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21.
Javed A. Shaik Nima Estharabadi Ronda S. Farah Maria K. Hordinsky 《Experimental dermatology》2020,29(10):1004-1011
Platelet α-granules release growth factors (GFs) that promote healing and tissue regeneration. Platelet-rich plasma (PRP) is shown to be beneficial in treating alopecia, and however, clinical response can be inconsistent. Due to several fold enrichment of platelets secreting large quantities of GFs following PRP injections, heterogeneity in amounts of GFs secreted by platelets may contribute to inconsistent clinical responses. Herein, we evaluated factors that could potentially contribute to heterogeneous secretion of GFs by platelets. We measured platelet secretion of transforming growth factor beta1 (TGFβ1), platelet-derived growth factor (PDGF-BB), epidermal growth factor (EGF), vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF2) in aliquots of de-identified PRP samples from female patients undergoing therapy in the hair disease clinic. Although secretion of GFs by platelets was comparable in PRP samples of patients with non-cicatricial and cicatricial alopecia, a Shapiro-Wilk test for normal distribution indicated significant variability across all patient samples. The amount of GF secreted by platelets was comparable when PRP prepared from two FDA-cleared devices with distinct techniques were compared. We provide evidence of platelets secreting heterogeneous amounts of GFs within each sample as high and low secretion of random factors could be simultaneously detected. These results suggest inherent heterogeneity in secretion of GFs by platelets in patient samples that are not influenced by the device used to prepare PRP. Since some GFs could have antagonistic effects on hair growth, a balance between amounts of growth promoting and inhibiting factors may be crucial in determining clinical response to PRP therapy. 相似文献
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Roberto V.P. Ribeiro Mitesh V. Badiwala Danny Ramzy Laura C. Tumiati Vivek Rao 《The Journal of thoracic and cardiovascular surgery》2019,157(2):615-625.e1
Objective
Hypertonic saline (HTS) has potent immune and vascular effects. We assessed recipient pretreatment with HTS on allograft function in a porcine model of heart transplantation and hypothesized that HTS infusion would limit endothelial and left ventricular (LV) dysfunction following transplantation.Methods
Heart transplants were performed after 6 hours of cold ischemic storage. Recipient pigs were randomized to treatment with or without HTS (7.5% NaCl) before cardiopulmonary bypass (CPB). Using a myograft apparatus, coronary artery endothelial-dependent (Edep) and -independent (Eind) relaxation was assessed. LV performance was determined using pressure-volume loop analysis. Pulmonary interleukin (IL)-2, IL-6, and tumor necrosis factor (TNF)-α expression was measured.Results
Weaning from CPB and LV performance after transplantation were improved in HTS-treated animals. Successful weaning from CPB was greater in the HTS-treated hearts (8 of 8 vs 2 of 8; P < .05). Mean LV functional recovery was improved in the HTS-treated animals, as assessed by preload recruitable stroke work (65 ± 10% vs 27 ± 10%; P < .001) and end-systolic elastance (55 ± 7% vs 37 ± 4%; P < .001). Treatment with HTS resulted in improved Edep (mean maximum elastance [Emax], 56 ± 5% vs 37 ± 7%; P < .001) and Eind (mean Emax%, 77 ± 6% vs 52 ± 4%; P < .001) vasorelaxation compared with control. Pulmonary expression of IL-2, IL-6, and TNF-α increased following transplantation, whereas HTS therapy attenuated IL production (P < .001). Transplantation increased plasma TNF-α levels and LV TNF-α expression, whereas HTS prevented this up-regulation (P < .001).Conclusions
Recipient HTS pretreatment preserves allograft vasomotor and LV function, and HTS therapy limits CPB-induced injury. HTS may be a novel recipient intervention to prevent graft dysfunction. 相似文献26.
