| 1. |
- Villa, Luisa L., et al.
(författare)
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Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions
- 2007
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 356:19, s. 1915-1927
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Human papillomavirus types 16 (HPV-16) and 18 (HPV-18) cause approximately 70% of cervical cancers worldwide. A phase 3 trial was conducted to evaluate a quadrivalent vaccine against HPV types 6, 11, 16, and 18 (HPV-6/11/16/18) for the prevention of high-grade cervical lesions associated with HPV-16 and HPV-18. METHODS: In this randomized, double-blind trial, we assigned 12,167 women between the ages of 15 and 26 years to receive three doses of either HPV-6/11/16/18 vaccine or placebo, administered at day 1, month 2, and month 6. The primary analysis was performed for a per-protocol susceptible population that included 5305 women in the vaccine group and 5260 in the placebo group who had no virologic evidence of infection with HPV-16 or HPV-18 through 1 month after the third dose (month 7). The primary composite end point was cervical intraepithelial neoplasia grade 2 or 3, adenocarcinoma in situ, or cervical cancer related to HPV-16 or HPV-18. RESULTS: Subjects were followed for an average of 3 years after receiving the first dose of vaccine or placebo. Vaccine efficacy for the prevention of the primary composite end point was 98% (95.89% confidence interval [CI], 86 to 100) in the per-protocol susceptible population and 44% (95% CI, 26 to 58) in an intention-to-treat population of all women who had undergone randomization (those with or without previous infection). The estimated vaccine efficacy against all high-grade cervical lesions, regardless of causal HPV type, in this intention-to-treat population was 17% (95% CI, 1 to 31). CONCLUSIONS: In young women who had not been previously infected with HPV-16 or HPV-18, those in the vaccine group had a significantly lower occurrence of high-grade cervical intraepithelial neoplasia related to HPV-16 or HPV-18 than did those in the placebo group.
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| 2. |
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| 3. |
- Kjaer, Susanne K., et al.
(författare)
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A Pooled Analysis of Continued Prophylactic Efficacy of Quadrivalent Human Papillomavirus (Types 6/11/16/18) Vaccine against High-grade Cervical and External Genital Lesions
- 2009
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Ingår i: Cancer Prevention Research. - 1940-6207. ; 2:10, s. 868-878
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Tidskriftsartikel (refereegranskat)abstract
- Quadrivalent human papillomavirus (HPV) vaccine has been shown to provide protection from HPV 6/11/16/18-related cervical, vaginal, and vulvar disease through 3 years. We provide an update on the efficacy of the quadrivalent HPV vaccine against high-grade cervical, vaginal, and vulvar lesions based on end-of-study data from three clinical trials. Additionally, we stratify vaccine efficacy by several baseline characteristics, including age, smoking status, and Papanicolaou (Pap) test results. A total of 18,174 females ages 16 to 26 years were randomized and allocated into one of three clinical trials (protocols 007, 013, and 015). Vaccine or placebo was given at baseline, month 2, and month 6. Pap testing was conducted at regular intervals. Cervical and anogenital swabs were collected for HPV DNA testing. Examination for the presence of vulvar and vaginal lesions was also done. Endpoints included high-grade cervical, vulvar, or vaginal lesions (CIN 2/3, VIN 2/3, or VaIN 2/3). Mean follow-up time was 42 months post dose 1. Vaccine efficacy against HPV 6/11/16/18-related high-grade cervical lesions in the per-protocol and intention-to-treat populations was 98.2% [95% confidence interval (95% CI), 93.3-99.8] and 51.5% (95% CI, 40.6-60.6), respectively. Vaccine efficacy against HPV 6/11/16/18-related high-grade vulvar and vaginal lesions in the per-protocol and intention-to-treat populations was 100.0% (95% CI, 82.6-100.0) and 79.0% (95% CI, 56.4-91.0), respectively. Efficacy in the intention-to-treat population tended to be lower in older women, women with more partners, and women with abnormal Pap test results. The efficacy of quadrivalent HPV vaccine against high-grade cervical and external anogenital neoplasia remains high through 42 months post vaccination.
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| 4. |
- Olsson, Sven-Eric, et al.
