Intradermal Research Articles

Wound Healing Effects of Liposomal Nanocurcumin and PL Pro Nanocurcumin on Thermal Burn and Skin Ulcer

Background Burn injuries and skin ulcers are important health problems resulting in physical and psychological scars and chronic disabilities. This study investigated the wound-healing effects of liposomal nanocurcumin and PL pro nanocurcumin on thermal burns in rats and doxorubicin-induced skin ulcers in mice and their systemic toxicity. Methods Having subjected to a cylindrical hot steel rod onto the dorsum, burned lesions were covered topically with silver sulfadiazine/liposomal nanocurcumin/PL pro nanocurcumin twice a day for 21 days. Besides, the other skin lesions which were induced by a single intradermal injection of doxorubicin on the dorsal region were topically administered with dimethyl sulfoxide/liposomal nanocurcumin/PL pro nanocurcumin twice a day for 21 days. Results The results indicated that liposomal nanocurcumin and PL pro nanocurcumin significantly reduced the wound size, increased the hydroxyproline content in animals’ skin, and improved the histopathological structure of the affected tissues. Specifically, liposomal nanocurcumin demonstrated better healing results than PL pro nanocurcumin on thermal burns. Furthermore, topical administration of liposomal and PL pro nanocurcumin was deemed not to exert any systemic toxicity to the wounded animals by not influencing considerably the hematological parameters and renal and hepatic functions and altering the histology of the liver and kidney. Additionally, liposomal nanocurcumin and PL pro nanocurcumin with average sizes of 206 nm and 344 nm were well-dispersed in water, accentuating that the disadvantages of limited water solubility have been overcome. Conclusion Thus, liposomal nanocurcumin and PL pro nanocurcumin exerted effective effects on burned wounds and skin ulcers whilst triggering no systemic toxicity in wounded animals.

Comparing Intradermal (ID) Rabies Vaccination with Conventional IM Regimen on Humoral Response of New Zealand White Rabbits for the Production of Animal-Derived Polyclonal Antibodies.

In developing countries, it is imperative to implement cost-effective strategies for animal humoral response development in the production of antiserum. This study compared the effect of immunization regimens on the humoral immune response of New Zealand White (NZW) rabbits (N = 24) using cell culture rabies vaccine (CCRV) through intradermal (ID) and traditional intramuscular (IM) routes. The rabbits were divided into three experimental groups: (a) IPC-R2 with a two-site one-week regimen; (b) TRC-R3 with a two-site twenty-eight-day regimen; and (c) Alternate-R4 with a four-site one-week regimen. These regimens were then compared to the standard IM schedule of five doses of rabies vaccine administered at days 0, 3, 7, 14, and 28 in control group R-1. The results were evaluated at days 14 and 35 postvaccination using rabies-specific Platelia II™ ELISA kit method. The results showed a better response to the ID regimen than the IM route regarding immunogenicity and volume consumption of the vaccine. The three selected ID regimes showed significantly higher mean titer values than the control IM regimen group R-1 (p < 0.001). The study aims to explore simple immunization strategies to enhance the RV-specific antibody titers for immunization donor animals. This method would produce polyclonal antibodies and strengthen local production of polyclonal antibodies in Pakistan to deal with vaccine and rabies immunoglobulin (RIG) shortage, thus providing effective postexposure prophylaxis (PEP) for better control of rabies in developing countries.

One-dose intradermal rabies booster enhances rabies antibody production and avidity maturation

