| 1. |
- Ingvast Larsson, Carina, et al.
(författare)
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Pharmacokinetics of meloxicam in adult goats and its analgesic effect in disbudded kids
- 2011
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Ingår i: Journal of Veterinary Pharmacology and Therapeutics. - : Wiley. - 0140-7783 .- 1365-2885. ; 34:1, s. 64-69
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Tidskriftsartikel (refereegranskat)abstract
- The pharmacokinetics and analgesic effect of the nonsteroidal anti-inflammatory drug meloxicam (0.5 mg/kg) in goats were investigated. In a randomized, cross-over design the pharmacokinetic parameters were investigated in adult goats (n = 8) after single intravenous and oral administration. The analgesic effect was evaluated in kids using a randomized, placebo controlled and blinded protocol. Kids received meloxicam (n = 6) once daily and their siblings (n = 5) got isotonic NaCl intramuscularly while still anaesthetized after cautery disbudding and injections were repeated on three consecutive days. In the adult goats after intravenous administration the terminal half-life was 10.9 ± 1.7 h, steady-state volume of distribution was 0.245 ± 0.06 L/kg, and total body clearance was 17.9 ± 4.3 mL/h/kg. After oral administration bioavailability was 79 ± 19%, C(max) was 736 ± 184 ng/mL, T(max) was 15 ±5 h, although the terminal half-life was similar to the intravenous value, 11.8 ± 1.7 h. Signs of pain using a visual analogue scale were smaller in kids treated with meloxicam compared with kids treated with placebo on the first day after disbudding, but subsequently no difference in pain was noticeable. Plasma cortisol and glucose concentrations did not differ between the two groups.
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| 2. |
- Tyden, Eva, et al.
(författare)
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Differential gene expression of CYP3A isoforms in equine liver and intestines
- 2012
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Ingår i: Journal of Veterinary Pharmacology and Therapeutics. - : Wiley. - 0140-7783 .- 1365-2885. ; 35, s. 588-595
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Tidskriftsartikel (refereegranskat)abstract
- Tyden, E., Lofgren, M., Pegolo, S., Capolongo, F., Tjalve, H., Larsson, P. Differential gene expression of CYP3A isoforms in equine liver and intestines. J. vet. Pharmacol. Therap. 35, 588595. Recently, seven CYP3A isoforms CYP3A89, CYP3A93, CYP3A94, CYP3A95, CYP3A96, CYP3A97 and CYP129 have been isolated from the horse genome. In this study, we have examined the hepatic and intestinal gene expression of these CYP3A isoforms using TaqMan probes. We have also studied the enzyme activity using luciferin-isopropyl acetal (LIPA) as a substrate. The results show a differential gene expression of the CYP3A isoforms in the liver and intestines in horses. In the liver, CYP3A89, CYP3A94, CYP3A96 and CYP3A97 were highly expressed, while in the intestine there were only two dominating isoforms, CYP3A93 and CYP3A96. The isoform CYP3A129 was not detected in the liver or the intestine, although this gene consists of a complete set of exons and should therefore code for a functional protein. It is possible that this gene is expressed in tissues other than the liver and intestines. In the intestine, both CYP3A96 and CYP3A93 showed the highest gene expression in the duodenum and the proximal parts of the jejunum. This correlated with a high protein expression in these tissues. Studies of the enzyme activity showed the same Km for the LIPA substrate in the liver and the intestine, while the maximum velocity (Vmax) in the liver was higher than in the intestine. Our finding of a differential gene expression of the CYP3A isoforms in the liver and the intestines contributes to a better understanding of drug metabolism in horses.
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| 3. |
- Tyden, Eva, et al.
