| 1. |
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| 2. |
- Madler, C.F., et al.
(författare)
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Non-invasive diagnosis of coronary artery disease by quantitative stress echocardiography : Optimal diagnostic models using off-line tissue Doppler in the MYDISE study
- 2003
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Ingår i: European Heart Journal. - 0195-668X .- 1522-9645. ; 24:17, s. 1584-1594
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To develop optimal methods for the objective non-invasive diagnosis of coronary artery disease, using myocardial Doppler velocities during dobutamine stress echocardiography. Methods and results: We acquired tissue Doppler digital data during dobutamine stress in 289 subjects, and measured myocardial responses by off-line analysis of 11 left ventricular segments. Diagnostic criteria developed by comparing 92 normal subjects with 48 patients with coronary disease were refined in a prospective series of 149 patients referred with chest pain. Optimal diagnostic accuracy was achieved by logistic regression models, using systolic velocities at maximal stress in 7 myocardial segments, adjusting for independent correlations directly with heart rate and inversely with age and female gender (all p<0.001). Best cut-points from receiveroperator curves diagnosed left anterior descending, circumflex and right coronary disease with sensitivities and specificities of 80% and 80%, 91% and 80%, and 93% and 82%, respectively. All models performed better than velocity cut-offs alone (p<0.001). Conclusion: Non-invasive diagnosis of coronary artery disease by quantitative stress echocardiography is best performed using diagnostic models based on segmental velocities at peak stress and adjusting for heart rate, and gender or age. © 2003 Published by Elsevier Ltd on behalf of The European Society of Cardiology.
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| 3. |
- Madler, C. F., et al.
(författare)
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Non-invasive diagnosis of coronary artery disease by quantitative stress echocardiography : optimal diagnostic models using off-line tissue Doppler in the MYDISE study
- 2003
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 24:17, s. 1584-1594
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Tidskriftsartikel (refereegranskat)abstract
- Aims To develop optimal methods for the objective non-invasive diagnosis of coronary artery disease, using myocardial Doppler velocities during dobutamine stress echocardiography. Methods and results We acquired tissue Doppler digital data during dobutamine stress in 289 subjects, and measured myocardial responses by off-line analysis of 11 left ventricular segments. Diagnostic criteria developed by comparing 92 normal subjects with 48 patients with coronary disease were refined in a prospective series of 149 patients referred with chest pain. Optimal diagnostic accuracy was achieved by logistic regression models, using systolic velocities at maximal stress in 7 myocardial segments, adjusting for independent correlations directly with heart rate and inversely with age and female gender (all p<0.001). Best cut-points from receiver-operator curves diagnosed left anterior descending, circumflex and right coronary disease with sensitivities and specificities of 80% and 80%, 91% and 80%, and 93% and 82%, respectively. All models performed better than velocity cut-offs alone (p<0.001). Conclusion Non-invasive diagnosis of coronary artery disease by quantitative stress echocardiography is best performed using diagnostic models based on segmental velocities at peak stress and adjusting for heart rate, and gender or age.
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| 4. |
- Girnita, L., et al.
(författare)
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Increased expression of insulin-like growth factor I receptor in malignant cells expressing aberrant p53 : Functional impact
- 2000
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Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 60:18, s. 5278-5283
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Tidskriftsartikel (refereegranskat)abstract
- We investigated the functional impact of p53 on insulin-like growth factor I receptor (IGF-IR) expression in malignant cells. Using the BL-41tsp53-2 cell line, a transfectant carrying temperature-sensitive (ts) p53 and endogenous mutant p53 (codon 248), we demonstrated a drastic down-regulation of plasma membrane-bound IGF-IRs on induction of wild-type p53, However, a similar response was obtained by treatment of BL-41tsp53-2 cells expressing mutant ts p53 with a p53 antisense oligonucleotide. Thus, even if the negative effect of wild-type p53 predominates under a competitive condition, these data indicate that mutant p53 may be important for up-regulation of IGF-IR, To further elucidate this issue, three melanoma cell lines (BE, SK-MEL-5, and SK-MEL-28) that over expressed p53 were investigated. The BE cell line has a hot spot mutation (codon 248) and expresses only codon 248-mutant p53, SK-MEL-28 has a point mutation at codon 145. SK-MEL-5 cells did not exhibit any p53 mutations, but the absence of p21(Waf1) expression suggested functionally aberrant p53. Our data suggest that interaction with Mdm-2 may underlie p53 inactivation in these cells, Using p53 antisense oligonucleotides, we demonstrated a substantial down-regulation of cell surface expression of IGF-IR proteins in all melanoma cell lines after 24 h, This was paralleled by decreased tyrosine phosphorylation of IGF-IR and growth arrest, and, subsequently, massive cell death was observed (this was also seen in BL-41tsp53-2 cells with mutant conformation of ts p53). Taken together, our results suggest that up-regulation of IGF-IR as a result of expression of aberrant p53 may be important for the growth and survival of malignant cells.