(författare)
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Evaluation of quadrivalent HPV 6/11/16/18 vaccine efficacy against cervical and anogenital disease in subjects with serological evidence of prior vaccine type HPV infection
- 2009
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Ingår i: Human Vaccines. - 1554-8600. ; 5:10, s. 696-704
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Tidskriftsartikel (refereegranskat)abstract
- Objective: In the quadrivalent (types 6/11/16/18) HPV vaccine (GARDASIL (R)/SILGARD (R)) clinical program, 73% of women aged 16-26 were naive to all vaccine HPV types. In these women, prophylactic administration of the vaccine was highly effective in preventing HPV 6/11/16/18-related cervical disease. Of the remaining women, 15% of had evidence of past infection with one or more vaccine HPV types (seropositive and DNA negative) at the time of enrollment. Here we present an analysis in this group of women to determine the efficacy of the HPV 6/11/16/18 vaccine against new cervical and external anogenital disease related to the same vaccine HPV type which had previously been cleared. Vaccine tolerability in this previously infected population was also assessed. Results: Subjects were followed for an average of 40 months. Seven subjects in the placebo group developed cervical disease, and eight subjects developed external genital disease related to a vaccine HPV type they had previously encountered. No subject receiving HPV 6/11/16/18 vaccine developed disease to a vaccine HPV type to which they were seropositive and DNA negative at enrollment. Methods: 18,174 women were enrolled into three clinical studies. The data presented comprise a subset of these subjects (n = 2,617) who were HPV seropositive and DNA negative at enrollment (for >= 1 vaccine type). In each study, subjects were randomized in a 1:1 ratio to receive HPV 6/11/16/18 vaccine or placebo at day 1, month 2 and month 6 (without knowledge of baseline HPV status). Procedures performed for efficacy data evaluation included detailed genital examination, Pap testing and collection of cervicovaginal and external genital specimens. Analyses of efficacy were carried out in a population stratified by HPV serology and HPV DNA status at enrollment. Conclusions: These results suggest that natural HPV infection-elicited antibodies may not provide complete protection over time, however the immune response to the HPV 6/11/16/18 vaccine appears to prevent reinfection or reactivation of disease with vaccine HPV types. Vaccine-related adverse experiences were higher among subjects receiving vaccine, mostly due to increased injection site adverse experiences.
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| 5. |
- Brown, Darron R., et al.
(författare)
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The Impact of Quadrivalent Human Papillomavirus (HPV; Types 6, 11, 16, and 18) L1 Virus-Like Particle Vaccine on Infection and Disease Due to Oncogenic Nonvaccine HPV Types in Generally HPV-Naive Women Aged 16-26 Years
- 2009
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Ingår i: Journal Of Infectious Diseases. - : Oxford University Press (OUP). - 0022-1899 .- 1537-6613. ; 199:7, s. 926-935
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Konferensbidrag (refereegranskat)abstract
- Background. Human papillomavirus (HPV)-6/11/16/18 vaccine reduces the risk of HPV-6/11/16/18-related cervical intraepithelial neoplasia (CIN) 1-3 or adenocarcinoma in situ (AIS). Here, its impact on CIN1-3/AIS associated with nonvaccine oncogenic HPV types was evaluated. Methods. We enrolled 17,622 women aged 16-26 years. All underwent cervicovaginal sampling and Pap testing at regular intervals for up to 4 years. HPV genotying was performed for biopsy samples, and histological diagnoses were determined by a pathology panel. Analyses were conducted among subjects who were negative for 14 HPV types on day 1. Prespecified analyses included infection of >= 6 months' duration and CIN1-3/AIS due to the 2 and 5 most common HPV types in cervical cancer after HPV types 16 and 18, as well as all tested nonvaccine types. Results. Vaccination reduced the incidence of HPV-31/45 infection by 40.3% (95% confidence interval [CI], 13.9% to 59.0%) and of CIN1-3/AIS by 43.6% (95% CI, 12.9% to 64.1%), respectively. The reduction in HPV-31/33/45/52/58 infection and CIN1-3/AIS was 25.0% (95% CI, 5.0% to 40.9%) and 29.2% (95% CI, 8.3% to 45.5%), respectively. Efficacy for CIN2-3/AIS associated with the 10 nonvaccine HPV types was 32.5% (95% CI, 6.0% to 51.9%). Reductions were most notable for HPV-31. Conclusions. HPV-6/11/16/18 vaccine reduced the risk of CIN2-3/AIS associated with nonvaccine types responsible for similar to 20% of cervical cancers. The clinical benefit of cross-protection is not expected to be fully additive to the efficacy already observed against HPV-6/11/16/18-related disease, because women may have >1 CIN lesion, each associated with a different HPV type.
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| 6. |
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| 7. |
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| 8. |
- Paavonen, J, et al.
