Should intravitreal dexamethasone implant in refractory diabetic macular edema be used as an adjuvant therapy or switch therapy?

ABSTRACT Purpose: To compare the outcomes of intravitreal dexamethasone implant used as either an adjuvant or a switching therapy for diabetic macular edema in patients with poor anatomic response after three consecutive monthly injections of ranibizumab. Methods: This retrospective study included patients with diabetic macular edema who received three consecutive doses of ranibizumab as initial therapy and demonstrated poor response. A single dose of intravitreal de xamethasone implant was administered to these patients. The patients were divided into two groups according to the treatment modalities: the adjuvant therapy group, consisting of patients who continued treatment with ranibizumab injection after receiving intravitreal dexamethasone implant, and the switch therapy group, consisting of patients who were switched from ranibizumab treatment to intravitreal dexamethasone implant as needed. The main outcome measurements were best corrected visual acuity and central retinal thickness at baseline and at 3, 6, 9, and 12 months of follow-up. Results: In this study that included 64 eyes of 64 patients, the best corrected visual acuity and central retinal thickness values did not significantly differ between the groups at baseline and at 6 months of follow-up (p>0.05). However, at 12 months, the best corrected visual acuity values in the adjuvant and switch therapy groups were 0.46 and 0.35 LogMAR, respectively (p=0.012), and the central retinal thickness values were 344.8 and 270.9, respectively (p=0.007). Conclusions: In a real-world setting, it seems more reasonable to use intravitreal dexamethasone implant as a switch therapy rather than an adjuvant therapy for diabetic macula edema refractory to ranibizumab despite three consecutive monthly injections of ranibizumab. Patients switched to intravitreal dexamethasone implant were found to have better anatomic and visual outcomes at 12 months than those who continued ranibizumab therapy despite their less-than-optimal responses.

Effects of Temperature and Time on the Denaturation of Transforming Growth Factor Beta-1 and Cytokines from Bovine Platelet-Rich Gel Supernatants.

There is a lack of information about transforming growth factor beta-1 (TGF-ß1) and cytokines contained in pure platelet-rich plasma (P-PRP) and release from pure-platelet-rich gel supernatants (P-PRGS) might be affected by the temperature and time factors; P-PRP from 6 heifers was activated with calcium gluconate. Thereafter, P-PRG and their supernatants (P-PRGS) were maintained at -80, -20, 4, 21, and 37 °C and collected at 3, 6, 12, 24, 48, 96, 144, 192, 240, and 280 h for subsequent determination of TGF-ß1, tumor necrosis factor alfa (TNF-α), interleukin (IL)-2, and IL-6; TGF-ß1 concentrations were significantly (p < 0.05) higher in PRGS maintained at 21 and 37 °C when compared to PRGS maintained at 4, -20, and -80 °C; PRGS TNF-α concentrations were not influenced by temperature and time factors. However, PRGS maintained at 4 °C showed significantly (p < 0.05) higher concentrations when compared to PRGS maintained at -20, and -80 °C at 144, and 192 h. IL-6 concentrations were significantly (p < 0.05) higher in PRGS stored at -20, and -80 over the first 48 h and at 10 days when compared to PRGS stored at 4, 21, and 37 °C. These results could suggest that P-PRP/P-PRGS could be maintained and well preserved for at least 12 days at room temperature for clinical use in bovine therapeutic massive protocols.

Effect of allogeneic pure platelet-rich plasma, sodium cloxacillin, and their combination for the treatment of subclinical mastitis in crossbred cows.