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| 5. |
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| 6. |
- Andersson, L., et al.
(författare)
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Effect of CO2 pneumoperitoneum on ventilation-perfusion relationships during laparoscopic cholecystectomy
- 2002
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 46:5, s. 552-560
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Tidskriftsartikel (refereegranskat)abstract
- Background: Previous studies have shown that pneumoperitoneum transiently reduces venous admixture as assessed by a calculation based on the shunt formula, and increases arterial oxygen tension (PaO2) in patients without heart or lung disease. The aim of the present study was to further explore the relationship between ventilation-perfusion ((V) over dot (A)/(Q) over dot) before and during pneumoperitoneum by using the multiple inert gas technique. Methods: Nine patients without heart or lung disease (ASA I), with a mean age of 42 years, scheduled for laparoscopic cholecystectomy were included. After premedication and induction of anaesthesia, radial artery and pulmonary artery catheters were introduced percutaneously. The (V) over dot (A)/(Q) over dot relationships were evaluated by the multiple inert gas elimination technique before and during pneurnoperitoneum to obtain a direct measure of the pulmonary shunt. Results: Induction of pneumoperitoneum decreased the pulmonary shunt from 5.8 (4.5) to 4.1 (3.2)% (P<0.05) and increased PaO2 from 21.7 (5.9) to 24.7 (4.8) kPa (P<0.01). During surgery, the shunt increased from 3.2 (2.8) to 5.2 (3.4)% to the same level as before pneumoperitoneum induction. No area with low (V) over dot (A)/(Q) over dot was seen. Dead space ventilation amounted to 20.0 (1.2)% in the supine position and did not change during the investigation. Conclusions: In patients without heart or lung disease, pneumoperitoneum at an intra-abdominal pressure level of 11-13 mmHg- causes a transient reduction of the pulmonary shunt. The mechanisms underlying the present finding remain to be elucidated.
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| 7. |
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| 8. |
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| 9. |
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| 10. |
- Gustafsson, A. C., et al.
(författare)
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HPV-related cancer susceptibility and p53 codon 72 polymorphism
- 2001
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Ingår i: Acta Dermato-Venereologica. - : Medical Journals Sweden AB. - 0001-5555 .- 1651-2057. ; 81, s. 125-
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Tidskriftsartikel (refereegranskat)abstract
- Conflicting results regarding the association of a polymorphism at codon 72 of the p53 tumour suppressor gene and susceptibility to develop human papilloma virus (HPV)-associated cervical cancer have been published over the last year, implicating differences in ethnic background, sample origin, sample size and/or detection assay, The material for this study was collected in the identical geographical region as for 2 previous reports with contradictory results regarding the association of codon 72 genotype with squamous cell cancer (SCC), We have used an alternative detection assay, based on pyrosequencing technology, that interrogates the variable position by the accuracy of DNA polymerase. In addition to cervical clinical specimens from SCC, HPV16- and HPV18-infected adenocarcinoma cases as well as cervical intraepithelial neoplasia (CM) were investigated. No significant association was found between p53 codon 72 genotype and the risk to develop adenocarcinoma, SCC or CIN in the Swedish population.
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| 11. |
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| 12. |
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| 13. |
- Sarkar, N., et al.
