Platelet Growth Research Articles

Platelets Feeding Bacteria with Lactate during Room Temperature Storage: Mitigated By Refrigeration

Introduction: Platelet transfusion related sepsis is a serious concern limiting platelet storage time to 5 days. Room temperature (RT) storage of platelets increases the risk of bacterial growth and necessitates implementation of bacterial contamination monitoring. Cold storage of platelets represents an attractive alternative for improving platelet safety. In this study, we assessed bacterial growth in platelets stored either at room temperature (22oC) or refrigerated (4oC).Methods: Apheresis platelets in plasma (PLT) were obtained from healthy donors using the Terumo Trima Accel Automated Blood Collection System (Terumo BCT). Platelet poor plasma (PPP) was obtained from PLT aliquots centrifuged twice at 2,500 x g for 5 min. In some experiments aliquots of PPP were supplemented with 5 to 20 mM lactic acid. Aliquots of PLT or PPP were transferred to pH SAFE minibags (Blood Cell Storage, Inc) and inoculated with Acinetobacter baumannii strains Ci77 or Ci79, Escherichia coli, Pseudomonas aeruginosa, or PBS (uninfected control). Minibag aliquots stored at RT were agitated using an orbital shaker set to 60 rpm while refrigerated aliquots were stored under static conditions. Bacterial growth was monitored daily through dilution plating. Lactate levels in PLT aliquots were assessed by iSTAT (Abbott) using CG4+ test cartridges. Platelet activation and aggregation were assessed on days 0, 1, 3, and 5 by flow cytometry and Multiplate platelet aggregometry respectively.Results: Growth of A. baumannii progressed exponentially over the first 3 days post-collection in PLT aliquots stored at RT. However, growth was significantly (p < 0.05) reduced in PPP units. Growth of E. coli and P. aeruginosa, both of which are capable of utilizing glucose present in the anticoagulant used, grew at significantly faster rates and did not seem to be dependent on metabolically active PLTs. Lactate levels were assessed in PLT units and found to mirror growth of A. baumannii . Furthermore, addition of ≥ 15 mM lactic acid to RT stored PPP restored A. baumannii growth. Although lactate levels did not appear to contribute to growth of E. coli, lactate levels began to decrease in PLT units contaminated with the bacterium at a rapid rate after day 3. Lactate levels in units contaminated with P. aeruginosa increased throughout the observation window. Bacterial growth remained static throughout under all treatment conditions stored refrigerated and lactate levels were reduced. PLT also appeared to retain function throughout cold storage irrespective of bacterial contamination while RT storage resulted in a decrease in aggregation over time which was exacerbated by bacterial contamination.Conclusions: Bacterial growth remained static throughout under cold storage. Additionally, PLT lactate production was increased at RT and correlated with increased growth of A. baumannii . Growth of E. coli and P. aerugionsa appeared to proceed independently of lactate production or metabolically active PLTs. However, E. coli did appear to utilize lactate as a carbon source at later time points. These data demonstrate that bacterial growth can be controlled through refrigeration without loss of function and RT stored platelets may potentiate growth of certain bacterial strains through accelerated metabolism relative to cold storage. DisclosuresNo relevant conflicts of interest to declare.