(författare)
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Baseline demographic characteristics of subjects enrolled in international quadrivalent HPV (types 6/11/16/18) vaccine clinical trials
- 2008
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Ingår i: Current Medical Research and Opinion. - : Informa Healthcare. - 1473-4877 .- 0300-7995. ; 24:6, s. 1623-1634
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In Phase II/III trials, administration of quadrivalent human papillomavirus (HPV) (types 6/11/16/18) L1 virus-like-particle vaccine was highly effective in preventing HPV6/11/16/18-related cervical intraepithelial neoplasia and non-invasive cervical cancer in women aged 16-26 years who were naïve to these HPV types at enrollment. However, the makeup and extent of catch-up vaccination programs among young women is unclear, because a proportion of this population will likely already have been exposed to one or more vaccine-HPV-types. OBJECTIVE: Herein we analyze baseline data from the quadrivalent HPV vaccine clinical trial program to investigate variables which may help shape catch-up vaccine implementation policies. METHODS: Female adolescents and young adults aged 16-26 years were randomized into five clinical trials. Baseline data regarding demographics, sexual history, pregnancy history, and other characteristics were collected at enrollment. At the baseline gynecological examination during enrollment, specimens were obtained for Pap testing. Swabs of external genital, lateral vaginal, and cervical sites for HPV polymerase chain reaction (PCR) testing were taken, and serum samples were obtained for HPV serology testing. Regional analyses of data were conducted. RESULTS: Overall, 72% of subjects enrolled worldwide were naïve by both serology and PCR to all four vaccine HPV types. Few subjects were seropositive and/or PCR positive for more than two vaccine-related HPV types. Of all subjects with HSIL at enrollment, 78% were positive to at least one vaccine-related HPV type at enrollment. Regional differences in HPV and STD prevalence were evident. Study limitations included under-representation of women with >/=4 sexual partners and possible underestimation of prior HPV exposure. CONCLUSIONS: Our findings demonstrate that sexually active 16-26 year-old women with
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| 9. |
- Villa, L., et al.
(författare)
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Effect of prophylactic human papillomavirus L1 virus-like-particle vaccine on risk of cervical intraepithelial neoplasia grade 2, grade 3, and adenocarcinoma in situ: a combined analysis of four randomised clinical trials
- 2007
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Ingår i: The Lancet. - 1474-547X. ; 369:9576, s. 1861-1868
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Tidskriftsartikel (refereegranskat)abstract
- Background Cervical cancer and its obligate precursors, cervical intraepithelial neoplasia grades 2 and 3 (CIN2/3), and adenocarcinona in situ (AIS), are caused by oncogenic human papillomavirus (HPV). In this combined analysis of four clinical trials we assessed the effect of prophylactic HPV vaccination on these diseases. Methods 20 583 women aged 16-26 years were randomised to receive quadrivalent HPV6/11/16/18 vaccine (n=9087), its HPV16 vaccine component (n=1204), or placebo (n=10292). They underwent periodic Papanicolaou testing, with colposcopy or biopsy for detected abnormalities. The primary composite endpoint was the combined incidence of HPV16/18-related CIN2/3, AIS, or cervical cancer. These trials are registered at ClinicalTrials.gov, numbers NCT00365378, NCT00365716, NCT00092521, and NCT00092534. Findings Mean follow-up was 3.0 years (SD 0.66) after first dose. In women negative for HPV16 or HPV18 infection during the vaccination regimen (n=17129, per protocol), vaccine efficacy was 99% for the primary endpoint (95% Cl 93-100), meeting the statistical criterion for success. In an intention-to-treat analysis of all randomised women (including those who were HPV16/18 naive or HPV16/18-infected at day 1), efficacy was 44% (95% Cl 31-55); all but one case in vaccine recipients occurred in women infected with HPV16 or HPV18 before vaccination. In a second intention-to-treat analysis we noted an 18% reduction (95% CI 7-29) in the overall rate of CIN2/3 or AIS due to any HPV type. Interpretation Administration of HPV vaccine to HPV-naive women, and women who are already sexually active, could substantially reduce the incidence of HPV16/18-related cervical precancers and cervical cancer.
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| 10. |
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| 11. |
- Wheeler, Cosette M., et al.
(författare)
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The Impact of Quadrivalent Human Papillomavirus (HPV; Types 6, 11, 16, and 18) L1 Virus-Like Particle Vaccine on Infection and Disease Due to Oncogenic Nonvaccine HPV Types in Sexually Active Women Aged 16-26 Years
- 2009
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Ingår i: Journal Of Infectious Diseases. - : Oxford University Press (OUP). - 0022-1899 .- 1537-6613. ; 199:7, s. 936-944
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Konferensbidrag (refereegranskat)abstract
- Background. We evaluated the impact of a quadrivalent human papillomavirus (HPV) vaccine on infection and cervical disease related to 10 nonvaccine HPV types (31, 33, 35, 39, 45, 51, 52, 56, 58, and 59) associated with >20% of cervical cancers. The population evaluated included HPV-naive women and women with preexisting HPV infection and/or HPV-related disease at enrollment. Methods. Phase 3 efficacy studies enrolled 17,622 women aged 16-26 years. Subjects underwent cervicovaginal sampling and Pap testing on day 1 and then at 6-12-month intervals for up to 4 years. HPV typing was performed on samples from enrollment and follow-up visits, including samples obtained for diagnosis or treatment of HPV-related disease. All subjects who received >= 1 dose and returned for follow-up were included. Results. Vaccination reduced the rate of HPV-31/33/45/52/58 infection by 17.7% (95% confidence interval [CI], 5.1% to 28.7%) and of cervical intraepithelial neoplasia (CIN) 1-3 or adenocarcinoma in situ (AIS) by 18.8% (95% CI, 7.4% to 28.9%). Vaccination also reduced the rate of HPV-31/58/59-related CIN1-3/AIS by 26.0% (95% CI, 6.7% to 41.4%), 28.1% (95% CI, 5.3% to 45.6%), and 37.6% (95% CI, 6.0% to 59.1%), respectively. Although a modest reduction in HPV-31/33/45/52/58-related CIN2 or worse was observed, the estimated reduction was not statistically significant. Conclusions. These cross-protection results complement the vaccine's prophylactic efficacy against disease associated with HPV-6, -11, -16, and - 18. Long-term monitoring of vaccinated populations are needed to fully ascertain the population-based impact and public health significance of these findings.
