Bone marrow stromal cell antigen-1 (CD157) regulated by sphingosine kinase 2 mediates kidney fibrosis.

Chronic kidney disease is a progressive disease that may lead to end-stage renal disease. Interstitial fibrosis develops as the disease progresses. Therapies that focus on fibrosis to delay or reverse progressive renal failure are limited. We and others showed that sphingosine kinase 2-deficient mice (Sphk2 -/-) develop less fibrosis in mouse models of kidney fibrosis. Sphingosine kinase2 (SphK2), one of two sphingosine kinases that produce sphingosine 1-phosphate (S1P), is primarily located in the nucleus. S1P produced by SphK2 inhibits histone deacetylase (HDAC) and changes histone acetylation status, which can lead to altered target gene expression. We hypothesized that Sphk2 epigenetically regulates downstream genes to induce fibrosis, and we performed a comprehensive analysis using the combination of RNA-seq and ChIP-seq. Bst1/CD157 was identified as a gene that is regulated by SphK2 through a change in histone acetylation level, and Bst1 -/- mice were found to develop less renal fibrosis after unilateral ischemia-reperfusion injury, a mouse model of kidney fibrosis. Although Bst1 is a cell-surface molecule that has a wide variety of functions through its varied enzymatic activities and downstream intracellular signaling pathways, no studies on the role of Bst1 in kidney diseases have been reported previously. In the current study, we demonstrated that Bst1 is a gene that is regulated by SphK2 through epigenetic change and is critical in kidney fibrosis.

Compressed air injection technique to standardize block injection pressures.

PURPOSE: Presently, no standardized technique exists to monitor injection pressures during peripheral nerve blocks. Our objective was to determine if a compressed air injection technique, using an in vitro model based on Boyle's law and typical regional anesthesia equipment, could consistently maintain injection pressures below a 1293 mmHg level associated with clinically significant nerve injury. METHODS: Injection pressures for 20 and 30 mL syringes with various needle sizes (18G, 20G, 21G, 22G, and 24G) were measured in a closed system. A set volume of air was aspirated into a saline-filled syringe and then compressed and maintained at various percentages while pressure was measured. The needle was inserted into the injection port of a pressure sensor, which had attached extension tubing with an injection plug clamped "off". Using linear regression with all data points, the pressure value and 99% confidence interval (CI) at 50% air compression was estimated. RESULTS: The linearity of Boyle's law was demonstrated with a high correlation, r = 0.99, and a slope of 0.984 (99% CI: 0.967-1.001). The net pressure generated at 50% compression was estimated as 744.8 mmHg, with the 99% CI between 729.6 and 760.0 mmHg. The various syringe/needle combinations had similar results. CONCLUSION: By creating and maintaining syringe air compression at 50% or less, injection pressures will be substantially below the 1293 mmHg threshold considered to be an associated risk factor for clinically significant nerve injury. This technique may allow simple, real-time and objective monitoring during local anesthetic injections while inherently reducing injection speed.

Compressed air injection technique to standardize block injection pressures : [La technique d'injection d'air comprimé pour normaliser les pressions d'injection d'un blocage nerveux].