Deferasirox Boosts Hematopoietic Recovery after ALLO-Sct

The attainment of transfusion independence after transplant is sometimes hampered by a combination of factors, ranging from infections to the need of combined therapy for clinical complications, as well as control of GVHD. Iron overload is frequently observed in hematological patients before and after hematopoietic stem cell transplantation (HSCT). Whereas several reports have focused on iron overload before transplant, up to now, this is the only report that show full recovery of hematopoiesis and correlate this to deferasirox chelation performed on this particular subset of patients. We report on 19 patients, transplanted for hematological diseases (17 acute leukemia, 1 aplastic anemia, 1 multiple myeloma) heavily transfused before transplant that, considering the iron overload, were treated with deferasirox after HSCT. Before starting deferasirox, the patients were fully engrafted and in complete remission, although transfusion dependent, and with incomplete hematological reconstitution after allogeneic HSCT. Patients were selected according to the following inclusion criteria: 1) transfused pre-transplant with more than 20 RBC units; 2) incomplete hematological recovery; 3) transfusion-dependence; 4) serum ferritin > 1000 ng/mL; 5) normal creatinine value. The workup for other aetiologies resulted negative. All patients received an initial dose of deferasirox 10 mg/kg/day, later adjusted according to side effects. All patients experienced an increase in hemoglobin levels, with a reduction in the frequency of RBC transfusions, followed by transfusion independence (median time: 24 days from the first dose of deferasirox). In addition, it was promptly (median time: 27 days) associated with hematological improvement, with sustained values and no further platelet support or growth factors administration. No relevant modifications with immunosuppressive or myelosuppressive drugs were made during deferasirox treatment. Deferasirox was well tolerated. Basing on our results, we think that deferasirox determined stimulatory, and/or depressive effects on hematopoiesis after allo-HSCT. In conclusion, this clinical experience raises the possibility of a potential additive benefit on hematopoiesis after transplant following iron chelation therapy with oral deferasirox. Further long term studies, in larger cohorts of patients are needed to confirm these data and design an efficient strategy to reduce iron loading after transplant. Acknowledgments: supported in part by AIL Pesaro Onlus. DisclosuresIsidori:Lundbeck: Consultancy, Honoraria.

Expression of angiogenesis-related proteins in bone marrow mesenchymal stem cells induced by osteoprotegerin during osteogenic differentiation in rats

This study aimed to discuss the expression of angiogenesis-related proteins in bone marrow mesenchymal stem cells (BMSCs) induced by osteoprotegerin (OGP) during osteogenic differentiation in rats, and to analyze the effect of fracture healing inflammatory factor TNF-ɑ on the osteogenic differentiation of BMSCs of rats. BMSCs isolated and cultured from the third generation rats were taken as the research object. According to the addition amount of OGP, BMSCs were divided into control group, OGP (10−7 mol/L) group, OGP (10−8 mol/L) group, and OGP (10−9 mol/L) group. The cell growth and morphological characteristics of each group were observed by inverted phase contrast microscope, the cell proliferation rate was measured by MTT method, angiogenesis-related markers (platelet growth factor (VEGF), cingulate protein 5 (Fbln5), and angiogenin-like protein 4 (Angptl4)) were quantitatively detected by Western blot, and the effect of TNF-ɑ on osteogenic differentiation was detected by CCK. Compared with the control group, MTT results showed that the value-added rate of cells in the OGP (10−8 mol/L) group reached the maximum at 9 days (P < 0.05). The ALP activity in osteoblasts in the OGP (10−8 mol/L) group reached the maximum at 9 days (P < 0.01). The OGP (10−8 mol/L) group had the highest expression of vascular regeneration proteins (VEGF, Fbln5, and Angptl4) (P < 0.05). CCK analysis showed that the TNF-ɑ (1.0 ng/mL) group showed a significant increase in absorbance compared with the control group on 6 days (P < 0.05), and the OD value of the TNF-ɑ (10 ng/mL) group decreased at all time points (P < 0.05). Overall, 10−8 mol/L OGP can induce the proliferation and osteogenic differentiation of MSCs, and promote the expression of angiogenesis-related proteins (VEGF, Fbln5, and Angptl4) during osteogenic differentiation. Besides, 1.0 ng/mL of TNF-ɑ can also promote osteogenesis differentiation of BMSCs in the short term.

