| 1. |
- Hellgren, Johan, 1966-
(författare)
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Compensation for hearing loss and cancellation of acoustic feedback indigital hearing aids
- 2000
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The development of integrated circuits during the last decades has made it possible to incorporate digital signal processing in hearing aids that fit into the ear canal and are powered by small zink-air batteries. The digital signal processing provides new possibilities for the hearing aid to modify the signal to fit the impaired ear. A linear phase filter bank that is intended as a basic building block of the signal processing in digital hearing aids is introduced in this dissertation. The filterbank is computationally very efficient and divides the input signal into a number of narrow band signals for further signal processing. The filter bank was combined with band specific gains and two compressors to form the signal processing of a hearing aid. The compressors allow leveldependent gain. Three alternative fitting strategies used to adjust the characteristics of this hearing aid to the individual hearing impaired listener were evaluated. The three fitting strategies differed mainly in the characteristics of the compressors. The strategies were evaluated by hearing impaired subjects in a field test and in laboratory tests. When the subjects were grouped according to their preference among the fitting strategies, the results showed significant differences in the hearing loss configuration between the groups.One of the main tasks of a hearing aid is to amplify the signal to make it audible for the hearing impaired user. The maximum gain that can be used in a hearing aid will be controlled by the feedback from the output to the microphone, as the hearing aid will be a part of a closed loop system. The feedback path depends on several factors such as the position of the microphone (differs between hearing aid categories), size of vent, and the acoustics around the hearing aid. The feedback, and thus the maximum gain that can be used in a hearing aid, has been identified with a number of different hearing aids in a number of conditions that can be expected when the hearing aid is used under real-life conditions.Feedback cancellation can be used to reduce the negative effects of feedback on the performance of the hearing aid. An internal feedback in the hearing aid that is an estimate of the external feedback is then used to cancel the feedback signal. The external feedback path will vary as the hearing aid is used ( e.g. when a telephone set is placed by the ear). It is thus desirable to continuously identify the feedback path. One approach to do this is to utilize closed loop identification with the direct method and some recursive identification method. The output and input signals of the hearing aid are then considered as input and output signal of the system to be identified, i.e. the feedback path. An advantage with this method is that the identification can be done without modifying the output signal. A drawback is that the estimate may be biased, depending on the characteristics of the input signal. A difference from many other closed loop identification problems is that the data used for identification will depend on previous estimates of the system. A feedback cancellation algorithm where Filtered-X LMS is used with the direct method has been analyzed. Filtered-XLMS is computationally efficient and gives a possibility to incorporate known characteristics of the feedback path in the model set used. Prefiltering was also used in the algorithm as it can provide an unbiased estimate if the spectrum of the input signal is known.
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| 2. |
- Hällgren, Mathias, 1972-
(författare)
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Hearing and cognition in speech comprehension. Methods and applications
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Central auditory processing is complex and can not be evaluated by a single method. This thesis focuses on assessment of some aspects of central auditory functions by the use of dichotic speech tests and cognitive tests that tax functions important for speech processing.Paper A deals with the cognitive effects in dichotic speech testing in elderly hearing-impaired subjects. It was found that different listening tasks in the dichotic tests put different demands on cognitive ability, shown by a varying degree of correlation between cognitive functions and dichotic test parameters. Age-related cognitive decline was strongly connected with problems to perceive stimuli presented to the left ear.Paper B presents a new cognitive test battery sensitive for functions important for speech processing and understanding, performed in text, auditory and audiovisual modalities. The test battery was evaluated in four groups, differing in age and hearing status, and has proven to be useful in assessing the relative contribution of different input-modalities and the effect of age, hearingimpairment and visual contribution on functions important for speech processing.In Paper C the test battery developed in Paper B was used to study listening situations with different kinds of background noise. Interfering noise at +10 dB signal-to-noise ratio has significant negative effects on performance in speech processing tasks and on the effort perceived. Hearing-impaired subjects showed poorer results in noise with temporal variations, and elderly subjects were more distracted by noise with temporal variations, especially by noise with meaningful content. In noise, all subjects, particularly those with impaired hearing, were more dependent upon visual cues than in the quiet condition.Hearing aid benefit in speech processing with and without background noise was studied in Paper D. The test battery developed in Paper B was used together with a standard measure of speech recognition. With hearing aids, speech recognition was improved in the background condition without noise and in the background condition of ordinary speech. Significantly less effort was perceived in the cognitive tests when hearing aids were used, although only minor benefits of hearing aid amplification were seen. This underlines the importance of considering perceived effort as a dimension when evaluating hearing aid benefit, in further research as well as in clinical practice.The results from the studies contribute to the knowledge about speech processing but also to the search for more specific evaluation of speech understanding, incorporating both sensory and cognitive factors.
