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| 3. |
- Gondalia, Jagdish Shivlal, 1959, et al.
(författare)
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Relationships between free radical levels during carotid endarterectomy and markers of arteriosclerotic disease
- 2007
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Ingår i: Int J Med Sci. - 1449-1907. ; 14:3, s. 124-130
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Tidskriftsartikel (refereegranskat)abstract
- Background: Free radical production is elevated in jugular venous blood emerging from the brain in conjunction with carotid endarterectomy. This study explores the relationships between markers for lesion progression in arteriosclerosis, production of radicals and clinical characteristics. Methods: The radical production during carotid endarterectomy was studied in 13 patients with an ex vivo spin trap method using OXANOH as a spin trap. MCP-1, ICAM-1, MMP-9 and oxLDL were determined in venous blood samples before, during and after clamping of the carotid artery. Principal component analysis (PCA) as well as partial least square regression analysis (PLS) was applied to interpret the data. Results: PCA and PLS analysis revealed that high values of MMP-9 and low values of ICAM-1 were associated with high radical production whereas MCP-1 and oxLDL were not correlated to radical production. MMP-9 was elevated at diabetes, high haemoglobin, high leucocyte counts and thrombocyte counts as well as at contralateral stenosis, whereas ICAM-1 showed reversed relationships to these clinical variables. MCP-1 increased during surgery. Conclusions: The main finding in our study is that MMP-9 in plasma is asscociated with radical production during carotid endarterectomy, suggesting that this enzyme might be involved in the pathogenesis of brain damage in conjunction with ischaemia-reperfusion.
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| 7. |
- Lindahl, Katarina, et al.
(författare)
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Allele dependent silencing of COL1A2 using small interfering RNAs
- 2008
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Ingår i: International Journal of Medical Sciences. - 1449-1907. ; 5:6, s. 361-365
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Tidskriftsartikel (refereegranskat)abstract
- Osteogenesis imperfecta (OI) is generally caused by a dominant mutation in Collagen I, encoded by the genes COL1A1 and COL1A2. To date there is no satisfactory therapy for OI, but inactivation of the mutant allele through small interfering RNAs (siRNA) is a promising approach, as siRNAs targeting each allele of a polymorphism could be used for allele-specific silencing irrespective of the location of the actual mutations. In this study we examined the allele dependent effects of several tiled siRNAs targeting a region surrounding an exonic COL1A2 T/C polymorphism (rs1800222) in heterozygous primary human bone cells. Relative abundances of COL1A2 alleles were determined by cDNA sequencing and overall COL1A2 abundance was analyzed by quantitative PCR. One of the siRNAs decreased overall COL1A2 abundance by 71% of which 75% was due to silencing of the targeted T-allele. In conclusion, allele-preferential silencing of Collagen type I genes may be a future therapeutic approach for OI.
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| 8. |
- Lindahl, Katarina, et al.