Hemodialysis exacerbates proteolytic imbalance and pro-fibrotic platelet dysfunction

Multi-organ fibrosis among end stage renal disease (ESRD) patients cannot be explained by uremia alone. Despite mitigation of thrombosis during hemodialysis (HD), subsequent platelet dysfunction and tissue dysregulation are less understood. We comprehensively profiled plasma and platelets from ESRD patients before and after HD to examine HD-modulation of platelets beyond thrombotic activation. Basal plasma levels of proteolytic regulators and fibrotic factors were elevated in ESRD patients compared to healthy controls, with isoform-specific changes during HD. Platelet lysate (PL) RNA transcripts for growth and coagulative factors were elevated post-HD, with upregulation correlated to HD vintage. Platelet secretome correlations to plasma factors reveal acutely induced pro-fibrotic platelet phenotypes in ESRD patients during HD characterized by preferentially enhanced proteolytic enzyme translation and secretion, platelet contribution to inflammatory response, and increasing platelet dysfunction with blood flow rate (BFR) and Vintage. Compensatory mechanisms of increased platelet growth factor synthesis with acute plasma matrix metalloproteinase (MMP) and tissue inhibitor of MMPs (TIMP) increases show short-term mode-switching between dialysis sessions leading to long-term pro-fibrotic bias. Chronic pro-fibrotic adaptation of platelet synthesis were observed through changes in differential secretory kinetics of heterogenous granule subtypes. We conclude that chronic and acute platelet responses to HD contribute to a pro-fibrotic milieu in ESRD.

Comparing novel versus conventional technique of platelet-rich plasma therapy in periorbital hyperpigmentation: A randomized prospective split-face study.

Platelet-rich plasma (PRP) has been found to be effective in treating periorbital hyperpigmentation (POH). PRP prepared by double-spin (DS) method and activated by calcium has been used conventionally. PRP can be prepared by single spin (SS) and activated at low temperature (novel method), but the evidence is limited. To compare the novel and conventional PRP in the treatment of periorbital hyperpigmentation. We selected 21 patients of POH and randomly divided the face into two halves. One-half of the face (group A) was treated with novel PRP (SS and low-temperature activation). The other half (group B) was treated with conventional PRP (DS and calcium activation). A total of 3 PRP injections were given at 4 weekly intervals. Patients were observed and assessed on 12th week by photography, dermoscopy, visual analog scale (VAS) score, and Dermatology life quality index (DLQI). Platelet counts and growth factors were assessed in PRP. Mean platelet count in novel and conventional PRP was 7.41±1.76 lacs and 8.17±2.23 lacs (p=0.348). Mean photographic and dermoscopic assessment at the end of the study in group A and group B was 52.33±6.468 and 53.14±6.99 (p=0.151). Change in VAS in groups A and B was 3.85±1.27 and 3.90±1.04 (p=0.895). Levels of various growth factors assessed by ELISA did not differ significantly. There was significant decline in DLQI. The novel method is not inferior to conventional method of PRP in the treatment of periorbital hyperpigmentation.

In-situ synthesis of TiN and TiB2 compounds during reactive spark plasma sintering of BN–Ti composites

A BN-TiB2-TiN composite was produced via reactive sintering of the hexagonal BN (hBN) with 20 wt% Ti. Spark plasma sintering (SPS) was used as the fabrication method and the sample was characterized by X-ray diffractometry, energy-dispersive X-ray spectroscopy, and scanning electron microscopy. According to the results, the Ti was utterly consumed during the SPS, led to the in-situ TiB2 and TiN0.9 formations. Additionally, the microstructural study revealed the nucleation and growth of new hBN platelets from the initial fine hBN particles. Anyway, the final composite reached a relative density of 95%, because of the remaining free spaces between the hBN platelets. It was found that some nitrogen and boron atoms could leave the TiN and TiB2 microstructures, respectively, and diffuse into the opposing phase.

Effect of Intrauterine Infusion of Equine Fresh Platelets-Rich Plasma (PRP) or Lyophilized PRP (L-GFequina) on Ovarian Activity and Pregnancy Rate in Repeat Breeder Purebred Arabian Mares.