The incidence of rabies in Thailand reached its peak in 2018 with 18 human deaths. Preexposure prophylaxis (PrEP) vaccination is thus recommended for high-risk populations. WHO has recently recommended that patients who are exposed to a suspected rabid animal and have already been immunized against rabies should receive a 1-site intradermal (ID) injection of 0.1 mL on days 0 and 3 as postexposure prophylaxis (PEP). In Thailand, village health and livestock volunteers tasked with annual dog vaccination typically receive only a single lifetime PrEP dose and subsequent boosters solely upon confirmed animal bites. However, the adequacy of a single PrEP dose for priming and maintaining immunity in this high-risk group has not been evaluated. Therefore, our study was designed to address two key questions: (1) sufficiency of single-dose PrEP—to determine whether a single ID PrEP dose provides adequate long-term immune protection for high-risk individuals exposed to numerous dogs during their vaccination duties. (2) Booster efficacy for immune maturation—to investigate whether one or two additional ID booster doses effectively stimulate a mature and sustained antibody response in this population. The level and persistence of the rabies antibody were determined by comparing the immunogenicity and booster efficacy among the vaccination groups. Our study demonstrated that rabies antibodies persisted for more than 180 days after cost-effective ID PrEP or the 1st or the 2nd single ID booster dose, and adequate antibody levels were detected in more than 95% of participants by CEE-cELISA and 100% by indirect ELISA. Moreover, the avidity maturation of rabies-specific antibodies occurred after the 1st single ID booster dose. This smaller ID booster regimen was sufficient for producing a sufficient immune response and enhancing the maturation of anti-rabies antibodies. This safe and effective PrEP regimen and a single visit involving a one-dose ID booster are recommended, and at least one one-dose ID booster regimen could be equitably implemented in at-risk people in Thailand and other developing countries. However, an adequate antibody level should be monitored before the booster is administered.

Injectable platelet-rich fibrin for treatment of female pattern hair loss

ABSTRACT This case series evaluated use of injectable platelet rich fibrin (termed i-PRF+) for the treatment of female pattern hair loss (FPHL). Eleven individuals underwent 3-monthly intradermal injections of i-PRF+ using a mesotherapy gun. The mean number of hair follicles containing hairs per unit area improved at 3- and 6-months follow-up (p < .001), and all participants had a negative hair pull test. Hair volume and thickness, and patient-reported outcome scores also improved at follow-up (p < .001). Adverse effects were minor and self-limited. A series of three i-PRF+ injection sessions were effective for the treatment of FPHL, as shown by improved hair analysis parameters and patient self-assessment scores.

Co-Delivery of Recombinant Super-Affinity VEGF and PDGF-BB Accelerates Diabetic Wound Healing by Improving Angiogenesis, Arteriogenesis and Blood Flow

Abstract Background Diabetic ulcers are characterized by local ischemia, usually without macroangiopathy. We have previously found that the combination of VEGF and PDGF-BB in a fibrin matrix is effective in stimulating arterial growth to diabetic wounds. Aims We developed modified forms of VEGF and PDGF-BB to bear super-affinity for the extracellular matrix (SA-VP), in order to decorate the wound tissue without the need for a biomaterial. We investigated the dose-dependent effects on local blood flow and wound healing, by applying the treatment either to the healthy tissue around the wound or to the damaged wound bed. Methods Full thickness wounds were created on the dorsal skin of diabetic (db/db) mice. SA-VP or saline were applied to the wound bed or divided into 4 injections around the wound edge. Wound closure and blood flow were measured on days 4 and 8 after treatment and tissues were harvested for histology on day 8. Data were analysed by Anova with Tukey’s post-hoc test for multiple comparisons. Results Wound healing was improved dose-dependently by SA-VP by both delivery routes. Histologically, angiogenic areas and total amount of angiogenesis were significantly increased by the highest SA-VP dose, again independent of delivery route (p = 0.034). However, the total amount of recruited arterioles was significantly increased only in the healthy tissue around the wound and only by intradermal injections of SA-VP (p = 0.008). In agreement with the arteriogenic effect, the blood flow at day 4 was significantly increased only by injections of the highest SA-VP dose around the wound (p = 0.018). Conclusion SA-VP treatment significantly accelerates wound healing in a diabetic murine model with a clear dose-dependent effect. Targeting the undamaged tissue around the wound by injections induces more effective arteriogenesis. However, direct treatment of the wound bed is equally effective for healing. These results support further development for a potential clinical use.

Pre-Incisional and Multiple Intradermal Injection of N-Acetylcysteine Slightly Improves Incisional Wound Healing in an Animal Model.

