Browsing by Subject "Permeability"

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  • Hewetson, Michael; Sykes, Ben W; Hallowell, Gayle D; Tulamo, Riitta-Mari (BioMed Central, 2017)
    Abstract Background Equine gastric ulcer syndrome (EGUS) is common in adult horses, particularly those involved in performance disciplines. Currently, detection of EGUS by gastroscopy is the only reliable ante mortem method for definitive diagnosis; however it is unsuitable as a screening test because it is expensive, time consuming, and is not readily available to most veterinarians. Sucrose permeability testing represents a simple, economical alternative to gastroscopy for screening purposes, and the feasibility of this approach in the horse has been previously reported. The aim of this study was to determine the diagnostic accuracy of blood sucrose as a screening test for EGUS in a large group of adult horses with and without naturally occurring gastric disease. Results One hundred and one adult horses with or without naturally occurring gastric ulceration were studied. The diagnostic accuracy of blood sucrose for diagnosis of gastric lesions (GL), glandular lesions (GDL), squamous lesions (SQL), and clinically significant lesions (CSL) at 45 and 90 min after administration of 1 g/kg of sucrose via nasogastric intubation was assessed using receiver operator characteristics (ROC) curves and calculating the area under the curve (AUC). For each lesion type, sucrose concentration in blood was compared to gastroscopy, as the gold standard, and sensitivities (Se) and specificities (Sp) were calculated across a range of sucrose concentrations. Ulcer grading was performed blindly by one observer; and the results were validated by comparing them with that of two other observers, and calculating the level of agreement. Cut-off values were selected manually to optimize Se. The prevalence of GL, GDL, SQL, and CSL was 83, 70, 53 and 58% respectively. At the selected cut-offs, Se ranged from 51 to 79% and Sp ranged from 43 to 72%, depending upon the lesion type and time of sampling. Conclusions Blood sucrose is neither a sensitive or specific test for detecting EGUS in this population of adult horses with naturally occurring gastric ulceration. Further studies aimed at evaluating the performance characteristics of the test in different study populations are warranted. Given the limitations of endoscopy, due consideration should also be given to alternative methods for comparison of blood sucrose with a gold standard.
  • Hewetson, Michael; Sykes, Ben William; Hallowell, Gayle Davina; Tulamo, Riitta-Mari (2017)
    Background: Equine gastric ulcer syndrome (EGUS) is common in adult horses, particularly those involved in performance disciplines. Currently, detection of EGUS by gastroscopy is the only reliable ante mortem method for definitive diagnosis; however it is unsuitable as a screening test because it is expensive, time consuming, and is not readily available to most veterinarians. Sucrose permeability testing represents a simple, economical alternative to gastroscopy for screening purposes, and the feasibility of this approach in the horse has been previously reported. The aim of this study was to determine the diagnostic accuracy of blood sucrose as a screening test for EGUS in a large group of adult horses with and without naturally occurring gastric disease. Results: One hundred and one adult horses with or without naturally occurring gastric ulceration were studied. The diagnostic accuracy of blood sucrose for diagnosis of gastric lesions (GL), glandular lesions (GDL), squamous lesions (SQL), and clinically significant lesions (CSL) at 45 and 90 min after administration of 1 g/kg of sucrose via nasogastric intubation was assessed using receiver operator characteristics (ROC) curves and calculating the area under the curve (AUC). For each lesion type, sucrose concentration in blood was compared to gastroscopy, as the gold standard, and sensitivities (Se) and specificities (Sp) were calculated across a range of sucrose concentrations. Ulcer grading was performed blindly by one observer; and the results were validated by comparing them with that of two other observers, and calculating the level of agreement. Cut-off values were selected manually to optimize Se. The prevalence of GL, GDL, SQL, and CSL was 83, 70, 53 and 58% respectively. At the selected cut-offs, Se ranged from 51 to 79% and Sp ranged from 43 to 72%, depending upon the lesion type and time of sampling. Conclusions: Blood sucrose is neither a sensitive or specific test for detecting EGUS in this population of adult horses with naturally occurring gastric ulceration. Further studies aimed at evaluating the performance characteristics of the test in different study populations are warranted. Given the limitations of endoscopy, due consideration should also be given to alternative methods for comparison of blood sucrose with a gold standard.