Simple SummaryPersistent endometritis is one of the major causes of infertility in mares and results in endometrium degeneration, namely, endometrosis. Platelets-rich plasma (PRP) is an emerging therapeutic application in tissue regeneration because of its high concentration of growth factors with a high mitogenic and anti-inflammatory potential, but reduced preservation time. L-GFequina is a freeze-dried, stabilized, platelet-rich plasma product (PP) that can be stored at 2 to 8 °C for several months. It can be easily used after reconstitution with sterile saline or water, eliminating the need for repeated blood product collection and special equipment. The intrauterine infusion of equine platelet-rich plasma or L-GFequina can be used indistinctly in repeat breeder mares, shortening the estrous cycle, with no significant effect on the follicular diameter, as well as increasing pregnancy rate in Arabian purebred mares.This study was designed to examine the effect of the intrauterine infusion of platelet-rich plasma (PRP) or equine lyophilized growth factor (L-GFequina) on the follicular growth, endometrial thickness, estrus cycle length, and pregnancy rate in purebred Arabian mares. A total of 73 purebred Arabian mares who experienced repeat breeding for three successive cycles were randomly divided into the following three groups: control group, without treatment; second Group (PRP group), in which mares were intrauterine infused with 20 mL of fresh PRP on the second day after the end of physic estrus phase; and the third group (L-GFequina Group), consisting of mares that were intrauterine infused with 20 mL of reconstituted lyophilized horse platelets growth factors (L-GFequina) on the second day after the estrus phase. The results showed no significant difference between control and treated groups in the diameter of the preovulatory follicles during the post treatment cycle. The endometrium thickness increased significantly in the L-GFequina and PRP groups ahead of the non-treated group. Intrauterine L-GFequina or PRP administration shortened the estrus cycle length. A higher pregnancy rate was recorded in the L-GFequina and PRP treated mares. In conclusion, the intrauterine infusion of L-GFequina or PRP increased the endometrial thickness and pregnancy rate and could be used to improve fertility in Arabian purebred mares who experienced from repeat breeding.

Current applications of platelet gels in wound healing-A review.

Human platelets play important roles in several physiologic and pathologic processes. Platelet concentrates are activated with thrombin or calcium, resulting in a viscous coagulum (platelet gel [PG]), composed of 95% platelets at least. PG is increasingly used for the treatment of a variety of soft and hard tissue defects, most notably in the management of chronic non-healing wounds. During wound healing, platelets not only play a critical role in primary hemostasis and thrombosis, but also release growth factors and cytokines to promote tissue regeneration, enhance collagen synthesis, and trigger an immune response. This review addresses a variety of aspects relevant to the functions of well-known platelet growth factors, animal and clinical studies of PG in the last decade, and different sources of platelets for PG. PG is used for non-healing chronic wounds, such as oral ulcerations related to epidermolysis bullosa and chronic graft-versus-host disease, for those, the traditional treatment effect is poor. PG maybe provide a new therapeutic direction for these diseases. Nevertheless, some uncertainty is present, the number of clinical studies is not enough. Hence, randomized controlled trials are still required to study the potential of the use of PG in the near future.

A Prospective, Randomized, Controlled Trial Comparing Clinical Outcomes of Intraarticular Platelet Plasma Concentrate and Growth Factors versus Corticosteroid Injections in the Treatment of Knee Osteoarthritis

A Prospective, Randomized, Controlled Trial Comparing Clinical Outcomes of Intraarticular Platelet Plasma Concentrate and Growth Factors versus Corticosteroid Injections in the Treatment of Knee Osteoarthritis

On the formation of α-alumina single crystal platelets through eggshell membrane bio-templating

The formation of α-Al2O3 platelets by a bio-templating route using eggshell membranes is investigated. A facile solution soakage method was employed for the synthesis of Al2O3. X-ray diffraction results indicated the Al2O3 phase transformations occurring with the calcination temperature. The growth of α-Al2O3 platelets were carefully studied using scanning and transmission electron microscopes. The biomacromolecules and functional groups present on the eggshell membrane bio-template played a crucial role in the formation of α-Al2O3 platelets. A plausible growth mechanism based on the oriented attachment growth process involving the role of eggshell membrane has been proposed. This study paves the insight for the development of α-Al2O3 anisotropic structures through bio-templated approach.

Does Platelet-Rich Fibrin Enhance the Early Angiogenetic Potential of Different Bone Substitute Materials? An In Vitro and In Vivo Analysis.

