Clinical Efficacy and Safety of Low-Energy Extracorporeal Shock Wave Therapy for Various Conditions of Deep Dermal and Subdermal Fibrosis.

BACKGROUND: Extracorporeal shock wave therapy (ESWT) enhances extracellular matrix remodeling and tissue regeneration by promoting growth factor release, regulating blood and lymphatic flows, and reducing fat and fibrotic tissues. Focused shock wave therapy (F-SWT), radial shock wave therapy (R-SWT), and combined F-SWT and R-SWT have been used to deliver different patterns of shock energy depending on the characteristics of the target lesions. METHODS: We investigated the efficacy and safety of ESWT in patients with dermal and subdermal fibrosis. Fifty-two patients treated with F-SWT and/or R-SWT for dermal and subdermal fibrosis caused due to various reasons were retrospectively analyzed by reviewing their medical records, clinical images, and ultrasound study images. RESULTS: The mean number of pulses administered for F-SWT on the cheek, temple, and chin were 2600.0 ± 1040.8 shocks/session and for R-SWT were 5080.0 ± 2234.6 pulses/session, and the number of treatment sessions were 8.0 ± 4.4. In patients who were treated with ESWT on the abdomen, the mean number of pulses for F-SWT were 2600.0 ± 2408.3 shocks/session and for R-SWT were 8400.0 ± 894.4 pulses/session, and the number of treatment sessions were 3.2 ± 1.6. Most patients were satisfied with the results. Pain during ESWT was well tolerated and post-ESWT edema was more common in R-SWT than in F-SWT. CONCLUSION: Our data demonstrated that ESWT effectively and safely improved the clinical appearance and functional movement of patients with dermal and subdermal fibrosis caused due to various reasons.

Analyzing secretory proteins in human dermal fibroblast-conditioned medium for angiogenesis: A bioinformatic approach.

BACKGROUND: The conditioned medium from human dermal fibroblasts (dermal fibroblast-conditioned medium; DFCM) contains a diverse array of secretory proteins, including growth factors and wound repair-promoting proteins. Angiogenesis, a crucial process that facilitates the infiltration of inflammatory cells during wound repair, is induced by a hypoxic environment and inflammatory cytokines. METHODS: In this study, we conducted a comprehensive bioinformatic analysis of 337 proteins identified through proteomics analysis of DFCM. We specifically focused on 64 DFCM proteins with potential involvement in angiogenesis. These proteins were further classified based on their characteristics, and we conducted a detailed analysis of their protein-protein interactions. RESULTS: Gene Ontology protein classification categorized these 64 DFCM proteins into various classes, including metabolite interconversion enzymes (N = 11), protein modifying enzymes (N = 10), protein-binding activity modulators (N = 9), cell adhesion molecules (N = 6), extracellular matrix proteins (N = 6), transfer/carrier proteins (N = 3), calcium-binding proteins (N = 2), chaperones (N = 2), cytoskeletal proteins (N = 2), RNA metabolism proteins (N = 1), intercellular signal molecules (N = 1), transporters (N = 1), scaffold/adaptor proteins (N = 1), and unclassified proteins (N = 9). Furthermore, our protein-protein interaction network analysis of DFCM proteins revealed two distinct networks: one with medium confidence level interaction scores, consisting of 60 proteins with significant connections, and another at a high confidence level, comprising 52 proteins with significant interactions. CONCLUSIONS: Our bioinformatic analysis highlights the presence of a multitude of secretory proteins in DFCM that form significant protein-protein interaction networks crucial for regulating angiogenesis. These findings underscore the critical roles played by DFCM proteins in various stages of angiogenesis during the wound repair process.

Human dermal fibroblast-derived secretory proteins for regulating nerve restoration: A bioinformatic approach.