  • Hewetson, Michael; Venner, Monica; Volquardsen, Jan; Sykes, Ben William; Hallowell, Gayle Davina; Vervuert, Ingrid; Fosgate, Geoffrey Theodore; Tulamo, Riitta-Mari (2018)
    Background: Equine gastric ulcer syndrome is an important cause of morbidity in weanling foals. Many foals are asymptomatic, and the development of an inexpensive screening test to ensure an early diagnosis is desirable. The objective of this study was to determine the diagnostic accuracy of blood sucrose for diagnosis of EGUS in weanling foals. Results: 45 foals were studied 7 days before and 14 days after weaning. The diagnostic accuracy of blood sucrose for diagnosis of gastric lesions (GL); glandular lesions (GDL); squamous lesions (SQL) and clinically significant gastric lesions (CSL) at 45 and 90 min after administration of 1 g/kg of sucrose via nasogastric intubation was assessed using ROC curves and calculating the AUC. For each lesion type, sucrose concentration in blood was compared to gastroscopy; and sensitivities (Se) and specificities (Sp) were calculated across a range of sucrose concentrations. Cut- off values were selected manually to optimize Se. Because of concerns over the validity of the gold standard, additional Se, Sp, and lesion prevalence data were subsequently estimated and compared using Bayesian latent class analysis. Using the frequentist approach, the prevalence of GL; GDL; SQL and CSL before weaning was 21; 9; 7 and 8% respectively; and increased to 98; 59; 97 and 82% respectively after weaning. At the selected cut- off, Se ranged from 84 to 95% and Sp ranged from 47 to 71%, depending upon the lesion type and time of sampling. In comparison, estimates of Se and Sp were consistently higher when using a Bayesian approach, with Se ranging from 81 to 97%; and Sp ranging from 77 to 97%, depending upon the lesion type and time of sampling. Conclusions: Blood sucrose is a sensitive test for detecting EGUS in weanling foals. Due to its poor specificity, it is not expected that the sucrose blood test will replace gastroscopy, however it may represent a clinically useful screening test to identify foals that may benefit from gastroscopy. Bayesian latent class analysis represents an alternative method to evaluate the diagnostic accuracy of the blood sucrose test in an attempt to avoid bias associated with the assumption that gastroscopy is a perfect test.
  • Hewetson, Michael; Venner, Monica; Volquardsen, Jan; Sykes, Ben W; Hallowell, Gayle D; Vervuert, Ingrid; Fosgate, Geoffrey T; Tulamo, Riitta-Mari (BioMed Central, 2018)
    Abstract Background Equine gastric ulcer syndrome is an important cause of morbidity in weanling foals. Many foals are asymptomatic, and the development of an inexpensive screening test to ensure an early diagnosis is desirable. The objective of this study was to determine the diagnostic accuracy of blood sucrose for diagnosis of EGUS in weanling foals. Results 45 foals were studied 7 days before and 14 days after weaning. The diagnostic accuracy of blood sucrose for diagnosis of gastric lesions (GL); glandular lesions (GDL); squamous lesions (SQL) and clinically significant gastric lesions (CSL) at 45 and 90 min after administration of 1 g/kg of sucrose via nasogastric intubation was assessed using ROC curves and calculating the AUC. For each lesion type, sucrose concentration in blood was compared to gastroscopy; and sensitivities (Se) and specificities (Sp) were calculated across a range of sucrose concentrations. Cut-off values were selected manually to optimize Se. Because of concerns over the validity of the gold standard, additional Se, Sp, and lesion prevalence data were subsequently estimated and compared using Bayesian latent class analysis. Using the frequentist approach, the prevalence of GL; GDL; SQL and CSL before weaning was 21; 9; 7 and 8% respectively; and increased to 98; 59; 97 and 82% respectively after weaning. At the selected cut-off, Se ranged from 84 to 95% and Sp ranged from 47 to 71%, depending upon the lesion type and time of sampling. In comparison, estimates of Se and Sp were consistently higher when using a Bayesian approach, with Se ranging from 81 to 97%; and Sp ranging from 77 to 97%, depending upon the lesion type and time of sampling. Conclusions Blood sucrose is a sensitive test for detecting EGUS in weanling foals. Due to its poor specificity, it is not expected that the sucrose blood test will replace gastroscopy, however it may represent a clinically useful screening test to identify foals that may benefit from gastroscopy. Bayesian latent class analysis represents an alternative method to evaluate the diagnostic accuracy of the blood sucrose test in an attempt to avoid bias associated with the assumption that gastroscopy is a perfect test.
