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  • Al-Hunaiti, Afnan (Helsingin yliopisto, 2015)
    The catalytic oxidation by using transition metal complexes offers attractive opportunities for industrial applications following environmentally benign manufacturing processes. However, the number of such catalytic methods has substantially decreased. In this thesis, we developed and utilized three iron based catalysts (FeIII/thymine-1-acetic acid, FeIII/Phenanthroline, and FeII/Nmethylimidazole) and one organic catalysts (1,2-Di(1-naphthyl)-1,2-ethanediamine (NEDA)). The iron/THA catalyst (iron/thymine-1-acetic acid) is efficiently capable of oxidizing both primary and secondary aliphatic alcohols into their corresponding carbonyl compounds, acids and ketones. The system can also oxidize alkanes with different steric and electronic environment. We also presented a new method for the oxidation of benzylic and aliphatic primary and secondary alcohols using iron-based catalyst, which is [Fe(phen)2Cl2]NO3 (iron/Phenanthroline), with hydrogen peroxide as a terminal oxidant. The easily accessible catalyst (iron/N-methylimidazole) was developed to form dehydrogenative coupling reaction between benzaldehydes and styrenes. The CH activation to produce α,β unsaturated ketones has been also developed. The organic (metal-free) catalyst (1,2-Di(1-naphthyl)-1,2-ethanediamine (NEDA)) has shown to be an efficient catalyst for the oxidation of secondary alcohols with t-BuOOH as a terminal oxidant. Under mild reaction conditions, a secondary alcohol is converted into its corresponding ketone.
  • Lehtonen, Mari (Helsingin yliopisto, 2012)
    Novel food products are fortified with plant sterols and stanols because of their ability to lower the LDL-cholesterol levels in plasma up to 10−15%. These compounds are added to food either in their free form or as fatty acyl esters. Like other unsaturated lipids, sterols are also prone to oxidation in the presence of oxygen and initiators such as heat, light, metal ions and enzymes. Oxidation may occur already during the manufacture of sterol preparations or during food processing and storage. The known adverse health effects of the oxidation products of cholesterol have prompted the evaluation of the biological effects of plant sterol oxides. The oxidation behaviour of free cholesterol has been extensively studied, whereas those of plant sterols have been less thoroughly examined. The oxidation behaviour of mainly free sterols has been investigated, but knowledge on those of fatty acyl esters or other conjugates is deficient. This study investigated the effects of chemical (i.e., esterification, unsaturation degree of the acyl moiety and sterol structure) and external (i.e., temperature and medium) factors on the oxidation of sterols. Development of solid-phase extraction and HPLC-DAD-ELSD methods for the isolation and determination of intact steryl ester monohydroperoxides allowed the primary oxidation of steryl esters to be followed both in neat preparations and in saturated lipid media. The oxidation of steryl and acyl moieties could be distinguished; therefore, the oxidation of both moieties could be followed in intact molecules. Further reactions of the monohydroperoxides were followed in terms of secondary oxidation products of sterol and oligomers. Introduction of an acyl moiety to a sterol altered the physical state and polarity of the sterol and affected its oxidation. In neat preparations at 100 °C, esterified sterols were liquefied and thus oxidised greatly, whereas the free sterol remained in a solid state and was therefore unaltered. Increased unsaturation of the acyl moiety increased the oxidation rate of both the steryl and acyl moieties. No differences in the initial reactivities of these two moieties were observed, but they oxidised concomitantly. For esters with monounsaturated acyl moieties, greater contents of steryl than of acyl moiety hydroperoxides were measured, whereas for an ester with polyunsaturated acyl moiety, greater contents of the acyl moiety hydroperoxides were measured. Increased temperature (140 °C) induced the oxidation of both steryl esters and free sterol. In a saturated lipid medium at 100 °C, the oxidation of steryl esters was decelerated, whereas the oxidation of free sterol was accelerated. Due to reduced oxidation rates, the accumulation of further reaction products was also delayed. In neat preparations and in the lipid medium, the steryl ester hydroperoxides decomposed into traditionally determined sterol secondary oxidation products and also underwent polymerisation as a rival reaction. By altering the chemical and physical properties of sterols, their oxidisabilities may be affected. If these factors are regulated in the manufacture of the preparations and in the food processing, formation of oxidation products may be controlled and the desired functionality of plant sterols preserved.