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| 12. |
- Zander, PO, et al.
(författare)
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Toward a Value Theory of the Interface
- 2006
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Ingår i: DHRS 2006. Proceedings of the Sixth Danish Human-Computer Interaction Research Symposium.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 13. |
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| 14. |
- Majewski, S., et al.
(författare)
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The impact of a quadrivalent human papillomavirus (types 6, 11, 16, 18) virus-like particle vaccine in European women aged 16 to 24
- 2009
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Ingår i: Journal of the European Academy of Dermatology and Venereology. - : Wiley. - 1468-3083 .- 0926-9959. ; 23:10, s. 1147-1155
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Tidskriftsartikel (refereegranskat)abstract
- Background Quadrivalent human papillomavirus (HPV types 6/11/16/18) L1 VLP vaccine is highly effective in preventing HPV 6/11/16/18-related cervical and external genital disease. Herein, we evaluated the impact of the quadrivalent HPV 6/11/16/18 L1 VLP vaccine on prevention of HPV-associated cervico-genital lesions in a broad population of sexually active European women. Methods Female subjects (N = 9265) aged 16-24 with four or fewer lifetime sexual partners were enrolled and randomized to quadrivalent HPV vaccine or placebo. Subjects underwent cervicovaginal sampling for HPV DNA detection. Papanicolaou testing and anti-HPV 6/11/16/18 serology testing was also performed. Results Vaccine efficacy against lesions representing immediate cervical cancer precursors (cervical intraepithelial neoplasia grade 2/3 or adenocarcinoma in situ) related to HPV 6/11/16/18 in the per-protocol population was 100.0%[95% confidence interval (95% CI), 89.8-100.0]. Efficacy against external genital lesions (vulvar or vaginal intraepithelial neoplasia, condyloma, vulvar or vaginal cancer) related to vaccine HPV types in the per-protocol European population was 99.0% (95% CI, 94.4-100.0). Conclusion These data demonstrate that quadrivalent HPV 6/11/16/18 vaccination programs in 16- to 24-year-old European women can be beneficial. NCT0009252, NCT00092534, NCT00092495.
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| 15. |
- Smebye, M. L., et al.
(författare)
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Effect of hemoglobin levels on cardiovascular outcomes in patients with isolated systolic hypertension and left ventricular hypertrophy (from the LIFE study)
- 2007
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Ingår i: Am J Cardiol. - : Elsevier BV. - 0002-9149. ; 100:5, s. 855-9
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Tidskriftsartikel (refereegranskat)abstract
- The optimal hemoglobin level in patients with hypertension or heart failure is not yet defined. The aim of the present investigation was to examine the relation of hemoglobin with cardiovascular outcomes in high-risk patients with isolated systolic hypertension (ISH) and left ventricular hypertrophy (LVH). In 1,326 patients with ISH in the Losartan Intervention For Endpoint Reduction in Hypertension (LIFE) study, hemoglobin and cardiovascular outcomes were examined using Cox proportional hazard models. Baseline hemoglobin was negatively related to rate of cardiovascular death (hazard ratio 0.81 per 1 g/dl, 95% confidence interval [CI] 0.67 to 0.98, p = 0.032) after adjusting for baseline Framingham risk score, LVH, treatment, and estimated glomerular filtration rate. Hemoglobin decreased slightly during the study and the decrease was more pronounced in the losartan group (13.9 +/- 1.3 to 13.6 +/- 1.4 g/dl) than in the atenolol group (13.9 +/- 1.2 to 13.8 +/- 1.4 g/dl). Hemoglobin as a time-varying covariate was negatively associated with rate of cardiovascular death (hazard ratio 0.75, 95% CI 0.63 to 0.90, p <0.001) and stroke (hazard ratio 0.84, 95% CI 0.72 to 0.99, p = 0.040) after adjusting for baseline Framingham risk score, LVH, treatment, and estimated glomerular filtration rate. In conclusion, in this high-risk population with ISH and LVH, lower hemoglobin at baseline was associated with higher probability of cardiovascular death, and decrease in hemoglobin over time was associated with higher probability of cardiovascular death or stroke; this effect was attenuated by treatment with losartan.
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| 16. |
- Stiewe, C, et al.
