Soluble perlecan domain i enhances vascular endothelial growth factor-165 activity and receptor phosphorylation in human bone marrow endothelial cells

<p>Abstract</p> <p>Background</p> <p>Immobilized recombinant perlecan domain I (PlnDI) binds and modulates the activity of heparin-binding growth factors, <it>in vitro</it>. However, activities for PlnDI, in solution, have not been reported. In this study, we assessed the ability of soluble forms to modulate vascular endothelial growth factor-165 (VEGF₁₆₅) enhanced capillary tube-like formation, and VEGF receptor-2 phosphorylation of human bone marrow endothelial cells, <it>in vitro</it>.</p> <p>Results</p> <p>In solution, PlnDI binds VEGF₁₆₅in a heparan sulfate and pH dependent manner. Capillary tube-like formation is enhanced by exogenous PlnDI; however, PlnDI/VEGF₁₆₅mixtures combine to enhance formation beyond that stimulated by either PlnDI or VEGF₁₆₅alone. PlnDI also stimulates VEGF receptor-2 phosphorylation, and mixtures of PlnDI/VEGF₁₆₅reduce the time required for peak VEGF receptor-2 phosphorylation (Tyr-951), and increase Akt phosphorylation. PlnDI binds both immobilized neuropilin-1 and VEGF receptor-2, but has a greater affinity for neuropilin-1. PlnDI binding to neuropilin-1, but not to VEGF receptor-2 is dependent upon the heparan sulfate chains adorning PlnDI. Interestingly, the presence of VEGF₁₆₅but not VEGF₁₂₁significantly enhances PlnDI binding to Neuropilin-1 and VEGF receptor-2.</p> <p>Conclusions</p> <p>Our observations suggest soluble forms of PlnDI are biologically active. Moreover, PlnDI heparan sulfate chains alone or together with VEGF₁₆₅can enhance VEGFR-2 signaling and angiogenic events, <it>in vitro</it>. We propose PlnDI liberated during basement membrane or extracellular matrix turnover may have similar activities, <it>in vivo</it>.</p

Relevance of ratio of neck circumference to thyromental distance in predicting difficult intubation

Background and Objectives: Airway assessment is the most important aspect of anaesthetic practice as a difficult intubation may be unanticipated. A study was done to know the relevance of ratio of neck circumference to thyromental distance in predicting difficult intubation in general Indian population coming for surgery. Materials and methods: 500 Patients with ASA PS I&amp; II were enrolled in the study were preoperatively assessed for airway parameters such as Modified mallampati classification, thyromental distance, sternomental distance, neck circumference to thyromental distance ratio and Wilson score. Intra-operatively all patients were classified according to Cormack and Lehane laryngoscopic view. Results: The mean age, Weight, Height and BMI of patients in our study was 34.43 years, 61.07 kg,69.2cms and 21.2 respectively. In our study we had a total of 15 difficult intubation with all of them belonging to Cormack-Lehane grade III. In our study we noted that among 15 patients with CLIII/IV only 4 had a SMD≤15.75 cm. With that we noted a sensitivity, specificity, PPV and NPV of 26.7%,75.1%,3.2% and 97.1%. Among 15 patients with CLIII/IV only 2 of them had Wilson score of more than 3.&nbsp

Preoperative ultrasound guided inferior venacava collapsibility index as a guide to predict hypotension following spinal anaesthesia in patients scheduled for elective surgery

Background: Spinal anaesthesia is the most commonly employed anaesthetic technique for infraumbilical surgeries. Post spinal hypotension is a commonly encountered complication which can lead to organ under perfusion and ischemia. Severe episodes of intraoperative hypotension have been proposed as an independent risk factorin the development of postoperative adverse outcomes and prolonged hospital stay. However, there are no reliable methods to determine which patients are at risk for spinal induced hypotension. This study investigated whether preoperative ultrasound guided inferior venacava collapsibility index (IVC-CI) could predict hypotension following spinal anaesthesia. Objectives were to measure inferior venacava collapsibility index and to compare the incidence of hypotension following spinal anaesthesia among patients with IVC-CI&gt;50% and patients with IVC-CI&lt;50%. Materials and Methods: This prospective observational study was conducted in the department of anaesthesia, Yenepoya Medical College Hospital, Mangalore during the period between October 2016 to October 2018. After ethical committee approval and informed consent, 73 patients belonging to “American society of Anesthesiology” (ASA) grade I &amp; II, aged between 18 to 65 years, scheduled for elective surgeries which require spinal anaesthesia were selected. Preoperative ultrasonography was done to determine the IVC-CI in these patients. All ultrasonographic examinations were performed by the same anaesthesiologist.&nbsp

The fibroblast growth factor receptor, FGFR3, forms gradients of intact and degraded protein across the growth plate of developing bovine ribs.

Point mutations in the human fibroblast growth factor (FGF) receptor 3 gene (Fgfr3) produce a constitutively active receptor, which disrupts chondrocyte differentiation in the growth plate and results in skeletal dysplasias with severe shortening of the limbs. Alternative splicing of the Fgfr3 transcript gives rise to two isoforms, IIIc and IIIb, which vary in their specificity for FGF ligands. We examined the expression of these FGFR3 isoforms in the bovine fetal rib growth plate to determine whether levels of FGFR3 expression are zone-related. Transcripts for both Fgfr3 isoforms are expressed in rib growth plate, with maximum expression in the hypertrophic region and the least expression in the reserve zone. Fgfr3 IIIc is the predominant isoform in the growth plate. Western-blot analysis revealed the presence of full-length FGFR3 (135 kDa) for both isoforms in the reserve zone, a major 98 kDa fragment in all zones and smaller fragments primarily in the hypertrophic zone. Immunostaining localized FGFR3 to the pericellular region of reserve chondrocytes and to the extracellular matrix in the hypertrophic zone. These results suggest that the transmembrane form of FGFR3 increasingly undergoes proteolytic cleavage towards the hypertrophic zone to produce an extracellular-domain fragment of FGFR3, which is present in large amounts in the matrix of hypertrophic cells. These findings suggest a proteolytic regulatory mechanism for FGFR3, whereby Fgfr3 fragments could control availability of FGF for the intact receptor, and by which proteolysis could inactivate the receptor