  • Pehrman, Reijo (Helsingin yliopisto, 2012)
    This doctoral thesis is focused on the radiation induced oxidative dissolution of spent nuclear fuel. UO2 is typically used as a model substance for spent nuclear fuel on the dissolution simulation experiments, but transuranium elements and fission products are expected to influence the redox chemistry involved. The dissolution behaviour of NpO2 and PuO2 in H2O2 solution without complexing agent was compared to UO2. Based on the measured rates, the dissolution of the actinides is not expected to be congruent, with Np and Pu release rates lower than the U release rate. The oxidative dissolution of PuO2 was found to be enhanced by the presence of Fe2+ in solution. This enhancement was attributed to hydroxyl radicals produced in the Fenton reaction between Fe2+ and radiolytically produced H2O2. The presence of solid UO2 pellet was found to prolong the lifetime of Fe2+ in solution, leading to further enhancement on the Pu dissolution. Fission product doping of UO2 was found to not have significant effect on the catalytic decomposition of H2O2. Fission product doping was however observed to hinder the reaction of UO2 with oxidants MnO4- and IrCl62-, and the effect of doping to decrease with increasing reduction potential of the oxidants. Uranyl peroxide solid phase formation on UO2 surface was observed to depend strongly on the peroxide concentration on the solution. In high peroxide concentrations oriented UO4∙nH2O crystals formed plate-like formations covering the whole surface, and with decreasing H2O2 concentration the crystals became unoriented and covered the UO2 surface only partially. In situ study showed the phase formation in high H2O2 concentration to take place in hours, and no intermediate phases were detected. Method development was performed on two areas: H2O2 measurement in small solution volumes down to nanomolar concentrations by chemiluminescence was tested and optimal parameters studied, and reference Raman spectra for studtite, schoepite, becquerelite and soddyite was measured.
  • Soupas, Laura (Helsingin yliopisto, 2006)
    An important safety aspect to be considered when foods are enriched with phytosterols and phytostanols is the oxidative stability of these lipid compounds, i.e. their resistance to oxidation and thus to the formation of oxidation products. This study concentrated on producing scientific data to support this safety evaluation process. In the absence of an official method for analyzing of phytosterol/stanol oxidation products, we first developed a new gas chromatographic - mass spectrometric (GC-MS) method. We then investigated factors affecting these compounds' oxidative stability in lipid-based food models in order to identify critical conditions under which significant oxidation reactions may occur. Finally, the oxidative stability of phytosterols and stanols in enriched foods during processing and storage was evaluated. Enriched foods covered a range of commercially available phytosterol/stanol ingredients, different heat treatments during food processing, and different multiphase food structures. The GC-MS method was a powerful tool for measuring the oxidative stability. Data obtained in food model studies revealed that the critical factors for the formation and distribution of the main secondary oxidation products were sterol structure, reaction temperature, reaction time, and lipid matrix composition. Under all conditions studied, phytostanols as saturated compounds were more stable than unsaturated phytosterols. In addition, esterification made phytosterols more reactive than free sterols at low temperatures, while at high temperatures the situation was the reverse. Generally, oxidation reactions were more significant at temperatures above 100°C. At lower temperatures, the significance of these reactions increased with increasing reaction time. The effect of lipid matrix composition was dependent on temperature; at temperatures above 140°C, phytosterols were more stable in an unsaturated lipid matrix, whereas below 140°C they were more stable in a saturated lipid matrix. At 140°C, phytosterols oxidized at the same rate in both matrices. Regardless of temperature, phytostanols oxidized more in an unsaturated lipid matrix. Generally, the distribution of oxidation products seemed to be associated with the phase of overall oxidation. 7-ketophytosterols accumulated when oxidation had not yet reached the dynamic state. Once this state was attained, the major products were 5,6-epoxyphytosterols and 7-hydroxyphytosterols. The changes observed in phytostanol oxidation products were not as informative since all stanol oxides quantified represented hydroxyl compounds. The formation of these secondary oxidation products did not account for all of the phytosterol/stanol losses observed during the heating experiments, indicating the presence of dimeric, oligomeric or other oxidation products, especially when free phytosterols and stanols were heated at high temperatures. Commercially available phytosterol/stanol ingredients were stable during such food processes as spray-drying and ultra high temperature (UHT)-type heating and subsequent long-term storage. Pan-frying, however, induced phytosterol oxidation and was classified as a rather deteriorative process. Overall, the findings indicated that although phytosterols and stanols are stable in normal food processing conditions, attention should be paid to their use in frying. Complex interactions between other food constituents also suggested that when new phytosterol-enriched foods are developed their oxidative stability must first be established. The results presented here will assist in choosing safe conditions for phytosterol/stanol enrichment.