(författare)
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Nanostructured Co1-xNix(Sb1-yTey)(3) skutterudites : Theoretical modeling, synthesis and thermoelectric properties
- 2005
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Ingår i: Journal of Applied Physics. - : AIP Publishing. - 0021-8979 .- 1089-7550. ; 97:4
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Tidskriftsartikel (refereegranskat)abstract
- The properties of Te-doped Co(Sb1-yTey)(3) and Te-Ni double-doped Co1-xNix(Sb1-yTey)(3) nanostructured skutterudites were evaluated by means of x-ray powder diffraction, and transport properties measured on the synthesized samples have been compared with ab initio theoretical modeling. Theoretical optimal dopant contents have been evaluated according to the maximum value of the power factor, calculating the electronic transport properties from the ab initio material band structure using semiclassical Boltzmann transport theory. The samples have been synthesized by chemical alloying with Te substitution for Sb up to 2.5 at. % and Ni substitution for Co up to 2.0 at. %. X-ray powder diffraction has been performed on all samples to reveal information about phase purity and Rietveld refinement was performed for the phase composition and cell parameter. The thermoelectric properties of the resulting consolidates were investigated in a temperature range from 300 to 723 K using various measurement facilities. A standardization and round robin program was started among the participating evaluation laboratories in order to ensure reliability of the data obtained. The significant reduction in thermal conductivity, when compared to highly annealed CoSb3, could be proved which is caused by the nanostructuring, resulting in a high concentration of grain boundaries. A combination of substitution levels for Ni and Te has been found resulting in the largest ZT value of 0.65 at 680 K among unfilled skutterudite materials.
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| 17. |
- Bivol, Liliana Monica, et al.
(författare)
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Tetradecylthioacetic acid downregulates cyclooxygenase 2 in the renal cortex of two-kidney, one-clip hypertensive rats.
- 2008
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Ingår i: American Journal of Physiology. Regulatory Integrative and Comparative Physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 295:6, s. R1866-73
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Tidskriftsartikel (refereegranskat)abstract
- The effect of tetradecylthioacetic acid (TTA) on the cyclooxygenase (COX) system was investigated in two-kidney, one-clip (2K1C) hypertensive rats. The systolic blood pressure (BP) was increased 6 wk after clipping to 183 +/- 4 vs.127 +/- 3 mmHg in TTA-treated 2K1C rats. The COX1 protein expression was not affected either by the 2K1C procedure or by TTA treatment. COX2 expression was upregulated in both kidneys, but to a greater extent in the clipped kidney. COX2 activity was 16 +/- 3% in control and 38 +/- 2% (P < 0.001) in the clipped kidney, and COX2 protein expression was 1.3 +/- 0.04 in control and 1.6 +/- 0.12 in the clipped kidney (P = 0.006). TTA reduced COX2 activity to control levels. Subcutaneously infusion of a COX2 inhibitor did not reduce BP. Peroxisome proliferator-activated receptors (PPARs) were detected in both kidneys, and PPARdelta was upregulated in the nonclipped kidney after TTA treatment. PGE2 in renal cortex was increased in 2K1C (31 +/- 0.3 in the clipped and 28 +/- 0.2 pg/ml nonclipped kidney, P < 0.001 compared with control). TTA lowered the PGE2 to control levels. Renal blood flow (RBF) response to exogenous ANG II injected in the control and nonclipped kidney was exaggerated after indomethacin treatment but unchanged in the nonclipped kidney of the K1C TTA group. Overall, these results indicate that, after 6 wk of treatment, TTA downregulated the COX2 activity, which have potentially important effects on the regulation of renal hemodynamics but does not explain TTAs ability to lower BP.
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| 18. |
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| 19. |
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| 20. |
- Gudbrandsen, Oddrun Anita, et al.
(författare)
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Prevention of hypertension and organ damage in 2-kidney, 1-clip rats by tetradecylthioacetic acid.
- 2006
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Ingår i: Hypertension. - 0194-911X .- 1524-4563. ; 48:3, s. 460-6
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Tidskriftsartikel (refereegranskat)abstract
- Dietary lipids are reported to affect the blood pressure in both humans and experimental animal models with hypertension. In the present study, 2-kidney, 1-clip (2K1C) hypertensive rats were treated with the modified fatty acid tetradecylthioacetic acid (TTA) from the time of clipping or after hypertension was established. TTA treatment attenuated the development of hypertension and reduced established 2K1C hypertension. The mRNA level of renin in the clipped kidney and the plasma renin activity were markedly reduced, and the plasma angiotensin II level tended to decrease after TTA treatment. In addition, TTA reduced the mRNA level of angiotensinogen in white adipose tissue. Prevention of organ damage was demonstrated by normal urinary excretion of protein, maintained serum albumin, lower heart weight, and clearly reduced vascular, glomerular, and tubulointerstitial damage in the nonclipped kidney. Renal function was not affected as estimated by unchanged plasma creatinine. Furthermore, the serum levels of triacylglycerol and cholesterol were reduced by TTA. The serum fatty acid composition was changed, resulting in a favorable increase of oleic acid. However, the levels of all of the omega-3 fatty acids and of linoleic acid were reduced, and no change was seen in the level of arachidonic acid, but the urinary excretion of 8-iso-prostaglandin F2alpha was declined. In conclusion, TTA attenuated the development of hypertension, reduced established hypertension, and prevented the development of organ damage in 2K1C rats, possibly by reducing the amounts of the vasoconstrictors angiotensin II and 8-iso-prostaglandin F2alpha and by inducing a favorable increase of oleic acid in serum.