Introduction: Bovine subclinical mastitis (SCM) caused by Gram-positive bacteria is a major cause of economic loss in the dairy industry, exacerbated in situations where antimicrobial resistance is present. Pure platelet-rich plasma (P-PRP) may be a therapeutic alternative for SCM, when used alone or with antibiotics, such as sodium cloxacillin (SC). This study aimed 1) to evaluate the therapeutic efficacy of allogeneic P-PRP, SC, and their combination (P-PRP+SC) in cows with SCM caused by Staphylococcus aureus and by streptococci (Staphylococcus aureus and S. dysgalactiae); 2) to determine the concentrations of somatic cells (SCC), interleukin 1 beta (IL-1ß), tumor necrosis factor-alpha (TNF-α) and TGF-ß1 in milk samples of the cows. Methods: 130 cows from 4 dairy herds completed the study, of which 40 cows were treated with P-PRP (10 mL), 28 cows with SC (5g), 36 with P-PRP+SC (10mL/5g), and 26 did not receive no treatment (negative control group, NCG). Results: The overall bacteriological cure was observed in 10/40 (25%) cows in the P-PRP group, 9/28 (32.14%) animals in the SC group, 26/36 (72.22%) cows in the P-PRP+SC group, and 10/26 (38.46%) animals in the NCG. SCM caused by S. aureus (82/130, 63.08%), was cured in 6/24 (25%) cows treated with P-PRP, 7/24 (29.2%) cows treated with SC, 8/16 (50%) animals treated with P-PRP+SC, and in 8/18 (44.4%) cows in NCG. For SCM caused by the streptococci (48/130, 36.91%), the cure was achieved in 4/12 (33.3%) cows treated with P-PRP, 2/4 (50%) cows treated with SC, 18/20 (90%) cows treated with P-PRP+SC, and in 2/8 (25%) cows of the NCG. SCC was significantly (p < 0.001) affected by the treatment, herd, cure, bacteria group, and number of calvings factors. IL-1ß milk concentrations were significantly (p < 0.001) influenced by treatment and farm factors, and the interaction between these factors. TNF-α milk concentrations were significantly (p < 0.001) influenced by time factor. TGF-ß1 milk concentrations were significantly affected by the time and cure factors. Conclusion: The combination of P-PRP and SC showed the best therapeutic response (90%) against bovine SCM caused by streptococci. However, none of the treatments showed an effective therapeutic response against S. aureus.

Safety of intraoperative autologous plasma incubation of corneal grafts for reducing endothelial cell loss: a pilot study.

Background/aims: Corneal endothelial cell loss contributes to transplant failure. Autologous plasma products (APP) activate salvaging pathways that can prevent oxidative stress perioperatively. This study aimed to evaluate the safety of intraoperative incubation of full-thickness corneal grafts in platelet-rich plasma (aPRP) and plasma rich in growth factors (PRGF-Endoret) in mitigating postoperative corneal endothelial cell loss (ECL). Methods: Pilot study including patients undergoing penetrating keratoplasty (PK) for various indications between June 2021 and December 2022. Patients were randomly assigned to receive either aPRP or PRGF-Endoret incubation, while those who declined intervention served as the control group. Demographic and clinical data were collected, including preoperative and postoperative endothelial cell count, intraocular pressure, pachymetry, and adverse reactions. Results: Thirty individuals who underwent PK completed follow-up: eight from the aPRP group, 10 from the PRGF-Endoret group, and 12 from the control group. No adverse events related to APP treatment were recorded. In the first and third postoperative months, the APP group had significantly lower ECL percentages (37% vs. 25%, p = 0.02, and 44% vs. 33%, p = 0.02, respectively); this trend was maintained in the sixth month. When stratified, the PRGF-Endoret group showed significant differences in ECL reduction compared to controls at both time points (p = 0.03 and p = 0.05, respectively). The aPRP group showed a similar statistically significant outcome exclusively on the third postoperative month (p = 0.04). APP tended to reduce corneal edema faster than controls. Hexagonality was significantly better in the APP groups in the first and third months, particularly in the PRGF-Endoret group (p < 0.005). Conclusion: Preoperative incubation with APP is safe and promotes better endothelial cell quality and quantity in the early postoperative period following PK. These findings suggest a potential clinical benefit in enhancing graft outcomes and warrant further investigation.

The Effect of the Overexpression or Addition of IGF1 and FGF2 in Human Chondrocytes Included in a Fibrin Matrix and Cultivated in a Dynamic Environment.

Hyaline cartilage is a highly specialized tissue. When injured, its repair capacity is low, which results in the massive destruction of the articular surface. Using tissue engineering and genetic engineering techniques, it is possible to provide a suitable microenvironment providing chondrocyte growth factors involved in the development of hyaline cartilage proteins, as well as cell proliferation and differentiation. Our aim was to stimulate the synthesis of an extracellular matrix via the chondrocytes included in a fibrin matrix through the addition or overexpression of IGF1 and/or FGF2, while maintaining a constant agitation of the culture medium. Collagen type II and glycosaminoglycans increased during the entire incubation time. In contrast, collagen type I decreased its expression under the same culture conditions, transfecting or supplementing growth factors to chondrocytes. However, chondrocytes that were not transfected or supplemented showed a general increase in the proteins analyzed in this study. The presence of IGF1 and FGF2 increased the protein synthesis of the hyaline cartilage, regardless of which one was the source of growth factors. Continuous agitation using the spinner flask allows for the adequate nutrition of chondrocytes included in the fibrin matrix. However, they require growth factors to up-regulate or down-regulate collagenous proteins.