  • Damerau, Annelie (Helsingin yliopisto, 2015)
    The consumption of whole grain foods high in fibre is of interest because of the health-promoting effects associated with dietary fibre. Therefore, there is interest in developing new fibre-rich cereal foods. However, these kinds of foods also contain polyunsaturated lipids, which are prone to oxidation. Further, lipids are dispersed in a heterogeneous matrix of starch, proteins and fibre, which increases their tendency to oxidize because of a large surface area and possible contact with prooxidants. The oxidation of lipids decreases nutritional quality and causes the formation of undesirable flavours. Knowledge of the oxidation behaviour of dispersed lipids in solid cereal foods, and of how factors like process parameters, structural features of the products and storage conditions affect lipid oxidation, is limited. In this thesis, the oxidative behaviour of foods with dispersed lipids was studied using two model systems. The first model system was a spray-dried emulsion containing sunflower oil encapsulated in a Na-caseinate-maltodextrin matrix, with either non-cross-linked or cross-linked proteins. The stability of the total and surface lipid fractions was determined during storage under different relative humidities (RHs). Further, the effect of RH on the amount of volatiles released from oxidized spray-dried emulsions was studied. The second model system consisted of extruded cereals produced from either whole grain oats or rye bran (coarse or fine) using different extrusion parameters. Their oxidative stability was studied during storage at 40 ºC, after milling and standardization to RH 33%. The primary oxidation was measured by peroxide values in the spray-dried emulsions and by losses of tocopherols and tocotrienols in the spray-dried emulsions and rye bran extrudates. Secondary oxidation was determined based on volatile secondary lipid oxidation products analysed by static head space (SHS-GC-FID) in the spray-dried emulsions and by head space solid-phase micro extraction (HS-SPME-GC-MS) in the extruded cereals. In addition to the oxidation parameters, enzymatic hydrolysis of lipids in the oat extrudates and the fatty acid composition of all models were studied by measuring the neutral lipid and fatty acid profiles, respectively. Increasing the RH improved the oxidative stability of both the total and surface lipid fractions of the stored spray-dried emulsions. This behaviour was mainly linked to the loss of individual powder particles upon caking and collapsing of the matrix at RH 75%. In addition, excess protein may have delayed oxidation via its radical scavenging activity. At RH 54%, cross-linking of the protein slightly improved the oxidative stability. The profiles of the volatile oxidation products from the spray-dried emulsions analysed by HS-SPME were also influenced by the RH. The effect was related to water-induced changes in hydrophilicity, structure and binding ability of the matrix, and to partitioning and solubility of the volatiles. The highest overall amount of volatiles released was obtained at water contents of 3.1% and 5.2% (RH 11% and 33%). The enzymatic hydrolysis of lipids in oats was effectively prevented by extrusion, even at the lowest temperature of 70 °C. The extrusion temperature could be increased to 110 °C without subjecting the lipids to non-enzymatic oxidation. However, by increasing the temperature to 130 °C, lipid oxidation was promoted, which also yielded losses of neutral lipids over time. In the case of the rye bran, the low water content (13% or 16%) in the extrusion of coarse or fine bran led to the most stable lipids during storage. The improved oxidative stability at low water contents in extrusion was connected with the higher formation of Maillard reaction products, which could have acted as antioxidants. The grinding of rye bran prior to extrusion caused a loss of tocols and increased the amounts of Maillard reaction products formed. The oxidative stability of the dispersed lipids was shown to be highly related to water induced physical changes in the matrix structure, which makes controlling the RH in the surrounding atmosphere an important factor in storage. Further, the RH affected the amount of volatile lipid oxidation products released, and this needs to be considered in determining lipid oxidation by HS-SPME. Extrusion was shown to inactivate lipases in oats. For the lipid stability in cereal extrudates, low temperature and low water content during extrusion were shown to be beneficial.