The impaired angiogenic potential of bone substitute materials (BSMs) may limit regenerative processes. Therefore, changes in the angiogenetic properties of different BSMs in combination with platelet-rich fibrin (PRF) in comparison to PRF alone, as well as to native BSMs, were analyzed in vitro and in vivo to evaluate possible clinical application. In vitro, four BSMs of different origins (allogeneic, alloplastic, and xenogeneic) were biofunctionalized with PRF and compared to PRF in terms of platelet interaction and growth factor release (vascular endothelial growth factor (VEGF), tissue growth factor ß (TGFß) and platelet-derived growth factor (PDGF)) after 15 min. To visualize initial cell–cell interactions, SEM was performed. In vivo, all BSMs (±PRF) were analyzed after 24 h for new-formed vessels using a chorioallantoic membrane (CAM) assay. Especially for alloplastic BSMs, the addition of PRF led to a significant consumption of platelets (p = 0.05). PDGF expression significantly decreased in comparison to PRF alone (all BSMs: p < 0.013). SEM showed the close spatial relation of each BSM and PRF. In vivo, PRF had a significant positive pro-angiogenic influence in combination with alloplastic (p = 0.007) and xenogeneic materials (p = 0.015) in comparison to the native BSMs. For bio-activated xenogeneic BSMs, the branching points were also significantly increased (p = 0.005). Finally, vessel formation was increased for BSMs and PRF in comparison to the native control (allogeneic: p = 0.046; alloplastic: p = 0.046; and xenogeneic: p = 0.050). An early enhancement of angiogenetic properties was demonstrated when combining BSMs with PRF in vitro and led to upregulated vessel formation in vivo. Thus, the use of BSMs in combination with PRF may trigger bony regeneration in clinical approaches.

A Multi-Donor Ex Vivo Platelet Activation and Growth Factor Release Study Using Electric Pulses With Durations Up to 100 Microseconds

In vitro platelet activation is established in various clinical settings for wound healing and tissue regeneration. After separating platelet rich plasma (PRP) from whole blood, a biochemical activator, typically bovine thrombin (BT), is applied to activate PRP, which clots the PRP and releases growth factors beneficial for wound healing. BT’s drawbacks, particularly cost, availability, workflow challenges, and potential immune responses, motivated the development of ex vivo electrical activation of PRP using pulsed electric fields (PEFs) with durations on the order of hundreds of nanoseconds and electric field strengths from $\sim 10$ -100 kV/cm. PEFs permeabilize platelets to facilitate Ca2+ transport into the cells to induce platelet activation; however, membrane permeabilization does not require PEFs of such short duration and high intensity. This study demonstrates that 5- $100~\mu \text{s}$ duration PEFs effectively activate platelets. Treating PRP with ten different single pulse waveforms with durations between 5 and $100~\mu \text{s}$ induces similar or higher levels of platelet derived, vascular endothelial, and epidermal growth factor release compared to BT. These results indicate the potential clinical relevance of microsecond PEFs for platelet stimulation, which may reduce the expense and device footprint for PEF mediated platelet stimulation compared to nanosecond pulse generators, facilitating technology transition for clinical and trauma applications.

Biological coaching: Treatment with plaquet growth factors, report of a case of partial ACL tear

The injury of the anterior cruciate ligament of the knee represents an entity of great importance, both for its frequency and for the absenteeism at work and sport it causes. In total fractures, the resulting residual instability alters normal biomechanics and predisposes to the development of degenerative changes. In partial ruptures, described more than 50 years ago, the current management is controversial, between suturing the extremities, physiotherapy and / or regenerative therapies such as intra-articular use of platelet growth factors, and we decided for the latter to apply it in the case that we present, in a male patient of 25 years, who suffered a partial break of right ACL when injured playing soccer. The application was made 72 hours after the lesion. MRI controls were performed before and after the intra-articular application of Growth Factors.