The Biological Role of Platelet Derivatives in Regenerative Aesthetics.

Bioproducts derived from platelets have been extensively used across various medical fields, with a recent notable surge in their application in dermatology and aesthetic procedures. These products, such as platelet-rich plasma (PRP) and platelet-rich fibrin (PRF), play crucial roles in inducing blood vessel proliferation through growth factors derived from peripheral blood. PRP and PRF, in particular, facilitate fibrin polymerization, creating a robust structure that serves as a reservoir for numerous growth factors. These factors contribute to tissue regeneration by promoting cell proliferation, differentiation, and migration and collagen/elastin production. Aesthetic medicine harnesses these effects for diverse purposes, including hair restoration, scar treatment, striae management, and wound healing. Furthermore, these biological products can act as adjuvants with other treatment modalities, such as laser therapy, radiofrequency, and microneedling. This review synthesizes the existing evidence, offering insights into the applications and benefits of biological products in aesthetic medicine.

Short-Term Effects of Two COX-2 Selective Non-Steroidal Anti-Inflammatory Drugs on the Release of Growth Factors and Cytokines from Canine Platelet-Rich Gel Supernatants.

(1) Background: There is a lack of knowledge about how a single dose of COX-2 selective non-steroidal anti-inflammatory drugs (NSAIDs) might affect the release of growth factors (GFs) and cytokines from canine platelet-rich gels (PRGs) and other hemocomponents. (2) Methods: A crossover study was conducted in six adult mongrel dogs. Animals were randomized to receive a single dose of either carprofen or firocoxib. PRG, temperature-induced platelet lysate (TIPL), chemically induced PL (CIPL), and plasma hemocomponents were obtained from each dog before (1 h) and after (6 h) the treatments. Platelet and leukocyte counts and determination of the concentrations of platelet-derived growth factor-BB, (PDGF-BB), transforming growth factor beta-1 (TGF-ß1), interleukin 1 beta (IL-1ß), tumor necrosis factor-alpha (TNF-α) and IL-10 concentrations were assayed by ELISA in all hemocomponents. (3) Results: Both platelet and leukocyte counts and PDGF-BB concentrations were not affected by NSAIDs and time. Total TGF-ß1 concentrations were not affected by NSAIDs; however, the release of this GF was increased in PRG supernatants (PRGS) at 6 h. IL-1ß and TNF-α concentrations were significantly (p < 0.001) lower in both firocoxib PRGS and plasma at 6 h, respectively. IL-10 concentrations were significantly (p < 0.001) lower at 6 h in all hemocomponents treated with both NSAIDs. (4) Conclusions: The clinical implications of our findings could indicate that these drugs should be withdrawn from patients to allow their clearance before the clinical use of PRP/PRG. On the other hand, the prophylactic use of NSAIDs to avoid the inflammatory reactions that some patients might have after PRP/PRG treatment should be performed only in those animals with severe reactive inflammation to the treatment.

Prophylactic zinc and therapeutic selenium administration in adult rats prevents long-term cognitive and behavioral sequelae by a transient ischemic attack.