(författare)
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Allele Dependent Silencing of Collagen Type I Using Small Interfering RNAs Targeting 3'UTR Indels : a Novel Therapeutic Approach in Osteogenesis Imperfecta
- 2013
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Ingår i: International Journal of Medical Sciences. - : Ivyspring International Publisher. - 1449-1907. ; 10:10, s. 1333-1343
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Tidskriftsartikel (refereegranskat)abstract
- Osteogenesis imperfecta, also known as "brittle bone disease", is a heterogeneous disorder of connective tissue generally caused by dominant mutations in the genes COL1A1 and COL1A2, encoding the α1 and α2 chains of type I (pro)collagen. Symptomatic patients are usually prescribed bisphosphonates, but this treatment is neither curative nor sufficient. A promising field is gene silencing through RNA interference. In this study small interfering RNAs (siRNAs) were designed to target each allele of 3'UTR insertion/deletion polymorphisms (indels) in COL1A1 (rs3840870) and COL1A2 (rs3917). For both indels, the frequency of heterozygous individuals was determined to be approximately 50% in Swedish cohorts of healthy controls as well as in patients with osteogenesis imperfecta. Cultures of primary human bone derived cells were transfected with siRNAs through magnet-assisted transfection. cDNA from transfected cells was sequenced in order to measure targeted allele/non-targeted allele ratios and the overall degree of silencing was assessed by quantitative PCR. Successful allele dependent silencing was observed, with promising results for siRNAs complementary to both the insertion and non-insertion harboring alleles. In COL1A1 cDNA the indel allele ratios were shifted from 1 to 0.09 and 0.19 for the insertion and non-insertion allele respectively while the equivalent resulting ratios for COL1A2 were 0.05 and 0.01. Reductions in mRNA abundance were also demonstrated; in cells treated with siRNAs targeting the COL1A1 alleles the average COL1A1 mRNA levels were reduced 65% and 78% compared to negative control levels and in cells treated with COL1A2 siRNAs the average COL1A2 mRNA levels were decreased 26% and 49% of those observed in the corresponding negative controls. In conclusion, allele dependent silencing of collagen type I utilizing 3'UTR indels common in the general population constitutes a promising mutation independent therapeutic approach for osteogenesis imperfecta.
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| 9. |
- Luo, Guanghua, et al.
(författare)
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Rosiglitazone Enhances Apolipoprotein M (Apom) Expression in Rat's Liver.
- 2014
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Ingår i: International Journal of Medical Sciences. - : Ivyspring International Publisher. - 1449-1907. ; 11:10, s. 1015-1021
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Tidskriftsartikel (refereegranskat)abstract
- Apolipoprotein M (APOM) has been suggested as a vasculoprotective constituent of high density lipoprotein (HDL), which plays a crucial role behind the mechanism of HDL-mediated anti-atherosclerosis. Previous studies demonstrated that insulin resistance could associate with decreased APOM expressions. In agreement with our previous reports, here, we further confirmed that the insulin sensitivity was also reduced in rats treated with high concentrations of glucose; such effect could be reversed by administration of rosiglitazone, a peroxisome proliferator-activated receptor-γ (PPARγ). The present study shows that Apom expression is significantly affected by either rosiglitazone or hyperglycemia alone without cross interaction with each other, which indicates that the pathway of Apom expression regulating by hyperglycemia might be differed from that by rosiglitazone. Further study indicated that hyperglycemia could significantly inhibit mRNA levels of Lxrb (P=0.0002), small heterodimer partner 1 (Shp1) (P<0.0001), liver receptor homologue-1 (Lrh1) (P=0.0012), ATP-binding cassette transporter 1 (Abca1) (P=0.0012) and Pparb/d (P=0.0043). Two-way ANOVA analysis demonstrated that the interactions between rosiglitazone and infusion of 25% glucose solution on Shp1 (P=0.0054) and Abca1 (4E, P=0.0004) mRNA expression was statistically significant. It is concluded that rosiglitazone could increase Apom expression, of which the detailed mechanism needs to be further investigated. The downregulation of Apom by hyperglycemia might be mainly through decreasing expression of Pparg and followed by inhibiting Lxrb in rats.
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| 10. |
- Palmblad, Jan, et al.