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| 21. |
- Gustavsson, M. T., et al.
(författare)
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Modification of cellulose fiber surfaces by use of a lipase and a xyloglucan endotransglycosylase
- 2005
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Ingår i: Biomacromolecules. - : American Chemical Society (ACS). - 1525-7797 .- 1526-4602. ; 6:1, s. 196-203
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Tidskriftsartikel (refereegranskat)abstract
- A strategy for the modification of cellulose fiber surfaces was developed that used the ability of Candida antarctica lipase B (CALB) to acylate carbohydrates with high regioselectivity, combined with the transglycosylating activity of the Populus tremula x P. tremuloides xyloglucan endotransglycosylase 16A (PttXET16A). Xyloglucan oligosaccharides (XGOs) prepared from tamarind xyloglucan were acylated with CALB as a catalyst and vinyl stearate or gamma-thiobutyrolactone as acyl donors to produce carbohydrate molecules with hydrophobic alkyl chains or reactive sulfhydryl groups, respectively. The modified XGOs were shown to act as glycosyl acceptors in the transglycosylation reaction catalyzed by PttXET16A and could therefore be incorporated into high M-r xyloglucan chains. The resulting xyloglucan molecules exhibited a high affinity for cellulose surfaces, which enabled the essentially irreversible introduction of fatty acid esters or thiol groups to cellulose fibers.
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| 22. |
- Hultström, Michael, et al.
(författare)
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AT(1) receptor activation regulates the mRNA expression of CAT1, CAT2, arginase-1, and DDAH2 in preglomerular vessels from angiotensin II hypertensive rats.
- 2009
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Ingår i: American Journal of Physiology - Renal Physiology. - : American Physiological Society. - 0363-6127 .- 1522-1466 .- 1931-857X. ; 297:1, s. F163-8
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Tidskriftsartikel (refereegranskat)abstract
- Previously, we found increased expression of l-arginine metabolizing enzymes in both kidneys from two-kidney, one-clip (2K1C) hypertensive rats (Helle F, Hultstrom M, Skogstrand T, Palm F, Iversen BM. Am J Physiol Renal Physiol 296: F78-F86, 2009). In the present study, we investigate whether AT(1) receptor activation can induce the changes observed in 2K1C. Four groups of rats were infused with 80 ng/min ANG II or saline for 14 days and/or given 60 mg x kg(-1) x day(-1) losartan. Gene expression was studied in isolated preglomerular vessels by RT-PCR. Dose-responses to ANG II were studied in isolated preglomerular vessels with and without acute NOS inhibition [10(-4) mol/l N(G)-nitro-l-arginine methyl ester (l-NAME)]. Expressions of endothelial nitric oxide synthase (eNOS), caveolin-1, and arginase-2 were not changed by ANG II infusion. CAT1 (0.3 8 +/- 0.07 to 0.73 +/- 0.12, P < 0.05), CAT2 (1.14 +/- 0.29 to 2.74 +/- 0.48), DDAH2 (1.09 +/- 0.27 to 2.3 +/- 0.46), and arginase-1 (1.08 +/- 0.17 to 1.82 +/- 0.22) were increased in ANG II-infused rats. This was prevented by losartan treatment, which reduced the expression of eNOS (0.97 +/- 0.26 to 0.37 +/- 0.11 in controls; 0.8 +/- 0.16 to 0.36 +/- 0.1 in ANG II-infused rats) and caveolin-1 (2.49 +/- 0.59 to 0.82 +/- 0.24 in controls and 2.59 +/- 0.61 to 1.1 +/- 0.25 in ANG II-infused rats). ANG II (10(-10) mol/l) caused vessels from ANG II-infused animals to contract to 53 +/- 15% of baseline diameter and 90 +/- 5% of baseline diameter in controls (P < 0.05) and was further enhanced by l-NAME to 4 +/- 4% of baseline diameter (P < 0.05). In vivo losartan treatment reduced the reactivity of isolated vessels to 91 +/- 2% of baseline in response to 10(-7) mol/l ANG II compared with 82 +/- 3% in controls (P < 0.05) and prevented the increased responsiveness caused by ANG II infusion. In conclusion, CAT1, CAT2, DDAH2, and arginase-1 expression in renal resistance vessels is regulated through the AT(1) receptor. This finding may be of direct importance for NOS and the regulation of preglomerular vascular function.
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| 23. |
- Hultström, Michael, et al.