(författare)
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Expression and localization of BCRP, MRP1 and MRP2 in intestines, liver and kidney in horse
- 2010
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Ingår i: Journal of Veterinary Pharmacology and Therapeutics. - : Wiley. - 0140-7783 .- 1365-2885. ; 33, s. 332-340
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Tidskriftsartikel (refereegranskat)abstract
- The gene and protein expression and the cellular localization of the ABC transport proteins breast cancer resistance protein (BCRP), multidrug resistance-associated protein 1 (MRP1) and multidrug resistance-associated protein 2 (MRP2) have been examined in the intestines, liver and kidney in horse. High gene and protein expression of BCRP and MRP2 were found in the small intestines, with cellular localization in the apical membranes of the enterocytes. In the liver, MRP2 was present in the bile canalicular membranes of the hepatocytes, whereas BCRP was localized in the cytoplasm of hepatocytes in the peripheral parts of the liver lobuli. In the kidney both BCRP and MRP2 were predominantly present in the distal tubuli and in the loops of Henle. In most tissues, the gene and protein expression of MRP1 were much lower than for BCRP and MRP2. Immunostaining of MRP1 was detectable only in the intestines and with localization in the cytoplasm of enterocytes in the caecum and colon and in the cells of serous acini of Brunner's glands in the duodenum and the upper jejunum. The latter cells were also stained for BCRP, but not for MRP2. Many drugs used in horse are substrates for one or more of the ABC transport proteins. These transporters may therefore have important functions for oral bioavailability, distribution and excretion of substrate compounds in horse.
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| 4. |
- Wambugu, S. N., et al.
(författare)
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Effects of opioids in the formalin test in the Speke's hinged tortoise (Kinixy's spekii)
- 2010
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Ingår i: Journal of Veterinary Pharmacology and Therapeutics. - : Wiley. - 0140-7783 .- 1365-2885. ; 33:4, s. 347-351
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Tidskriftsartikel (refereegranskat)abstract
- Little is known about analgesia in lower vertebrates such as the Speke's hinged tortoise (Kinixy's spekii), yet of late they are increasingly being adopted as pets. The effects of morphine (5, 7.5, 10 and 20 mg/kg), pethidine (10, 20, and 50 mg/kg) and naloxone (5 mg/kg) on nociception induced by the formalin test (12.5%, 100 mu L) were studied in the Speke's hinged tortoise. Formalin induced a monophasic limb retraction behavioural response and its duration was recorded. The behaviour lasted for 16.4 +/- 0.8 min. Morphine (7.5, 10 and 20 mg/kg) and pethidine (20 and 50 mg/kg) induced significant decrease in the duration of limb retraction in the formalin test. The anti-nociceptive effects were naloxone (5 mg/kg) reversible. The data suggest that the formalin test is a good test for studying nociception and anti-nociception in tortoises and that the opioidergic system plays a role in the control of nociception in these animals.
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| 5. |
- Gabrielsson, Johan, et al.
(författare)
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Animal Health Modeling & Simulation Society: a new society promoting model-based approaches in veterinary pharmacology
- 2013
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Ingår i: Journal of Veterinary Pharmacology and Therapeutics. - : Wiley. - 0140-7783 .- 1365-2885. ; 36, s. 417-419
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The Animal Health Modeling & Simulation Society (AHM&S) is a newly founded association (2012) that aims to promote the development, application, and dissemination of modeling and simulation techniques in the field of Veterinary Pharmacology and Toxicology. The association is co-chaired by Pr. Johan Gabrielsson (Europe), Pr. Jim Riviere (USA), and secretary Dr. Jonathan Mochel (Switzerland). This short communication aims at presenting the membership, rationale and objectives of this group.
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| 6. |
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| 7. |
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| 8. |
- Tyden, Eva, et al.