(författare)
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TPO, but not soluble-IL-6 receptor, levels increase after anagrelide treatment of thrombocythemia in chronic myeloproliferative disorders
- 2008
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Ingår i: International Journal of Medical Sciences. - Lake Haven : Ivyspring international publishers. - 1449-1907. ; 5:2, s. 87-91
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Tidskriftsartikel (refereegranskat)abstract
- Anagrelide is often used in the treatment of thrombocythemia in myeloproliferative disease (MPD), but information concerning effects of treatment on cytokines involved in regulation of blood platelet levels is limited. Here, we investigated serum levels of thrombopoietin (TPO) and soluble IL-6 receptor (sIL-6R) in relation to response to treatment with and plasma concentrations of anagrelide. Samples from 45 patients with thrombocythemia due to MPD (ET=31, PV=14), being treated with anagrelide for 6 months, were analyzed for TPO, sIL-6R and anagrelide levels. The mean baseline platelet count was 983x10(9)/L. A reduction of platelets to <600 in asymptomatic or <400 x 10(9)/L in symptomatic patients was defined as a complete remission (CR), a reduction with >50% of baseline as partial remission, and <50% reduction as failure. At 6 months, 35 patients were in CR, 1 had a partial remission and 9 were treatment failures. For all patients, there was an increase in TPO of 44% from baseline; this change was more pronounced for patients with partial remission and failure. sIL-6R levels did not change significantly. There was no correlation between levels of anagrelide and cytokine levels at 6 months, and changes of cytokine levels did not relate to changes of platelet counts. Thus, a pronounced increase of TPO levels after 6 months of anagrelide treatment indicated that this treatment affected a major regulatory mechanism for megakaryocyte and platelet formation in MPD.
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| 12. |
- Regula, Naresh, et al.
(författare)
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Carbon Flux as a Measure of Prostate Cancer Aggressiveness : [11C]-Acetate PET/CT
- 2020
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Ingår i: International Journal of Medical Sciences. - : Ivyspring International Publisher. - 1449-1907. ; 17:2, s. 214-223
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Dynamic [11C]-acetate positron emission tomography (PET) can be used to study tissue perfusion and carbon flux simultaneously. In this study, the feasibility of the quantification of prostate cancer aggressiveness using parametric methods assessing [11C]-acetate kinetics was investigated in prostate cancer subjects. The underlying uptake mechanism correlated with [11C]-acetate influx and efflux measured in real-time in vitro in cell culture.Methods: Twenty-one patients with newly diagnosed low-to-moderate risk prostate cancer underwent magnetic resonance imaging (MRI) and dynamic [11C]-acetate PET/CT examinations of the pelvis. Parametric images of K1 (extraction × perfusion), k2 (oxidative metabolism) and VT (=K1/k2, anabolic metabolism defined as carbon retention) were constructed using a one-tissue compartment model with an arterial input function derived from pelvic arteries. Regions of interest (ROIs) of the largest cancer lesion in each patient and normal prostate tissue were drawn using information from MRI (T2 and DWI images), biopsy results, and post-surgical histopathology of whole prostate sections (n=7). In vitro kinetics of [11C]-acetate were studied on DU145 andPC3 cell lines using LigandTracer® White equipment for the measurement of the radioactivity uptake in real-time at 37°C.Results: Mean prostate specific antigen (PSA) was 8.33±3.92 ng/mL and median Gleason Sum 6 (range 5-7). K1,VT and standardized uptake values (SUVs) were significantly higher in cancerous prostate tissues compared to normal ones for all patients (p<0.001), while k2 was not (p=0.26). PSA values correlated to early SUVs (r=0.50,p=0.02) and K1 (r=0.48, p=0.03). Early and late SUVs correlated to VT (r>0.76, p<0.001) and K1 (r>0.64,p<0.005). In vitro studies demonstrated higher extraction and retention (p<0.01) of [11C]-acetate in the more aggressive PC3 cells.Conclusion: Parametric images could be used to visualize the [11C]-acetate kinetics of the prostate cancer exhibiting elevated extraction associated with the cancer aggressiveness. The influx rate of [11C]-acetate studied in cell culture also showed dependence on the cancer aggressiveness associated with elevated lipogenesis. Dynamic [11C]-acetate/PET demonstrated potential for prostate cancer aggressiveness estimation using parametric-based K1 and VT values.
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| 13. |
- Roel, Eduardo, et al.