BACKGROUND: Human dermal fibroblasts secrete diverse proteins that regulate wound repair and tissue regeneration. METHODS: In this study, dermal fibroblast-conditioned medium (DFCM) proteins potentially regulating nerve restoration were bioinformatically selected among the 337 protein lists identified by quantitative liquid chromatography-tandem mass spectrometry. Using these proteins, protein-protein interaction network analysis was conducted. In addition, the roles of DFCM proteins were reviewed according to their protein classifications. RESULTS: Gene Ontology protein classification categorized these 57 DFCM proteins into various classes, including protein-binding activity modulator (N = 11), cytoskeletal protein (N = 8), extracellular matrix protein (N = 6), metabolite interconversion enzyme (N = 5), chaperone (N = 4), scaffold/adapter protein (N = 4), calcium-binding protein (N = 3), cell adhesion molecule (N = 2), intercellular signal molecule (N = 2), protein modifying enzyme (N = 2), transfer/carrier protein (N = 2), membrane traffic protein (N = 1), translational protein (N = 1), and unclassified proteins (N = 6). Further protein-protein interaction network analysis of 57 proteins revealed significant interactions among the proteins that varied according to the settings of confidence score. CONCLUSIONS: Our bioinformatic analysis demonstrated that DFCM contains many secretory proteins that form significant protein-protein interaction networks crucial for regulating nerve restoration. These findings underscore DFCM proteins' critical roles in various nerve restoration stages during the wound repair process.

Effect of sequential delivery of 1- and 2-MHz bipolar microneedling radiofrequency energy on thermal tissue reactions in a minipig model.

BACKGROUND: Bipolar microneedling radiofrequency (RF) treatment generates different patterns of thermal reactions, depending on the skin impedance and RF treatment parameters, including the frequency, power, conduction time, settings of sub-pulse packs, and penetrating depth and type of microneedles used. We compared the effect of sequential delivery of 1- and 2-MHz bipolar RF energy to in vivo minipig skin on thermal tissue reaction. METHODS: RF treatments at frequencies of 1 and 2 MHz were sequentially delivered to minipigs' skin in vivo. A histological study was performed to analyze RF-induced skin reactions at 1-h and at 3-, 7-, and 14-days post-treatment. RESULTS: The skin specimens demonstrated that the two different frequencies of RF treatment generated mixed patterns of the peri-electrode coagulative necrosis (PECN) according to the experimental settings and tissue impedance. In the PECN zone, the tissue coagulation induced by the first RF treatment was surrounded by the effect of the later RF treatment at the other RF frequency. In the inter-electrode non-necrotic thermal reaction zone, the effect of the latter RF treatment was widespread and deep through the dermis, which had received RF treatment at the other frequency first. The delivery of pulsed-type RF energy at sub-pulse packs of 6 or 10 provided effective RF delivery over long conduction time without excessive thermal damage of the epidermis. Nonetheless, by sequential delivery of two different RF frequencies, RF-induced tissue reactions were found to be markedly enhanced. CONCLUSION: The sequential delivery of 1- and 2-MHz RF energy induces novel histological patterns of tissue reactions, which can synergistically enhance the thermostimulatory effects of each RF setting. Moreover, variations in patterns of tissue reactions can be generated by regulating the order of frequencies and the number of sub-pulse packs of RF used.

Antibacterial and anticandidal effects of atmospheric-pressure, non-thermal, nitrogen- and argon-plasma pulses.

Atmospheric-pressure, non-thermal plasma destroys microorganisms by directly reacting with hydrocarbon molecules in the cell wall and/or by damaging the cytoplasmic membrane, proteins, and DNA with charged particles and reactive species. The aim of our study was to evaluate the antibacterial and anticandidal effects of atmospheric-pressure, non-thermal, nitrogen- and argon-plasma pulses on various pathogen preparations. The resultant antibacterial and anticandidal effects were assessed by evaluating percent and log reduction values for pathogen colonies. Nitrogen-plasma pulses emitted at an energy of 1.5 J and argon-plasma pulses generated at 0.5 J elicited remarkable antibacterial effects on Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus (MRSA) and anticandidal effects on Candida albicans. Nitrogen-plasma pulses at a pulse count of five elicited remarkable antibacterial effects on Cutibacterium acnes at the energy settings of 1.75, 2.5, and 3 J, but not at 1 J. Meanwhile, argon-plasma pulses showed antibacterial effects on C. acnes at an energy of 0.5 and 0.65 J. Nitrogen- or argon-plasma pulses exert antibacterial and anticandidal effects on bacterial and fungal pathogens.