(författare)
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The genes of all seven CYP3A isoenzymes identified in the equine genome are expressed in the airways of horses
- 2013
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Ingår i: Journal of Veterinary Pharmacology and Therapeutics. - : Wiley. - 0140-7783 .- 1365-2885. ; 36, s. 370-375
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Tidskriftsartikel (refereegranskat)abstract
- In the present study, we examined the gene expression of cytochrome P450 3A (CYP3A) isoenzymes in the tracheal and bronchial mucosa and in the lung of equines using TaqMan probes. The results show that all seven CYP3A isoforms identified in the equine genome, that is, CYP3A89, CYP3A93, CYP3A94, CYP3A95, CYP3A96, CYP3A97 and CYP3A129, are expressed in the airways of the investigated horses. Though in previous studies, CYP3A129 was found to be absent in equine intestinal mucosa and liver, this CYP3A isoform is expressed in the airways of horses. The gene expression of the CYP3A isoenzymes varied considerably between the individual horses studied. However, in most of the horses CYP3A89, CYP3A93, CYP3A96, CYP3A97 and CYP3A129 were expressed to a high extent, while CYP3A94 and CYP3A95 were expressed to a low extent in the different parts of the airways. The CYP3A isoenzymes present in the airways may play a role in the metabolic degradation of inhaled xenobiotics. In some instances, the metabolism may, however, result in bioactivation of the xenobiotics and subsequent tissue injury.
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| 9. |
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| 10. |
- Diamanti, E., et al.
(författare)
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Endoplasmic reticulum stress and mineralization inhibition mechanism by the resinous monomer HEMA
- 2013
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Ingår i: International Endodontic Journal. - : Wiley-Blackwell. - 0143-2885 .- 1365-2591. ; 46:2, s. 160-168
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To investigate the expression of two endoplasmic reticulum (ER)-resident key chaperone proteins, ERdj5 and BiP, under the influence of resinous monomers and its relationship with the inhibition of mineralization caused by the monomer 2-hydroxyethyl methacrylate (HEMA).METHODOLOGY: The ERdj5 and BiP expression was studied in vitro, in primary human pulp cell cultures after treatment with three different HEMA concentrations at different time periods. Subsequently, the expression of both the odontoblast markers dentine sialoprotein (DSP) and osteonectin (OSN) was studied in human pulp cells under the same conditions.RESULTS: The ERdj5 and BiP expression was upregulated in the pulp cells. DSP and OSN were largely dispersed in the cytoplasm in control cell cultures but accumulated in a perinuclear area after exposure to HEMA. Their expression levels were not affected.CONCLUSIONS: The increased expression of ERdj5 and BiP may reflect activation of ER stress. DSP and OSN accumulation into the cells may lead to their secretion arrest and inhibition of dentine matrix formation. These events may elucidate the mechanism by which HEMA inhibits the mineralization process.
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| 11. |
- Fransson, Helena, et al.
(författare)
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Dentine sialoprotein and Collagen I expression after experimental pulp capping in humans using Emdogain(R) Gel
- 2011
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Ingår i: International Endodontic Journal. - : John Wiley & Sons. - 0143-2885 .- 1365-2591. ; 44:3, s. 259-267
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Tidskriftsartikel (refereegranskat)abstract
- Aim To characterize the hard tissue formed in human teeth experimentally pulp capped either with calcium hydroxide or with Emdogain®Gel (Biora AB, Malmö, Sweden) – , a derivative of enamel matrix (EMD), using two markers for dentine; dentine sialoprotein (DSP) and type 1 collagen (Col I). Formation of hard tissue following pulp capping in these teeth has previously been observed and reported. Methodology Affinity-purified rabbit anti-Col I and anti-DSP polyclonal antibodies were used to stain histological sections from 9 pairs of contra-lateral premolars, that had been experimentally pulp amputated and randomly capped with EMDgel or calcium hydroxide. The teeth were extracted 12 weeks after being pulp capped. Results In the calcium hydroxide treated teeth DSP was seen in the new hard tissue which formed a bridge. DSP was also seen in the newly formed hard tissue in the EMDgel treated teeth. Proliferated pulp tissue partly filled the space initially occupied by EMDgel and DSP-stained hard tissue was observed alongside exposed dentine surfaces as well as in isolated masses within the proliferated pulp tissue, although the new hard tissue did not cover the pulp exposure. DSP staining was also seen in the cells lining the hard tissue in both groups. Col I staining was seen in the newly formed hard tissue in both groups. Conclusions The new hard tissue formed after pulp capping with EMDgel or calcium hydroxide contained DSP and Col I, considered to be markers for dentine.