  • Kairisalo, Minna (Helsingin yliopisto, 2010)
    Oxidative stress is the result of an imbalance in the cellular pro-/antioxidant homeostasis which leads to the overproduction of reactive oxygen species (ROS). Usually, oxidative stress leads to structural and functional disruption within the cells, which in turn may cause cell death through different mechanisms. The brain is very sensitive to oxidative damage because of its high oxygen consumption, and oxidative stress is known to be involved e.g. in neurodegenerative diseases such as Huntington s disease (HD). X-linked Inhibitor of Apoptosis Protein (XIAP), one of the best-characterized apoptosis inhibitor proteins, is expressed both during development, and in the adult brain. Overexpression of XIAP is known to protect cells against various injuries and cell degeneration. XIAP can prevent cell death through various signalling cascades, e.g. by preventing caspases which are essential for apoptotic cell death. The function of XIAP in oxidative stress-related reactions is not that well-studied, which led us to examine it more closely. We found out that XIAP is able to reduce oxidative stress and cell death caused by ROS in vitro in neuron-like PC6.3-cells. We also noticed that XIAP increases the activation of transcription factor NFkappaB in these cells. Via NFkappaB, XIAP also increased two mitochondrial antioxidants: superoxide dismutase 2 (SOD2) and thioredoxin 2 (TRX2), and the significance of NFkappaB in this effect was also shown by using fibroblast cell lines from NFkappaB p65-/- mice. Furthermore, we observed that XIAP enhances BDNF signalling through NFkappaB in E17 hippocampal neurons. In the PC6.3-cell model of HD there was a correlation between the increased amount of ROS and the enhanced number of glutamine repeats. The protein levels of intracellular antioxidants and NFkappaB were decreased in cells expressing mutant huntingtin (htt) proteins compared to control cells. Last but not least, we observed that resveratrol (RSV) pre-treatment is able to reduce oxidative stress and cell death caused by ROS in PC6.3-cells. RSV also increased the amount of SOD2, TRX2 and XIAP, and the NFkappaB system may be involved in the increase of antioxidant proteins mediated by RSV. Altogether, these results bring us closer to understanding the role of XIAP in the control of oxidative stress and the function of XIAP in NFkappaB and BDNF signalling. In view of this, modulation of XIAP is an interesting possibility to consider in various therapies to reduce cell injuries caused by enhanced oxidative stress. RSV would also be a really interesting compound to examine as a drug candidate in disorders where oxidative stress is involved. However, studies to analyse its kinetics, actions and pharmacological and toxicological profiles are still lacking.
  • Gorbikova, Elena (Helsingin yliopisto, 2009)
    Energy conversion by living organisms is central dogma of bioenergetics. The effectiveness of the energy extraction by aerobic organisms is much greater than by anaerobic ones. In aerobic organisms the final stage of energy conversion occurs in respiratory chain that is located in the inner membrane of mitochondria or cell membrane of some aerobic bacteria. The terminal complex of the respiratory chain is cytochrome c oxidase (CcO) - the subject of this study. The primary function of CcO is to reduce oxygen to water. For this, CcO accepts electrons from a small soluble enzyme cytochrome c from one side of the membrane and protons from another side. Moreover, CcO translocates protons across the membrane. Both oxygen reduction and proton translocation contributes to generation of transmembrane electrochemical gradient that is used for ATP synthesis and different types of work in the cell. Although the structure of CcO is defined with a relatively high atomic resolution (1.8 Å), its function can hardly be elucidated from the structure. The electron transfer route within CcO and its steps are very well defined. Meanwhile, the proton transfer roots were predicted from the site-specific mutagenesis and later proved by X-ray crystallography, however, the more strong proof of the players of the proton translocation machine is still required. In this work we developed new methods to study CcO function based on FTIR (Fourier Transform Infrared) spectroscopy. Mainly with use of these methods we answered several questions that were controversial for many years: [i] the donor of H+ for dioxygen bond splitting was identified and [ii] the protolytic transitions of Glu-278 one of the key amino acid in proton translocation mechanism was shown for the first time.
  • Simojoki, Asko (Helsingin yliopisto, 2001)
  • Zhou, You (Helsingin yliopisto, 2013)
    Lipids, as the major components of cell membranes, are multi-functional molecules that also critically contribute to signal transduction, transcriptional regulation and membrane trafficking. The voice from single lipid molecule mixes together to create a balancing symphony or chorus called lipid homeostasis. Disturbances in the molecular song by lipids trigger profound physiological responses, which are reflected as metabolic disorders, such as obesity, metabolic syndrome, and atherosclerosis. Hence, it is important to understand the semiotics of this molecular language. Lipid homeostasis is context-dependent and regulated coordinately by a variety of lipids per se andproteins. Oxysterol binding protein (OSBP) and its homologues (ORPs) are implicated to regulate lipid homeostasis, sterol transfer and cell signaling. In this thesis, two ORPs, ORP11 and ORP7 have been extensively studied. ORP11 is abundant in human ovary, testis, kidney, liver, stomach, brain and adipose tissue and resides at the Golgi-Late endosome interface. ORP11 forms a dimer with its close homologue, ORP9, the interaction occuring in the region of aa154-292 in ORP11 and 98-372 in ORP9, which maintains the subcellular distribution of ORP11. ORP7 interacts with GATE-16 and might be involved in autophagosome biogenesis. Excess ORP7 induces recruitment of GATE-16 from Golgi to autophagosomes. ORP7 thereby regulates the proteosome-dependent degradation of Golgi v-SNARE protein, GS28, another binding partner of GATE-16. 25-hydroxycholesterol, a ligand of ORP7, modifies GS28 protein stability, an effect which is influenced by ORP7. Being the largest endocrine organ in human body, adipose tissue is the primary place to store fat. However, there is no study to compare expression patterns of ORPs in white adipose depots and adipose cells. In this thesis, we showed that human subcutaneous and visceral adipose depots as well as Simpson-Golabi-Behmel syndrome (SGBS) adipocytes sharesimilar ORP expression patterns, indicating that the mRNA signals of ORPs in adipose tissues predominantly originate from adipocytes. During adipogenesis, ORP2, ORP3, ORP4, ORP7 and ORP8 mRNA levels were downregulated, whereas ORP11 was upregulated. Silencing of ORP11 resulted in a decreased expression of adiponectin and aP2, while overexpression of ORP8 down-regulated the aP2 mRNA. Interestingly, silencing of ORP11 and overexpression of ORP8 significantly impaired triglyceride storage in the adipocytes. Taken together, the work in this thesis identifies protein binding partners of ORPs and indicates their potential roles in protein distribution and stability, intracellular trafficking, sterol sensing, and the adipocyte phenotype.