Wound Healing Profile After 1064- and 532-nm Picosecond Lasers With Microlens Array of In Vivo Human Skin.

BACKGROUND AND OBJECTIVES: The aim of this study is to histologically characterize the wound healing process of in vivo human skin treated with 1064- and 532-nm microlens array (MLA)-type picosecond lasers. STUDY DESIGN/MATERIALS AND METHODS: Three patients (Fitzpatrick skin types II-IV), who were undergoing future cosmetic abdominoplasties, were treated with 1064- and 532-nm MLA-type lasers under different fluence settings. Treatments were performed 2 weeks, 1 week, and immediately prior to surgery. Skin samples were harvested from the resected tissue with 8 mm punch biopsies immediately after the abdominoplasties were performed. RESULTS: The study demonstrates that intraepidermal vacuoles, created from tissue damage induced by the laser, are histologically resolved within 1 week without persistent damage to the dermoepidermal junction or vasculature. After 2 weeks, all foci of microscopic epidermal necrotic debris had either resolved or migrated to more superficial levels in the stratum corneum. There was no evidence of persistent vascular damage, increased melanophages, or accumulation of melanin in the dermis at 2 weeks. Furthermore, the 1064-nm picosecond laser with the high fluence setting demonstrated the capacity to fractionally ablate the epidermis and induce multifocal fibrosis in the papillary dermis in lighter skin types. CONCLUSION: This is the first study to demonstrate the wound healing profile of in vivo human skin after treatment with the picosecond 1064- and 532-nm MLA-type lasers. It shows that laser-induced tissue damage is histologically resolved within 2 weeks, clinically reflecting a favorable safety profile and short downtime. The study also shows that the picosecond laser can be used to induce either fractional ablative or non-ablative effects, depending on the fluence settings used. Lasers Surg. Med. © 2021 Wiley Periodicals LLC.

Effects of argon and nitrogen plasma pulses on the skin and skin appendages in an in vivo animal model.

BACKGROUND: For medical purposes, plasma can be generated from inert gaseous sources in a device by ultra-high-frequency generators and emitted to target tissue at a pulse duration in the milliseconds. OBJECTIVE: To evaluate argon and nitrogen plasma pulse-induced tissue reactions in the skin and skin appendages of an in vivo animal model. METHODS: Argon and nitrogen plasma pulses were non-invasively delivered to in vivo rat skin at various experimental settings. Specimens were histologically evaluated following hematoxylin and eosin and Masson's trichrome staining. RESULTS: At low-energy settings of 1.0, 1.5, and 2.0 J, nitrogen plasma treatments generated noticeable tissue coagulation at the depths of 31.5 ± 8.3, 94.9 ± 16.9, and 171.6 ± 19.7 µm, respectively, at Day 0. At high-energy settings of 2.5 and 3.0 J, nitrogen plasma treatments generated marked tissue coagulation at the depths of 381.7 ± 33.6 µm and 456.3 ± 75.7 µm, respectively, at Day 0. CONCLUSIONS: Treatment with argon plasma induces microscopic changes in the epidermis, dermis, and sebaceous glands without generating excessive thermal injury, whereas that with nitrogen plasma elicits energy-dependent thermal coagulation in the epidermis and dermis with remarkable neocollagenesis.

Interactive tissue reactions of 1064-nm focused picosecond-domain laser and dermal cohesive polydensified matrix hyaluronic acid treatment in in vivo rat skin.