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| 12. |
- Fransson, Helena, et al.
(författare)
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Effects of bacterial products on the activity of odontoblast-like cells and their formation of type 1 collagen
- 2014
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Ingår i: International Endodontic Journal. - : John Wiley & Sons. - 0143-2885 .- 1365-2591. ; 47:4, s. 397-404
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To study how products released from different bacteria in a deep carious lesion affect the metabolic activity of odontoblast-like cells and their ability to produce the major organic component of dentine, collagen 1. METHODOLOGY: MDPC-23 cells were exposed to supernatants from biofilm cultures of strains isolated from the deepest part of a carious lesion as well as from a clinical isolate of Enterococcus faecalis. Lipoteichoic acid (LTA) and lipopolysaccharide (LPS) were used for comparison. Cell activity was assessed using an methyl-thiazolyl-diphenyl tetrazolium bromide (MTT) assay, and collagen 1 levels were determined by ELISA. RESULTS:The lesion microflora was dominated by Lactobacillus spp. Neither extracellular products from the isolates nor LPS affected the activity of the MDPC-23 cells, whereas extracellular products from E. faecalis and LTA significantly reduced total cell activity (P < 0.01). Enterococcus faecalis had an inhibitory effect upon collagen 1 production by the cells, whereas no such effect or even a slight stimulatory effect was seen for the isolates from the deep carious lesion. CONCLUSIONS: These studies indicate that culture supernatants from E. faecalis reduced the metabolic activity of odontoblast-like cells as shown using the MTT assay. No effect was seen for supernatants from biofilms of bacteria recovered from a deep carious lesion. Different bacteria varied in their effects upon collagen 1 production suggesting that the nature of the bacterial species in a carious lesion may have a direct influence upon the ability of the odontoblasts to produce tertiary dentine.
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| 13. |
- Fransson, Helena, et al.
(författare)
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Efficacy of lasers as an adjunct to chemo-mechanical disinfection of infected root canals : a systematic review
- 2013
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Ingår i: International Endodontic Journal. - : Wiley-Blackwell. - 0143-2885 .- 1365-2591. ; 46:4, s. 296-307
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Tidskriftsartikel (refereegranskat)abstract
- The aim was to evaluate the efficacy of various types of lasers used as an adjunct to chemo-mechanical disinfection of infected root canals with the outcome measures 'normal periapical condition' or 'reduction of microbial load'. PubMed, CENTRAL and ISI Web of Knowledge literature searches with specific indexing terms and a subsequent hand search were made with stated limits and criteria. Relevant publications were retrieved, followed by interpretation. The quality of each included publication was assessed as high, moderate or low. The initial search process yielded 234 publications. All abstracts of these publications were read, and the reference lists of relevant publications were hand-searched. Ten articles were read in full text and interpreted according to a data extraction form. Five were included in the systematic review and were assessed. A meta-analysis was impossible to perform because the included studies were heterogeneous with regard to study design, treatment and outcome measures. Positive effects were reported; however, no concluding evidence grade could be made because each included study was judged to have low quality, primarily due to lack of a power analysis, blinding and reproducibility. The evidence grade for whether lasers can be recommended as an adjunct to chemo-mechanical disinfection of infected root canals was insufficient. This does not necessarily imply that laser should not be used as an adjunct to root canal treatment but instead underscores the need for future high-quality studies.
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| 14. |
- Koch, Margaretha, et al.
