Interstitial fluid drainage from rat apical area takes place via vessels in the mandibular canal.

We sought to investigate the transport route for protein‐rich fluid from the apical area towards the draining lymph nodes. The first mandibular molar root canals in 24 female Wistar rats were instrumented and filled with radioactive‐labelled human serum albumin. The rats were sacrificed at different intervals beginning after 10 min (time 0) and continuing up to 72 h. Three jaw segments, gingiva around the first molar, blood samples, submandibular and cervical lymph nodes were collected and analyzed for radioactivity. The starting volume of tracer (control) for all experiments was calculated from measurements at time 0. At time 0, radioactivity was only detected in the jaw segments. Within lymph nodes and serum, the tracer was found after 4 h, with the highest amount recorded in serum up to 24 h. Lymphatics were found within the mandibular canal along blood vessels and nerves and exiting via foramen mandibularis, after immunohistochemical staining in four untreated rats. Our results show tracer distribution from the apical area towards the mandibular canal in a posterior direction. The tracer washout rate was low, and the fluid was mainly absorbed into blood vessels. The lymphatics in the mandibular canal may be more important for immune cell transport than for fluid drainage.publishedVersio

Impaired vascular responses to parasympathetic nerve stimulation and muscarinic receptor activation in the submandibular gland in non-obese diabetic mice

Introduction Decreased vascular responses to salivary gland stimulation are observed in Sjögren's syndrome patients. We investigate whether impaired vascular responses to parasympathetic stimulation and muscarinic receptor activation in salivary glands parallels hyposalivation in an experimental model for Sjögren's syndrome. Methods Blood flow responses in the salivary glands were measured by laser Doppler flowmeter. Muscarinic receptor activation was followed by saliva secretion measurements. Nitric oxide synthesis-mediated blood flow responses were studied after administration of a nitric oxide synthase inhibitor. Glandular autonomic nerves and muscarinic 3 receptor distributions were also investigated. Results Maximal blood flow responses to parasympathetic stimulation and muscarinic receptor activation were significantly lower in nonobese diabetic (NOD) mice compared with BALB/ c mice, coinciding with impaired saliva secretion in nonobese diabetic mice (P < 0.005). Nitric oxide synthase inhibitor had less effect on blood flow responses after parasympathetic nerve stimulation in nonobese diabetic mice compared with BALB/c mice (P < 0.02). In nonobese diabetic mice, salivary gland parasympathetic nerve fibres were absent in areas of focal infiltrates. Muscarinic 3 receptor might be localized in the blood vessel walls of salivary glands. Conclusions Impaired vasodilatation in response to parasympathetic nerve stimulation and muscarinic receptor activation may contribute to hyposalivation observed in nonobese diabetic mice. Reduced nitric oxide signalling after parasympathetic nerve stimulation may contribute in part to the impaired blood flow responses. The possibility of muscarinic 3 receptor in the vasculature supports the notion that muscarinic 3 receptor autoantibodies present in nonobese diabetic mice might impair the fluid transport required for salivation. Parasympathetic nerves were absent in areas of focal infiltrates, whereas a normal distribution was found within glandular epithelium.publishedVersio

Preoperative plasma growth-differentiation factor-15 for prediction of acute kidney injury in patients undergoing cardiac surgery

Covariate plot of the predictions from the random forest model. Four variables are displayed. Within each box, the x-axis denotes plasma creatinine (Îźmol/l), the y-axis the probability of developing cardiac-surgery-associated acute kidney injury (CSA-AKI). Within each column of plots, the additive Euroscore increases from bottom to top (legend, right). Within each row of plots the growth-differentiation factor-15 (GDF-15) levels increase from left to right. Significant non-linear interaction takes place between GDF-15 and creatinine. Within each additive Euroscore category (row of plots), increases in GDF-15 (plots more to the right within each row) increase the probability of developing CSA-AKI. However, this effect is more prominent in patients with normal creatinine (x-axis label of each plot). (TIFF 3197 kb