Hearing dynamics in acute traumatic perforation of the tympanic membrane after application of blood plasma enriched with platelet growth factors

The article considers the possibility of treating patients with acute traumatic perforation of the eardrum with a single application of blood plasma enriched with platelet-derived growth factors in the perforation area. As a result of the studies, it was found that the acceleration of its closure and the restoration of hearing. The study included 43 patients with unilateral acute PBP of various etiologies (Table 1). Patients were divided into 2 groups - the main - 24 patients (10 men and 14 women), the average age - 30±9.7 years and the control - 19 patients (9 men and 10 women), the average age - 26.5±6.37 years. The compared groups did not reliably differ in age, gender, frequency and severity of hearing impairment. Analyzing the results, we can confidently talk about the beneficial effect of blood plasma enriched in platelet-derived growth factors on the speed, completeness of closure of traumatic perforation of the eardrum and the dynamics of restoration of auditory function. The use of blood plasma enriched with platelet growth factors led to a regular reduction in the time and increase in the frequency of cases of early closure of perforated eardrum, as well as improvement and restoration of auditory function according to the results of tonal threshold audiometry and otoacoustic emission in dynamics. Being generally available even in outpatient practice, the method of a single application of blood plasma enriched with platelet growth factors in the area of perforation of the tympanic membrane can significantly accelerate the healing process of the tympanic membrane, while improving the quality of life of the patient.

Application of platelet-rich plasma for canine osteoarthritis treatment - a clinical series

Osteoarthritis, also known as degenerative joint disease (DJD), is defined as a progressive and permanent long-term deterioration of the cartilage surrounding the joints. There is no known cause for primary DJD. However, there are a wide variety of causes for secondary DJD, such as trauma, abnormal wear of joints and cartilage, or a congenital defect present at birth such as an improperly formed hip. One of the most popular methods used to biologically enhance healing in the fields of orthopaedic surgery and medicine includes the use of autologous blood products, namely, platelet rich plasma (PRP). Reports suggest that PRP, presumably containing high levels of platelet growth factors, may promote the recovery of the affected cartilage. This case series presents clinical and radiographic findings of three dogs with osteoarthritis of the elbow and knee joints. Pain score were assessed by CBPI (Canine Brief Pain Inventory). Treatment with three-fold intra-articular application of PRP, obtained by double centrifugation method, resulted in significant improvement in the function of the affected joint. Therefore, it could be concluded that PRP was clinically effective in the treatment of osteoarthritis in these three cases.

Экспериментальное обоснование клинического применения стимуляторов остеогенеза в травматологии и ортопедии (обзор литературы)

Analysis of scientifi c publications devoted to effi cacy assessment and experimental justifi cation of cell technology and growth factors application for osteogenesis stimulation in clinical practice of traumatologists-orthopaedists.The search was performed for papers published in PubMed and E-library digital databases within the period of 2010-2020. The search filter was set to explore randomised clinical trials. Th e key words were: “platelet growth factor OR vascular endothelial growth factor OR bone morphogenetic proteins OR autologous bone marrow stromal cells AND bone defect AND human”. Works dated 2010-2020 were selected for analysis of experimental studies using the following key word combinations: “mesenchymal stromal cells AND osteogenesis OR bone regeneration”, “growth factors AND mesenchymal stromal cells AND osteogenesis OR bone regeneration”. In addition, essential literatures describing properties of multipotent mesenchymal stromal cells (MSCs) were cited as well as issues in their osteogenic diff erentiation. Despite the great number of experimental works related to cell technology application for bone growth stimulation, a large variety of unresolved issues associated with optimal means to create such cells, their cultivation and combined application with morphogenetic proteins and growth factors remains. Clinical application of rhBMP-2, PDGF has demonstrated effi cacy in complex treatment of patients with bone defects. Th erewith, growth factors may be effi caciously used in diff erent combinations with MSCs. In a number of cases, application of implants enriched with growth factors may become an alternative for autogenic grafts. To the present day, there is crucial defi cit in the number of works presenting results of randomised controlled clinical trials devoted to stimulation of bone tissue repair. The controversial results of the publications analysed may be based on a low number of patients enrolled. With consideration for active development of reparative medicine as a whole, further investigation of possibilities in bone growth stimulation with local application of cell-engineering constructions is considered to be a promising trend for traumatology and orthopaedics.