(författare)
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A cost-minimization analysis of root canal treatment before and after education in nickel-titanium rotary technique in general practice
- 2012
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Ingår i: International Endodontic Journal. - : Wiley. - 0143-2885 .- 1365-2591. ; 45:7, s. 633-641
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Tidskriftsartikel (refereegranskat)abstract
- AIM:To compare root canal treatments performed before and after education in a nickel-titanium rotary technique (NiTiR) with respect to costs for instrumentation and number of instrumentation sessions in a County Public Dental Service in Sweden.METHODOLOGY: Following education, 77% of the general dental practitioners adopted completely the NiTiR. The randomly selected sample comprised 850 root canal treatments: 425 performed after the education, mainly using the NiTiR-technique (group A) and 425 performed before, using mainly stainless steel hand instrumentation (SSI) (group B). The number of instrumentation sessions in root canal treatments in group A and B was calculated. A CMA was undertaken on the assumption that treatment outcome was identical in group A and B. Direct costs associated with SSI and NiTiR were estimated and compared. Investment costs required for implementation of NiTiR were calculated, but not included in the CMA.RESULTS:Instrumentation sessions were counted in 418 (98%) root canal treatments performed in group A and 419 (99%) in group B. The number of instrumentation sessions in group A was significantly lower; 2.38, compared with 2.82 in group B (P < 0.001). Thus, on average, for every second root canal treatment performed after the education, one instrumentation session was saved. Root canal treatments in teeth with one canal, and three or more canals, were completed in significantly fewer instrumentation sessions after the education (P < 0.001). Direct costs of instrumentation sessions were SEK 2587 (USD 411) for group A and SEK 2851 (USD 453) for group B, for teeth with one canal, and SEK 2946 (USD 468) for group A and SEK 3510 (USD 558) for group B, for teeth with three or more canals (year 2011). Root canal treatments of teeth with two canals showed no significant difference with respect to number of instrumentation sessions and costs.CONCLUSIONS:Significantly fewer instrumentation sessions were required in group A, and root canal instrumentation therefore costs less than in group B. On the assumption that treatment outcome is identical in group A and B, root canal instrumentation performed after the education was more cost-effective.
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| 15. |
- Mejare, I. A., et al.
(författare)
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Diagnosis of the condition of the dental pulp: a systematic review
- 2012
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Ingår i: International Endodontic Journal. - : Wiley. - 0143-2885 .- 1365-2591. ; 45:7, s. 597-613
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Tidskriftsartikel (refereegranskat)abstract
- Mejare IA, Axelsson S, Davidson T, Frisk F, Hakeberg M, Kvist T, Norlund A, Petersson A, Portenier I, Sandberg H, Tran ae us S, Bergenholtz G. Diagnosis of the condition of the dental pulp: a systematic review. International Endodontic Journal, 45, 597613, 2012. Abstract The aim of this systematic review was to appraise the diagnostic accuracy of signs/symptoms and tests used to determine the condition of the pulp in teeth affected by deep caries, trauma or other types of injury. Radiographic methods were not included. The electronic literature search included the databases PubMed, EMBASE, The Cochrane Central Register of Controlled Trials and Cochrane Reviews from January 1950 to June 2011. The complete search strategy is given in an Appendix S1 (available online as Supporting Information). In addition, hand searches were made. Two reviewers independently assessed abstracts and full-text articles. An article was read in full text if at least one of the two reviewers considered an abstract to be potentially relevant. Altogether, 155 articles were read in full text. Of these, 18 studies fulfilled pre-specified inclusion criteria. The quality of included articles was assessed using the QUADAS tool. Based on studies of high or moderate quality, the quality of evidence of each diagnostic method/test was rated in four levels according to GRADE. No study reached high quality; two were of moderate quality. The overall evidence was insufficient to assess the value of toothache or abnormal reaction to heat/cold stimulation for determining the pulp condition. The same applies to methods for establishing pulp status, including electric or thermal pulp testing, or methods for measuring pulpal blood circulation. In general, there are major shortcomings in the design, conduct and reporting of studies in this domain of dental research.