Inflammatory mediators in saliva and gingival fluid of children with congenital heart defect

Objectives (a) To compare levels of pro- and anti-inflammatory mediators in saliva and gingival crevicular fluid (GCF) in children with and without congenital heart defects (CHD cases and controls) and to test whether a systemic component exists in CHD cases by controlling for gingivitis and plaque scores. (b) To correlate the levels of pro- and anti-inflammatory mediators in GCF and saliva with plaque bacterial composition among CHD cases and controls. Materials and Methods Whole un-stimulated saliva and GCF samples were collected (60 CHD cases, 60 controls [Sudan]) and were analysed for levels of prostaglandin E2 (PGE2), interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α), interleukin-1ra (IL-1ra) and interleukin-10 (IL-10) levels. These levels were correlated with the previously reported levels of four red complex bacteria. Results Significantly elevated levels of PGE2 and IL-1β in GCF and IL-1β and TNF-α in saliva were detected among CHD cases compared with controls. General linear model (GLM) analyses revealed that PGE2 and IL-1β levels remained significantly higher in GCF and saliva samples, respectively, among CHD cases after controlling for gingivitis and plaque score, whereas TNF-α and IL-10 levels were significantly lower in their GCF samples. Additionally, IL-1β level was significantly positively correlated to the counts of the four red complex species in their GCF. Conclusion In addition to higher levels of some pro-inflammatory mediators in saliva and GCF corresponding to more gingivitis in CHD cases, also a systemic inflammatory component exists and is reflected in these two oral fluids.publishedVersio

Human gingival epithelial cells stimulate proliferation, migration, and tube formation of lymphatic endothelial cells in vitro

Objective The aim of this study was to investigate the response of gingival epithelial cells to microbial and inflammatory signals. Background The gingival epithelial barrier provides the first line of defense and supports tissue homeostasis by maintaining the cross-talk between gingival epithelium, oral microbiota, and immune cells. Lymphatic vessels are essential to sustaining this homeostasis. The gingival epithelial cells have been shown to produce prolymphangiogenic factors during physiologic conditions, but their role in response to microbial and inflammatory signals is unknown. Methods Immortalized human gingival epithelial cells (HGEC) and human dermal lymphatic microvascular endothelial cells (LEC) were cultured. HGEC were exposed to Porphyromonas gingivalis derived-LPS, human IL-1 beta/IL-1F2 protein, or recombinant human IL-6/IL-6R. Levels of vascular growth factors (VEGF-A, VEGF-C, and VEGF-D) in cell supernatants were determined by ELISA. LEC were grown to confluence, and a scratch was induced in the monolayer. Uncovered area was measured up to 48 h after exposure to conditioned medium (CM) from HGEC. Tube formation assays were performed with LEC cocultured with labelled HGEC or exposed to CM. Results VEGF-A, VEGF-C, and low levels of VEGF-D were constitutively expressed by HGEC. The expression of VEGF-C and VEGF-D, but not VEGF-A, was upregulated in response to proinflammatory mediators. VEGF-C was upregulated in response to P. gingivalis LPS, but not to Escherichia coli LPS. A scratch migration assay showed that LEC migration was significantly increased by CM from HGEC. Both the CM and coculture with HGEC induced significant tube formation of LEC. Conclusions HGEC can regulate production of lymphangiogenic/angiogenic factors during inflammatory insults and can stimulate proliferation, migration, and tube formation of LEC in vitro in a paracrine manner.publishedVersio

Conditioned Medium from Bone Marrow Mesenchymal Stem Cells Restored Oxidative Stress-Related Impaired Osteogenic Differentiation