(författare)
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Effects of intramyocardial injection of phVEGF-A(165) as sole therapy in patients with refractory coronary artery disease - 12-month follow-up : Angiogenic gene therapy
- 2001
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 250:5, s. 373-381
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To test the safety and bioactivity of phVEGF-A(165) after intramyocardial injection during 12-month follow-up. Design. Open-labelled study. Subjects. Inclusion criteria were angina pectoris, Canadian Cardiovascular Society (CCS) class III-IV, unamenable to further revascularization, ejection fraction (EF) >30%, perfusion defects extending over >10% of the anterolateral left ventricle wall detectable with adenosine single photon emission computerized tomography (SPECT) and at least one patent vessel visible by coronary angiography. Seven of 39 patients referred for gene therapy were included. Intervention. Via a mini-thoracotomy under general anaesthesia, phVEGF-A(165) was injected directly into the myocardium at four sites in the anterolateral region of the left ventricle. Results. Operative procedures were uneventful. Perioperative release of myocardial markers and electrocardiogram (ECG) changes were detected in two patients. There were no perioperative deaths but one patient died 7 months postoperatively because of myocardial infarction. Plasma vascular endothelial growth factor (VEGF)-A levels increased two to threefold peaking 6 days postoperatively (P<0.004) and returning to baseline by day 30. A significant reduction in angina pectoris was reported. The CCS class improved from 3.30.2 to 1.9 +/-0.3 (P<0.01) and nitroglycerine intake decreased from 3915 to 12 +/-5 tablets week(-1) (P<0.001) 2 months after gene transfer. Improvements remained after 12 months when nitroglycerine consumption approached zero. Improved myocardial function in the phVEGF-A(165) injection region was documented in all patients (P<0.016) by tissue velocity imaging (TVI). Reduced reversible ischaemia was detected by adenosine SPECT in four patients. Improved collateralization was detected in four patients with coronary angiography. Conclusion. Intramyocardial injection of phVEGF-A(165) is safe and may lead to improved myocardial perfusion and function with longstanding symptomatic relief in end-stage angina pectoris. Based on these results this therapeutic potential is being tested in a double-blind placebo controlled multicentre trial, EUROINJECT ONE.
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| 14. |
- Sylven, C., et al.
(författare)
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Myocardial Doppler tissue velocity improves following myocardial gene therapy with VEGF-A(165) plasmid in patients with inoperable angina pectoris
- 2001
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Ingår i: Coronary Artery Disease. - : Ovid Technologies (Wolters Kluwer Health). - 0954-6928 .- 1473-5830. ; 12:3, s. 239-243
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Tidskriftsartikel (refereegranskat)abstract
- Background Myocardial tissue velocity and perfusion were studied in patients with severe angina pectoris following gene therapy by intramyocardial injection of phVEGF-A(165) via thoracotomy. Plasma concentrations of VEGF-A increased postoperatively. Two months after treatment anginal status and myocardial tissue velocity improved and perfusion showed a tendency to improve. Tissue velocity imaging appears to be a sensitive, objective method for detecting changes in myocardial function following gene therapy. Objective To study effects on myocardial tissue velocity and perfusion in patients with angina pectoris following intramyocardial injection of phVEGF-A(165) via thoracotomy. Design Open label, phase I/II. Methods Six patients with Canadian Cardiovascular Society (CCS) angina pectoris functional Glass III - IV and with major defects at adenosine stress single-photon emission computerized tomography (SPECT) were studied. In addition to SPECT, coronary angiography and dobutamine stress echocardiography with tissue Doppler velocity imaging were performed before and two months after gene transfer. Results Plasma concentrations of VEGF-A increased 2 to 3 times (P < 0.04) over baseline from 2 to 14 days after injection with normalization after 4 weeks. The CCS class improved about 40%, from 3.3 +/- 0.2 to 2.0 +/- 0.3 (P < 0.02) and nitroglycerine consumption decreased 30 - 40%, from 44 +/- 17 to 15 +/- 5 tablets per week (P < 0.05). The maximal systolic myocardial tissue velocity increased in all patients about 25% (P < 0.02) but did not reach the reference range. Myocardial perfusion at SPECT improved in four of the six patients. Conclusions Anginal status, myocardial tissue velocity and perfusion can be improved by phVEGF-A(165) intramyocardial injection. Tissue velocity imaging appears to be a sensitive, objective method for detecting changes in myocardial function following gene therapy. Coron Artery Dis 12:239-243
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| 15. |
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| 16. |
- Torp, A. H., et al.