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| 16. |
- Mota de Almeida, Fernando José, et al.
(författare)
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Diagnostic thinking and therapeutic decision confidence after cone beam computed tomography in endodontics measured by a visual analogue scale (VAS)
- 2014
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Ingår i: International Endodontic Journal. - : John Wiley & Sons. - 0143-2885 .- 1365-2591. ; 47:1, s. 52-52
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Aim To determine if Cone Beam Computed Tomography (CBCT) used in accordance with the European Commission guidelines has an impact on the diagnostic thinking confidence and therapeutic decision confidence in a population referred for endodontic problems. Methodology The study includes data collected from October 2011 until December 2012. From two different endodontic clinics consecutive patients were referred to a CBCT examination using criteria in accordance with the European Commission guidelines. The CBCT examinations were performed with similar equipment and standardized between clinics. After a thorough clinical examination and before CBCT examination, the endodontist scored the confidence for both diagnosis and therapeutic decision on a 100 mm visual analogue scale (VAS). After the CBCT examination both diagnosis and therapy plan were revised by the same dentist and a new VAS-score of confidence was performed. The VAS-scores before and after the CBCT examination were plotted for all teeth. Before and after assessments were analyzed with paired samples t-test. Results Fifty-seven patients were referred for a CBCT examination, representing 4% of all patients examined by both endodontic clinics during the study period. Four patients were excluded from the analysis as the protocol was not followed. The final data included 53 patients, and 81 teeth. For all teeth the mean score for diagnostic confidence before CBCT examination was 63 mm (SD 30). After CBCT-examination, the mean of the changes in diagnostic confidence for each patient was 23 mm (SD 27) (P < 0.01). The mean therapeutic decision confidence score Before CBCT was 67 mm (SD 25). The mean of the changes in therapeutic decision confidence after CBCT was 22 mm (SD 28) P < 0.01. Conclusions CBCT examination used in accordance with the European Commission guidelines increased the clinician’s confidence in both diagnostic thinking and therapeutic decision in a population with endodontic problems.
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| 17. |
- Petersson, Arne, et al.
(författare)
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Radiological diagnosis of periapical bone tissue lesions in endodontics: a systematic review
- 2012
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Ingår i: International Endodontic Journal. - : Wiley. - 0143-2885 .- 1365-2591. ; 45:9, s. 783-801
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Tidskriftsartikel (refereegranskat)abstract
- Petersson A, Axelsson S, Davidson T, Frisk F, Hakeberg M, Kvist T, Norlund A, Mejare I, Portenier I, Sandberg H, Tranaeus S, Bergenholtz G. Radiological diagnosis of periapical bone tissue lesions in endodontics: a systematic review. International Endodontic Journal, 45, 783801, 2012. Abstract This systematic review evaluates the diagnostic accuracy of radiographic methods employed to indicate presence/absence and changes over time of periapical bone lesions. Also investigated were the leads radiographic images may give about the nature of the process and the condition of the pulp in nonendodontically treated teeth. Electronic literature search included the databases PubMed, Embase and CENTRAL from January 1950 to June 2011. All languages were accepted provided there was an abstract in English. The MeSH terms were Cone beam computed tomography (CBCT), Radiography, panoramic, Periapical diseases, Dental pulp diseases, Sensitivity and specificity, receiver operating characteristics (ROC) curve, Cadaver, Endodontics and Radiography dental. Two reviewers independently assessed abstracts and full text articles. An article was read in full text if at least one of the two reviewers considered an abstract to be potentially relevant. Altogether, 181 articles were read in full text. The GRADE approach was used to assess the quality of evidence of each radiographic method based on studies of high or moderate quality. Twenty-six studies fulfilled criteria set for inclusion. None was of high quality; 11 were of moderate quality. There is insufficient evidence that the digital intraoral radiographic technique is diagnostically as accurate as the conventional film technique. The same applies to CBCT. No conclusions can be drawn regarding the accuracy of radiological examination in identifying various forms of periapical bone tissue changes or about the pulpal condition.