(författare)
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Upregulation of tissue inhibitor of metalloproteases-1 (TIMP-1) and procollagen-N-peptidase in hypertension-induced renal damage.
- 2008
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Ingår i: Nephrology, Dialysis and Transplantation. - : Oxford University Press (OUP). - 0931-0509 .- 1460-2385. ; 23:3, s. 896-903
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Hypertensive renal damage starts in the juxtamedullary cortex (JMC) and gradually extends towards the outer cortex (OC). The intention of the study was to examine if the increase of fibrous tissue in the JMC of the spontaneously hypertensive rat (SHR) is dependent on an increase of collagen synthesis or a decreased collagen breakdown compared to the normotensive control (WKY). METHODS AND RESULTS: The renal damage was evaluated by light microscopy, and the amount of fibrosis was quantified using Sirius red staining. Real-time RT-PCR was used to quantify mRNA for: collagen-type-1-alpha-1 (col1a1), procollagen-n- and -c-proteinase, matrix metalloproteases, MMP-2 and MMP-9, tissue inhibitor of metalloproteases, TIMP-1 and TIMP-2. Western blot was used to quantify the proteins of MMP-2, MMP-9, TIMP-1 and TIMP-2. The relative activities of MMP-2 and MMP-9 were assayed by zymography. The JMC in SHR had an increased amount of collagen as measured by Sirius red, and a 15-fold increase in the mRNA for col1a1. The gene expression of procollagen-c-proteinase was unchanged while procollagen-n-proteinase was increased in SHR and had the highest expression in the JMC. The mRNA for MMP-2 and MMP-9 showed increased expression in SHR, but not specifically in the JMC. Protein analysis showed increased expression for MMP-2 in SHR and in the JMC. MMP-9 protein was lower in SHR. TIMP-1 was increased in SHR at both mRNA and protein level and more so in the JMC. The mRNA and protein analysis of TIMP-2 showed small differences between SHR and WKY. CONCLUSION: An imbalance of collagen metabolism featuring increased synthesis and inhibition of breakdown favours renal interstitial fibrosis in SHR.
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| 24. |
- Iversen, Bjarne M., et al.
(författare)
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Nitrogen oxyd (NO) og nyrearteriestenose
- 2008
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Ingår i: Nefrologisk forum. - : Norsk nyremedisinskforening. ; 14:2, s. 6-9
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Forskningsöversikt (övrigt vetenskapligt/konstnärligt)
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| 30. |
- Pedersen, A. T., et al.
(författare)
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Impact of recent studies on attitudes and use of hormone therapy among Scandinavian gynaecologists
- 2007
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Ingår i: Acta Obstet Gynecol Scand. - 1600-0412. ; 86:12, s. 1490-5
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Climacteric medicine has been in focus during the last 2 decades, and an intensive debate has been ongoing regarding the positive and negative aspects of postmenopausal hormone therapy (HT). Recent randomised controlled studies have been unable to confirm data from observational studies of primary or secondary preventive effects of HT on coronary heart disease, and other studies have indicated an increased risk of breast cancer, stroke and venous thromboembolism among HT users. In 2001, we reported on knowledge, attitudes, management strategies and use of HT among Scandinavian gynaecologists. The aim of the present study was to re-assess the same parameters concerning HT among Scandinavian gynaecologists in 2002-2003, and compare the results with the data collected in 1995-1997. METHODS: All practicing gynaecologists in Denmark, Sweden and Norway were invited by letter to complete and return a questionnaire regarding their knowledge, attitudes and management strategies concerning HT. Female gynaecologists were questioned if they were currently using HT, and the same question was posed concerning spouses of male gynaecologists. RESULTS: The questionnaire was completed and returned by 60, 76 and 72%, respectively of gynaecologists in Denmark, Sweden and Norway. Of the 1,591 physicians who responded, 13% thought that all women should be offered HT provided there were no contraindications, while 86% recommended HT only to selected women after considering the individual advantages and disadvantages of the treatment. Of the gynaecologists, 37% considered HT to be without relevance in the primary prevention of osteoporosis in healthy women. As for duration of the treatment, 40% of the gynaecologists would recommend HT for <5 years for the treatment of climacteric complaints, and only 8% would recommend HT for >10 years. The prevalence of HT use among the menopausal female gynaecologists varied between 71 and 74%. Among the menopausal spouses of male gynaecologists, 68-72% were current users of HT. CONCLUSION: During the last years of ongoing debate, gynaecologists from Denmark, Sweden and Norway have become more modest in their recommendations of postmenopausal HT. Scandinavian specialists are more cautious in prescribing hormones for women with symptomatic CVD or previously treated for breast cancer, however, their personal use of HT has not changed dramatically and still reflects a positive attitude.
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| 31. |
- Poulsen, R. D., et al.