(författare)
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Why are some children with early onset of asthma getting better over the years? - Diagnostic failure or salutogenetic factors
- 2009
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Ingår i: International Journal of Medical Sciences. - : Ivyspring International Publisher. - 1449-1907. ; 6:6, s. 348-357
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Tidskriftsartikel (refereegranskat)abstract
- Among children earlier having been identified with a hospital or primary care diagnosis of asthma at least once between 0-7 years of age, almost 40 % of their parents reported in the ISAAC-questionnaire as never having had asthma (NA). These are further analysed and compared with the persisting asthma cases (A) in this study. All these childrens medical records were scrutinized concerning their asthma diagnose retrospectively. The aim of this study was to analyse possible factors related to the outcome in an Asthma diagnosis reassessment by parental questionnaire at the age of ten of the children earlier having been identified with a hospital or primary health care diagnosis of asthma at least once between 0-7 years of age in a total birth-year cohort in a defined Swedish geographical area. A multiple logistic analysis revealed four significant and independent factors associated to the improvement/non-report of asthma at the age of ten. These factors were; not having any past experiences of allergic symptoms (pless than0.0001), only having one or two visits at the hospital for asthma diagnosis in the 0-7 interval (p=0.001), not living in a flat but a villa at the age of ten (p=0.029) and no previous perception of mist or mould damage in the house (p=0.052). In the early postnatal stage, obstructive and bronchospastic symptoms typical of asthma may be unspecific, and those cases not continuing to persisting disease tend to have identifiable salutogenetic factors of constitutional rather than environmental nature, namely, an overall reduced allergic predisposition.
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| 14. |
- Sahdo, Berolla, 1984-, et al.
(författare)
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Body temperature during hibernation is highly correlated with a decrease in circulating innate immune cells in the brown bear (Ursus arctos) : a common feature among hibernators?
- 2013
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Ingår i: International Journal of Medical Sciences. - Sydney, Australia : Ivyspring International Publisher. - 1449-1907. ; 10:5, s. 508-514
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Tidskriftsartikel (refereegranskat)abstract
- Background: Hibernation involves periods of severely depressed metabolism (torpor) and decreases in body temperature (Tb). Small arctic mammals (<5kg), in which Tb generally drop drastically, display leukopenia during hibernation. This raised the question of whether the decreased leukocyte counts in mammalian hibernators is due to torpor per se or is secondary to low Tb. The present study examined immune cell counts in brown bears (Ursus arctos), where torpor is only associated with shallow decreases in Tb. The results were compared across hibernator species for which immune and Tb data were available.Methods and Results: The white blood cell counts were determined by flow cytometry in 13 bears captured in the field both during summer and winter over 2 years time. Tb dropped from 39.6+/-0.8 to 33.5+/-1.1 degrees C during hibernation. Blood neutrophils and monocytes were lower during hibernation than during the active period (47%, p=0.001; 43%, p=0.039, respectively), whereas no change in lymphocyte counts was detected (p=0.599). Further, combining our data and those from 10 studies on 9 hibernating species suggested that the decline in Tb explained the decrease in innate immune cells (R-2=0.83, p<0.0001).Conclusions: Bears have fewer innate immune cells in circulation during hibernation, which may represent a suppressed innate immune system. Across species comparison suggests that, both in small and large hibernators, Tb is the main driver of immune function regulation during winter dormancy. The lack of a difference in lymphocyte counts in this context requires further investigations.
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| 15. |
- Silins, Isabella, 1983-, et al.