BACKGROUND: Picosecond-domain laser treatment using a microlens array (MLA) or a diffractive optical element (DOE) generates micro-injury zones in the epidermis and upper dermis. OBJECTIVE: To investigate interactive tissue reactions between MLA-type picosecond laser pulses and cohesive polydensified matrix hyaluronic acid (CPMHA) filler in the dermis. METHODS: In vivo rats with or without CPMHA pretreatment were treated with a 1064-nm picosecond-domain neodymium:yttrium-aluminum-garnet (Nd:YAG) laser using an MLA or DOE. Skin samples were obtained at post-treatment days 1, 10, and 21 and histologically and immunohistochemically analyzed. RESULTS: Picosecond-domain Nd:YAG laser treatment with an MLA-type or a DOE-type handpiece generated fractionated zones of pseudo-cystic cavitation along the lower epidermis and/or upper papillary dermis at Day 1. At Day 21, epidermal thickness, dermal fibroblasts, and collagen fibers had increased. Compared to CPMHA-untreated rats, rats pretreated with CPMHA showed marked increases in fibroblasts and collagen fibers in the papillary dermis. Immunohistochemical staining for the hyaluronic acid receptor CD44 revealed that MLA-type picosecond laser treatment upregulated CD44 expression in the basilar epidermis and dermal fibroblasts. CONCLUSIONS: We suggest that the hyaluronic acid-rich environment associated with CPMHA treatment may enhance MLA-type picosecond-domain laser-induced tissue reactions in the epidermis and upper dermis.

Interactive thermal tissue reactions of 7-MHz intense focused ultrasound and 1-MHz and 6-MHz radiofrequency on cadaveric skin.

BACKGROUND: Intense focused ultrasound (IFU) and radiofrequency (RF) systems generate thermal tissue reactions in multiple zones in the skin, with the microscopic features thereof varying according to energy sources and treatment parameters. OBJECTIVE: To evaluate interactive thermal tissue reactions of IFU and RF in cadaveric skin. METHODS: Thermal reaction patterns generated by IFU, invasive bipolar RF, and non-invasive monopolar RF treatments were analyzed in cadaveric skin of the inner thigh. Additionally, combination treatment, including IFU and invasive bipolar RF, IFU and non-invasive monopolar RF, invasive bipolar RF and IFU, and non-invasive monopolar RF and IFU, was delivered to cadaveric skin and microscopically evaluated. RESULTS: Combination treatment with 1.5-mm IFU followed by 1.5-mm invasive RF elicited multiple thermal injury zones of coagulation and ablation in the mid to lower dermis. Therein, IFU-induced thermal reactions were indistinguishable from RF-induced thermal reactions. Non-invasive RF treatment on IFU-pretreated cadaveric tissue specimens exhibited greater degrees of thermal injury, with wider and deeper penetration, compared to non-invasive RF treatment alone. Furthermore, RF-pretreated tissues showed marked differences in the patterns of IFU-induced thermal tissue reactions. CONCLUSION: Our data suggest that combination treatments with IFU and RF elicit various patterns of interactive thermal tissue reactions.

Sequential delivery of long-pulsed 755-nm alexandrite laser and long-pulsed 1,064-nm neodymium:yttrium-aluminum-garnet laser treatment for pigmented disorders.

BACKGROUND: Long-pulsed (LP) lasers at pulse durations of 1-300 ms have been used to destroy nests of nevi cells by selectively targeting pigment chromophores. OBJECTIVE: To evaluate dual-wavelength LP laser-induced tissue reactions. METHODS: The patterns of LP 755-nm alexandrite (Alex) and/or 1064-nm neodymium (Nd):yttrium-aluminum-garnet (YAG) laser-induced tissue reactions were macroscopically evaluated using a tattoo-embedded phantom. Additionally, a pilot in vivo human study was performed for common acquired melanocytic nevus, of which dermoscopic images and high-speed cinematographs were obtained. RESULTS: Combinations of Nd:YAG and Alex laser treatments at interpulse intervals of 10 or 20 ms generated round to oval zones of photothermal and photoacoustic injury in two distinctive areas containing disintegrated tattoo particles. Treatment at interpulse intervals of 10 or 20 ms between Alex and Nd:YAG pulses elicited lesser degrees of thermal damage to surrounding tissues, compared to treatment at 100 or 200 ms. Immediately after combined LP laser treatment of human nevus lesions in vivo, Nd:YAG-Alex treatment at a 20-ms interpulse interval exhibited more remarkable crusting and erosive appearances than Alex-Nd:YAG treatment. CONCLUSION: For treating pigmented disorders, sequential delivery of LP Nd:YAG and Alex pulses at short interpulse intervals of 10-20 ms can effectively destroy nests of pigment chromophores.