  • Ahlfors, Reetta (University of Helsinki, 2008)
    Tropospheric ozone (O3) is one of the most common air pollutants in industrialized countries, and an increasing problem in rapidly industrialising and developing countries in Asia, Africa and South America. Elevated concentrations of tropospheric O3 can lead to decrease in photosynthesis rate and therefore affect the normal metabolism, growth and seed production. Acute and high O3 episodes can lead to extensive damage leading to dead tissue in plants. Thus, O3 derived growth defects can lead to reduction in crop yield thereby leading to economical losses. Despite the extensive research on this area, many questions remain open on how these processes are controlled. In this study, the stress-induced signaling routes and the components involved were elucidated in more detail starting from visual damage to changes in gene expression, signaling routes and plant hormone interactions that are involved in O3-induced cell death. In order to elucidate O3-induced responses in Arabidopsis, mitogen-activated protein kinase (MAPK) signaling was studied using different hormonal signaling mutants. MAPKs were activated at the beginning of the O3 exposure. The activity of MAPKs, which were identified as AtMPK3 and AtMPK6, reached the maximum at 1 and 2 hours after the start of the exposure, respectively. The activity decreased back to clean air levels at 8 hours after the start of the exposure. Both AtMPK3 and AtMPK6 were translocated to nucleus at the beginning of the O3 exposure where they most likely affect gene expression. Differences were seen between different hormonal signaling mutants. Functional SA signaling was shown to be needed for the full protein levels and activation of AtMPK3. In addition, AtMPK3 and AtMPK6 activation was not dependent on ethylene signaling. Finally, jasmonic acid was also shown to have an impact on AtMPK3 protein levels and AtMPK3 activity. To further study O3-induced cell death, an earlier isolated O3 sensitive Arabidopsis mutant rcd1 was mapped, cloned and further characterized. RCD1 was shown to encode a gene with WWE and ADP-ribosylation domains known to be involved in protein-protein interactions and cell signaling. rcd1 was shown to be involved in many processes including hormonal signaling and regulation of stress-responsive genes. rcd1 is sensitive against O3 and apoplastic superoxide, but tolerant against paraquat that produces superoxide in chloroplast. rcd1 is also partially insensitive to glucose and has alterations in hormone responses. These alterations are seen as ABA insensitivity, reduced jasmonic acid sensitivity and reduced ethylene sensitivity. All these features suggest that RCD1 acts as an integrative node in hormonal signaling and it is involved in the hormonal regulation of several specific stress-responsive genes. Further studies with the rcd1 mutant showed that it exhibits the classical features of programmed cell death, PCD, in response to O3. These include nuclear shrinkage, chromatin condensation, nuclear DNA degradation, cytosol vesiculation and accumulation of phenolic compounds and eventually patches of HR-like lesions. rcd1 was found to produce extensive amount of salicylic acid and jasmonic acid in response to O3. Double mutant studies showed that SA independent and dependent processes were involved in the O3-induced PCD in rcd1 and that increased sensitivity against JA led to increased sensitivity against O3. Furthermore, rcd1 had alterations in MAPK signature that resembled changes that were previously seen in mutants defective in SA and JA signaling. Nitric oxide accumulation and its impact on O3-induced cell death were also studied. Transient accumulation of NO was seen at the beginning of the O3 exposure, and during late time points, NO accumulation coincided with the HR-like lesions. NO was shown to modify defense gene expression, such as, SA and ethylene biosynthetic genes. Furthermore, rcd1 was shown to produce more NO in control conditions. In conclusion, NO was shown to be involved in O3-induced signaling leading to attenuation of SA biosynthesis and other defense related genes.
