The priming/completion paradigm to explain growth factor-dependent cell cycle progression

Approximately 50 years ago, researchers established conditions to maintain cells in tissue culture Likely et al. (1952) [Further studies on the proliferation in vitro of single isolated tissue cells. J Natl Cancer Inst 13, 177–184]; Scherer et al. (1953) [Studies on the propagation in vitro of poliomyelitis viruses. IV. Viral multiplication in a stable strain of human malignant epithelial cells (strain HeLa) derived from an epidermoid carcinoma of the cervix. J Exp Med 97, 695–710]; Eagle (1955a) [The specific amino acid requirements of a mammalian cell (strain L) in tissue culture. J Biol Chem 214, 839–852]; (1955b) [Nutrition needs of mammalian cells in tissue culture. Science 122, 501–514]. This simple model system set the stage for discovery of growth factors and the signaling systems that they engage to mediate cellular responses such as proliferation. The purpose of this review is to present the original view of how growth factors regulate cell cycle progression and an updated (priming/completion) version of how growth factors advance resting cells through the cell cycle.     

Relationship between Young’s Modulus and Planar Density of Unit Cell,Super Cells (2 × 2 × 2), Symmetry Cells of Perovskite (CaTiO3) Lattice

Calcium titanate-CaTiO₃ (perovskite) has been used in various industrial applications due to its dopant/doping mechanisms. Manipulation of defective grain boundaries in the structure of perovskite is essential to maximize mechanical properties and stability; therefore, the structure of perovskite has attracted attention, because without fully understanding the perovskite structure and diffracted planes, dopant/doping mechanisms cannot be understood. In this study, the areas and locations of atoms and diffracted planes were designed and investigated. In this research, the relationship between Young’s modulus and planar density of unit cell, super cells (2 × 2 × 2) and symmetry cells of nano CaTiO₃ is investigated. Elastic constant, elastic compliance and Young’s modulus value were recorded with the ultrasonic pulse-echo technique. The results were C₁₁ = 330.89 GPa, C₁₂ = 93.03 GPa, C₄₄ = 94.91 GPa and E = 153.87 GPa respectively. Young’s modulus values of CaTiO₃ extracted by planar density were calculated 162.62 GPa, 151.71 GPa and 152.21 GPa for unit cell, super cells (2 × 2 × 2) and symmetry cells, respectively. Young’s modulus value extracted by planar density of symmetry cells was in good agreement with Young’s modulus value measured via ultrasonic pulse-echo.     

The efficacy comparison of on-demand boluses with and without basal infusion of 0.1 % bupivacaine via perineural femoral catheter after arthroscopic ACL reconstruction

Purpose

Optimal postoperative analgesia after anterior cruciate ligament repair remains challenging. The objective of this prospective experimental clinical study was to compare the postoperative analgesic efficacy of two infusion regimens of 0.1 % bupivacaine administered via perineural femoral catheter.

Methods

Forty adult ASA I and II patients undergoing anterior cruciate ligament reconstruction were enrolled. Surgery was performed under spinal anesthesia combined with femoral nerve block. A perineural femoral catheter was connected to the patient controlled analgesia infusion pump filled with 0.1 % bupivacaine for postoperative pain control. Subjects were assigned to one of two groups according to the bupivacaine infusion regimen: (1) 5 mL/h basal infusion with on-demand 5 mL boluses and 30-min refractive periods, and (2) only on-demand 5 mL boluses and 15-min refractive periods. Quality of postoperative analgesia, adjunctive analgesic consumption, and overall patient satisfaction were recorded for 48 h.

Results

Pain control was better in Group I on the day of surgery (P = 0.001) and on the first postoperative day at rest and during mobilization (P = 0.02 and P = 0.009). On the second postoperative day, only pain control during mobilization was better in Group I (P = 0.047). Adjunctive analgesic consumption and patient satisfaction were similar.

Conclusion

Perineural femoral infusion of on-demand 5 mL boluses of 0.1 % bupivacaine combined with 5 mL/h basal infusion was more efficient than on-demand regimen alone for postoperative pain management after reconstruction of anterior cruciate ligament of the knee.

Level of evidence

II.     

Plasmin is the major protease responsible for processing PDGF-C in the vitreous of patients with proliferative vitreoretinopathy