The transient hypoxic-ischemic attack, also known as a minor stroke, can result in long-term neurological issues such as memory loss, depression, and anxiety due to an increase in nitrosative stress. The individual or combined administration of chronic prophylactic zinc and therapeutic selenium is known to reduce nitrosative stress in the first seven days post-reperfusion and, due to an antioxidant effect, prevent cell death. Besides, zinc or selenium, individually administered, also causes antidepressant and anxiolytic effects. Therefore, this work evaluated whether combining zinc and selenium could prevent stroke-elicited cognition and behavior deficits after 30 days post-reperfusion. Accordingly, we assessed the expression of growth factors at 7 days post-reperfusion, a four-time course of memory (from 7 to 28 days post-learning test), and cell proliferation, depression, and anxiety-like behavior at 30 days post-reperfusion. Male Wistar rats with a weight between 190 and 240 g) were treated with chronic prophylactic zinc administration with a concentration of 0.2 mg/kg for 15 days before common carotid artery occlusion (10 min) and then with therapeutic selenium (6 µg/kg) for 7 days post-reperfusion. Compared with individual administrations, the administration combined of prophylactic zinc and therapeutic selenium decreased astrogliosis, increased growth factor expression, and improved cell proliferation and survival in two regions, the hippocampus, and cerebral cortex. These effects prevented memory loss, depression, and anxiety-like behaviors. In conclusion, these results demonstrate that the prophylactic zinc administration combined with therapeutic selenium can reduce the long-term sequelae caused by the transient ischemic attack. Significance statement. A minor stroke caused by a transient ischemic attack can result in psychomotor sequelae that affect not only the living conditions of patients and their families but also the economy. The incidence of these micro-events among young people has increased in the world. Nonetheless, there is no deep understanding of how this population group responds to regular treatments (Ekker and et al., 2018) [1]. On the basis that zinc and selenium have antioxidant, anti-inflammatory, and regenerative properties in stroke animal models, our work explored whether the chronic combined administration of prophylactic zinc and therapeutic selenium could prevent neurological sequelae in the long term in a stroke rat model of unilateral common carotid artery occlusion (CCAO) by 10-min. Our results showed that this combined treatment provided a long-term neuroprotective effect by decreasing astrogliosis, memory loss, anxiety, and depression-like behavior.

Comparison of the Clinical Effectiveness of Intra-Articular Injection with Different Substances After TMJ Arthroscopy: A Systematic Review and Meta-Analysis.

Objective: This systematic review aims to describe the clinical outcomes after TMJ arthroscopy followed by intra articular infiltration with different substances. Materials and Methods: A literature search was carried out, the variables were Arthroscopy with different substances, pain and maximal mouth opening. The inclusion criteria were articles that reported infiltration of different substances after arthroscopy. Case series, observational studies, and randomized clinical trials were included. Exclusion criteria were studies that included arthrocentesis, animal studies, connective tissue disease, patients with previous surgeries. Results: Of the 5 studies finally included, the population studied were 346 subjects, of which 315 were female. The mean age was 34.7 (16-77). Regarding diagnoses, Wilkes III and Wilkes IV were taken into account. The most commonly used substance was sodium hyaluronate/hyaluronic acid in 4 of the 5 studies. Conclusion: Multiple substances have been infiltrated within the temporomandibular joint, with sodium hyaluronate/hyaluronic acid being the most studied. However, the benefit of substances like ATM artroscopia adyuvantes has not been clearly established. It is recommended in future studies that the substances and results be evaluated in the same way to obtain more homogeneous studies.

Recombinant Human Peptide Growth Factors, Bone Morphogenetic Protein-7 (rhBMP7), and Platelet-Derived Growth Factor-BB (rhPDGF-BB) for Osteoporosis Treatment in an Oophorectomized Rat Model.

Bone morphogenetic protein (BMP) and platelet-derived growth factor (PDGF) are known to regulate/stimulate osteogenesis, playing vital roles in bone homeostasis, rendering them strong candidates for osteoporosis treatment. We evaluated the effects of recombinant human BMP-7 (rhBMP7) and PDGF-BB (rhPDGF-BB) in an oophorectomy-induced osteoporosis rat model. Forty Sprague Dawley rats underwent oophorectomy surgery; treatments commenced on the 100th day post-surgery when all animals exhibited signs of osteoporosis. These peptide growth factors were administered intraocularly (iv) once or twice a week and the animals were monitored for a total of five weeks. Two weeks after the conclusion of the treatments, the animals were euthanized and tissues were collected for assessment of alkaline phosphatase, X-ray, micro-CT, and histology. The results indicate that the most promising treatments were 20 µg/kg rhPDGF-BB + 30 µg/kg rhBMP-7 twice a week and 30 µg/kg BMP-7 twice a week, showing significant increases of 15% (p < 0.05) and 13% (p < 0.05) in bone volume fraction and 21% (p < 0.05) and 23% (p < 0.05) in trabecular number, respectively. In conclusion, rhPDGF-BB and rhBMP-7 have demonstrated the ability to increase bone volume and density in this osteoporotic animal model, establishing them as potential candidates for osteoporosis treatment.