(författare)
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Effects of Weak Intermolecular Interactions on the Molecular Isomerism of Tricobalt Metal Chains
- 2009
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 1520-5126 .- 0002-7863. ; 131:22, s. 7580-7591
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Tidskriftsartikel (refereegranskat)abstract
- Depending on the number of interstitial solvent molecules, n, crystals of the linear chain compound Co-3(dipyridylamide)(4)Cl-2 center dot nCH(2)Cl(2) adopt either symmetrical or unsymmetrical metal chain structures. We explore here the possible reasons for such behavior using Hirshfeld surface analysis of intermolecular interactions as well as the charge density determined from 100(1) K X-ray diffraction data on the unsymmetrical complex Co-3(dipyridylamide)(4)Cl-2 center dot 2.11CH(2)Cl(2), u-1, and crystal structures of u-1 determined from single crystal synchrotron X-ray diffraction data at 20, 150, and 300 K. The new crystal structures are compared with previous structural results on a crystal with slightly different solvent content. This change in solvent content only affects the bond distances to atom Co(3), which are also strongly affected by temperature changes due to a spin crossover transition. Large differences in intermolecular interactions are revealed by the Hirshfeld surface analysis between symmetrical (s-1) and unsymmetrical (u-1) crystal solvates, suggesting that the molecular isomerism is strongly influenced by crystal packing effects. Topological analysis of the static electron density of u-1 suggests that there is direct metal-metal bonding for both the shorter Co(1)-Co(2) and the longer Co(2)-Co(3) contact. The approximate description of the system as a (Co2)(2+)-dimer and an isolated Co2+-ion is reflected in the character of the metal-ligand interactions, which are more ionic for the isolated Co(3) atom, and the topological charges Co(1)(+0.50), Co(2)(+0.77), and Co(3)(+1.36). The two termini of u-1 are found to be very different, both in terms of structural surroundings as well as topology. The central Co(2) atom is similar to a cobalt atom in a tetragonally distorted octahedral environment resulting in preferred occupancy in the t(2g) orbitals. The Co(1) atom has significant deformation in the xz and yz planes (z along the chain axis, x and y toward ligands) reflecting covalent interactions with the terminal chlorine atom Cl(1). The Co(3) atom has a relatively high occupancy of the d(x2-y2) orbital and a relatively low occupancy of the d(xy) orbital confirming that these orbitals are involved in the spin crossover process and predominantly responsible for the observed variation in bond lengths with temperature.
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| 32. |
- Sun, Y, et al.
(författare)
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Thermoelectric transport properties of highly oriented FeSb2 thin films
- 2009
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Ingår i: JOURNAL OF APPLIED PHYSICS. - : AIP Publishing. - 0021-8979 .- 1089-7550. ; 106:3
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Tidskriftsartikel (refereegranskat)abstract
- Highly textured FeSb2 films were produced on quartz wafers by a sputtering method. Their resistivity and Seebeck coefficient (S) were measured and a maximum absolute value of S similar to 160 mu V K-1 at 50 K was obtained. Hall measurements were employed to study the charge carrier concentrations and Hall mobilities of the FeSb2 films. By comparing with the transport properties of FeSb2 single crystals and an extrinsically doped FeSb1.98Te0.02 single crystal, the thermoelectric properties of the FeSb2 films are demonstrated to be dominated by the intrinsic properties of FeSb2 at a high charge carrier concentration.
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| 33. |
- Villa, Luisa L., et al.
(författare)
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Prophylactic efficacy of a quadrivalent human papillomavirus (HPV) vaccine in women with virological evidence of HPV infection
- 2007
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 196:10, s. 1438-1446
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Tidskriftsartikel (refereegranskat)abstract
- Background. A quadrivalent (types 6, 11, 16, and 18) human papillomavirus (HPV) L1 virus-like-particle (VLP) vaccine has been shown to be 95%-100% effective in preventing cervical and genital disease related to HPV-6,-11,-16, and-18 in 16-26-year-old women naive for HPV vaccine types. Because most women in the general population are sexually active, some will have already been infected with >= 1 HPV vaccine types at the time vaccination is offered. Here, we assessed whether such infected women are protected against disease caused by the remaining HPV vaccine types. Methods. Two randomized, placebo-controlled trials of the quadrivalent (types 6, 11, 16, and 18) HPV vaccine enrolled 17,622 women without consideration of baseline HPV status. Among women infected with 1-3 HPV vaccine types at enrollment, efficacy against genital disease related to the HPV vaccine type or types for which subjects were naive was assessed. Results. Vaccination was 100% effective (95% confidence interval [CI], 79%-100%) in preventing incident cervical intraepithelial neoplasia 2 or 3 or cervical adenocarcinoma in situ caused by the HPV type or types for which the women were negative at enrollment. Efficacy for preventing vulvar or vaginal HPV-related lesions was 94% (95% CI, 81%-99%). Conclusions. Among women positive for 1-3 HPV vaccine types before vaccination, the quadrivalent HPV vaccine protected against neoplasia caused by the remaining types. These results support vaccination of the general population without prescreening.
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