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| 3. |
- Johansson, Magnus, 1973-
(författare)
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On noise and hearing loss : Prevalence and reference data
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Noise exposure is one of the most prevalent causes of irreversible occupational disease in Sweden and in many other countries. In hearing conservation programs, aimed at preventing noise-induced hearing loss, audiometry is an important instrument to highlight the risks and to assess the effectiveness of the program. A hazardous working environment and persons affected by it can be identified by monitoring the hearing thresholds of individual employees or groups of employees over time. However, in order to evaluate the prevalence of occupational noise-induced hearing loss, relevant reference data of unexposed subjects is needed.The first part of this dissertation concerns the changes in hearing thresholds over three decades in two occupational environments with high noise levels in the province of Östergötland, Sweden: the mechanical and the wood processing industries. The results show a positive trend, with improving median hearing thresholds from the 1970s into the 1990s. However, the hearing loss present also in the best period, during the 1990s, was probably greater than if the occupational noise exposure had not occurred. This study made clear the need for a valid reference data base, representing the statistical distribution of hearing threshold levels in a population not exposed to occupational noise but otherwise comparable to the group under study.In the second part of the dissertation, reference data for hearing threshold levels in women and men aged from 20 to 79 years are presented, based on measurements of 603 randomly selected individuals in Östergötland. A mathematical model is introduced, based on the hyperbolic tangent function, describing the hearing threshold levels as functions of age. The results show an age-related gender difference, with poorer hearing for men in age groups above 50 years.The prevalence of different degree of hearing loss and tinnitus is described for the same population in the third part of the dissertation. The overall prevalence of mild, moderate, severe or profound hearing loss was 20.9% collectively for women and 25.0% collectively for men. Tinnitus was reported by 8.9% of the women and 17.6% of the men. Approximately 2.4% of the subjects under study had been provided with hearing aids. However, about 7.7% were estimated to potentially benefit from hearing aids as estimated from their degree of hearing loss.Noise-induced hearing loss primarily causes damage to the outer hair cells of the inner ear. The fourth and last part of the dissertation evaluates the outer hair cell function, using otoacoustic emission measurements (OAE). Prevalence results from three different measuring techniques are presented: spontaneous otoacoustic emissions (SOAE), transient evoked otoacoustic emissions (TEOAE) and distortion product otoacoustic emissions (DPOAE). Gender and age effects on the recorded emission levels were also investigated. Women showed higher emission levels compared to men and for both women and men the emission levels decreased with increasing age. The results from the OAE recordings were shown to be somewhat affected by the state of the middle ear. The study included tympanometry, and the relation of the outcome ofthis test to the otoacoustic emissions is described, where high middle ear compliance resulted in low emission level. Reference data for the tympanometric measurements are also presented.The results of this project form an essential part of the important work against noiseinduced hearing loss, which needs continuous monitoring. The reference data presented here will provide a valid and reliable data base for the future assessment of hearing tests performed by occupational health centres in Sweden. This data base will in turn prove useful for comparison studies for Sweden as a responsible fellow EU member country setting high standards for work force safety. The statistical distribution of hearing threshold levels as a function of age for men and women in tabulated form is available on the Swedish Work Environment Authority (Arbetsmiljöverket) web site: http://www.av.se/publikationer/bocker/fysiskt/h293.shtm.