Clinicopathological and immunohistochemical characteristics of bullous pilomatricoma: a retrospective, single-center study, and comparison with ordinary pilomatricoma.

BACKGROUND: Bullous pilomatricoma is a rare variant of pilomatricoma. As it has been published in sporadic case reports, a limited understanding of its clinicopathological characteristics restricts its effective diagnosis and treatment. OBJECTIVES: This study aimed to analyze the clinicopathological and immunohistochemical characteristics of bullous pilomatricoma to better understand the bullous transformation of pilomatricoma. METHODS: The authors conducted a retrospective study of 12 patients with bullous pilomatricoma and compared their clinical, histopathological, and immunohistochemical data with those of patients with ordinary pilomatricoma. RESULTS: Bullous pilomatricoma showed no sex preference, with a mean onset age of 31.2 years. The common sites were the upper extremities and trunk. Bullous pilomatricoma had a shorter disease duration, a larger diameter, and a greater tendency to increase in size than those of ordinary pilomatricoma. Histopathologically, bullous pilomatricoma had a shorter duration, lesser calcification, more mitotic figures, and distinct dermal features from those of ordinary pilomatricoma. Immunohistochemically, the expression of Matrix Metalloprotease (MMP)-2, MMP-9, vascular endothelial growth factor receptor-3 (VEGFR-3), and VEGF-C was elevated. STUDY LIMITATIONS: The study was retrospective, and the sample size was small. CONCLUSION: The distinctive features of bullous pilomatricoma potentially result from dermal changes associated with the release of angiogenic factors and proteolytic enzymes. This comprehensive analysis provides novel insights into the clinical features and pathogenesis of bullous pilomatricoma.

Safety of Plasma Rich in Growth Factors (PRGF) as additive to healthy human sperm samples: a pilot study.

OBJECTIVE: The aim of our study was to assess if the addition of PRGF to healthy human sperm affects its motility and vitality. METHODS: This was a prospective study, with 44 sperm donors on whom sperm analysis was performed. Nine mL of blood was collected and PRGF was obtained using PRGF-Endoret® technology. The influence of different dilutions of PRGF (5%, 10%, 20%, 40%) applied to 15 sperm donors was compared, and sperm motility was assessed after 30 minutes. In the second part of the study, 29 sperm donors were studied to analyze the influence of 20% dilution of PRGF at 15, 30 and 45 minutes in fresh and thawed sperm samples. Motility was assessed after the addition of PRGF and after analysis each aliquot was frozen. After thawing, concentration and motility were assessed at the same time periods. RESULTS: There were no differences in sperm motility in fresh samples between dilutions of PRGF when assessed 30 minutes after administration, nor between them, nor when compared to the control group immediately prior to treatment. No trend was observed between motility and PRGF dilution in linear regression analysis. There were no significant differences in thawed samples. CONCLUSIONS: The administration of 20% PRGF dilution had no effect on sperm motility compared to samples without PRGF. In addition, there was no change in sperm vitality when comparing samples with and without PRGF. More studies focusing on subnormal sperm samples, analyzing different PRGF concentrations and increasing the number of study variables are needed.

Effects of plasma rich in growth factors on wound healing in patients with venous ulcers.

Introduction: Significant evidence suggests that plasma-rich in growth factors (PRGF) favor the repair of chronic wounds, enabling a rapid return to functionality. However, components of PRGF and their effects on persistent ulcers and epithelial tissues are not well characterized. The goals of this research were to analyze the biological properties of platelet-derived factors, to examine their effectiveness on healing of venous ulcers, and to establish a correlation with clinical and sociodemographic data. Methods: For the preparation of PRGF, the centrifugation technique was used, obtaining a 100 % autologous and biocompatible blood sample that was treated with sodium citrate and calcium chloride. The patients were attended weekly at the outpatient clinic for nursing consultation and wound dressing changes, with PRGF application every 15 days. The treatment protocols are described, and follow-up results are reported. Results: Initially, the patients' ulcers ranged in sizes from 4 to 84 cm2. After 12 weeks of treatment, there was a significant mean reduction of 46.2 % in ulcer area. At baseline, epithelial tissue was absent in all venous ulcers, but its presence grew significantly by the treatment period. However, the reduction of the area of the ulcers did not show significant correlation with the concentrations of the patient's growth factors. Conclusions: Using the established protocol for PRGF isolating, it was possible to obtain a product with the presence of the six growth factors related to tissue regeneration and observed a positive response on wound healing following treatment of venous ulcers, with capacity to accelerate re-epithelialization and restore the skin functional integrity.