The objective of this study was to investigate if delivering multiple doses of N-acetylcysteine (NAC) post-surgery in addition to pre-incisional administration significantly impacts the wound healing process in a rat model. Full-thickness skin incisions were carried out on the dorsum of 24 Sprague-Dawley rats in six locations. Fifteen minutes prior to the incision, half of the sites were treated with a control solution, with the wounds on the contralateral side treated with solutions containing 0.015%, 0.03% and 0.045% of NAC. In the case of the NAC treated group, further injections were given every 8 h for three days. On days 3, 7, 14 and 60 post-op, rats were sacrificed to gather material for the histological analysis, which included histomorphometry, collagen fiber organization analysis, immunohistochemistry and Abramov scale scoring. It was determined that scars treated with 0.015% NAC had significantly lower reepithelization than the control at day 60 post-op (p = 0.0018). Scars treated with 0.045% NAC had a significantly lower collagen fiber variance compared to 0.015% NAC at day 14 post-op (p = 0.02 and p = 0.04) and a lower mean scar width than the control at day 60 post-op (p = 0.0354 and p = 0.0224). No significant differences in the recruitment of immune cells and histological parameters were found. The results point to a limited efficacy of multiple NAC injections post-surgery in wound healing.

Different Dilutions of Mesobotox in Facial Rejuvenation: Which is Better?

BackgroundMicrobotulinum toxin A treatment is a technique of delivering multiple intradermal injections of diluted botulinum toxin type A into the dermis or the interface between the dermis and the superficial layer of the facial muscles to preserve the facial mobility. The current study aimed to evaluate and compare the clinical effect of different dilutions of microbotulinum toxin A in periorbital and mid-facial rejuvenation.MethodsThis randomized prospective interventional study included 30 female patients with different types of wrinkles in periorbital and/or mid-face. Patients were divided into three groups: group I (10 patients): 100U botulinum toxin in 5 ml saline, group II (10 patients): 100U botulinum toxin in 7 ml saline and group III (10 patients): 100U botulinum toxin in 10 ml saline.ResultsA statistically significant better global esthetic improvement scale (GAIS) scores after 1 month were observed in group I compared to groups II and III. Also, after 6 months better GAIS scores were observed in group I compared to group II and in group II compared to group III. Assessment of different esthetic parameters measured by the Antera 3D camera revealed a statistically significant improvement in all parameters (periorbital and mid-face) in group I and in most of parameters (periorbital and mid-face) in groups II and III with more evident improvement after 1 month compared to after 6 months.ConclusionIntradermal microbotulinum toxin A is a cost-effective method for improving periorbital and mid-face wrinkles with a better effect of 1:5 than 1:7 and 1:10 dilutions.Facial wrinkles possess a great burden on patients' psychological status, and the emergence of novel rejuvenation technique with minimal side effects is necessary.MicroBoNT-A usage in the literature was through variety of dilutions and concentrations. Therefore, a conclusive and comparative study was essential to compare the effect of different microBoNT-A dilutions.In this context, the current study aimed to evaluate and compare the clinical effect of different dilutions of microBoNT-A in periorbital and mid-facial rejuvenation.Level of Evidence IIIThis journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Promotion of hair growth by a conditioned medium from human umbilical cord mesenchymal stem cells cultivated in a 3D scaffold of gelatin sponge

BackgroundThis study aims to investigate the effects of a conditioned medium (CM) from human umbilical cord mesenchymal stem cells (HuMSCs) cultivated in gelatin sponge (GS-HuMSCs-CM) on hair growth in a mouse model.MethodsCM was collected from the HuMSCs cultivated in a monolayer or in a gelatin sponge. Vascular endothelial growth factor (VEGF), insulin-like growth factor-1 (IGF-1), keratinocyte growth factor (KGF), and hepatocyte growth factor (HGF) levels in CMs were measured by enzyme-linked immunosorbent assays (ELISAs). A hair loss model by a C57 BL/6J mouse was prepared. The effects of GS-HuMSCs-CM and HuMSCs on hair regrowth in mice were investigated by intradermal injection in the depilated back skin with normal saline (NS) as the control. The time for hair regrowth and full covering in depilated areas was observed, and the hair growth was evaluated histologically and by grossly measuring hair length and diameter.ResultsCompared with monolayer cultured cells, the three-dimensional (3D) culture of HuMSCs in gelatin sponge drastically increased VEGF, IGF-1, KGF, and HGF production. GS-HuMSCs-CM and HuMSCs injection both promoted hair regeneration in mice, while GS-HuMSCs-CM presented more enhanced effects in hair length, hair diameter, and growth rate. GS-HuMSCs-CM significantly promoted angiogenesis in injected skin areas, which might also contribute to faster hair regrowth.ConclusionGS-HuMSCs-CM exerted significant effects on inducing hair growth and promoted skin angiogenesis in C57BL/6J mice.