Broadband light treatment using static operation and constant motion techniques for skin tightening in Asian patients.

BACKGROUND: Broadband light (BBL) devices irradiate photons of different wavelength to induce photothermal reactions on various aging-related chromophores. OBJECTIVES: To evaluate three BBL treatment settings for skin tightening in Asian patients. METHODS: A total of 27 patients underwent three sessions of BBL treatment via (1) an 800-nm cutoff filter using a static operation technique and a 695-nm cutoff filter using a constant motion technique (group 1, N = 9), (2) an 800-nm cutoff filter using a constant motion technique (group 2, N = 9), and (3) a 590-nm cutoff filter using a constant motion technique (group 3, N = 9). RESULTS: The patients in group 1 presented marked clinical improvements in zygomatic wrinkles, nasolabial folds, and marionette lines, with a median overall global aesthetic improvement scale (GAIS) score of 3. Meanwhile, patients in group 2 exhibited noticeable improvements in zygomatic wrinkles, nasolabial folds, perioral expression wrinkles at the cheek, and marionette lines, with a median GAIS score of 3. Patients in group 3 experienced improvement in skin tone and texture, zygomatic wrinkles, nasolabial folds, and marionette lines, with a median GAIS score of 2. CONCLUSIONS: Our data demonstrated that BBL treatment for nonablative, noninvasive skin tightening elicits satisfactory clinical outcomes.

Pattern analysis of 532- and 1064-nm microlens array-type, picosecond-domain laser-induced tissue reactions in ex vivo human skin.

Optical pulses from picosecond lasers can be delivered to the skin using microlens array (MLA) optics or a diffractive beam splitter to generate multiple, focused, high-intensity, micro-injury zones in the epidermis and dermis. The aim of our study was to histopathologically and immunohistochemically evaluate the patterns of 532- and 1064-nm MLA-type, picosecond laser-induced tissue reactions in human skin immediately after treatment. Picosecond neodymium:yttrium-aluminum-garnet (Nd:YAG) laser treatment using an MLA-type beam at the wavelengths of 532 nm and 1064 nm was delivered ex vivo to human skin. Irradiated skin specimens were then microscopically analyzed after hematoxylin and eosin staining and CD31 and Melan-A immunostaining. A single pulse of 532-nm MLA-type, picosecond laser treatment elicited cystic cavitation lesions at sizes of 83.4 ± 16.5 µm × 70.2 ± 17.3 µm (31-mm distance step) and 91.0 ± 44.7 µm × 81.2 ± 36.3 µm (48-mm distance step) in the epidermis and papillary dermis. Meanwhile, a single pulse of 1064-nm laser treatment generated cystic cavitation lesions at sizes of 107.0 ± 18.1 µm × 83.3 ± 37.4 µm (single-pulse mode) and 100.8 ± 40.4 µm × 83.1 ± 29.4 µm (dual-pulse mode) throughout the lower epidermis and upper papillary dermis. Lining epithelial cells in cystic cavitation lesions in the epidermis showed Melan-A-positive immunoreactivity, while cystic cavitation lesions in the dermis exhibited CD31-positive or CD31-negative/Melan-A-negative immunoreactivity. The present data can be used to predict 532- and 1064-nm MLA-type, picosecond-domain laser-induced tissue reactions in human skin.

Pregnancy outcomes in patients with vitiligo: A nationwide population-based cohort study from Korea.