  • Vahala, Jorma (Helsingin yliopisto, 2003)
  • Kainov, Denis (Helsingin yliopisto, 2005)
  • Taipale, Anni (Helsingin yliopisto, 2013)
    Background:Otorhinolaryngological (ORL) diseases and hearing loss frequently occur among the children of developing countries, but they remain poorly characterized. A need therefore exists for more comprehensive understanding of the background and clinical features of these diseases in resource-poor settings. Patients and methods: Voluntary paediatric outpatients of various specialties were examined at Hospital Pediátrico in Luanda, Angola. Study participants underwent medical history-taking, a thorough physical and ORL examination, hearing screening by brainstem auditory-evoked potential (BAEP), and, at age 5 or older, pure-tone audiometry. Nasopharyngeal smears (NPS) were obtained from 102 children with respiratory symptoms and screened by polymerase chain reaction (PCR) for human rhino- (HRV) and enterovirus (HEV). We took 18 bacterial culture smears from children with chronic suppurative otitis media (CSOM). Clinical data collected were compared between 23 children with CSOM vs. 23 age- and gender-matched controls, between 61 children with sickle-cell disease (SCD) vs. 61 controls, and between 78 human immunodeficiency virus (HIV) -positive children vs. 78 controls. Results: In virus screening of 102 NPS specimens, 37 (36%) were positive: 27 (26%) for HRV alone, 3 (3%) for HEV alone, and 7 (7%) for HRV+HEV. HRV prevalence was highest during the coolest month, July, 47% (26/53), compared to 22% (8/49) (p=0.021) in April-to-June. In the CSOM study, HIV positivity occurred in 14/22 (64%) of the CSOM children vs. none of the controls (p<0.001) and tuberculosis in 8/22 (36%) vs. none (p=0.002). The most frequent CSOM pathogens were Proteus (8/18, 44%) and Pseudomonas (4/18, 22%) species. CSOM resulted in hearing loss of >25 dB HL in pure-tone averages or BAEP in 17/33 (52%) of the affected ears. In the SCD study of 61 SCD children vs. 61 controls, bilateral hearing loss of >25 dB HL at any frequency occurred in 9 (36%) SCD children vs. 3 (11%) controls (p=0.047), whereas the prevalence of other ORL findings showed no significant difference. Of 78 HIV-positive children vs. 78 controls, ORL pathology was present in 72 (92%) HIV-positive vs. 61 (72%) control children (p=0.022). Dental caries occurred in 44 (56%) of the HIV-positive children vs. 25 controls (32%) (p<0.001), cervical lymphadenopathy >1cm in 35 (45%) vs. 8 (10%) (p<0.001), facial skin lesions in 25 (32%) vs. 4 (5%) (p<0.001), CSOM in 21 (26%) vs. 3 (4%) (p<0.001), and bilateral hearing loss of >25 dB HL in PTA or BAEP in 10 (13%) vs. one (1%) (p=0.009). Conclusions: In children of tropical Luanda, HRV and HEV emerged during respiratory symptoms. CSOM was associated with co-morbidity and hearing loss. Hearing loss occurred in SCD. ORL manifestations of HIV infection were common and various. In resource-poor settings, ORL and hearing services deserve a higher priority.