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| 4. |
- Ziegert, Kristina
(författare)
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Everyday Life among Next of Kin of Haemodialysis Patients
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Everyday life can be complex when next of kin of haemodialysis patients are preoccupied with taking care of the patient and his/her health, which implies the difficulties and requirements needed. The general aim of this thesis was to explore and describe everyday life among next of kin of haemodialysis patients with focus on the life situation, health, time and professional support. Two perspectives of the thesis was applied: a holistic perspective on the everyday life of next of haemodialysis patient and a social perspective with focus on human communication and understanding of next of kin’s experience of everyday life. A qualitative descriptive and explorative design, comprising a phenomenographic and content analysis was used in Studies I-IV. The data collected in the studies consisted of interviews with next of kin to haemodialysis patient and analysis of professional support for next of kin to chronic haemodialysis patients in nursing documentation from two hospitals in Sweden. The experience of time in everyday life among next of kin of haemodialysis patients demonstrated that time for them is minimised and life space contracted. Next of kin experienced ambivalence towards their own health, especially in cases of patients’ spouses When next of kin of haemodialysis patient’s became involved in the patients’ care, they experienced arduousness in relation to their own health as well as less uninterrupted time for themselves in everyday life, and their life situation was characterised by confinement and social isolation. They were aware of the prognosis of renal disease and the fact that haemodialysis is a life-sustaining treatment, which forced them to live for the moment. The everyday life among the next of kin changed when the family became involved in the care, which in turn lead to a changed life situation and restrictions in everyday life. Lack of knowledge in nursing documentation of professional support revealed necessity of the readiness of next of kin. It is therefore important to be familiar with this in the nursing process, especially when the patient and their next of kin need support and attention in everyday life.Original papers not included.
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| 5. |
- Aardal-Eriksson, Elisabeth
(författare)
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Salivary cortisol and posttraumatic stress reactions : methodological and applied studies before and after trauma
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The field of psychotraumatology has its roots in ancient history. During the past decades, the surveillance of the psychobiological background of reactions to and consequences of traumatic stress has made great progress and the complexity of the human stress response system stands out. The hypothalamic-pituitary-adrenocortical axis activity, modulated by various neuroimmunological substances, seems to play a major role in the stress response. However, there are still inconsistencies in explanations of relationships between biological and psychological changes following traumatic stress. Moreover, the matter of predictive factors for the development of posttraumatic morbidity is still in a speculative phase.The aims of the present thesis were to further develop a commercial serum cortisol radioimmunoassay (RIA) for determination of cortisol in saliva and to test its reliability, specificity and sensitivity as a biochemical assay. The saliva sampling procedures and sample storage stability were also to be tested. Further issues were to investigate determinations of salivary cortisol and serum prolactin in relation to selfratings of posttraumatic psychological distress and general psychological health. Possible predictive and concurrent validity of salivary cortisol as a biochemical marker for posttraumatic psychological distress were to be tested.Cortisol is present in saliva mainly in non-protein form, representing the free, biologically active fraction of the total plasma cortisol concentration. In a first phase of the present thesis, the commercial serum cortisol RIA was modified for determination of cortisol in saliva. The relation between salivary and serum cortisol concentrations was tested. Reference ranges at 8 AM and 10 PM for the salivary cortisol assay were established from 195 healthy subjects. Salivary cortisol concentrations were tested in relation to serum cortisol in estimating adrenocortical function during endocrine dynamic function tests in 37 patients and 13 healthy controls. In testing salivary cortisol as a marker for stress for fieldwork use, a screening study was performed on 66 male rescue workers. Salivary cortisol at 8 AM and 10 PM and serum prolactin were determined and general psychological health and posttraumatic psychological distress were estimated with the self-rating scales General Health Questionnaire, Impact of Event Scale and Posttraumatic Symptom Scale. These scales were used in the second phase of the thesis. Three applied follow-up studies were performed with sampling of salivary cortisol and self-ratings: (a) a study of 31 UN-soldiers five days, two and nine months after a mine accident; (b) a study of 145 UN-soldiers before, at return, and two and six month after a six month mission. (c) a study of 101 UN-soldiers six and twelve months after a six month mission with severe combat exposure.The results from the present thesis indicate that the modified method of salivary cortisol determination possesses sufficient precision, accuracy, sample storage stability and procedural advantages for laboratory, clinical and field application. Moreover, it possesses moderate predictive information and moderate to high concurrent validity as a biochemical marker for posttraumatic psychological distress.