BACKGROUND: Vitiligo is a chronic autoimmune skin disorder affecting 1% of populations worldwide. Few large-scale studies have explored adverse pregnancy outcomes in patients with vitiligo. OBJECTIVE: To investigate adverse pregnancy outcomes in patients with vitiligo. METHODS: We performed a retrospective cohort study on 4738 pregnancies of women with vitiligo and 47,380 pregnancies of age-matched controls without vitiligo using the Korean National Health Insurance Claims database from 2007 to 2016. Multivariate logistic regression models were used to evaluate the associations between vitiligo and pregnancy outcomes, including live births, spontaneous abortion, cesarean delivery, preterm delivery, gestational diabetes mellitus, stillbirth, pre-eclampsia/eclampsia, and intrauterine growth retardation. RESULTS: Patients with vitiligo exhibited a significantly lower live birth rate (odds ratio, 0.870; 95% confidence interval, 0.816-0.927) and a higher incidence of spontaneous abortion (odds ratio, 1.250; 95% confidence interval, 1.148-1.362) than the control group. LIMITATION: The Korean National Health Insurance Claims database lacks detailed clinical information on individual patients. CONCLUSION: Vitiligo was significantly associated with an increased risk of spontaneous abortion. Further studies are needed to determine whether systemic autoimmunity explains our finding.

Multimodal Approach for Treating Horizontal Neck Wrinkles Using Intensity Focused Ultrasound, Cohesive Polydensified Matrix Hyaluronic Acid, and IncobotulinumtoxinA.

BACKGROUND: For the restoration of horizontal neck wrinkles, multimodal approaches using neuromodulators, intensity focused ultrasound (IFU), and fine line fillers are recommended. OBJECTIVE: To evaluate the efficacy and safety of a 1-day, multimodal approach for horizontal neck wrinkles. METHODS: Twelve female patients with horizontal neck wrinkles were treated with a combined treatment of IFU, cohesive polydensified matrix hyaluronic acid (CPMHA), and incobotulinumtoxinA. Therapeutic outcomes were assessed on Day 0 and 1, 2, 3, and 6 months thereafter. RESULTS: Horizontal neck wrinkles decreased significantly in length from a median at baseline of 269.75 mm (interquatile range [IQR], 235.35-302.94 mm) to 91.5 mm (IQR, 51.4-108.61 mm) at 1 month, 92.3 mm (IQR, 69.66-132.07 mm) at 2 months, 101.88 mm (IQR, 86-146.77 mm) at 3 months, and 109.48 mm (IQR, 85.06-148.17 mm) at 6 months after the combined treatment. The median global aesthetic improvement scale scores were 3.5 (IQR, 2-4) at 1 month, 3 (IQR, 3-3.5) at 2 months, 3 (IQR, 2-4) at 3 months, and 3 (IQR, 3-3) at 6 months. Post-treatment petechiae resolved completely within 7 days, and CPMHA-induced lumps disappeared within 1 month. CONCLUSION: The present data demonstrated that the multimodal, combined treatment used in the present study provides satisfactory and long-lasting therapeutic outcomes by targeting different pathogenetic factors of horizontal neck wrinkles.

Treatment of café-au-lait macules with a high-fluenced 1064-nm Q-switched neodymium:yttrium aluminum garnet laser.

Café-au-lait macules (CALMs) are light to dark brown macules or patches of increased melanin concentration found along the dermoepidermal junction. Although many attempts to treat CALMs using various kinds of laser/light-based devices have been reported, CALMs remain refractory thereto with high recurrence rates. In this case series, we describe four patients with idiopathic CALMs that were effectively and safely treated with a non-ablative, high-fluenced, Q-switched (QS), 1064-nm neodymium:yttrium aluminum garnet (Nd:YAG) laser. The typical laser parameters for treating CALMs, including a spot size of 7-7.5 mm, a fluence of 2.4-2.5 J/cm2, and one to two passes until the appearance of mild erythema, but not petechiae, were utilized in this study over 12-24 treatment sessions at 2-week intervals. We suggest that high-fluenced QS 1064-nm Nd:YAG laser treatment can be used as an effective and alternative treatment modality for CALMs with minimal risk of side effects.

Therapeutic efficacy and safety of a 1927-nm fractionated thulium laser on pattern hair loss: an evaluator-blinded, split-scalp study.