Intracellular Oxygen Transient Quantification in Vivo During Ultra-High Dose Rate FLASH Radiation Therapy

Large, rapid extracellular oxygen transients (ΔpO2) have been measured in vivo during ultra-high dose rate radiation therapy; however, it has been unclear if they match intracellular oxygen levels. Here, the endogenously produced protoporphyrin IX (PpIX) delayed fluorescence signal was measured as an intracellular in-vivo oxygen sensor to quantify these transients, with direct comparison to extracellular pO2. Intracellular ΔpO2 is closer to the cellular DNA, the site of major radiobiological damage, and therefore should help elucidate radiochemical mechanisms of the FLASH effect and potentially be translated to human tissue measurement. PpIX was induced in mouse skin through intraperitoneal injection of 250 mg/kg of aminolevulinic acid. The animals were also administered a 50 µL intradermal injection of 10 µM oxyphor G4 (PdG4) for phosphorescence lifetime pO2 measurement. Paired oxygen transients were quantified in leg or flank tissues while delivering 10 MeV electrons in 3 µs pulses at 360 Hz for a total dose of 10 to 28 Gy. Transient reductions in pO2 were quantifiable in both PpIX delayed fluorescence and oxyphor phosphorescence, corresponding to intracellular and extracellular pO2 values, respectively. Reponses were quantified for 10, 22, and 28 Gy doses, with ΔpO2 found to be proportional to the dose on average. The ΔpO2 values were dependent on initial pO2 in a logistic function. The average and standard deviations in ΔpO2 per dose were 0.56 ± 0.18 mm Hg/Gy and 0.43 ± 0.06 mm Hg/Gy for PpIX and oxyphor, respectively, for initial pO2 > 20 mm Hg. Although there was large variability in the individual animal measurements of ΔpO2, the average values demonstrated a direct and proportional correlation between intracellular and extracellular pO2 changes, following a linear 1:1 relationship. A fundamentally new approach to measuring intracellular oxygen depletion in living tissue showed that ΔpO2 transients seen during ultra-high dose rate radiation therapy matched those quantified using extracellular oxygen measurement. This approach could be translated to humans to quantify intracellular ΔpO2. The measurement of these transients could potentially allow the estimation of intracellular reactive oxygen species production.

Abstract PO3-05-12: Randomized Phase 2 of Bria-IMT, an Allogenic Human Cell Line with Antigen Presenting Activity, in Heavily Pretreated Metastatic Breast Cancer