(författare)
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Automatic detection and tracking of left ventricular landmarks in echocardiography
- 2004
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Ingår i: 2004 IEEE Ultrasonics Symposium, Vols 1-3. - 078038413X ; , s. 474-477
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Konferensbidrag (refereegranskat)abstract
- We introduce a method for automatic detection and tracking of the apex and two landmarks defining the atrioventricular plane in apical views of the left ventricle. The method is based on using tissue Doppler to track a set of candidate points in a cardiac cycle. Each candidate point is given a score based on the gray-scale, the velocity, and depth profiles. The landmarks with the lowest costs are selected, and measurements are calculated automatically. The method is evaluated by comparing with manual selection by four cardiologists, and the presented results show that the method is robust and extracted measurements are comparable with manual selection.
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| 17. |
- Xie, YT, et al.
(författare)
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SYT-SSX is critical for cyclin D1 expression in synovial sarcoma cells: A gain of function of the t(X;18)(p11.2;q11.2) translocation
- 2002
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Ingår i: Cancer Research. - 1538-7445 .- 0008-5472. ; 62:13, s. 3861-3867
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Tidskriftsartikel (refereegranskat)abstract
- The SYT-SSX fusion gene has been implicated in the malignant tumor cell growth of synovial sarcoma, but the underlying molecular mechanisms are still poorly understood. Here we demonstrate that SYT-SSX is critical for the protein level of cyclin D1 in synovial sarcoma cells. Antisense oligonucleotides to SYT-SSX mRNA rapidly and drastically decreased cyclin D1 and subsequently inhibited cell growth. This effect is specific for SYT-SSX, without involving the wild-type genes SYT or SSX. The decrease in cyclin D1 expression, which occurred shortly after inhibition of SYT-SSX expression, was found to be primarily dependent on an increased degradation of the cyclin D1 protein, as assessed by pulse-chase experiments using [S-35]methionine. Furthermore, transfection of mouse fibroblasts with SYT-SSX cDNA increased the stability of cyclin D1. Because treatment with a proteasome inhibitor restored cyclin D1 expression, it seems like SYT-SSX interferes with ubiquitin-dependent degradation of cyclin D1. However, SYT-SSX-regulated cyclin D1 expression was proven to be independent of the glycogen synthetase kinase-3beta pathway. Taken together, our study provides evidence that SYT-SSX stabilizes cyclin D1 and is critical for cyclin D1 expression in synovial sarcoma cells. SYT-SSX-dependent expression of cyclin D1 may be an important mechanism in the development and progression of synovial sarcoma and also raises the possibility for targeted therapy.
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| 18. |
- Zetterberg, H, et al.
(författare)
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The Epstein-Barr virus ZEBRA protein activates transcription from the early lytic F promoter by binding to a promoter-proximal AP-1-like site
- 2002
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Ingår i: The Journal of general virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 83:Pt 8, s. 2007-2014
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Tidskriftsartikel (refereegranskat)abstract
- The ZEBRA protein encoded by the Epstein–Barr virus (EBV) genome activates a switch from the latent to the lytic gene expression programme of the virus. ZEBRA, a member of the basic leucine zipper family of DNA-binding proteins, is a transcriptional activator capable of inducing expression from several virus lytic cycle promoters by binding to activator protein 1 (AP-1)-like sites. The Epstein–Barr virus BamHI F promoter, Fp, was for some time believed to initiate EBNA1-specific transcription in EBV-transformed latent cells. More recent data, however, show that Fp is an early lytic promoter and that the dominant EBNA1 gene promoter in latent cells is Qp, located about 200 bp downstream of Fp. In the present investigation we confirm that Fp displays the characteristics of a lytic promoter. Fp is downregulated in latently EBV-infected cells, both in the endogenous virus genome and in reporter plasmids that carry Fp regulatory sequences upstream of position −136 and down to +10 relative to the Fp transcription start site (+1), and is activated on induction of the virus lytic cycle. We show that the repression of Fp in latent stages of infection can be abolished by ZEBRA, and demonstrate that ZEBRA activates Fp through a direct interaction with an AP-1-like site at position −52/−46 in the promoter-proximal Fp region.
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| 19. |
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| 20. |
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| 21. |
- Brodin, B., et al.