  • Suominen, Irmgard (Helsingin yliopisto, 2005)
  • Perttunen, Kristiina (Helsingin yliopisto, 2003)
  • Saastamoinen, Peppiina (Helsingin yliopisto, 2010)
    The overall objective of this study was to gain epidemiological knowledge about pain among employee populations. More specifically, the aims were to assess the prevalence of pain, to identify socio-economic risk groups and work-related psychosocial risk factors, and to assess the consequences in terms of health-related functioning and sickness absence. The study was carried out among the municipal employees of the City of Helsinki. Data comprised questionnaire survey conducted in years 2000-2002 and register data on sickness absence. Altogether 8960 40-60 year old employees participated to the survey (response rate 67%). Pain is common among ageing employees. Approximately 29 per cent of employees reported chronic pain and 15 per cent acute pain, and about seven per cent reported moderately or severely limiting disabling chronic pain. Pain was more common among those with lower level of education or in a low occupational class. -- Psychosocial work environment was associated with pain reports. Job strain, bullying at workplace, and problems in combining work and home duties were associated with pain among women. Among men combining work and home duties was not associated with pain, whereas organizational injustice showed associations. Pain affects functional capacity and predicts sickness absence. Those with pain reported lower level of both mental and physical functioning than those with no pain, physical functioning being more strongly affected than mental. Bodily location of pain or whether pain was acute or chronic had only minor impact on the variation in functioning, whereas the simple count of painful locations was associated with widest variation. Pain accounted for eight per cent of short term (1-3 day) sickness absence spells among men and 13 per cent among women. Of absence spells lasting between four and 14 days pain accounted for 23 per cent among women and 25 per cent among men, corresponding figures for over 14 day absence spells being 37 and 30 per cent. The association between pain and sickness absence was relatively independent of physical and psychosocial work factors, especially among women. The results of this study provide a picture of the epidemiology of pain among employees. Pain is a significant problem that seriously affects work ability. Information on risk groups can be utilized to make prevention measures more effective among those at high risk, and to decrease pain rates and thereby narrow the differences between socio-economic groups. Furthermore, the work-related psychosocial risk factors identified in this study are potentially modifiable, and it should be possible to target interventions on decreasing pain rates among employees.
  • Kuivalainen, Anna-Maria (Helsingin yliopisto, 2015)
    Background: Bone marrow aspiration and/or biopsy (BMAB) is a procedure used to diagnose and follow up various haematological diseases. It is usually performed at either the sternum or the iliac crest. The procedure often causes pain despite local infiltration anaesthesia. The objective of this study was to evaluate different means of pain relief during BMAB in adult patients. Special attention was paid to pre-procedural anxiety and its effect on pain. The commonly used local anaesthetic lidocaine was compared with articaine, an anaesthetic known for its ability to penetrate bone tissue. The effect of warming and buffering the lidocaine solution, measures expected to improve the anaesthetic action, was examined. Also investigated were sublingual fentanyl and inhaled 50% nitrous oxide (N2O) in oxygen (O2) as means of analgesia and sedation during BMAB. Patients: The patient population comprised 646 adult outpatients from the Department of Haematology, Helsinki University Central Hospital, Finland. Patients were randomized to treatment groups in trials comparing one intervention with another or with placebo. The studies were all patient-blinded. One study was observational and investigated the association between pain and pre-procedural anxiety. Patient recruitment was performed between 2007 and 2014. Main results: Pre-procedural anxiety intensified pain during BMAB in all trials. Median NRS (Numeral Rating Scale, 0 = no pain, 10 = worst pain imaginable) during infiltration was 3.0 (range 0 10, interquartile range (IQR) 3.0), puncture 2.0 (range 0 10, IQR 3.0), aspiration 4.0 (range 0 10, IQR 4.0), biopsy 4.0 (range 0 10, IQR 4.0) and immediately after BMAB 0 (range 0 9.0, IQR 1.0). Scores of 8 10 comprised 8.1%, 4.7%, 13.9%, and 12.4% of the scores for infiltration, puncture, aspiration and biopsy, respectively. Possible supplemental analgesia or sedation given on patient request in addition to local anaesthesia and study intervention did not lower pain scores during BMAB. Articaine was not found to be superior to lidocaine as a local anaesthetic. Warming and buffering the lidocaine solution diminished pain during infiltration, but did not lower the pain scores during other phases of BMAB. Sublingual fentanyl (200 µg or 100 µg) did not provide significant pain relief relative to placebo when administered 6 64 minutes before BMAB. Dizziness was a frequent side-effect. Inhalation of 50% N2O in O2 was no more effective than inhalation of 50% O2. No significant differences in adverse effects emerged between patients receiving N2O/O2 and those receiving 50% O2. Interestingly, 86% of N2O patients and 83% of placebo patients would choose the same analgesia method during their next BMAB. Conclusions: Many patients undergoing BMAB suffer intense pain during the procedure. Pre-procedural anxiety was strongly associated with pain during the various phases of BMAB. The pain from local anaesthetic infiltration with articaine and lidocaine was similar. Buffering and warming the local anaesthetic solution clearly reduced the infiltration pain. However, neither these measures nor the use of sublingual fentanyl or inhalation of N2O had an impact on the pain caused by aspiration and biopsy.