Abstract Introduction Despite progress in MBC, too many continue to succumb due to treatment resistance or intolerance. SV-BR-1-GM is an allogenic human breast cancer cell line with antigen presenting cell activity designed to overcome the immune-suppressive tumor microenvironment while being acceptable to extensively pretreated contemporary MBC patients. We report interim exploratory analysis of the ongoing RCT of the Bria-IMT regimens. Methods An interim exploratory analysis using preliminary partially available evaluable data of the ongoing prospective, randomized phase 2 (NCT03328026; 2018-present) of Bria-IMT (irradiated SV-BR-1-GM) with a PD-1check point inhibitor (CPI) every 3 weeks (25 patients dosed to date). Both regimens include cyclophosphamide 300 mg/m2 48-72 hours prior to intradermal Bria-IMT (~20 x 106 cells) followed by interferon-alpha at the inoculation sites 2 days later. The control arm used the original sequence with simultaneous start of Bria-IMT and CPI in cycle 1. The experimental arm started CPI in cycle 2 after the 2nd inoculation. Candida skin test was performed before cycle 1 to determine anergy status while delayed-type hypersensitivity skin test (DTH), defined as &amp;gt;5mm erythema &amp; induration, was done at every cycle by intradermal injection of a small test dose of Bria-IMT prior to full dose inoculation. Results Median age: 58 (range 37-81); median prior therapies: 8 lines (range 4-18); 89% were grade 2/3 (n=18); 68% hormone receptor positive; 61% HER2 negative, 33% HER2 low, and 6% HER2 high; 33% triple negative. Overall, 53% of subjects had a clinical benefit as best response by BICR, PI or target lesion measurement. The two treatment arms were similar with a trend showing longer median durations on therapy (mDOT) of 3.7 mo in the experimental delayed CPI arm compared with mDOT = 2.9 for original sequence control arm. 47% of patients were anergic to candida. Among all anergic subjects, the mDOT was 3.5 compared to 2.5 mo for non-anergic patients. However, among anergic subjects, the alternative treatment arm had a lower risk of treatment discontinuation (improved HR) with mDOT of 3.7 compared to the 3.3 mo mDOT of the original treatment. 50% of anergic subjects eventually developed DTH to SV-BR-1-GM. mDOT was 4.0 mo for DTH+ pts vs 3.0 mo for those who did not mount DTH. Median OS was not yet reached; mean OS was higher in non-anergic vs anergic pts. Among those who developed an inoculation site reaction to Bria-IMT, OS was greater than for those who did not. Time on the Bria-IMT regimen exceeded the time on penultimate treatment in 22% of subjects while 33% of subjects with prior CPI use exceeded last therapy. AEs were mild with 28% of subjects (n=7) having &amp;gt; grade 3 events. The most common grade 3+ AE was lipase increase (n=3). One subject with encouraging changes in peripheral blood tumor markers and CTCs completed a PET study using Zr-89 crefmirlimab berdoxam, a zirconium-89 labelled truncated antibody specific to human CD8α (CD8 Immuno-PET) and demonstrated increased uptake in some metastatic lesions and draining lymph nodes. Updated results will be provided at the meeting. Conclusion Sequencing of CPI with Bria-IMT is associated with differential clinical outcome trends but not statistically significant in this interim preliminary exploratory analysis regardless of prior CPI use. Bria-IMT is immunogenic with clinical benefit demonstrated for both treatment schedules among patients with inducible DTH reactions. Patients who develop an immune response to Bria-IMT had an increase in OS compared to those who did not. The nodal localization of CD8+ cells on PET may indicate a systemic activation of CD8 positive lymphoid cells. It also provides support that the Bria-IMT + CPI combination immune-based therapy can result in an increase of CD8+ tumor infiltrating lymphocytes in breast cancer metastatic sites. These preliminary results will be evaluated in the ongoing randomized phase 3 pivotal registrational trial. Citation Format: Carmen Calfa, Chaitali Nangia, Minal Barve, John Knecht, Jarrod Holmes, Kendrith Roland, Ralph Boccia, Frances Valdes-Albini, Zach Gostout, Mingjin Chang, William Williams, Charles Wiseman, Bonnie Guerin, Shaker Dakhil, Giuseppe Del Priore, Saranya Chumsri. Randomized Phase 2 of Bria-IMT, an Allogenic Human Cell Line with Antigen Presenting Activity, in Heavily Pretreated Metastatic Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-05-12.

Abstract PO3-19-05: Phase III study to evaluate the efficacy and safety of GLSI-100 (GP2 + GM-CSF) in breast cancer patients with residual disease or high-risk PCR after both neo-adjuvant and postoperative adjuvant anti-HER2 therapy, Flamingo-01