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| 18. |
- Pigg, Maria, et al.
(författare)
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Diagnostic yield of conventional radiographic and cone-beem computed tomographic images in patients with atypical odontalgia
- 2011
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Ingår i: International Endodontic Journal. - : John Wiley & Sons. - 0143-2885 .- 1365-2591. ; 12:44, s. 1092-1101
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Tidskriftsartikel (refereegranskat)abstract
- Abstract AIM: To investigate whether the additional diagnostic yield of a cone-beam computed tomography (CBCT) examination over conventional radiographs in patients primarily suspected of having atypical odontalgia (AO) improves differentiation between AO and symptomatic apical periodontitis (SAP) in patients with severe chronic intraoral pain. METHODOLOGY: In this clinical study, 25 patients (mean age 54 ± 11 years, range 34-72) participated; 20 were diagnosed with AO and 5 with SAP. All patients were recruited from the clinics of the Faculty of Odontology, Malmö University. AO inclusion criteria were chronic pain (>6 months) in a region where a tooth had been endodontically or surgically treated, with no pathological cause detectable in clinical or radiologic examinations. SAP inclusion criteria were recurrent pain from a tooth diagnosed with apical periodontitis in clinical and radiographic examinations. Assessments comprised a self-report questionnaire on pain characteristics, a comprehensive clinical examination and a radiographic examination including panoramic and intraoral radiographs and CBCT images. The main outcome measure was periapical bone destruction. RESULTS: Sixty per cent of patients with AO had no periapical bone destructions detectable with any radiographic method. Overall, CBCT rendered 17% more periapical bone destructions than conventional radiography. Average pain intensity in patients with AO was 5.6 (± 1.8) on a 0-10 numerical rating scale, and average pain duration was 4.3 (± 5.2) years. CONCLUSION: Cone-beam computed tomography improves identification of patients without periapical bone destruction, which may facilitate differentiation between AO and SAP.
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| 19. |
- Quah, S. Y., et al.
(författare)
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Fusobacterium nucleatum induces cytokine production through Toll-like-receptor-independent mechanism
- 2014
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Ingår i: International Endodontic Journal. - : Wiley. - 0143-2885 .- 1365-2591. ; 47:6, s. 550-559
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Tidskriftsartikel (refereegranskat)abstract
- AimTo determine whether Fusobacterium nucleatum's ability to invade cells allows the bacteria to activate pro-inflammatory response through cytosolic pattern recognition receptors, independent of surface Toll-like receptors (TLRs). MethodologyHEK293T cells, which lack endogenous TLRs, and overexpressing dominant negative myeloid differentiation primary response gene 88 (MyD88DN) protein, were infected with F.nucleatum and the production of interleukin-8 (IL-8) was determined. The necessity for intracellular invasion of the bacteria for cytokine production was also investigated by blocking bacterial invasion with cytochalasin D. The roles of NF?B and p38 mitogen-activated protein kinase (MAPK) and nucleotide-binding oligomerization domain-1 (NOD-1) signalling pathways in F.nucleatum-induced IL-8 secretion were determined. ResultsFusobacterium nucleatum-infected HEK293T cells produced IL-8 independent of the MYD88 signalling. This response was inhibited by preventing F.nucleatum invasion into HEK293T cells. p38 MAPK but not the NF?B signalling pathway was required for F.nucleatum-mediated IL-8 production. HEK293T cells expressed NOD-1 but not NOD-2. Yet, inhibition of NOD-1 signalling did not affect F.nucleatum-induced IL-8 secretion. ConclusionsFusobacterium nucleatum invasion led to cytokine production, which is mediated by the p38 MAPK signalling but independent of TLRs, NOD-1, NOD-2 and NF?B signalling.
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