  • Vuorimaa, Hanna (Helsingin yliopisto, 2010)
    Juvenile idiopathic arthritis (JIA) is a severe childhood disease usually characterized by long-term morbidity, unpredictable course, pain, and limitations in daily activities and social participation. The disease affects not only the child but also the whole family. The family is expected to adhere to an often very laborious regimen over a long period of time. However, the parental role is incoherently conceptualized in the research field. Pain in JIA is of somatic origin, but psychosocial factors, such as mood and self-efficacy, are critical in the perception of pain and in its impact on functioning. This study examined the factors correlating and possibly explaining pain in JIA, with a special emphasis on the mutual relations between parent- and patient-driven variables. In this patient series pain was not associated with the disease activity. The degree of pain was on average fairly low in children with JIA. When the children were clustered according to age, anxiety and depression, four distinguishable cluster groups significantly associated with pain emerged. One of the groups was described by concept vulnerability because of unfavorable variable associations. Parental depressive and anxiety symptoms accompanied by illness management had a predictive power in discriminating groups of children with varying distress levels. The parent’s and child’s perception of a child’s functional capability, distress, and somatic self-efficacy had independent explanatory power predicting the child’s pain. Of special interest in the current study was self-efficacy, which refers to the belief of an individual that he/she has the ability to engage in the behavior required for tackling the disease. In children with JIA, strong self-efficacy was related to lower levels of pain, depressive symptoms and trait anxiety. This suggests strengthening a child’s sense of self-efficacy, when helping the child to cope with his or her disease. Pain experienced by a child with JIA needs to be viewed in a multidimensional bio-psycho-social context that covers biological, environmental and cognitive behavioral mechanisms. The relations between the parent-child variables are complex and affect pain both directly and indirectly. Developing pain-treatment modalities that recognize the family as a system is also warranted.
  • Pesonen, Anne (Helsingin yliopisto, 2011)
    The proportion of patients over 75 years of age, receiving all different types of healthcare, is constantly increasing. The elderly undergo surgery and anaesthetic procedures more often than middle-aged patients. Poor pain management in the elderly is still an issue. Although the elderly consumes the greatest proportion of prescribed medicines in Western Europe, most clinical pharmacological studies have been performed in healthy volunteers or middle-aged patients. The aim of this study was to investigate pain measurement and management in cognitively impaired patients in long term hospital care and in cognitively normal elderly patients after cardiac surgery. This thesis incorporated 366 patients, including 86 home-dwelling or hospitalized elderly with chronic pain and 280 patients undergoing cardiac surgery with acute pain. The mean age of patients was 77 (SD ± 8) years and approximately 8400 pain measurements were performed with four pain scales: Verbal Rating Scale (VRS), the Visual Analogue Scale (VAS), the Red Wedge Scale (RWS), and the Facial Pain Scale (FPS). Cognitive function, depression, functional ability in daily life, postoperative sedation and postoperative confusion were assessed with MMSE, GDS, Barthel Index, RASS, and CAM-ICU, respectively. The effects and plasma concentrations of fentanyl and oxycodone were measured in elderly (≥ 75 years) and middle-aged patients (≤ 60 years) and the opioid-sparing effect of pregabalin was studied after cardiac surgery. The VRS pain scores after movement correlated with the Barthel Index. The VRS was most successful in the groups of demented patients (MMSE 17-23, 11-16 and ≤ 10) and in elderly patients on the first day after cardiac surgery. The elderly had a higher plasma concentration of fentanyl at the end of surgery than younger patients. The plasma concentrations of oxycodone were comparable between the groups. Pain intensity on the VRS was lower and the sedation scores were higher in the elderly. Total oxycodone consumption during five postoperative days was reduced by 48% and the CAM-ICU scores were higher on the first postoperative day in the pregabalin group. The incidence of postoperative pain during movement was lower in the pregabalin group three months after surgery. This investigation demonstrates that chronic pain did not seem to impair daily activities in home-dwelling Finnish elderly. The VRS appeared to be applicable for elderly patients with clear cognitive dysfunction (MMSE ≤17) and it was the most feasible pain scale for the early postoperative period after cardiac surgery. After cardiac surgery, plasma concentrations of fentanyl in elderly were elevated, although oxycodone concentrations were at similar level compared to middle-aged patients. The elderly had less pain and were more sedated after doses of oxycodone. Therefore, particular attention must be given to individual dosing of the opioids in elderly surgical patients, who often need a smaller amount for adequate analgesia than middle-aged patients. The administration of pregabalin reduced postoperative oxycodone consumption after cardiac surgery. Pregabalin-treated patients had less confusion, and additionally to less postoperative pain on the first postoperative day and during movement at three months post-surgery. Pregabalin might be a new alternative as analgesic for acute postoperative and chronic pain management in the elderly. Its clinical role and safety remains to be verified in large-scale randomized and controlled studies. In the future, many clinical trials in the older category of patients will be needed to facilitate improvements in health care methods.