(författare)
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Cloning and characterization of spliced fusion transcript variants of synovial sarcoma : SYT/SSX4, SYT/SSX4v, and SYT/SSX2v. Possible regulatory role of the fusion gene product in wild type SYT expression
- 2001
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Ingår i: Gene. - 0378-1119 .- 1879-0038. ; 268:02-jan, s. 173-182
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Tidskriftsartikel (refereegranskat)abstract
- The synovial sarcoma translocation t(X;18)(p11.2; q11.2) results in the fusion of the SYT gene on chromosome 18 to exon 5 of either SSX1 or SSX2 genes on chromosome X. We recently reported that the SSX4 gene is also involved in such a translocation. In the present investigation we cloned and sequenced the full-length cDNA of SYT/SSX1, SYT/SSX2 and SYT/SSX4 from synovial sarcoma tissues. We isolated a novel fusion transcript type Variant involving the fusion of SYT with exon 6 of the SSX4 gene (SYT/SSX4v). The SYT/SSX4 and SYT/SSX2 open reading frame also differed from previously reported SYT/SSX sequences by an in-frame addition of 93bp exon located in the junction between exon 7 and 8 of the SYT. This exon is identical to that reported for the murine SYT but has not been previously found in the human transcript. Two SYT transcripts, with and without the 93 bp exon, were co-expressed in mouse NIH3T3 cells, human malignant cells and human testis tissue, but not in human normal fibroblasts. Stable transfection of an SYT/SSX4 expression vector into human and murine cell lines correlated with a down-regulation of SYT transcripts. This was also observed in a synovial sarcoma tumor expressing SYT/SSX4. This suggests that the SYT/SSX fusion gene may regulate SYT expression from the normal allele and as such alter the normal function of SYT.
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| 22. |
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| 23. |
- Brodin, L A, et al.
(författare)
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[Hopeful future for echocardiography. Progress within both the function and perfusion areas].
- 2000
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Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 97:46, s. 5302-4, 5307
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Tidskriftsartikel (refereegranskat)abstract
- Echocardiography is presently a feasible method for quantitative estimation of intracardiac flows, pressure levels and for hemodynamic evaluation of valvular disease. The evaluation of regional myocardial function is still based on subjective scrutiny, and no routine method for the estimation of myocardial blood flow is available. We present an overview of newly developed techniques that are beginning to gain purchase in clinical practice. The use of native second harmonic imaging to improve image quality and of tissue Doppler to provide objective measurements of regional myocardial function is discussed. This article describes the transformation of tissue Doppler information into parametric images as in strain rate imaging, and overviews the use of ultrasound contrast agents. Used together with new imaging modalities, myocardial contrast echocardiography holds promise for future quantification of myocardial blood volume and flow. Other emerging echocardiographic technologies discussed are non-invasive measurement of coronary flow reserve and three dimensional cineloop visualization, developed to increase our understanding of cardiovascular physiological and anatomical coupling.
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| 24. |
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| 25. |
- Ehrenberg, J., et al.
(författare)
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Retrograde crystalloid cardioplegia preserves left ventricular systolic function better than antegrade cardioplegia in patients with occluded coronary arteries
- 2000
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Ingår i: Journal of Cardiothoracic and Vascular Anesthesia. - : Elsevier BV. - 1053-0770 .- 1532-8422. ; 14:4, s. 383-387
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate retrograde and antegrade crystalloid cardioplegia in terms of cardiac cooling and postoperative cardiac function. Design: Prospective, randomized, and blinded. Setting: University hospital. Participants: Twenty male patients with triple-vessel disease and proximal occlusion of the circumflex or the left anterior descending coronary artery. Interventions: Left ventricular ejection fraction at rest and during exercise was evaluated by nuclear ventriculography the day before and 3 months after surgery. After induction of anesthesia and hourly for the first 5 postoperative hours, hemodynamic. echocardiographic, and electrocardiographic data were acquired. Myocardial temperature was measured with needle thermistors in 3 myocardial regions. Measurements and Main Results: Demographic and temperature data were analyzed by t-test. Hemodynamic and echocardiographic data were analyzed by analysis of variance. The groups were similar in baseline characteristics. Retrograde cardioplegia cooled the region distal to an occlusion better than antegrade cardioplegia (9.6 degrees C +/- 4.8 degrees C v 21.8 degrees C +/- 5.9 degrees C; p < 0.01). Hemodynamic, echocardiographic, and electrocardiographic data did not differ between the groups. Three months after surgery, the retrograde cardioplegia group showed a higher left ventricular ejection fraction at rest (58% +/- 10% v 47% +/- 10%; p < 0.02) and during exercise (58% +/- 13% v 47% +/- 10%; p < 0.05) compared with the antegrade cardioplegia group. Conclusions: Retrograde cardioplegia provides more homogenous myocardial cooling than antegrade cardioplegia in hearts with coronary artery occlusions. The use of retrograde cardioplegia seems to benefit long-term left ventricular function.