Receptor-driven invasion profiles in diffuse intrinsic pontine glioma.

BackgroundDiffuse intrinsic pontine glioma (DIPG) is a devastating pediatric cancer with unmet clinical need. DIPG is invasive in nature, where tumor cells interweave into the fiber nerve tracts of the pons making the tumor unresectable. Accordingly, novel approaches in combating the disease are of utmost importance and receptor-driven cell invasion in the context of DIPG is under-researched area. Here, we investigated the impact on cell invasion mediated by PLEXINB1, PLEXINB2, platelet growth factor receptor (PDGFR)α, PDGFRβ, epithelial growth factor receptor (EGFR), activin receptor 1 (ACVR1), chemokine receptor 4 (CXCR4), and NOTCH1.MethodsWe used previously published RNA-sequencing data to measure gene expression of selected receptors in DIPG tumor tissue versus matched normal tissue controls (n = 18). We assessed protein expression of the corresponding genes using DIPG cell culture models. Then, we performed cell viability and cell invasion assays of DIPG cells stimulated with chemoattractants/ligands.ResultsRNA-sequencing data showed increased gene expression of receptor genes such as PLEXINB2, PDGFRα, EGFR, ACVR1, CXCR4, and NOTCH1 in DIPG tumors compared to the control tissues. Representative DIPG cell lines demonstrated correspondingly increased protein expression levels of these genes. Cell viability assays showed minimal effects of growth factors/chemokines on tumor cell growth in most instances. Recombinant SEMA4C, SEM4D, PDGF-AA, PDGF-BB, ACVA, CXCL12, and DLL4 ligand stimulation altered invasion in DIPG cells.ConclusionsWe show that no single growth factor-ligand pair universally induces DIPG cell invasion. However, our results reveal a potential to create a composite of cytokines or anti-cytokines to modulate DIPG cell invasion.

Аміно-1,2,4-триазоли як сировина для промисловості тонкого органічного синтезу (огляд).

AMINO-1,2,4-TRIAZOLES AS A RAW MATERIAL FOR THE FINE ORGANIC SYNTHESIS INDUSTRY (REVIEW) © V.N. Nazarov, PhD in technical sciences, D.V. Miroshnichenko, Doctor of Technical Sciences, A.A. Ivakh, B.V. Uspensky (NTU "Kharkov Polytechnic Institute", 61002, Kharkov, Kirpicheva st., 2, Ukraine) The review summarizes the information on the industrial use of 3- and 4-amino-1,2,4-triazoles - the basic raw material for the industry of fine organic synthesis. 3 and 4-substituted amino-1,2,4-triazoles have been used for a long time in the production of agricultural products, pharmaceuticals, dyes, high-energy materials, and anti-corrosion additives. Less well known is their use for the production of analytical reagents, flotation reagents, as well as for the production of heat-resistant polymers, products with fluorescent properties and ionic liquids, which are used in applied sciences, biotechnology, energy, and chemistry. The purpose of this communication is to consider in detail the participation of 3- and 4-amino-1,2,4- triazoles in the production and use of various agricultural and medical products. Descriptions and schemes of chemical reactions of existing production methods for the synthesis of 3- and 4-amino-1,2,4-triazoles, as well as some methods of obtaining these substances in laboratory conditions, are given. The two main areas of use of these amines and their derivatives: agriculture and medicine have been highlighted. It is shown that one of the most well-known branches of widespread use of 3- and 4- amino-1,2,4-triazoles in agriculture is the production of plant protection products. On the basis of these substances, the mass production of various insecticides, fungicides, plant growth regulators, retardants (means for suppressing the growth of stems and shoots), inhibitors of nitrification of nitrogen fertilizers is organized. The use of these amines in medicine consists in the production of known drugs on their basis, such as furazonal (has a pronounced antimicrobial effect, is effective against Staphylococcus aureus, dysentery bacteria, salmonellosis), thiotriazoline and cardiotril (cardiological drugs with anti-ischemic and membrane stabilizing effects) (platelet growth factor antagonist). Keywords: amino-1,2,4-triazoles, production, raw materials for synthesis, pesticides, pharmaceuticals. Corresponding author V.N. Nazarov, е-mail: рiren66@ukr.net

Intraovarian insertion of autologous platelet growth factors as cell-free concentrate: Fertility recovery and first unassisted conception with term delivery at age over 40.