  • Peuhkuri, Katri; Vapaatalo, Heikki; Korpela, Riitta (2011)
  • Ansaranta, Maaria; Geneid, Ahmed; Kauppi, Paula; Malmberg, Leo Pekka; Vilkman, Erkki (2017)
    Objectives/Hypothesis. To examine the changes in the larynx, as well as self-reported voice and throat symptoms, among patients undergoing a histamine challenge test. Thus, to understand the possible clinical effects of histamine on the larynx. Study design. Controlled, open prospective study. Methods. Thirty adult patients with prolonged cough and suspicion of bronchial asthma underwent a histamine challenge test. Videolaryngostroboscopy was performed immediately before and after the challenge. Voice and throat symptoms immediately before and after the challenge test were assessed using a visual analog scale. Results. Videolaryngostroboscopy after exposure showed significant increases in edema (P <0.001) as well as redness (P <0.001) of the vocal folds after the exposure. Self-reported voice complaints increased significantly for 8 of 11 symptoms. Amoderate positive correlation was found between the increase in edema of the vocal folds and reported heartburn/regurgitation symptoms (r = 0.42, P <0.05). Atopy, asthma, nasal symptoms, or bronchial hyperreactivity during the histamine challenge test were not associated with laryngeal reactions. Conclusions. According to the results, the laryngeal mucosal reaction during a histamine challenge test can be objectively visualized. Videolaryngostroboscopy findings, together with an increase in self-reported voice and throat symptoms, show that histamine has potential effects on vocal folds. The mucosal reaction seems to be pronounced among patients with reflux symptoms, probably reflecting the permeability features of the vocal folds.
  • Donner, Thomas (Helsingin yliopisto, 2020)
    Research into the gut microbiome has increased in recent decades, in part due to advances in sequencing technologies. A number of different disease processes appear to be linked to disturbances in the microbiome and an increase in intestinal permeability. Thus, different methods of modulating the microbiome and intestinal permeability are of great interest when considering future treatment options for several diseases. The experimental part of this thesis examines the effects of a bacterial strain (Bacteroides Vulgatus) on intestinal permeability using a CaCo-2 cell model. The bacterial strain was chosen because previous research has suggested it has the ability to reduce production of interleukin-8 (IL-8). A reduced production of IL-8 is believed to have anti-inflammatory effects and possibly a positive effect on intestinal permeability.The literature review section of the thesis discusses the relationship between disturbances in the microbiome, increased intestinal permeability and inflammatory reactions, as well as possible ways to modulate these processes. Factors that may affect intestinal permeability are briefly discussed with special emphasis placed on dietary factors. Spondyloarthropathies are discussed as an example of a disease group with possible links to a disturbed microbiome and an increase in intestinal permeability. The results from the experimental part of this thesis suggest that the studied strain of B.vulgatus does not have any appreciable effect on intestinal permeability and is thus unlikely to be used for future therapeutic treatments targeting the microbiome.
  • Ramsay, Eva; Hagström, Marja; Vellonen, Kati-Sisko; Boman, Susanna; Toropainen, Elisa; del Amo, Eva M.; Kidron, Heidi; Urtti, Arto; Ruponen, Marika (2019)
    Retinal pigment epithelium (RPE) is a major part of blood-retinal barrier that affects drug elimination from the vitreous to the blood and drug distribution from blood circulation into the eye. Even though drug clearance from the vitreous has been well studied, the role of RPE in the process has not been quantified. The aim of this work was to study the role of RPE clearance (CLRpE) as part of drug elimination from the vitreous and ocular drug distribution from the systemic blood circulation. We determined the bidirectional permeability of eight small molecular weight drugs and bevacizumab antibody across isolated bovine RPE-choroid. Permeability of small molecules was 10(-6) -10(-5)cm/s showing 13-15 fold range of outward and inward permeation, while permeability of bevacizumab was lower by 2-3 orders of magnitude. Most small molecular weight drugs showed comparable outward (vitreous-to-choroid) and inward (choroid-to-vitreous) permeability across the RPEchoroid, except ciprofloxacin and ketorolac that had an over 6 and 14-fold higher outward than inward permeability, respectively, possibly indicating active transport, Six of seven tested small molecular weight drugs had outward CLRPE values that were comparable with their intravitreal clearance (CLIvr) values (0.84-2.6 fold difference). On the contrary, bevacizumab had an outward CLRPE that was only 3.5% of the CLIvt, proving that its main route of elimination (after intravitreal injection) is not RPE permeation. Experimental values were used in pharmacokinetic simulations to assess the role of the RPE in drug transfer from the systemic blood circulation to the vitreous (CLBv). We conclude that for small molecular weight drugs the RPE is an important route in drug transfer between the vitreal cavity and blood, whereas it effectively hinders the movement of bevacizumab from the vitreous to the systemic circulation.