Farmasian tiedekunta

 

Recent Submissions

  • Tseng, Kuan-Yin (UNIVERSITY OF HELSINKI, 2017)
    Stroke is one of the leading causes of death and a major cause of disabilities in adults. More than half of stroke victims suffer some type of disability, ranging from different levels of minor weak- ness in a limb to a complete loss of mobility. Currently, treatment of stroke requires a stringent re- habilitation programs. Nevertheless, two thirds of all patients will still have some type of difficulty with regular daily activities. Recent experimental findings raise the possibility that functional improvement after stroke may be achieved through neuronal replacement by endogenous neural stem cells (NSCs) residing in the adult brain. Therefore, additional understanding of the properties of NSCs will help to identify their optimal potential in cell-based therapy. Neurotrophic factors are a family of proteins that are important in neuronal development and function, and have been studied as possible drugs for ischemic brain injury. In addition to Brain-Derived Neurotrophic Factor (BDNF) and Glial cell line-Derived Neurotrophic Factor (GDNF), Mescenphalic Astrocyte-Derived Neurotrophic Factor (MANF) and Cerebral Dopamine Neurotrophic Factor (CDNF), that form a distinct family of evolutionary conserved proteins with neuroprotective effects, have potential in the treatment of stroke. While MANF has been shown to protect cortical neurons from death in a rodent model of ischemic brain injury, the effects of post-stroke MANF ad- ministration on cellular processes during the recovery phase are poorly understood. To shed light on the possible regenerative potential of MANF for the injured brain, we need to first investigate the roles of endogenous MANF in neural stem cells (NSC) in a normal or pathological condition. We developed and optimized a work platform for studying the regulation and effect of MANF on biological properties of NSCs and cortical development. Our findings reveal an important role of MANF in neurite outgrowth and neuronal migration in the developing cortex. In addition, we demonstrated that endogenous MANF has the potential to protect NSCs against oxygen and glucose-deprivation conditions. Next, using neurosphere and subventricular zone (SVZ) explant cultures, we further studied the effect of MANF administration on cell differentiation and migration. We presented the data that exogenously added MANF can induce neural/glial differentiation and promote cell migration out of SVZ explants. Also, utilizing the advantage of NSCs as a target for MANF, we discovered that exogenous MANF can induce the phosphorylation of STAT3 in NSCs. Finally, we used the rat model of ischemic stroke to compare the effects of MANF and GDNF in neurogenesis after stroke. While injection of GDNF into lateral ventricle has a strong mitogenic effect to increase neurogenesis in SVZ, it does not induce migration of neuroblasts towards the ischemic area. In contrast, MANF facilitates the migration of neuroblasts towards the lesioned cortex. Regarding long-term infusions in the peri-infarct zone, both GDNF and MANF recruited the neuroblasts in the infarct area. However, only MANF accelerated functional recovery after stroke. In summary, this work has extended the knowledge of MANF’s capacity for neuronal differentiation as well as migration, and the regenerative capacity for its therapeutic use in further studies.
  • Maddirala Venkata, Siva Prasada Reddy (2017)
    ABSTRACT Pharmacies are convenient for most people to get to and there is no need for an appointment to see pharmacist which makes them natural first port of call healthcare providers in the society. Worldwide, pharmacists are potentially a vital link in healthcare chain. Since public health services do not cater to all the population, pharmacies and private health providers can play a major role in the healthcare system. This also applies to India with a population of over 1.3 billion. Though there is a large presence, pharmacists both in public as well as in private sector remain largely an untapped resource in India. Aims and objectives The objective of this study was to assess public health and patient care aspects in pharmacy education and the role of pharmacists in national public health programs (NPHPs) in India. The research goal was to find out possibilities and ways of extending pharmacists involvement in national public health programs and how pharmacist education could partly facilitate this shift. The research was divided into four studies which were published as separate original publications. Two of the studies were programmatic studies (I, II) and two cross-sectional surveys (III, IV). The studies I-IV had the following specific objectives: to review pharmacy education system in India from public health and patient care perspective. to compare curriculum of different Indian pharmacy programs (DPharm, BPharm, and PharmD) to see overall differences with a focus on the amount of time devoted for pharmaceutical policies and public health, patient care and pharmacy practice aspects in the programs (I). to compare Indian pharmacy curriculum at all levels with pharmacy curriculum of USA, Finland and Denmark (II). to explore acquaintance of final year pharmacy students with 11 major National Public Health Programs and their attitude on pharmacists involvement in public health and patient care (III). to characterize physician perceptions on the role of pharmacists in public health and patient care (IV). Comparison of curricula (I,II) The programmatic studies (I, II) were conducted between March 2012 and 2014. The curricula collected from the statutory bodies were used for the comparison to see the overall differences with a focus on the amount of time devoted for pharmaceutical policies and public health, patient care and pharmacy practice aspects in the programs. (I) Syllabi of courses leading to 1) registered pharmacist title in India (DPharm, BPharm and PharmD), 2) USA (PharmD, curriculum from University of Florida), 3) Finland (Master of Science in Pharmacy