased cellular migration. As there is no molecular model that entirely describes the difference between infiltrative and pushing configurations we investigated if differences found in cell junctions between tumour cells (in the core of the tumour) could explain the different growth patterns. A PCR array targeting cell junction genes was performed on one infiltrative and one pushing tumour. Thirteen genes were selected for verification by real-time qRT-PCR in additional tumours and normal tissue from the colorectum of patients. GJB3, Gap Junction Protein beta 3 (also known as Connexin 31) was the best candidate for separating tumours of different growth patterns. GJB3 was down-regulated in tumours compared to normal tissue, suggesting that it may act as a tumour suppressor, and it was further decreased in tumours with a pushing growth pattern. Silencing the expression of GJB3 in the colon carcinoma cell line SW480 did not affect the proliferation or the migration of the cells, suggesting that GJB3 by itself cannot regulate proliferation or metastatic spread.

Interleukin 33 (IL-33) is a dual function cytokine. It is a member of the IL-1 family and it acts as a pro-inflammatory factor (18 kilo Dalton, 18 kD) like other cytokines in IL-1 family. IL-33 is also a transcription factor (32 kD - form) which can suppress or activate gene transcription in diverse cases. A variety of cell types and tissues in the central nervous system (CNS) can release IL-33 after injury. The 18 kD IL-33 binds to the membrane receptor protein ST2 ligand, then regulates downstream gene expression, triggers cytokine synthesis, and modulates the immune system response. After traumatic brain injury (TBI) in the CNS, glial cells become key players in the nervous tissue response. Astrocytes undergo activation, proliferation, release pro-inflammatory factors and, as a consequence, a glial scar barrier around the injury is formed. Simultaneously, resting microglia are activated and able to remove debris. Lastly, oligodendrocytes together with microglia and astrocytes are activated and communicate with the immune system. In addition, as a severe kind of injury to the CNS, brain tumours share some similar characteristics of brain injury, such as hypoxia and inflammation. Therefore, IL-33 may play a role in neuroinflammation and also in brain tumours. In this project, our aim was to investigate the role of IL-33 and the IL-33/ST2 pathway in traumatic brain injury and brain tumours (e.g glioma). We found that IL-33 can influence the CNS immune resonse, and may be important in CNS pathology.

Transforming growth factor beta (TGF-β) is a multifunctional cytokine that regulates cell differentiation, proliferation and migration depending on cell context. TGF-β has a growth inhibitory effect on epithelial cells via activation of Smad proteins (R-Smad/Co-Smad complex). TGF-β signaling is negatively regulated by the proto-oncogene Ski (Sloan Kettering Institute). Ski in turn is degraded by TGF-β signaling (Smads) via ubiquitin proteasome system. TGF-β acts like a tumor suppressor in early stages of cancer due to its inhibitory growth effect, but in late stages it acts like a tumor promoter. The main aim of this thesis was to study the regulation of corepressor Ski stability in normal and transformed hepatic cells by TGF-β signaling and Smad proteins as well as determine Ski protein subcellular localization by using immunoprecipitation and Western blot assays for these studies. The obtained data showed that the TGF-β/Smad signaling pathway caused a downregulation of Ski protein through its degradation via proteasome in HepG2 cells. In addition, the Ski protein levels were restored when Smads were restored in C9 and hepatocytes even though the activated Smads were still present. In the subcellular fractionation studies it was observed that Ski protein was mainly localized in the nucleus of HepG2 cells, whereas it was localized in both nucleus and cytoplasm in hepatocytes.  The presence of Ski in the cell cytoplasm could be explained because of low sensitivity in TGF-β signaling or translocation of Ski from nucleus to cytoplasm. C184M is a protein that binds to Ski in the cytoplasm and Ski in turn binds to Smads and inhibits their translocation from cytoplasm to nucleus, which in turn means inhibition of gene transcription that instead results in growth stimulation.

Bakgrund: Hjärtsvikt blir allt vanligare. Det krävs stor förändring och anpassning av livssituationen för både patienter och anhöriga. Många av de som får diagnosen saknar kunskap om hur de påverkas fysiskt, psykiskt och socialt. Syfte: Att belysa forskning som beskriver sjuksköterskans stöd i egenvårdsåtgärder som kan ge ökat välbefinnande hos patienter med kronisk hjärtsvikt. Metod: En litteraturstudie valdes där tretton artiklar har analyserats. Resultat: Av analysen framkom fyra huvudkategorier; Egenvård, Utbildning, Välbefinnande och Stöd. Under Stöd framkom tre underkategorier; Informativt, Professionellt och Socialt. Diskussion: Sjuksköterskan ska ge individinriktat stöd, information och utbildning för att patienten själv ska kunna ta ansvar för sin hälsa. Att tidigt informera och utbilda om sjukdomen och egenvård. Påpeka vikten av att kontrollera hälsostatus regelbundet, följa läkemedelsordinationer, förändra livsstilen, samt att involvera anhöriga utgör stor trygghet för patienten. Sjuksköterskans stödinsatser är betydande för patienten och leder till ett ökat välbefinnande.