PURPOSE: Proliferative vitreoretinopathy (PVR) is the primary cause of failure of retinal reattachment surgery. Growth factors such as platelet-derived growth factor (PDGF) are strongly associated with PVR. Of the five PDGF family members, PDGF-C predominates in the vitreous of experimental and clinical PVR. PDGF-C is secreted as a latent protein that requires proteolytic processing for activation. Although tissue plasminogen activator (tPA) is primarily responsible for processing PDGF-C in cultured cells, it constitutes a minority of the processing activity in the vitreous of experimental animals and in patients with PVR. Identifying the major PDGF-C processing protease was the purpose of this study. METHODS: The presence of serum proteins in the vitreous was detected by Coomassie blue staining and Western blotting. PDGF-C processing activity was detected in an in vitro processing assay using either native or recombinant PDGF-C as the substrate. Plasmin activity was blocked using alpha(2)-plasmin inhibitor. Phosphorylation of the PDGF receptor (PDGFR) was monitored by antiphosphotyrosine Western blotting. Vitreous specimens were collected from experimental rabbits or from patients undergoing vitrectomy to repair retinal detachment or for other reasons. RESULTS: A number of prominent serum proteins (albumin and IgG) were detected in the vitreous of all patients undergoing retinal surgery. The level of these proteins markedly increased in the vitreous of rabbits as they developed PVR. These observations suggested that serum-borne proteases are also likely to be present in the vitreous. Indeed, plasmin (a protease capable of processing PDGF-C) was present in the vitreous from PVR rabbits and retinal surgery patients. Plasmin was dramatically more effective than tPA in processing PDGF-C in an in vitro assay. Blocking plasmin activity eliminated most of the processing activity in the vitreous of patients and rabbits with PVR. CONCLUSIONS: Plasmin was the major PDGF-C processing protease in the vitreous of PVR rabbits and patients undergoing retinal surgery. Blocking plasmin prevented the generation of active PDGF-C, which is the major PDGF isoform relevant for PVR. These observations are the first report of an in vivo protease responsible for processing PDGF-C. In addition, plasmin was identified as a novel therapeutic target for patients with PVR.     

Prevalence of Malnutrition in Various Political,Economic, and Geographic Settings

Background: Disease‐related malnutrition (DRM) represents a critical public health concern. Therefore, Fight Against Malnutrition (FAM) should be a state priority, but the degree to which this is true appears to differ considerably among European countries. The aim of this study was to put the problem into perspective by comparing the prevalence of malnutrition in countries from opposite parts of the continent. Methods: Six countries—Croatia, Estonia, Greece, Lithuania, Poland, and Turkey—participated in the study. A short questionnaire was used to assess DRM: its prevalence, the current situation in hospitals, regulations for reimbursement, and general healthcare circumstances. Data from ESPEN's NutritionDay 2006 were used to broaden the perspective. Results: At admission in October 2012, 4068 patients were assessed. The study was performed in 160 hospitals and 225 units with 9143 beds. The highest proportions of patients with 3 or more points on the Nutritional Risk Screening 2002 were observed in Estonia (80.4%) and Turkey (39.4%), whereas the lowest were in Lithuania (14.2%). The provision of nutrition support was best in Turkey (39.4% required intervention, 34.4% received intervention) and Poland (21.9% and 27.8%, respectively). Nutrition support teams (NSTs) are active in some countries, whereas in others they virtually do not exist. Conclusion: The prevalence of malnutrition was quite high in some countries, and the nutrition approach differed among them. It could be the result of the lack of reimbursement, inactive or nonexistent NSTs, and low nutrition awareness. Those facts confirmed that the continuation of FAM activities is necessary.     

Effects of 5 wt.% Polycaprolactone,Polyhydroxybutyrate and Polyvinyltrimethoxysilane on the Properties of Ag/Zn/Mg Alloy

Mg-based alloys have several suitable properties for biomaterials, but they have major problems of being less antibacterial and have a low mechanical strength. To solve these problems, a new combination of Ag/Zn/Mg was prepared in this study, where the presence of Zn and Ag can help to increase the bioactivity. The use of 5 wt.% polymers consisting of PolyCaproLactone (PCL), PolyHydroxyButyrate (PHB) and PolyVinylTriMethoxySilane (PVTMS) is also investigated. DSC, XRD, TEM, FTIR, SEM, and EDAX analysis, as well as mechanical and bioactive behavior, were investigated to characterize the prepared composites. In the comparison, the best behavior was found when PHB was used. The results show that the strength values ranged from ~201 to 261 MPa.     

PI3K and PLCgamma play a central role in experimental PVR

PURPOSE: It has been reported that the platelet-derived growth factor (PDGF)-alpha receptor (alphaPDGFR) is required for experimental proliferative vitreoretinopathy (PVR) in rabbits. This study investigated which of the signaling enzymes downstream of the alphaPDGFR participate in PVR. METHODS: A panel of cell lines that expressed alphaPDGFR signaling mutants were made and characterized. These cell lines were used in a rabbit model of PVR and in an in vitro collagen type I contraction assay. RESULTS: Phosphoinositide 3-kinase (PI3K) and, to a lesser extent, phospholipase C (PLC)-gamma were the signaling enzymes required for the alphaPDGFR to mediate PVR. Furthermore, the cells lines that were the most effective at inducing PVR displayed the most potent activity in the in vitro contraction assay. CONCLUSIONS: PI3K and PLCgamma are necessary downstream effectors of the alphaPDGFR in experimental PVR. Consequently, these two signaling enzymes are required for one or more of the cellular responses (chemotaxis, proliferation, extracellular matrix production, contraction) that contribute to PVR.