Abstract Background: GP2 is a biologic nine amino acid peptide of the HER2/neu protein delivered in combination with Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) that stimulates an immune response targeting HER2/neu expressing cancers, the combination known as GLSI-100. In a prospective, randomized, single-blinded, placebo-controlled, multicenter Phase IIb study, no recurrences were observed in the HER2+ population after 5 years of follow-up, if the patient was treated with GLSI-100, survived, and was followed for more than 6 months (p = 0.0338). Immunotherapy elicited a potent response measured by skin tests and immunological assays. Of the 146 patients that have been treated with GLSI-100 over 4 clinical trials, GLSI-100 was well-tolerated and no serious adverse events observed were considered related to the immunotherapy. Methods: This Phase III trial is a prospective, randomized, double-blinded, multi-center study. After 1 year of trastuzumab-based therapy, 6 intradermal injections of GLSI-100 or placebo will be administered over the first 6 months and 5 subsequent boosters will be administered over the next 2.5 years for a total of 11 injections over 3 years. The participant duration of the trial will be 3 years treatment plus 1 additional year follow-up for a total of 4 years following the first year of treatment with trastuzumab-based therapy. Patients will be stratified based on residual disease status at surgery, hormone receptor status and region. Study Size – Interim Analysis: Approximately 498 patients will be enrolled. To detect a hazard ratio of 0.3 in invasive breast cancer free survival (IBCFS), 28 events will be required. An interim analysis for superiority and futility will be conducted when at least 14 events have occurred. This sample size provides 80% power if the annual rate of events in placebo patients is 2.4% or greater. Up to 100 non-HLA-A*02 subjects will be enrolled in an open-label arm. Eligibility Criteria: The patient population is defined by these key eligibility criteria: Objectives: Study Status: The study has been initiated at a number of sites in the US. The study is also expected to be opened in Spain, Germany, and France. Contact Information: Greenwich LifeSciences, Inc. Stafford, TX Email: Flamingo-01@greenwichlifesciences.com Website: greenwichlifesciences.com Funding: This trial is supported by Greenwich LifeSciences. Citation Format: Snehal Patel, Jaye Thompson, Mira Patel, F. Joseph Daugherty, Mothaffar Rimawi. Phase III study to evaluate the efficacy and safety of GLSI-100 (GP2 + GM-CSF) in breast cancer patients with residual disease or high-risk PCR after both neo-adjuvant and postoperative adjuvant anti-HER2 therapy, Flamingo-01 [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-19-05.

Comparison of the effect of intra-dermal injection of botulinum toxin and normal saline in the treatment of facial skin pores.

Skin pores (SPs) are normal and benign skin structures that are mostly located on the face (nose, cheeks, etc.) that cause many aesthetic concerns or complaints. One known effective treatment is botulinum toxin A (BTXA), which is also approved for the treatment of strabismus, blepharospasm, muscle spasm, cervical dystonia, glabella wrinkles, and primary axillary hyperhidrosis. Therefore, the aim of this study was to compare the effect of intra-dermal injection of botulinum toxin and normal saline serum (NSS) in the treatment of large facial pores. The study included 25 people who referred to the skin clinic of Imam Khomeini Hospital in Ahvaz from June 2021 to January 2022 for the treatment of large facial skin pores. Randomly, some subjects were injected with botulinum toxin at ten points, and each point was equivalent to 2.5 units of Masport (500 units vial of Masport diluted with 10 ml of NSS). Some other people were injected with 0.05 ml of NSS by intra-dermal injection at ten points. Finally, the data were analyzed using SPSS-Ver. 22 software. Based on optical coherence tomography results, it was determined that the diameter of facial pores decreased significantly (P = 0.011). Dermoscopy showed a significant decrease in the average size of facial pores (P < 0.011), and also, the pore score decreased significantly (P = 0.021). In addition, the results showed that the size of skin pores and facial fat on both sides of the face did not decrease significantly from the patients' point of view (P = 0.71). Based on the results of the present study, it can be concluded that intra-dermal injection of botulinum toxin is an effective and safe method to control facial pores, which showed acceptable results after 3 months.