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| 6. |
- Aboulaich, Nabila, 1976-
(författare)
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Expanding role of caveolae in control of adipocyte metabolism : proteomics of caveolae
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The primary function of adipose tissue is to store energy in the form of triacylglycerol, which is hydrolyzed to fatty acids to supply other tissues with energy. While insulin promotes the storage of triacylglycerol, catecholamines stimulate its hydrolysis. The development of type II diabetes is strongly associated with obesity, indicating a role of triacylglycerol metabolism in the pathogenesis of diabetes. Caveolae are plasma membrane invaginations found in most cells but are highly abundant in adipocytes. Insulin receptors are localized in caveolae and their function depends on intact caveolae structures. In the present thesis work, mass spectrometry-based methodology allowed identification of a number of new proteins and their posttranslational modifications in caveolae of human adipocytes. Variable N-terminal acetylation and phosphorylation of caveolin-1α and caveolin-1β were identified, which might regulate the function of caveolae. The transcription regulator protein PTRF was identified as the major caveolae associated protein. Specific proteolytic modifications of PTRF at the cytosolic surface of caveolae and phosphorylation on nine serine and one threonine residues were identified. Moreover, insulin induced translocation of PTRF from the plasma membrane to the nucleus. PTRF was previously shown to regulate the activity of both RNA polymerase I and polymerase II, thus a role of PTRF in mediating the anabolic action of insulin on protein synthesis and gene transcription is proposed.PTRF was also involved in an extranuclear function in the hormonal regulation of triacylglycerol metabolism in caveolae. PTRF was colocalized with the triacylglycerol regulator proteins perilipin and hormone-sensitive lipase (HSL) in the triacylglycerol-synthesizing caveolae subclass. We showed that, while perilipin was translocated to the plasma membrane, both PTRF and HSL were translocated from the plasma membrane to the cytosol as a complex in response to insulin. The perilipin recruited to the plasma membrane was highly threonine phosphorylated. By mass spectrometry, three phosphorylated threonine residues were identified and were located in an acidic domain in the lipid droplet targeting domain of perilipin. The insulin-induced recruitment of perilipin to the plasma membrane might, therefore be phosphorylation-dependent. Isoproterenol, which stimulates hydrolysis of triacylglycerol, induced a complete depletion of perilipin B from the plasma membrane, suggesting a function of perilipin B to protect newly synthesized triacylglycerol in caveolae from being hydrolyzed by HSL. The location of PTRF and HSL was not affected by isoproterenol, indicating that insulin is acting against a default presence of PTRF and HSL in caveolae.Taken together, this thesis expands our knowledge about caveolae and provided valuable information about their involvement in novel roles, particularly in the hormonal regulation of triacylglycerol metabolism.
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| 7. |
- Abrahamsson, Thomas, 1968-
(författare)
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Can Lactobacillus Reuteri Prevent Allergic Disease in Early Childhood?
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: An altered microbial exposure may be partly responsible for the increase of allergic diseases in populations with a western lifestyle. Activation of the immune system by microbes early in life is probably required for an accurate maturation of the immune system. Probiotics, live bacteria which are considered to confer health when ingested, have been suggested to prevent eczema and sensitisation infants.Aim: The general aim of this thesis was to assess the effect of oral supplementation with the probiotic bacterium Lactobacillus reuteri (L. reuteri) in infancy on the development of allergic disease and sensitisation during the first 2 years of life and to examine mechanisms possibly underlying eventual effects on allergic manifestations.Subjects: The thesis is based on results obtained from a prospective double-blind placebo-controlled multicenter trial, comprising 232 families with allergic disease, of whom 188 completed the study.Methods: The families were recruited at the antenatal clinic, and the mothers received L. reuteri ATCC 55730 (1 x 108 colony forming units) or placebo daily from gestational week 36 until delivery. Their babies then continued with the same study product from birth until 12 months of age and were followed up for another year. The primary outcomes were allergic disease, with or without positive skin prick test or circulating IgE to food allergens. Bacterial counts and prevalence were assessed in maternal breast milk and faeces and infant faeces, employing conventional cultivation methods. Cytokines and IgA antibodies were analysed in colostrum and mature milk from the mothers with ELISA, and Na/K- ratio in breast milk with ion selective electrodes. Circulating Th1/Th2-associated chemokines were analysed in cord and peripheral blood in the infants with Luminex or ELISA technique.Results: The incidence of eczema was similar, 36% in the treated versus 34% in the placebo group. The L. reuteri group had a lower cumulative incidence of IgE-associated allergic disease, 20% versus 35% (p=0.04), and less IgE-associated eczema during the second year, 8% versus 20% (p=0.02). The prevalence of L. reuteri was higher during the first year of life in stool samples from infants, as well as in colostrum, in the active as compared to the placebo treated group. Colostrum from L. reuteri supplemented mothers had lower levels of TGF-β2, and low levels of this cytokine were associated with less sensitisation. Low Th1- and high Th2-associated chemokine levels preceded allergic disease. The presence of L. reuteri in stool was associated with lower levels of the Th2-associated chemokines CCL17 and CCL22 and higher levels of the Th1-associated CXCL11.Conclusion: Although a preventive effect of probiotics on infant eczema was not confirmed, the L. reuteri treated infants had lower incidence of IgE-associated allergic disease at two years of age, and therefore possibly run a reduced risk to develop later respiratory allergic disease. The mechanisms underlying this effect require further elucidation.