Mesenchymal Stem Cell Therapy for Treating the Underlying Causes of Diabetes Mellitus and Its Consequences.

Diabetes mellitus (DM) is a multifaceted pathological condition, which at present is being considered an epidemic disease keeping the rampant rate of its increase in almost all population groups of the world in consideration. Out of the two types of DM described, T1D is characterized as an autoimmune condition that leads to the destruction of pancreatic ß-cells by macrophages and T-cells, thereby, adversely affecting the production of insulin. On the other hand, T2D, often caused by insulin resistance, is commonly related to unhealthy habits, and therefore, it can be prevented in most cases. In both of the conditions, high levels of proinflammatory cytokines like IL-6, TNF-α, and INF-Æ´, lead to chronic inflammation, and elevated oxidative stress resulting in apoptosis and destruction of tissues. Although several treatments are available to treat the symptoms, the underlying causes are not well addressed. One of the most promising approaches to tackle the ill effects and the primary causes of DM is mesenchymal stem cell (MSC) therapy. The use of MSC therapy, because of the immunomodulatory and regenerative properties recorded in this type of cells in a number of experiments carried out in animal models and clinical trials of the disease, has reported positive outcomes. This review covers the principal mechanisms of action induced during MSC therapy in reference to the described pathophysiological pathways of both T1D and T2D. In addition, how this therapeutic intervention can counteract the ill effects of this condition leading to the promotion of tissue regeneration has been covered.

New immunological aspects of peri-implantitis

ABSTRACT Objective: This study aimed to compare the levels of HIF1-α, VEGF, TNF-α, and IL-10 in the peri-implant crevicular fluid of patients with and without peri-implantitis. Methods: Forty patients, comprising 16 with and 24 without peri-implantitis were selected. Results: Patients with peri-implantitis exhibited significantly higher HIF-1α levels than those without peri-implantitis (p=0.0005). TNF-α revealed significant positive correlations with IL-10 (p=0.0008) and VEGF (p=0.0246), whereas HIF-1α and IL-10 levels (p=0.0041) demonstrated a negative and significative correlation in the peri-implantitis group. Conclusion: This study, for the first time demonstrates the balance of HIF-1α, TNFα, IL-10, and VEGF in peri-implantitis. It shows an elevated HIF-1α levels in patients with peri-implantitis, which could have stemmed from persistent inflammation- triggered hypoxia. Furthermore, the positive correlation between TNF-α and VEGF suggests intensified proinflammatory activity in peri-implantitis. Nevertheless, further studies are essential to understand these immune dynamics in peri-implantitis.

Clinicopathological and immunohistochemical characteristics of bullous pilomatricoma: a retrospective, single-center study, and comparison with ordinary pilomatricoma

Abstract Background Bullous pilomatricoma is a rare variant of pilomatricoma. As it has been published in sporadic case reports, a limited understanding of its clinicopathological characteristics restricts its effective diagnosis and treatment. Objectives This study aimed to analyze the clinicopathological and immunohistochemical characteristics of bullous pilomatricoma to better understand the bullous transformation of pilomatricoma. Methods The authors conducted a retrospective study of 12 patients with bullous pilomatricoma and compared their clinical, histopathological, and immunohistochemical data with those of patients with ordinary pilomatricoma. Results Bullous pilomatricoma showed no sex preference, with a mean onset age of 31.2 years. The common sites were the upper extremities and trunk. Bullous pilomatricoma had a shorter disease duration, a larger diameter, and a greater tendency to increase in size than those of ordinary pilomatricoma. Histopathologically, bullous pilomatricoma had a shorter duration, lesser calcification, more mitotic figures, and distinct dermal features from those of ordinary pilomatricoma. Immunohistochemically, the expression of Matrix Metalloprotease (MMP)-2, MMP-9, vascular endothelial growth factor receptor-3 (VEGFR-3), and VEGF-C was elevated. Study limitations The study was retrospective, and the sample size was small. Conclusion The distinctive features of bullous pilomatricoma potentially result from dermal changes associated with the release of angiogenic factors and proteolytic enzymes. This comprehensive analysis provides novel insights into the clinical features and pathogenesis of bullous pilomatricoma.