program from University of Helsinki), and 4) Denmark (Master of Science in Pharmacy program from University of Copenhagen) were used for comparison. (II) The results indicate that Indian DPharm and BPharm programs were industry focused, and only PharmD has focus on clinical pharmacy and patient oriented services (I). Indian and US PharmD programs contain most and Indian DPharm and BPharm least public health and patient care aspects (II). DPharm holders are mainstays of pharmacy practice in India but their degree least contains patient care and public health aspects. There is a gap in curriculum, particularly at DPharm level. (I) Pharmacy Students Perceived Knowledge and Attitude on their role in NPHPs (III) This study was conducted as a classroom survey among final year DPharm, BPharm and PharmD students in India to explore acquaintance with 11 major NPHPs and their attitude on pharmacists involvement in public health and patient care (III). A survey instrument was prepared and distributed in a classroom survey to 326 students from 5 randomly selected pharmacy colleges from Southern part of India. (III) Students had positive attitudes on pharmacists involvement in NPHPs, although their attitudes varied in different student groups, PharmD and DPharm students being most positive towards involvement in NPHPs (III). The study also revealed the need for increasing contents supporting NPHPs to all pharmacy programs, particularly to BPharm program. Physician perceptions on the role of pharmacists in NPHPs (IV) A cross-sectional survey was designed to a convenience sample of physicians in Southern part of India. This small-scale pilot study was designed to develop a method for characterizing physicians perceptions on the role of pharmacists in public health and patient care in India. Six volunteers visited 800 physicians in Southern region in India and collected data in 2014. Survey instrument consisted of 28 structured questions based on NPHPs. The data were collated and extracted and descriptive statistical analysis was conducted by SAS (version 9.3). (IV) Among 129 responding physicians, 98% were comfortable with pharmacists roles in general, 96% comfortable to collaborate and 82% regarded pharmacists as part of health care team (IV). Physicians with shorter professional practice experience were more positive on pharmacists involvement in NPHPs than physicians having at least 11 years experience. Overall response of accepting pharmacists role and involvement in NPHPs was positive, Pulse Polio, HIV/AIDS, Tuberculosis and Tobacco control, and Leprosy eradication programs being the top NPHPs where physicians perceived pharmacists had a role to play. Conclusions and recommendations Upcoming PharmD graduates with 6 years education (training initiated in 2008) focused mainly towards clinical and patient care aspects should be able to change collaborative practice models and pharmacists involvement in patient care and NPHPs. It also would be useful to have an alternative curriculum line focusing on patient care and pharmacy practice aspects in Indian DPharm and BPharm programs. Practicing pharmacists would benefit from easily accessible continuing education to cover their knowledge gaps in patient care and enhance their contributions to NPHPs. This study is first of its kind to evaluate pharmacy curriculum contents in India from patient care and public health perspective. It will be helpful to statutory authorities and curriculum reform committees in India and other countries where pharmacists role is continuing to evolve towards inclusion of public health and patient care. Further research with a scope of detailed national level analysis to identity pharmacists potential in NPHPs is needed.
  • Shawesh, Amna Mohammed (Helsingin yliopisto, 2015)
    Indomethacin (IND) is a potent non-steroidal anti-inflammatory drug used in the treatment of rheumatoid arthritis, osteoarthritis, acute gout and other disorders. IND is available worldwide mostly in the form of capsules and suppositories, however, these formulations usually create side effects. Consequently, an alternate route of administration to avoid or minimize side effects may be found in the form of semisolid dermatological formulations, now available in few countries. The specific goals of this study were: (I) to determine the solubility of IND using different co-solvents: hexylene glycol (HG), propylene glycol (PG), polyethylene glycol 300 (PEG), butylene glycols (1,2 BG; 1,3 BG and 1,4 BG) and ethanol (ETOH). 1% (w/w) Tween® 80 or polyvinyl pyrrolidone (PVP-25) were used as enhancers; (II) to develop suitable topical gel preparations using 20% (w/w) Pluronic® (PF-127) or 1% (w/w) Carbopol ETD® 2001 (C2001) as gelling agents and HG or PEG 300 as solvents (1% (w/w) Tween® 80 and PVP-25 were added as excipients); (III) To evaluate the effect of composition of prepared gel formulations on the following parameters: appearance, crystallization, pH and rheological behaviour and (IV) to investigate the influence of storage time and storage conditions on the characteristics of the gels. These results indicate that all the solvents tested increased the solubility of IND to varying degrees. Tween® 80 and PVP-25 only slightly enhanced the solubility of IND. 1% (w/w) IND was able to form a structural gel with both PF-127 and C2001. Storing the INDPF-127 gels at 6°C resulted in the precipitation of IND. All gels stored at room temperature exhibited good stability. The gels stored at 45°C developed a dark yellow colour. Gels with C2001 and PF-127/PEG had slightly decreased viscosities with increasing storage time, while the gels with PF-127/HG showed increase in viscosities with time. In conclusion, the water solubility of IND was increased by the addition of co-solvents. 1% (w/w) IND gel can be suitable for using as a gel formulation and it is stable at room temperature. The search for suitable gels for IND topical formulation needs to be continued with more stability studies. Moreover, in-vitro and in-vivo experiments will be necessary for providing data on bioavailability.