Laser- or light-assisted therapies have been used to improve the perifollicular environment by upregulating the expression of growth factors and signaling molecules for hair restoration. The aim of our study was to preclinically and clinically evaluate the therapeutic efficacy and safety of a 1927-nm fractionated thulium laser on pattern hair loss (PHL). An in vivo hairless mouse study and an in vivo human skin environmental scanning electron microscopy (ESEM) study were performed with different power and energy settings. Thereafter, an evaluator-blinded, split-scalp study was conducted to evaluate hair thickness and density in 10 PHL patients treated with 12 sessions of fractionated thulium laser treatment with or without post-laser treatment application of a growth factor-containing (GF) solution. In in vivo hairless mouse skin, inverted cone-shaped zones of thulium laser-induced tissue coagulation (LITC) were noted immediately after treatment in the epidermis and upper to mid-dermis without remarkable ablative tissue injury. The ESEM study revealed round to oval-shaped zones of non-ablative LITC on the surface of the stratum corneum of a human subject immediately after laser irradiation. In PHL patients, 12 sessions of thulium laser monotherapy at 1-week intervals resulted in significantly increased hair density and thickness. Post-laser treatment application of GF solution offered additional therapeutic efficacy by improving hair density and thickness on the split scalp. The use of a fractionated thulium laser with or without post-laser therapy application of GF solution to treat PHL elicited remarkable improvements in hair thickness and hair counts.

Cilostazol inhibits the expression of hnRNP A2/B1 and cytokines in human dermal microvascular endothelial cells.

OBJECTIVES: hnRNP A2/B1 has been identified as a target antigen of anti-endothelial cell IgA antibody in patients with Behçet's disease (BD). In addition, increased expression of cellular hnRNP A2/B1 is stimulated by Streptococcus sanguinis or the sera from patients with BD. We aimed to investigate the effects of cilostazol on the expression of hnRNP A2/B1 and chemokines in human dermal microvascular endothelial cells (HDMECs). METHODS: Expression of hnRNP A2/B1, cytokines, and chemokines in HDMECs was induced by tumour necrosis factor (TNF)-α, interleukin (IL)-1ß, and lipopolysaccharide (LPS). HDMECs were treated with cilostazol (10 µM) and the inhibitory effects were evaluated with real-time polymerase chain reaction and immunocytochemistry. RESULTS: Expression of hnRNP A2/B1, CXCL1, CXCL2, CXCL8, and IL-1ß mRNA was significantly increased in HDMECs treated with all three stimulants. In addition, mRNA expression of hnRNP A2/B1 and inflammatory mediators was significantly inhibited in HDMECs treated with various stimulants with cilostazol pretreatment. Immunocytochemistry demonstrated that cilostazol pretreatment effectively inhibited the stimulant-induced increased expression of hnRNP A2/B1 in the nucleus and cytoplasm of HDMECs. CONCLUSIONS: Cilostazol pretreatment can reduce the excessive expression of inflammatory cytokines and chemokines and hnRNP A2/B1 by the BD-related stimulants, including TNF-α, IL-1ß, and LPS, in HDMECs. We suggest that cilostazol may have therapeutic efficacy in inhibiting the major inflammatory reaction in the pathogenesis of BD.

Pressure- and dose-controlled transcutaneous pneumatic injection of hypertonic glucose solution for the treatment of atrophic skin disorders.

BACKGROUND: Needleless transcutaneous pneumatic injections (TPIs) are a minimally invasive way to deliver the solution into the skin for therapeutic purposes. The suggested action mechanisms of TPI therapy include mechanical stimulation, immediate tissue shrinkage and late wound healing. METHODS: Thirteen Korean patients were treated with TPI for atrophic skin disorders, including acne scars, striae albae, post-furuncle, or carbuncle scars, and horizontal wrinkles with lipoatrophy. At each TPI treatment session, a single pass was made along with the atrophic skin lesions without overlapping. Thereafter, two dermatologists objectively evaluated the clinical improvement in the lesions in the photographs via the global aesthetic improvement scale (GAIS). RESULTS: One month after the final treatment, the overall mean GAIS score was 2.3 ± 0.8. Six of the 13 (46.2%) patients exhibited clinical improvement of grade 3, five (38.5%) patients grade 2 and two (15.4%) patients grade 1. The overall mean subjective satisfaction score with the TPI treatment was 2.3 ± 0.9. Six of the 13 (46.2%) patients achieved subjective satisfaction of grade 3, six (46.2%) patients grade 2 and one (7.7%) patient grade 0. CONCLUSIONS: The present study demonstrated that the TPI treatment is effective and safe for treating atrophic skin disorders of varying causes in Korean patients.