PURPOSE: Presently, no standardized technique exists to monitor injection pressures during peripheral nerve blocks. Our objective was to determine if a compressed air injection technique, using an in vitro model based on Boyle's law and typical regional anesthesia equipment, could consistently maintain injection pressures below a 1293 mmHg level associated with clinically significant nerve injury. METHODS: Injection pressures for 20 and 30 mL syringes with various needle sizes ( 18G, 20G, 21 G, 22G, and 24G) were measured in a closed system. A set volume of air was aspirated into a saline-filled syringe and then compressed and maintained at various percentages while pressure was measured. The needle was inserted into the injection port of a pressure sensor, which had attached extension tubing with an injection plug clamped "off". Using linear regression with all data points, the pressure value and 99% confidence interval (CI) at 50% air compression was estimated. RESULTS: The linearity of Boyle's law was demonstrated with a high correlation, r = 0.99, and a slope of 0.984 (99% CI: 0.967-1.001). The net pressure generated at 50% compression was estimated as 744.8 mmHg, with the 99% CI between 729.6 and 760.0 mmHg. The various syringe/needle combinations had similar results. CONCLUSION: By creating and maintaining syringe air compression at 50% or less, injection pressures will be substantially below the 1293 mmHg threshold considered to be an associated risk factor for clinically significant nerve injury. This technique may allow simple, real-time and objective monitoring during local anesthetic injections while inherently reducing injection speed. OBJECTIF: Présentement, aucune technique normalisée ne permet de vérifier les pressions d'injection pendant les blocages nerveux périphériques. Nous voulions vérifier si une technique d'injection d'air comprimé, utilisant un modèle in vitro fondé sur la loi de Boyle et du matériel propre à l'anesthésie régionale, pouvait maintenir avec régularité les pressions d'injection sous les 1293 mmHg, pression associée à une lésion nerveuse cliniquement significative. MéTHODE: Les pressions d'injection pour des seringues de 20 et 30 mL et diverses tailles d'aiguilles (18G, 20G, 21G, 22G et 24G) ont été mesurées dans un système fermé. Un volume défini d'air a été aspiré dans une seringue rempli de solution saline, puis comprimé et maintenu à des pourcentages variés pendant la mesure de la pression. L'aiguille a été insérée dans l'ouverture à injection d'un détecteur de pression muni d'une extension avec un bouchon d'injection en position fermée. La valeur de la pression et l'intervalle de confiance de 99 % (IC) pour une compression d'air à 50 % ont été évalués en utilisant une régression linéaire avec tous les points de données. RéSULTATS: La linéarité de la loi de Boyle a été démontrée avec une forte corrélation, r = 0,99 et une pente de 0,984 (IC de 99 % : 0,967-1,001) La pression nette générée sous une compression de 50% a été de 744,8 mmHg avec un IC de 99 % entre 729,6 et 760,0 mmHg. Les diverses combinaisons de seringues et d'aiguilles ont présenté des résultats similaires. CONCLUSION: En créant et en maintenant dans la seringue une compression d'air à 50% ou moins, les pressions d'injection seront dans l'ensemble sous le seuil des 1293 mmHg associé à un facteur de risque de lésion nerveuse cliniquement significative. Cette technique peut permettre une surveillance simple, objective et en temps réel pendant les injections d'anesthésiques locaux tout en réduisant fondamentalement la vitesse d'injection.

Declining randomized clinical trials from Canadian anesthesia departments?

PURPOSE: The research productivity was estimated by publications from anesthesiology departments at Canadian universities over a five-year period, and the articles published were classified into several study designs. METHODS: In this observational study, the MEDLINE database was searched for publications listed by anesthesiology departments at Canadian universities as the primary corresponding source from 2000-2004. Abstracts were reviewed and each publication categorized into its respective methodological design. Impact factors of the journals in which the articles appeared were taken into consideration. "Total impact score" was defined as the total number of articles from a particular journal in a particular year multiplied by the impact factor value. Changes in overall publication numbers over the five-year period were compared and analyzed using Pearson correlation coefficients. RESULTS: Total Canadian anesthesia publications remained constant from 2000-2004. In this five-year time frame, the University of Toronto had the highest number of publications (271) followed by the University of Montreal (86), and McGill University (84). These universities conducted primarily randomized controlled trials (RCTs) whereas smaller Canadian universities mainly published case reports, reviews, and cohort studies. The number of RCTs conducted seems to be decreasing whereas the number of case reports and reviews being published are remaining constant over the five-year period. CONCLUSION: Although overall numbers in anesthesia publications do not suggest a significant decline, the number of RCTs decreased during the years 2000-2004. The quality of anesthesia research appears to be comparable to those in other medical specialties, with larger institutions conducting RCTs and smaller institutions publishing more case reports.