  • Zhou, Fang (Helsingin yliopisto, 2012)
    We propose network abstraction as a research area. It is motivated by the growth of networks in many areas of life. Consider, for instance, networks of thousands of genes, millions of people, or billions of web pages. They are too large to be directly analyzed by users. The aim of network abstraction is to summarize a large network as a smaller one. An abstracted network can then help users to see the overall topology of a large network, or to understand the connections of distant nodes. The general network abstraction task is: given a large network, transform it into a smaller one, which contains in some well-specified sense the most relevant information. In this thesis, we analyze this research area and propose methods to solve some instances of the problem. The methods also provide different trade-offs between the graph quality and simplicity, as well as between result quality and efficiency. More specifically, we propose two approaches to abstracting a network. The first one is to simplify a weighted network by removing edges under the constraint that distances between all pairs of nodes are preserved. We first empirically show that a number of edges can be removed from real biological networks without losing any graph connectivity. We next relax the constraint of fully preserving original graph connectivity, extend lossless network simplification to lossy network simplification, and demonstrate that many more edges can be removed with little loss of quality. The second approach we give for network abstraction is to compress a weighted network by grouping nodes and edges. We propose novel methods and experimentally show that real graphs can be compressed efficiently with relatively little error. We next consider graphs with weights also on the nodes, and utilize them as node importances to extend the definition of weighted graph compression. We present new compression operations and demonstrate that the compressed graph can preserve more information related to more important nodes. Furthermore, we propose the idea of using node weights and compression to summarize the metabolisms in a set of organisms, and apply the methodology to better understand the metabolic biodiversity between Archaea and Eubacteria, the two most fundamental branches of life.
  • Vellonen, Kati-Sisko (2010)
    Drug discovery and development from its very onset up to market approval is a long process lasting 10-15 years. New research tools are needed to accelerate and rationalize this process. Ocular drug research still relies heavily on animal testing with rabbits and other rodents. Computational methods and cell culture models are promising tools for early pharmacokinetic studies and may partly replace the animals in pharmacokinetic and toxicological studies. Computational methods are initially based on experimental data, but thereafter their application is straightforward and they can be used to reduce, partly replace and refine further experimental studies. Similarly, cell culture models may enable absorption and toxicity testing of drug candidates with continuously growing cells of human origin, and thereby reduce the need for animal experiments. The cornea is the main route of ocular drug absorption after topical administration, and the corneal epithelium is the most important barrier to drug permeation. Membrane transporter proteins play an important role in the general pharmacokinetics and toxicology. However, their role in ocular pharmacokinetics is still poorly understood. Based on literature analysis many ocular drugs seem to be substrates of transporters, but the expression of these proteins in the eye is largely unknown. The goal of this work was to develop and evaluate cellular and computational tools for ocular pharmacokinetics and toxicology, and to characterise the active drug transporters in the corneal epithelium. The expression of monocarboxylate transporters and ATP-binding cassette (ABC) class efflux proteins was studied in the corneal epithelium and human corneal epithelial (HCE) cell model. Human corneal epithelium expressed monocarboxylate transporters 1 and 4 (MCT1 and MCT4), efflux transporters multidrug resistance-associated protein 1 and 5 (MRP1 and MRP5), and breast cancer resistance protein (BCRP). Cultured human corneal epithelial cells over-expressed several ABC class efflux proteins and MCT1 and MCT4. The functionality of efflux and monocarboxylate transport was demonstrated in HCE cells and in the rabbit cornea ex vivo. The MTT test is a widely used cytotoxicity test in cell research. It was demonstrated that substrates and inhibitors of ABC class efflux proteins may interfere with the MTT test, presumably by inhibiting dye efflux from the cells. This may lead to an underestimation of toxicity in the MTT test. Quantitative structure property relationship (QSPR) models are commonly used in early drug discovery to predict ADME properties of novel compounds. Multivariate analysis was used to develop QSPR models for in silico prediction of the corneal permeability. Two factors, the distribution coefficient (logD7.4 /logD8.0) and hydrogen binding potential, were shown to be the parameters that determine the transcorneal permeability of a compound. These models were able to predict intracameral steady state drug concentrations in rabbit eyes. In conclusion, the new in silico QSPR model can make reliable predictions for passive drug permeability in the cornea, while the HCE model seems to over-express some membrane transporters as compared to the normal human corneal epithelium. Even if these investigated methods have some restrictions they are still very useful tools for drug discovery purposes.