BackgroundThe use of autologous platelet-rich plasma as an ovarian treatment has not been standardized and remains controversial.Case PresentationA 41½-year old woman with diminished ovarian reserve (serum anti- Müllerian hormone = 0.163 mg/mL) and a history of 10 unsuccessful in vitro fertilization cycles presented for reproductive endocrinology consult. She and her partner declined donor oocyte in vitro fertilization. They were both in good general health and laboratory tests were unremarkable, except for mild thrombocytosis (platelets = 386K; normal range 150-379K) discovered in the female. The patient underwent intraovarian injection of fresh platelet-derived growth factor concentrate administered as an enriched cell-free substrate. Serum anti- Müllerian hormone increased by 115% within 6 wks of treatment. Spontaneous ovulation occurred the month after injection and subsequently the serum human chorionic gonadotropin was noted at 804 mIU/mL. Following an uneventful obstetrical course, a male infant was delivered at term without complication.ConclusionThis is the first description of intraovarian injection of enriched platelet-derived growth factors followed by unassisted pregnancy and live birth. As a refinement of conventional ovarian platelet-rich plasma therapy, this procedure may be particularly valuable for refractory cases where prognosis for pregnancy appears especially bleak. A putative role for thrombocytosis is also viewed in parallel with mechanisms of action as advanced earlier. With continued experience in ovarian application of autologous platelet growth factors, additional research will evaluate laboratory protocol/sample preparation, injection technique, and patient selection.

Clinical features of reparative regeneration of bone tissue and optimization of treatment for compression fractures of the thoracic and lumbar vertebral bodies against the background of postmenopausal and senile osteoporosis

Introduction. Bone-destructive processes and injuries of the vertebral bodies of the thoracic and lumbar localization are a significant part of the pathology of this localization. According to etiological factors, mechanisms of pathogenesis and the nature of the course, they are a very heterogeneous groups of diseases.Objective: to identify the main factors that determine the development of disorders in compression fractures of vertebral bodies of thoracic and lumbar localization against the background of postmenopausal and senile osteoporosis for improving the prognostic criteria of the disease on the basis of an integrated assessment of the clinical course of the disease and optimizing treatment by activating reparative bone tissue regeneration according to the literature sources analyzed.Material and research methods. Depending on the treatment method used, patients were divided into 3 groups: in group 1 (control group) were 20 patients with compression fractures of vertebrae of thoracic and lumbar localization against a background of postmenopausal and senile osteoporosis, where we used standard methods of therapy. Group 2 (main group) consisted of 20 patients with compression fractures of vertebrae of thoracic and lumbar localization against the background of postmenopausal and senile osteoporosis, in the treatment of which platelet-rich plasma was also used in addition to standard methods of therapy.Research results. Based on the obtained results of the study, we developed an algorithm for surgical treatment of patients with pathological vertebral fractures against the background of osteoporosis. The choice of the method of surgical treatment depends on: the type of fracture, the level of damage, the degree of loss of bone mineral density, the degree of deformation of the spine, the general somatic state of the patient, the presence of stenosis of the spinal canal and signs of neurological deficit, the severity of the pain syndrome.Conclusion. The introduction of platelet-rich plasma to the area of the bone wound shortens the duration of the healing process, in our opinion, by eliminating the phase of inflammation, low intensification of the phase of formation of tissue-specific elements that are present in large amount in platelet growth factors. In order to accelerate the restoration of damaged bone, we used a platelet-rich plasma in addition to standard therapy, and found a positive effect on compressive fractures of the thoracic and lumbar vertebrae against the background of postmenopausal and senile osteoporosis, which justifies the advisability of further use platelet-rich plasma in clinical practice.