Ellagic acid protected the gingival tissue via fibroblast and epidermal growth factors in rats

Purpose: To investigate the effect of ellagic acid (EA) in gingival tissues injury in rats. Methods: Twenty rats were categorized into two groups. In burn group, an excisional wound area was created by removing a 4-mm diameter flap from the left molar region in the mucoperiosteal region of the gingiva. In burn + ellagic acid group, 1.2 mg/mL EA was administered as irrigation for one week. Animals was sacrificed under anesthesia at the end of experiment. Malondialdehyde (MDA), myeloperoxidase (MPO) and glutathione (GSH) level were measured. Hematoxylin and eosin, fibroblast growth factor (FGF) and epidermal growth factor (EGF) immunostainings were applied to tissues. Results: MDA, MPO, inflammation and leukocyte infiltration were high in burn group. Degeneration epithelium, edema and inflammatory cell infiltration in connective tissue areas, and dilatation and congestion in blood vessels were observed in burn group. In burn + EA group, the gingival epithelium improved, collagen fiber production increased and organized dermis were observed. After burn injury, FGF and EGF activity was increased in EA treated groups. Conclusions: We suggest that EA have the potential for better healing outcomes in oral wounds. EA seems to have promising therapeutic efficacy to enhance oral wound healing.

Clinical improvement after intraarticular and intraosseous injections of platelet rich plasma combined with hyaluronic acid for knee osteoarthritis. Case series / Mejoría clínica tras inyecciones intraarticulares e intraóseas de plasma rico en plaquetas combinado con ácido hialurónico para la artrosis de rodilla. Serie de casos

Abstract: Introduction: knee osteoarthritis (KOA) is known as the most common form of osteoarthrosis with a 6% prevalence in people over 30 years old, and more than 40% in the population over 70 years old. The use of PRP led to diverse results and this disparity can be attributed to the dissimilar methods of PRP preparation. This study aims to assess the functional effects of intraosseous (IO) and intraarticular (IA) injections of platelet rich plasma (PRP) followed by IA injections of hyaluronic acid (HA). Objectives: this study aimed to assess the functional effects of intraosseous (IO) and intraarticular (IA) injections of platelet rich plasma (PRP) followed by IA injections of hyaluronic acid (HA), administered 3 and 4 weeks after the initiation of treatment in 33 patients with grade II-III (Ahlback scale) knee osteoarthritis (KOA). Material and methods: retrospectively, 33 patients were assessed using the Western Ontario and McMaster Universities (WOMAC) osteoarthritis index and visual analogue scale (VAS) score. They were followed-up for 12.92 months on average. Patients were divided into three groups based on age and four groups based on the follow-up period. Results: the pre-operative mean of the WOMAC index was 44.35 ± 20.20 and the post-operative mean was 22.81 ± 17.25 (p < 0.001). The pre-operative and post-operative mean of the VAS scores were 5.79 ± 2.01 and 2.41 ± 1.43 (p < 0.001), respectively. The largest improvement in WOMAC (from 42.86 to 13.69) was observed in the youngest patients (44 to 55 years old) and the largest reduction in VAS (from 6.89 to 2.22) was seen in patients aged 56 to 70 years. Conclusion: the combination of IO and IA plasma rich in growth factor (PRGF) treatment with the IA-HA treatment yielded excellent results, diminishing pain and improving motor functionality in patients with KOA.

