| 1. |
- Kozian, Alf, 1969-, et al.
(författare)
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Increased Alveolar Damage after Mechanical Ventilation in a Porcine Model of Thoracic Surgery
- 2010
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Ingår i: Journal of Cardiothoracic and Vascular Anesthesia. - : Elsevier BV. - 1053-0770 .- 1532-8422. ; 24:4, s. 617-623
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Mechanical stress during one-lung ventilation (OLV) results in lung injury. This experiment compares effects of mechanical ventilation, OLV and surgical manipulation on diffuse alveolar damage (DAD) after application of different anesthetic regimes. Design: Prospective, randomized, controlled, blinded animal experiment. Setting: University hospital. Objects: Twenty-one piglets. Interventions: Animals (27.5kg) were randomized into four groups: spontaneous breathing (SB, n=3); two-lung ventilation (TLV, n=6); OLV during desflurane (n=6) and propofol anesthesia (n=6). SB pigs were killed after induction of anesthesia. Lung tissue samples were analyzed to obtain reference values for alveolar damage. TLV pigs underwent standard TLV (VT=10ml/kg, FIO2=0.40, PEEP=5cmH2O). In OLV pigs, after lung separation by a bronchial blocker, OLV (VT=10ml/kg) and thoracic surgery were performed. After the procedure the pigs were killed. Lung tissue samples were harvested for histological examination. Lung injury was quantified by DAD score; sequestration of leukocytes was assessed by recruitment of CD45+-cells into the lungs. Main Results: TLV resulted in increased DAD scores in both lungs (TLV vs. SB: 6.9 vs. 2.7; p<0.05); the number of CD45+-cells was not increased (TLV vs. SB: 8.7 vs. 5.0 cells/view). OLV and surgical manipulation increased DAD and leukocyte sequestration without differences between the ventilated and manipulated lungs. Leukocyte recruitment was not differently affected by the anesthetic regimen (propofol vs. desflurane: CD45+-cells/view: 13.5 vs. 11.3). Conclusions: TLV resulted in increased DAD scores in the lungs as compared with SB. OLV and thoracic surgery further increased lung injury and leukocyte recruitment independently of the administration of propofol or desflurane anesthesia.
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| 2. |
- Nilsson, Peter, et al.
(författare)
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Structural typing of systemic amyloidoses by luminescent-conjugated polymer spectroscopy.
- 2010
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Ingår i: The American journal of pathology. - : Elsevier BV. - 1525-2191 .- 0002-9440. ; 176:2, s. 563-574
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Tidskriftsartikel (refereegranskat)abstract
- Most systemic amyloidoses are progressive and lethal, and their therapy depends on the identification of the offending proteins. Here we report that luminescent-conjugated thiophene polymers (LCP) sensitively detect amyloid deposits. The heterodisperse polythiophene acetic acid derivatives, polythiophene acetic acid (PTAA) and trimeric PTAA, emitted yellow-red fluorescence on binding to amyloid deposits, whereas chemically homogeneous pentameric formic thiophene acetic acid emitted green-yellow fluorescence. The geometry of LCPs modulates the spectral composition of the emitted light, thereby reporting ligand-induced steric changes. Accordingly, a screen of PTAA-stained amyloid deposits in histological tissue arrays revealed striking spectral differences between specimens. Blinded cluster assignments of spectral profiles of tissue samples from 108 tissue samples derived from 96 patients identified three nonoverlapping classes, which were found to match AA, AL, and ATTR immunotyping. We conclude that LCP spectroscopy is a sensitive and powerful tool for identifying and characterizing amyloid deposits.
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| 3. |
- Sjölander, Daniel, et al.
(författare)
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Evaluation of the fluorescent amyloid ligand h-FTAA in human tissues with systemic and localized amyloid
- 2014
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Rapid and accurate detection of amyloid deposits in routine surgical pathology settings are of great importance. The use of fluorescence microscopy in combination with appropriate amyloid specific dyes is very promising in this regard. Most systemic amyloidosis are progressive and lethal. Disease specific therapy depends on the identification of the offending proteins. Here we report that a luminescent conjugated oligothiophene, h-FTAA, rapidly and with high sensitivity and selectivity detects amyloid deposits in verified clinical samples from systemic amyloidosis patients with AA, AL, and ATTR types; as well as in tissues laden with localized amyloidosis of AANF, AIAPP and ASem1 type. The probe h-FTAA emitted yellow red fluorescence on binding to amyloid deposits, whereas no apparent staining was observed in surrounding tissue. Screening of 114 amyloid containing tissues derived from §07 verified (Congo red birefringence and immunohistochemistry) amyloidosis patients revealed complete correlation between h-FTAA and Congo red fluorescence. We conclude that h-FTAA is a fluorescent hypersensitive, rapid and powerful tool for identifying amyloid deposits in tissue sections. H-FTAA staining can be utilized as a rapid complementary technique for accurate detection of amyloid in routine surgical pathology settings. It was also revealed that within 5 of 15 age matched Congo red negative control samples h-FTAA detects microdeposits of amyloid-like protein aggregates in liver and kidney. The results emphasize the potential of the dye for detection of prodromal amyloidosis as well as for discovery of novel amyloid-like protein aggregates in humans.
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