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| 26. |
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| 27. |
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| 28. |
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| 29. |
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| 30. |
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| 31. |
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| 32. |
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| 33. |
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| 34. |
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| 35. |
- Ohlson, Lena
(författare)
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In vivo studies of cell cycle regulating proteins in rats during liver regeneration and during promotion of liver carcinogenesis
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- There are more than one hundred different types of cancer in humans. However, the major platform for all types of cancer is automous and uncontrolled cell division and though most types of cancer are possible to treat and cure by surgery, chemical therapy or irradiation, more efficient and less toxic therapies are urgently needed. In the modern society we are exposed to more toxins than ever. The liver, as main detoxifier of our blood, is handling many hazardous compounds. Unfortunately, after being metabolised in the liver, many of these are able to act as promoters for one of the most lethal types of cancer, the hepatocellular carcinoma (HCC). Previous studies demonstrated that nuclear accumulation of p53 and other proteins is essential for efficient tumor suppression. Based on this, the aim of the study was to investigate whether altered localization and/or p53 protein expression is an early event in tumor development in liver that possibly contributes to the growth advantage of initiated hepatocytes. We also addressed the question of which impact 2-AAF exerts on cell cycle at early stages of tumor promotion. Preneoplastic foci were induced in rat liver by treatment with diethylnitroseamin (DEN), combined with either of the four tumor promoters, 2acetylaminofluorene, 17-alpha ethinylestradiol, choline-deficient diet or deoxycholic acid. This was combined with 2/3 partial hepatectomy as a proliferative stimulus. The immunohistochemical results showed that all four promoters decreased the focal expression of p53 and p21, two proteins known to inhibit replication upon DNA damage, in both nucleus and cytoplasm. In contrast, in surrounding tissue increased nuclear levels of p53 and p21 was observed. These data suggest that deregulation of p53 and p21 might be a common feature occurring early during promotion of HCC in vivo. We also found that treatment with 2-AAF prevented the induction of nuclear p53 in foci in response to gamma-irradiation in initiated male Wistar rats, which correlated with increased cytoplasmic expression of Mdm2 and Bcl-2 in foci. It is possible that complex formation with elevated Mdm2 together with increased Bcl-2 protein expression contributes to the sequestration and inactivation of p53 in cytoplasm. Growth signalling in regenerating liver was studied in non-initiated rats subjected to the tumor promoter 2-AAF. We found that 2-AAF exercise an almost complete mitoinhibitory effect in synchronised hepatocytes. Nuclear levels of cdk 4, cyclin D3, cyclin E, p53, p 130 and pRb were increased while the levels of PCNA, cdk 2, E2F- 1, -3 and -4 were decreased. Furthermore, both nuclear and cytoplasmic expression of cyclin A and - B proteins was lost. Finally, we found that p107 a member of the Rb-family and necessary for S-phase progression, but not pRB was increased in normal regenerating liver. In mitoinhibited liver the expression level of these two proteins was rather the opposit indicating slightly different roles for pRb and p107 during regeneration and cell cycle control, at least in this animal model.
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| 36. |
- Scherlund, M, et al.
(författare)
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Local anaesthetic block copolymer system undergoing phase transition on dilution with water
- 2001
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Ingår i: European Journal of Pharmaceutical Sciences. - 0928-0987 .- 1879-0720. ; 14, s. 53-61
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Tidskriftsartikel (refereegranskat)abstract
- The possibility of formulating a local anaesthetic system displaying in situ gelation on dilution with water, as well as its dependence on concentration of active ingredients and pH was investigated. For this purpose Lutrol F68, water, a eutectic mixture of lidocaine and prilocaine and Akoline MCM were mixed in different ratios and investigated using crossed polarisers, small-angle X-ray diffraction, rheology, conductivity and NMR self-diffusion measurements. In particular, an isotropic phase of low viscosity turning into a high viscous hexagonal phase upon dilution with water was found. The increase in viscosity is only weakly dependent on temperature in the temperature range of 20-37 degrees C. The rheology and in vitro drug release of these systems were studied and the elastic modulus was found to be fairly independent of concentration of active ingredients and pH in the investigated region. The in vitro release of lidocaine and prilocaine was found to increase with increasing concentration of the active ingredients and with decreasing pH, the latter as a consequence of the pH-dependent ionisation of these substances. The behaviour of the system is promising from a pharmaceutical point of view, since the isotropic low-viscous phase can be injected into, e.g. a periodontal pocket where the presence of saliva will cause a temporal transition into a rigid hexagonal phase thus making the formulation stay at the application site. At even higher water content, either as a result of longer application time or rinsing with water, the hexagonal phase is effectively dissolved through transformation to a water-rich micellar phase
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| 37. |
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| 38. |
- Scherlund, M, et al.