Resumen: Introducción: la artrosis de rodilla (OA) es conocida como la forma más común de osteoartrosis con una prevalencia de 6% en personas mayores de 30 años y más de 40% en la población mayor de 70 años. El uso de plasma rico en plaquetas (PRP) condujo a resultados diversos y esta disparidad puede atribuirse a los diferentes métodos de preparación del PRP. Este estudio tiene como objetivo evaluar los efectos funcionales de las inyecciones intraóseas (IO) e intraarticulares (IA) de plasma rico en plaquetas (PRP) seguidas de inyecciones IA de ácido hialurónico (AH). Objetivos: este estudio tuvo como objetivo evaluar los efectos funcionales de las inyecciones intraóseas (IO) e intraarticulares (IA) de plasma rico en plaquetas (PRP) seguidas de inyecciones IA de ácido hialurónico (AH), administrada 3 y 4 semanas después del inicio del tratamiento en 33 pacientes con osteoartrosis de rodilla (OR) grado II-III (escala de Ahlbäck). Material y métodos: retrospectivamente, se evaluó a 33 pacientes utilizando el índice de osteoartritis de las Universidades Western Ontario y McMaster (WOMAC) y la puntuación de la escala visual analógica (EVA). Se les realizó un seguimiento medio de 12.92 meses. Los pacientes se dividieron en tres grupos según la edad y cuatro grupos según el período de seguimiento. Resultados: la media preoperatoria del índice WOMAC fue de 44.35 ± 20.20 y la media postoperatoria fue de 22.81 ± 17.25 (p < 0.001). La media preoperatoria y postoperatoria de las puntuaciones de la EVA fue de 5.79 ± 2.01 y 2.41 ± 1.43 (p < 0.001), respectivamente. La mayor mejoría en WOMAC (de 42.86 a 13.69) se observó en los pacientes más jóvenes (44 a 55 años) y la mayor reducción de la EVA (de 6.89 a 2.22) se observó en pacientes de 56 a 70 años. Conclusión: la combinación del tratamiento de plasma rico en factores de crecimiento (PRGF) IO e IA con el tratamiento IA-AH produjo excelentes resultados, disminuyendo el dolor y mejorando la funcionalidad motora de los pacientes con OR.

BFNB Enhances Hair Growth in C57BL/6 Mice through the Induction of EGF and FGF7 Factors and the PI3K-AKT-ß-Catenin Pathway.

The objective of this study was to investigate the potential effects of a formulation derived from the bioactive fraction of nanostructured Bacopa procumbens (BFNB) on the promotion of hair growth in C57BL/6 mice. The characterization of the follicular phases and histomorphological analysis showed that the topical application of the formulation for 15 days significantly increased pigmentation and hair growth on the dorsum and head of the mice. Additionally, an acceleration of the follicular cycle phases was observed, along with an increase in the number of follicles, hair length, and diameter, compared to mice treated with minoxidil. In silico analysis and molecular characterization demonstrated that BFNB enhances the expression of epidermal growth factor (EGF) and fibroblast growth factor 7 (FGF7), activating the PI3K-AKT-ß-catenin signaling pathway, as well as the expression of PCNA, KI-67, Cyclin D1, and Cyclin E, regulating the cell cycle and cell proliferation, crucial events for hair regeneration. Our results strongly suggest the utility of BFNB as a therapeutic alternative to stimulate hair growth and promote hair health.

Using umbilical cord blood as a source of paediatric packed red blood cells: Processing and quality control.

BACKGROUND AND OBJECTIVES: Umbilical cord blood (UCB) has been used as a source of red blood cells (RBCs) for neonatal/paediatric transfusion purposes. This study adopted two different procedures to obtain umbilical RBC (U-RBC) to compare its quality control parameters to those of fractionated adult RBC (A-RBC), for paediatric purposes. MATERIALS AND METHODS: UCB units (24) were filtered and processed based on two different methods, namely, conventional/manual (P1;n12) and automatic (P2;n12). They were compared to five fractionated A-RBCs. U-RBC and A-RBC were stored for 14 days and had their haematological, biochemical, haemolytic and microbiological parameters analysed at D1, D7 and D14. Cytokines and growth factors (GFs) in residual U-RBC plasma were measured. RESULTS: Mean volume of processed U-RBC units was 45 mL for P1 and 39 mL for P2; the mean haematocrit level reached 57% for P1 and 59% for P2. A-RBC recorded a mean volume of 44 mL. Haematologic and biochemical parameters analysed in U-RBC and A-RBC presented similar behaviours during storage time, except for parameter values, which differed between them. Pro-inflammatory and immunomodulatory cytokines, as well as GFs, were higher in U-RBC residual plasma than in that A-RBC. CONCLUSION: UCB can be processed into RBC based on either manual or automated protocols. U-RBC units met the referenced quality parameters defined for A-RBC. Some features, mainly the biochemical ones, should be further investigated to help improve quality parameters, with emphasis on differences found in, and particularities of, this material and on recipients of this new transfusion practice.