《Journal of pharmaceutical sciences》2019,108(10):3425-3433
This study aimed at evaluating how encapsulation in a regular nanocarrier (NC) (providing extended circulation time) or in a brain-targeting NC (providing prolonged circulation time and increased brain uptake) may influence the therapeutic index compared with the unformulated drug and to explore the key parameters affecting therapeutic performance using a model-based approach. Pharmacokinetic (PK) models were built with chosen PK parameters. For a scenario where central effect depends on area under the unbound brain concentration curve and peripheral toxicity relates to peak unbound plasma concentration, dose-effect and drug-side effect curves were constructed, and the therapeutic index was evaluated. Regular NC improved the therapeutic index compared with the unformulated drug due to reduced peripheral toxicity, while brain-targeting NC enhanced the therapeutic index by lowering peripheral toxicity and increasing central effect. Decreasing drug release rate or systemic clearance of NC with drug still encapsulated could increase the therapeutic index. Also, a drug with shorter half-life would therapeutically benefit more from a NC encapsulation. This work provides insights into how a NC for brain delivery should be optimized to maximize the therapeutic performance and is helpful to predict if and to what extent a drug with certain PK properties would obtain therapeutic benefit from nanoencapsulation. 相似文献
27.
《Transfusion and apheresis science》2020,59(1):102608
Serum eye drops (SED) have shown beneficial effects in patients suffering from dry eye syndrome and are manufactured for an increasing number of patients in Australia every year. Previous studies have examined the stability of serum growth factors during storage in either experimental vessels not used as the final packaging system or in eye drop bottles. To ensure the quality and safety of SED product manufactured in Australia, the stability of growth factors in serum packaged into two different systems during storage at different temperatures was examined. Healthy blood donors provided a whole blood donation, from which serum was prepared, diluted to 20% and dispensed into either a tube or a vial packaging system. The stability of growth factors, fibronectin and total protein in tube segments was comparable to matched vials samples during storage at −30 °C, 4 °C, 22 °C and 37 °C, with the exception of EGF and fibronectin in 20% SED stored in tube segments, which were more sensitive to storage conditions at 4 °C and 22 °C when compared to vials. Additionally, the growth factor, fibronectin and total protein concentration in both tube segments and vials was stable during storage at −30 °C for at least 9 months. This study highlights the impact of different manufacturing procedures on serum growth factor stability during storage. 相似文献
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《Journal of Clinical Orthopaedics and Trauma》2020,11(2):184-190
ObjectiveProvide an update of the management options for early onset scoliosis patients, including general assessment, conservative and surgical options.MethodsWe included the updated information about the assessment and management options of Early Onset Scoliosis, taking into consideration the non-fusion methods, including the burden on the patient and their family.ResultsWith the heterogeneity of this population, it is difficult to get a consensus about a unified protocol for management. Accordingly, the surgeon dealing with these cases needs to be aware of the broad range of surgical and non-surgical methods when treating these patients.ConclusionThe main aim of early onset scoliosis treatment is to gain a flexible spine associated with normal lung development and thoracic growth. Management needs to be individualized between the surgeon and patient in relation to the etiology and patient conditions. 相似文献
30.
Rasaki Stephen Dauda 《The International journal of health planning and management》2019,34(1):324-337
Human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) is one of the leading causes of morbidity and mortality in West Africa. Prevalence among the most productive age group in West and Central Africa stood at 1.5%, 3.4.0%, 2.5%, and 2.1% in 1990, 2000, 2010, and 2015 respectively. This study examined the effect of HIV/AIDS on economic growth in West Africa with focus on 11 countries. The augmented Solow model, rooted in the neoclassical growth theory, was used, which was operationalized using dynamic panel data modeling approach. Incidence, prevalence, number of people living with HIV/AIDS (PLWHA), and AIDS‐related deaths were used to measure HIV/AIDS. Estimations using system GMM returned statistically significant results while those of first difference and difference GMM were not. From the outcome of system GMM analysis, a percentage increase in incidence, prevalence, PLWHA, and AIDS deaths correspondingly reduced growth significantly through their effects on life expectancy by 0.15%, 0.02%, 0.004%, and 0.03%. Acquired immune deficiency syndrome deaths and PLWHA lowered economic growth through enrolment but not significantly. The import of the findings is that HIV/AIDS threatens growth through life expectancy in West Africa. Therefore, its spread in the subregion should be effectively contained while proper treatment should be provided for all infected persons. 相似文献