Oxidative stress from high levels of intracellular reactive oxygen species (ROS) has been linked to various bone diseases. Previous studies indicate that mesenchymal stem cells (MSC) secrete bioactive factors (conditioned medium (MSC-CM)) that have antioxidant effects. However, the antioxidant role of MSC-CM on osteogenesis has not been fully studied. We aimed to identify antioxidant proteins in MSC-CM using mass spectrometry-based proteomics and to explore their effects on osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSC) exposed to oxidative stress induced by hydrogen peroxide (H2O2). Our analysis revealed that MSC-CM is comprised of antioxidant proteins that are involved in several biological processes, including negative regulation of apoptosis and positive regulation of cell proliferation. Then, hBMSC exposed to H2O2 were treated with MSC-CM, and the effects on their osteogenic differentiation were evaluated. MSC-CM restored H2O2-induced damage to hBMSC by increasing the antioxidant enzyme-SOD production and the mRNA expression level of the anti-apoptotic BCL-2. A decrease in ROS production and cellular apoptosis was also shown. MSC-CM also modulated mRNA expression levels of osteogenesis-related genes, runt-related transcription factor 2, collagen type I, bone morphogenic protein 2, and osteopontin. Furthermore, collagen type I protein secretion, alkaline phosphatase activity, and in vitro mineralization were increased. These results indicate that MSC-CM contains several proteins with antioxidant and anti-apoptotic properties that restored the impaired hBMSC osteogenic differentiation associated with oxidative stress.publishedVersio

Har satsingen på pedodonti gitt resultater? Henvisninger til spesialister i pedodonti i Hordaland i 2014-2019

Hovedmålet med denne studien var å vurdere om satsingen i pedodonti i vest fra 2013 hadde ført til en økning i henvisninger til spesialisttjenesten i pedodonti i Bergen sammenlignet med en tidligere kartlegging 2006–2013. Delmål var å registrere antall henvisninger, geografisk spredning, alderssammensetning, henvisningsårsaker, hvilke yrkesgrupper helsepersonell som henviste, ventetid, samt å sammenligne resultatene med andre norske og svenske studier. Grunnlaget for studien var alle mottatte henvisninger til spesialisttjenesten i pedodonti ved Tannhelsetjenestens kompetansesenter Vest/Hordaland i løpet av seksårsperioden 2014–2019. Totalt ble 1781 henvisninger registrert. Prosentandelen av den totale befolkningen barn og ungdom som ble henvist fra tidligere Hordaland, var markant høyere enn tilsvarende prosentandel rapportert i en tidligere studie i samme område (0,23 % vs. 0,03 %). Økt avstand fra behandlingsstedet resulterte i færre henvisninger, og særlig var henvisningsantallet fra tidligere Sogn & Fjordane fylke bekymringsfullt lavt. Aldersgruppen 7–15 år utgjorde nesten tre-fjerdedel av henvisningene, og erupsjonsproblematikk var årsaken til flest henvisninger. Den gjennomsnittlige ventetiden for spesialistbehandling var ca. 2 måneder. I tillegg utgjorde rådgivningstjeneste fra spesialister en viktig del av tilbudet. Studien viser at satsingen har gitt et bedre spesialisttilbud for barn og unge i vår region, men at det bør satses på å utdanne flere spesialister slik at en kan oppnå en bedre regional dekning.publishedVersio

Improving Systems Dynamics by Means of Advanced Signal Processing -Mathematical, Laboratorial and Clinical Evaluation of Propofol Monitoring in Breathing Gas