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| 8. |
- Adell, Gunnar, 1953-
(författare)
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Indicators of colorectal cancer prognosis and response to preoperative radiotherapy
- 2000
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Colorectal cancer is one of the three most common malignant diseases in Sweden, with about 5,000 new cases each year. Thirty-five percent of these are rectal cancer, for which local recurrence after surgery has been a serious problem. The five-year survival rate in colorectal cancer has improved from about 40% in 1960 to 55% in 1995. Adjuvant chemotherapy of colon cancer, preoperative radiotherapy and improved surgical techniques in rectal cancer have contributed to the improved results. To select patients best suited for pre- or postoperative therapy, we need indicators of both prognosis and response to therapy.Using antibodies against cytokeratin, we found that 39% of patients with colorectal carcinoma that had penetrated the muscularis propria but without lymph-node metastases by routine light microscopy, had got micrometastases. Survival among patients with micrometastases was not significantly different from that among patients without such metastases.We also identified subsets of tumour-infiltrating mononuclear cells and studied their pattern of distribution in relation to regressive tumour areas and Dukes class. Our interpretation is that the subsets of tumourinfiltrating mononuclear cells change with advancing Dukes class, indicating gradual deterioration of the local immune control.We also investigated the interaction between p53, Ki-67, apoptosis and the outcome in rectal cancer with and without short-term preoperative radiotherapy. The expression of nuclear p53 protein seemed to be a significant predictive factor for local treatment failure after preoperative radiotherapy. Low tumour cell proliferation measured with Ki-67 in the preoperative biopsy correlated with improved local control and disease-free survival after preoperative radiotherapy.High apoptotic index was associated with improved local control of rectal cancer even without pre-operative radiotherapy, whereas local control of tumours with low and intermediate apoptotic index was significantly improved by preoperative radiotherapy.In conclusion, micrometastases in regional lymph nodes are an interesting phenomenon but with limited prognostic value. The subsets of tumour-infiltrating mononuclear cells change with advancing Dukes class, and its seems that the local immune control is gradually broken down. In rectal cancer, p53 expression, tumour proliferation measured with Ki-67 and apoptotic index seem to be interesting indicators of rectal cancer prognosis and response to preoperative radiotherapy.
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| 9. |
- Adolfsson, Annsofie, 1960-, et al.
(författare)
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Miscarriage : women’s experience and its cumulative incidence
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Many women experience miscarriage every year. Every fourth woman who has given birth reports that she has previous experience of miscarriage. In a study of all women in the Swedish Medical Birth Register 1983-2003, we found that the number of cases of self reported miscarriage had increased in Sweden during this 21 year period. This increase can be explained by the introduction of sensitive pregnancy tests around 1990, as well as an increase in the mean age of the mothers, by approximately 3 years, during the observation period. The risk of miscarriage is 13% with the first child. With subsequent pregnancies, the risk of miscarriage is 8%, 6% and 4% with the second, third and fourth child, respectively.Thirteen of these women who had suffered a recent miscarriage were interviewed four months later, and their feelings of guilt and emptiness were explored. Their experience was that they wanted their questions to be answered, and that they wanted others to treat them as the mothers to be that they felt themselves to be. They also experienced the need for time to grieve their loss.Measurement of grief by means of the Perinatal Grief Scale (PGS) is used in research but has also been proposed for clinical use. We have translated this psychological instrument to Swedish, back-translated and tested it in a small pilot study. In a randomized controlled study, women with early miscarriage were allocated, either to a structured visit (study group) or a regular visit (control group) to a midwife. The structured visit was conducted according to the Swanson caring theory. We could conclude that the structured visit had no significant effect on grief compared to the regular visit, as measured using the PGS. However, women with the sub-diagnosis missed abortion have significantly more grief four months after early miscarriage, regardless of visit type.We also performed a content analysis of the tape-recorded structured follow-up visit. The code-key used was Bonanno and Kaltman’s general grief categorization. Women’s expression of grief after miscarriage was found to be very similar to the grief experienced following the death of a relative. Furthermore, the grief was found to be independent of number of children, women’s age, or earlier experience of miscarriage.Conclusions: Every fourth woman who gives birth reports that she has also experienced early miscarriage. The experience of these women is that they have suffered a substantial loss and their reaction is grief similar to that experienced following the death of a relative.