(författare)
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Para-chloro-2-[18F]fluoroethyl-etomidate : A promising new PET radiotracer for adrenocortical imaging
- 2021
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Ingår i: International Journal of Medical Sciences. - : Ivyspring International Publisher. - 1449-1907. ; 18:10, s. 2187-2196
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: [11C]Metomidate ([11C]MTO), the methyl ester analogue of etomidate, was developed as a positron emission tomography (PET) radiotracer for adrenocortical tumours and has also been suggested for imaging in primary aldosteronism (PA). A disadvantage of [11C]MTO is the rather high non-specific binding in the liver, which impacts both visualization and quantification of the uptake in the right adrenal gland. Furthermore, the short 20-minute half-life of carbon-11 is a logistic challenge in the clinical setting.Objectives: The aim of this study was to further evaluate the previously published fluorine-18 (T1/2=109.5 min) etomidate analogue, para-chloro-2-[18F]fluoroethyl etomidate; [18F]CETO, as an adrenal PET tracer.Methods: In vitro experiments included autoradiography on human and cynomolgus monkey (non-human primate, NHP) tissues and binding studies on adrenal tissue from NHPs. In vivo studies with [18F]CETO in mice, rats and NHP, using PET and CT/MRI, assessed biodistribution and binding specificity in comparison to [11C]MTO.Results: The binding of [18F]CETO in the normal adrenal cortex, as well as in human adrenocortical adenomas and adrenocortical carcinomas, was shown to be specific, both in vitro (in humans) and in vivo (in rats and NHP) with an in vitro Kd of 0.66 nM. Non-specific uptake of [18F]CETO in NHP liver was found to be low compared to that of [11C]MTO.Conclusions: High specificity of [18F]CETO to the adrenal cortex was demonstrated, with in vivo binding properties qualitatively surpassing those of [11C]MTO. Non-specific binding to the liver was significantly lower than that of [11C]MTO. [18F]CETO is a promising new PET tracer for imaging of adrenocortical disease and should be evaluated further in humans.
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| 16. |
- Taradaj, Jakub, et al.
(författare)
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Effect of laser therapy on expression of angio- and fibrogenic factors, and cytokine concentrations during the healing process of human pressure ulcers
- 2018
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Ingår i: International Journal of Medical Sciences. - : Ivyspring International Publisher. - 1449-1907. ; 15:11, s. 1105-1112
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To evaluate the effect of laser irradiation at different wavelengths on the expression of selected growth factors and inflammatory mediators at particular stages of the wound healing process. Methods: Sixty-seven patients were recruited, treated, and analyzed (group A - 940 nm: 17 patients; group B - 808 nm: 18 patients; group C - 658 nm: 16 patients; group D - sham therapy: 17 patients). Patients received a basic treatment, including repositioning and mobilization, air pressure mattress and bed support surfaces, wound cleansing and drug therapy. Additionally, patients received laser therapy once a day, 5 times a week for 1 month in use of a semiconductor lasers (GaAlAs) which emitted a continuous radiation emission at separate wavelengths of 940 nm (group A), 808 nm (group B) and 658 nm (group C). In group D (sham therapy), laser therapy was applied in the same manner, but the device was off during each session (only the applicator was switched on to scan pressure ulcers using none coherent red visible light). Results: The positive changes in the measured serum (IL-2, IL-6 and TNF-α) and wound tissue (TNF-α, VEGF and TGFβ1) parameters appeared to be connected only with the wavelength of 658 nm. The significant change in pro-inflammatory mediator levels [interleukin 2 (IL-2) with p=0.008 and interleukin 6 (IL-6) with p=0.016] was noticed after two weeks of laser therapy. In the other groups, the inflammation was also reduced, but the process was not as marked as in group C. Similarly, in the case of tumor necrosis factor (TNF-α) concentration, where after two weeks of treatment with irradiation at a wavelength of 658 nm, a rapid suppression was observed (p=0.001), whereas in the other groups, these results were much slower and not as obvious. Interestingly, again in the case of group C, the change in TNF-α concentration in wound tissue was most intensive (≈75% reduction), whereas the changes in other groups were not as obvious (≈50% reduction). After irradiation (658 nm), the VEGF expression increased significantly within the first two weeks, and then it decreased and maintained a stable level. In contrast, the TGFβ1 activity remained level, but always higher in comparison to other groups Conclusions: The effective healing of pressure ulcers is connected with laser irradiation at a wavelength of 658 nm. We believe that this effect is related to the inhibition of inflammatory processes in the wound and stimulation of angiogenesis and fibroblast proliferation at this specific radiation (based both on concentration of interleukins and TNF-α serum level and VEGF, TGFβ1, TNF-α activities in wound biopsies). Laser therapy at wavelengths of 940 and 808 nm does not significantly affect the above-mentioned repair processes, which explains its low effectiveness in the treatment of pressure ulcers.