Abstract: Electrochemical sensors are used in various gas measurement applications and are available for different gases. Depending on the application, the sensor might need to be installed far away from the actual measurement site, requiring the use of long sampling lines. Examples are portable gas measurement devices in which remote locations like tanks and chemical reactors need to be monitored. But also medical applications, where the sensors cannot be positioned in close vicinity to the patient, are common like, e.g., the side-stream measurement of breathing gas. Due to the characteristics of electrochemical sensors and to the adsorption and desorption behavior of sampling lines for different gases, the electrical sensor signal may indicate long response times. In this paper, we propose an on-line signal processing algorithm which is capable to significantly improve the performance. After characterizing the dynamic behavior of the sensor system, a properly designed deconvolution filter is used to reduce response time and signal noise. Within this article, we also provide an http://www.sensorsportal.com/HTML/DIGEST/P_2747.htm Sensors &amp; Transducers, Vol. 193, Issue 10, October 2015, pp. 145-153 146 example of this algorithm for a novel electrochemical sensor for the measurement of the anesthetic agent propofol in exhaled air. For this application, the acceleration is prerequisite for the measurement chain to be of practical use in a clinical setting. Our goals, to establish measurement dynamics to record the physiologic parameter and to reduce non-physiological disturbances, were achieved with additional reserves. This article is based o

Fluid transport from the dental pulp revisited.

In the dental pulp surrounded by rigid dentinal walls, an increase in fluid volume will be followed by a rapid increase in interstitial fluid pressure. To maintain pressure homeostasis, a fluid drainage system is required. The dental pulp and apical periodontal ligament lack lymphatic vessels, and the questions are how the transport can take place inside the pulp and where the lymphatic vessels draining fluid from the apical periodontal ligament are located. The drainage of fluid within the pulp must be governed by a tissue pressure gradient (driving pressure) and the fluid is likely transported in loose connective tissue (gaps) surrounding vessels and nerve fibers. We suggest that aging of the pulp tissue characterized by fibrosis will reduce the draining capacity and make it more vulnerable to circulatory failure. When the fluid leaves the pulp, it will follow the nerve bundles and vessels through the periapical ligament into bone channels, where lymphatic vessels are found. In the mandibular canal, lymphatic vessels are localized and the fluid washout rate from the canal is slow, but chewing may speed it up by increasing the fluid pressure. In acute apical periodontitis, inflammatory mediators and bacterial components can be spread to regional lymph nodes via lymphatic vessels inside the jaw bone

Impaired vascular responses to parasympathetic nerve stimulation and muscarinic receptor activation in the submandibular gland in non-obese diabetic mice

Introduction Decreased vascular responses to salivary gland stimulation are observed in Sjögren's syndrome patients. We investigate whether impaired vascular responses to parasympathetic stimulation and muscarinic receptor activation in salivary glands parallels hyposalivation in an experimental model for Sjögren's syndrome. Methods Blood flow responses in the salivary glands were measured by laser Doppler flowmeter. Muscarinic receptor activation was followed by saliva secretion measurements. Nitric oxide synthesis-mediated blood flow responses were studied after administration of a nitric oxide synthase inhibitor. Glandular autonomic nerves and muscarinic 3 receptor distributions were also investigated. Results Maximal blood flow responses to parasympathetic stimulation and muscarinic receptor activation were significantly lower in nonobese diabetic (NOD) mice compared with BALB/ c mice, coinciding with impaired saliva secretion in nonobese diabetic mice (P < 0.005). Nitric oxide synthase inhibitor had less effect on blood flow responses after parasympathetic nerve stimulation in nonobese diabetic mice compared with BALB/c mice (P < 0.02). In nonobese diabetic mice, salivary gland parasympathetic nerve fibres were absent in areas of focal infiltrates. Muscarinic 3 receptor might be localized in the blood vessel walls of salivary glands. Conclusions Impaired vasodilatation in response to parasympathetic nerve stimulation and muscarinic receptor activation may contribute to hyposalivation observed in nonobese diabetic mice. Reduced nitric oxide signalling after parasympathetic nerve stimulation may contribute in part to the impaired blood flow responses. The possibility of muscarinic 3 receptor in the vasculature supports the notion that muscarinic 3 receptor autoantibodies present in nonobese diabetic mice might impair the fluid transport required for salivation. Parasympathetic nerves were absent in areas of focal infiltrates, whereas a normal distribution was found within glandular epithelium