Morphometric analysis of high-intensity focused ultrasound-induced lipolysis on cadaveric abdominal and thigh skin.

Non-focused ultrasound and high-intensity focused ultrasound (HIFU) devices induce lipolysis by generating acoustic cavitation and coagulation necrosis in targeted tissues. We aimed to investigate the morphometric characteristics of immediate tissue reactions induced by 2 MHz, 13-mm focused HIFU via two-dimensional ultrasound images and histologic evaluation of cadaveric skin from the abdomen and thigh. Acoustic fields of a 2 MHz, 38-mm HIFU transducer were characterized by reconstruction of the fields using acoustic intensity measurement. Additionally, abdominal and thigh tissues from a fresh cadaver were treated with a HIFU device for a single, two, and three pulses at the pulse energy of 130 J/cm2 and a penetration depth of 13 mm. Acoustic intensity measurement revealed characteristic focal zones of significant thermal injury at the depth of 38 mm. In both the abdomen and thigh tissue, round to oval ablative thermal injury zones (TIZs) were visualized in subcutaneous fat layers upon treatment with a single pulse of HIFU treatment. Two to three HIFU pulses generated larger and more remarkable ablative zones throughout subcutaneous fat layers. Finally, experimental treatment in a tumescent infiltration-like setting induced larger HIFU-induced TIZs of an oval or columnar shape, compared to non-tumescent settings. Although neither acoustic intensity measurement nor cadaveric tissue exactly reflects in vivo HIFU-induced reactions in human tissue, we believe that our data will help guide further in vivo studies in investigating the therapeutic efficacy and safety of HIFU-induced lipolysis.

Therapeutic efficacy of autologous platelet-rich plasma and polydeoxyribonucleotide on female pattern hair loss.

Autologous platelet-rich plasma (PRP) exerts positive therapeutic effects on hair thickness and density in patients with pattern hair loss. The aim of our study was to evaluate the efficacy of intra-perifollicular autologous PRP and polydeoxyribonucleotide (PDRN) injections in treating female pattern hair loss (FPHL). Twenty FPHL patients were treated with a single session of PRP injection, followed by 12 sessions of PDRN intra-perifollicular injection, along the scalp at weekly intervals. Additionally, another 20 FPHL patients were treated with 12 sessions of PDRN injection only. Meanwhile, one half of the backs of two rabbits was injected with the PRP preparation, while the other half was injected with phosphate buffered saline as a control. Tissue samples from the rabbits were analyzed by real-time polymerase chain reaction and Western blotting. Compared with baseline values, patients treated with PRP and PDRN injections exhibited clinical improvement in mean hair counts (23.2 ± 15.5%; p < 0.001) and mean hair thickness (16.8 ± 10.8%; p < 0.001). In addition, patients treated with the 12 sessions of intra-perifollicular PDRN injection alone also showed clinical improvement in mean hair counts (17.9 ± 13.2%; p < 0.001) and mean hair thickness (13.5 ± 10.7%; p < 0.001). Comparison analyses between the two groups revealed that combined therapy with PRP and PDRN induces greater improvement in hair thickness than treatment with PDRN therapy alone (p = 0.031), but not in hair counts (p > 0.05). The pilot animal study revealed significant up-regulation of WNT, platelet-derived growth factor, and fibroblast growth factor expression in rabbit skin treated with the PRP preparation, compared with control skin. In conclusion, intra-perifollicular injections of autologous PRP and/or PDRN generate improvements in hair thickness and density in FPHL patients.