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| 10. |
- Adolfsson, Per, 1967-
(författare)
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Regulatory importance of cyclic nucleotides in smooth muscle growth of the urogenital tract
- 2001
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Smooth muscle hyperplasia/hypertrophy is, if not responsible for, so at least involved in those diseases, which impair life quality for most people in today's society.This thesis, presents a pharmacological investigation, related to the regulatory role of cyclic nucleotides, of smooth muscle hyperplasia/hypeitrophy in human uterine leiomyoma and benign prostate hyperplasia (BPH).Four main aspects, with cAMP as a connecting thought, have been analyzed, namely expression and characterization of the adrenergic receptors (AR), determination of adenylyl cyclase (AC)- and phosphodiesterase (PDE)-activity, and finally the connection between mentioned issues and proliferation of cultured smooth muscle cells (smc).In the frrst paper, characterization of the a 2-adrenergic receptor (az-AR) subtypes in human myometrium at term pregnancy was examined by combining radioligand binding-studies with reverse transcriptase-polymerase chain reaction (RT-PCR). Results demonstrated a significant eo-expression of α2A and α2B, and a weak indication of the α2C-AR, which however was identified at the mRNA level by the RT-PCR analysis.In the next investigatio~ smooth muscle tissue of human uterine leiomyoma (benign smooth muscle tumor) was compared with surrounding myometrial tissue (control). The expression of AR, AC- and PDE-activity was analyzed, as well as the effect of cAMP with respect to growth regulation of cultured leiomyoma smc. Primarily, a significantly reduced ß2-AR expression and AC-activity was detected in leiomyoma compared to control tissue, whereas the PDE-activity was approximately 100% higher. In addition, the α2-AR population in leiomyoma was slightly increased. When cultured leiomyoma smc was treated with cAMP increasing agents as forskolin, an AC stimulating agent, or papaverin, a general PDE inhibitor, a considerable inhibition of DNA replication and protein synthesis was obtained.In the thh·d paper, a proliferation study was made on cultured benign prostate hyperplasia smc, were the mitogen effect of lysophosphatidic acid (LPA) and cAMP/cGMP increasing agents was investigated. LPA generated a dose-dependent mitogen response, which was efficiently inhibited, both by forskolin, and by papaverin. In addition, sildenafil (Viagra®), which serve as a potent and selective PDE5 inhibitor, also decreased the LPA mediated growth promotion in a dose dependent manner.The last study, demonstrate primarily the expression pattem of LPA receptors (Edg) in BPH smc. Further, the intracellular cAMP changes in LPA stimulated BPH smc and the proliferative effect of the LPA analogue sphingosine 1-phosphate (SIP) was considered. First, all Edg was identified with exception of Edg6. Moreover, the cAMP level was unchanged by LPA per se, whereas co-incubation with forskolin generated a rapid and transient response. Further, SIP generated a divergent response including a LPA equivalent mitogen effect at low concentrations whereas inhibition of DNA replication was obtained at higher concentrations.In summary, this project demonstrates that cyclic nucleotides inhibit smooth muscle hyperplasia/hypertrophy in the luogenital tract. These results also suggest that manipulation of cyclic nucleotide level using tissue specific PDE inhibitors might constitute a new therapeutic approach for hyperplasia/hypertrophy related diseases in the urogenital tract.
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