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| 17. |
- Zheng, Lu, et al.
(författare)
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Decreased activities of apolipoprotein m promoter are associated with the susceptibility to coronary artery diseases.
- 2014
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Ingår i: International Journal of Medical Sciences. - : Ivyspring International Publisher. - 1449-1907. ; 11:4, s. 365-372
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Tidskriftsartikel (refereegranskat)abstract
- The present study investigated the correlation among genetic polymorphisms of the proximal promoter region of apolipoprotein M (apoM) gene, the polymorphisms in relation to apoM expressions and the susceptibility to coronary artery diseases (CAD) in a Han Chinese population. Four common polymorphic sites, i.e., T-1628G, C-1065A, T-855C and T-778C, were confirmed, and a new deletion mutation C-724del was found, in 206 CAD patients and 209 non-CAD patients using direct DNA sequencing analyses. Occurrences of alleles T-1628G, T-855C and C-724del were significantly higher in CAD patients compared to non-CAD patients. Moreover we examined all these polymorphisms in relation to apoM expression by applying luciferase reporter assay. It demonstrated that constructs -855C and 724del showed obvious decreased luciferase activities, i.e., (0.93±0.15 vs. 2.11±0.15; P=0.012) and (1.13±0.25 vs. 2.11±0.15; P=0.009) respectively, which indicates these two polymorphisms could confer decreased apoM expressions. Meanwhile the occurrences of these two SNP were also significantly higher in the CAD patients than in non-CAD patients. It is therefore reasonable to speculate that down-regulated apoM expressions in relation to these polymorphisms may affect HDL and cholesterol metabolism in vivo and further influence the susceptibility to CAD, although the underlying mechanisms need further investigation.
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| 18. |
- Åkerberg, Daniel, et al.
(författare)
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Prevention of pleural adhesions by bioactive polypeptides - a pilot study.
- 2013
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Ingår i: International Journal of Medical Sciences. - : Ivyspring International Publisher. - 1449-1907. ; 10:12, s. 1720-1726
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Postoperative pleural adhesions lead to major problems in repeated thoracic surgery. To date, no antiadhesive product has been proven clinically effective. Previous studies of differently charged polypeptides, poly-L-lysine (PL) and poly-L-glutamate (PG) have shown promising results reducing postoperative abdominal adhesions in experimental settings. This pilot study examined the possible pleural adhesion prevention by using the PL+PG concept after pleural surgery and its possible effect on key parameters; plasmin activator inhibitor-1 (PAI-1) and tissue growth factor beta 1 (TGFb) in the fibrinolytic process. Methods: A total of 22 male rats were used in the study, one control group (n=10) and one experimental group (n=12). All animals underwent primary pleural surgery, the controls receiving saline in the pleural cavity and the experimental group the PL+PG solution administered by spray. The animals were evaluated on day 7. Macroscopic appearance of adhesions was evaluated by a scoring system. Histology slides of the adhesions and pleural biopsies for evaluation of PAI-1 and TGFb1 were taken on day 7. Results: A significant reduction of adhesions in the PL+PG group (p<0.05) was noted at day 7 both regarding the length and severity of adhesions. There were no significant differences in the concentration of PAI-1 and TGFb1 when comparing the two groups. Conclusions: PL+PG may be used to prevent pleural adhesions. The process of fibrinolysis, and fibrosis was though not affected after PLPG administration.
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