(författare)
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Micellization and gelation in block copolymer systems containing local anesthetics
- 2000
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Ingår i: International Journal of Pharmaceutics. - 0378-5173 .- 1873-3476. ; 211, s. 37-49
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Tidskriftsartikel (refereegranskat)abstract
- A formulation consisting of a eutectic mixture of lidocaine and prilocaine, Lutrol(R) F68 and Lutrol(R) F127, suitable for anesthetizing the periodontal pocket has previously been developed. This consists of discrete micelles with a diameter of 20-30 nm and has a suitable gelation temperature, a good release profile and excellent long-term stability. In this study, the unimer/micelle transition and gel formation of the formulation, in its concentrated state, are investigated using differential scanning calorimetry (DSC), dye solubilization, rheology, and nuclear magnetic resonance (NMR) self-diffusion. The critical micellization temperature (cmt) and gelation temperature are found to be interconnected and influenced by cosolutes, such as electrolytes and hydrophobic substances, the latter as found particularly for the eutectic mixture of the local anesthetic agents lidocaine and prilocaine. Both cmt and the gelation temperature decrease with increasing pH of the system, i.e. at reduced solubility of the active ingredients. Moreover, both cmt and the gelation temperature increase upon diluting the system with water. The ratio between the two block copolymers present in the system also has an impact on both cmt and the gelation temperature, resulting in a decrease in onset tt temperature of both processes with an increase of Lutrol(R) F127, The amount of the active ingredients present in the micelle phase depends on the pH of thc system bring approximately 0% w/w at pH 5, 50-60% w/w at pH 7.8 and 80% w/w at pH 9.
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| 39. |
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| 40. |
- Scherlund, M, et al.
(författare)
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Nonionic cellulose ethers as potential drug delivery systems for periodontal anesthesia
- 2000
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Ingår i: Journal of Colloid and Interface Science. - 0021-9797 .- 1095-7103. ; 229, s. 365-374
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Tidskriftsartikel (refereegranskat)abstract
- Nonionic cellulose ethers displaying a lower consolute temperature, or cloud-point, close to body temperature were investigated as potential carrier systems for the delivery of local anesthetic agents to the periodontal pocket. The interaction between the polymers, i.e., ethyl(hydroxyethyl)cellulose (EHEC) and hydrophobically modified EHEC (HM-EHEC), and ionic surfactants was determined in the absence and in the presence of the local anesthetic agents lidocaine and prilocaine. The cloud-point and rheology data indicate interactions between the polymer and both anionic and cationic surfactants. More precisely, a number of ionic surfactants were found to result in an increase in cloud-point at higher surfactant concentrations, a surfactant-concentration-dependent thickening, and a temperature-induced gelation upon heating. Upon addition of the local anesthetic agents lidocaine and prilocaine in their uncharged form to EHEC and HM-EHEC, in the absence of surfactants, only minor interaction with the polymer could be inferred. However, these substances were found to affect the polymer-surfactant interaction. In particular, the drug release rate in vitro as well as the stability and temperature-dependent viscosity were followed for an EHEC/SDS system and EHEC/myristoylcholine bromide system upon addition of lidocaine and prilocaine. The data indicate a possibility of formulating a local anesthetic drug delivery system suitable for administration into the periodontal pocket where at least small amounts of active ingredients can be incorporated into the system without severely affecting the gelation behavior. The results found for the cationic myristoylcholine bromide system are particularly interesting for the application in focus here since this surfactant is antibacterial and readily biodegradable.
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| 41. |
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