Fractional CO2 laser, platelet rich plasma and combination of both in treatment of female pattern hair loss

Background Female pattern hair loss (FPHL) is one of the most common chronic problems seen by dermatologists worldwide. Hair loss has a significant influence on the quality of life and is associated with low self-esteem and depression. The treatment modalities vary from medical approaches to surgical interventions. However, limited perceived efficacy of a therapeutic regimen may lead to premature stoppage of treatment. Objective To evaluate the efficacy of platelet rich plasma (PRP), fractional CO2 laser and combination of both in treatment of FPHL. Patients and methods This is a split-scalp prospective interventional study in which thirty patients presenting with FPHL received PRP in one area, fractional CO2 in another one, combined fractional CO2 and PRP in a third one and saline intradermal injection in the fourth area in frontal and mid scalp region of scalp. The sessions were scheduled every 2 weeks for 4 sessions, then monthly for 2 months. Patients were evaluated after each session and 3months after the last session. The results were evaluated by trichoscopic and folliscopic examination in the four examined areas. Assessment of treatment response was done according to the count of terminal and vellus hair, the thickness and density of hair shafts and the percentage of change, determined by folliscopic examination. Patients’ satisfaction and side effects were evaluated. Results There was significant difference between the studied groups as regards percentage of change of terminal hair, vellus hair, hair thickness and hair density after treatment. Pairwise comparisons showed that the combined group was statistically better than either PRP, fractional CO2, or saline group as regards all studied parameters (P value was &lt;0.05 for each). Conclusion Combination of fractional CO2 laser and topical PRP application would have a synergistic effect in treatment of FPHL. The technique would be an excellent alternative to injections in order to stimulate hair growth in patients with FPHL.

Внутрикожное введение туберкулина безыгольным инъектором при диагностике туберкулеза

Внутрикожное введение туберкулина безыгольным инъектором при диагностике туберкулеза

The impact of purified protein derivative prior to intravesical bacillus Calmette-Guérin for the treatment of patients with non-muscle invasive bladder cancer.

The aim of this study is to investigate the impact of the intradermal injection of purified protein derivative (PPD) and PPD skin test reactions on the oncological outcomes of patients with non-muscle invasive bladder cancer (NMIBC) treated by trans-urethral resection of bladder tumor (TURBT) and adjuvant intravesical BCG. The study included 100 consecutive patients with NMIBC prospectively given intradermal PPD 1-2 weeks before starting BCG therapy. Another 100 patients with NMIBC not given intradermal PPD before starting BCG were chosen as a historical control. The control group was chosen to be matching with the study group regarding baseline characteristics. The study group was divided into 2 subgroups with positive and negative reaction to PPD skin test. Oncological outcomes, immunological markers (TNF-α and IL-6) changes and BCG side effects were evaluated. There were no significant differences between patients who received PPD or not regarding the 2-year recurrence free survival (RFS) rates and progression-free survival (PFS) rates and immunological markers changes. The 2-year RFS and PFS rates were significantly higher in patients with positive reactions. Post-induction values of immunological markers increased in all patients with a significant increase in patients with positive reactions. BCG side effects were significantly higher in patients with positive reactions. The intradermal injection of PPD before intravesical BCG has no impact on oncological outcomes of patients with NMIBC treated with TURBT and intravesical BCG. However, the PPD skin test reactions before BCG therapy can predict the oncological outcomes, BCG side effects and the immunological outcomes of patients.

Gram-negative anaerobes elicit a robust keratinocytes immune response with potential insights into HS pathogenesis.

Hidradenitis Suppurativa (HS) is a chronic autoinflammatory skin disease with activated keratinocytes, tunnel formation and a complex immune infiltrate in tissue. The HS microbiome is polymicrobial with an abundance of commensal gram-positive facultative (GPs) Staphylococcus species and gram-negative anaerobic (GNA) bacteria like Prevotella, Fusobacterium and Porphyromonas with increasing predominance of GNAs with disease severity. We sought to define the keratinocyte response to bacteria commonly isolated from HS lesions to probe pathogenic relationships between HS and the microbiome. Type strains of Prevotella nigrescens, Prevotella melaninogenica, Prevotella intermedia, Prevotella asaccharolytica, Fusobacterium nucleatum, as well as Staphylococcus aureus and the normal skin commensal Staphylococcus epidermidis were heat-killed and co-incubated with normal human keratinocytes. RNA was collected and analysed using RNAseq and RT-qPCR. The supernatant was collected from cell culture for protein quantification. Transcriptomic profiles between HS clinical samples and stimulated keratinocytes were compared. Co-staining of patient HS frozen sections was used to localize bacteria in lesions. A mouse intradermal injection model was used to investigate early immune recruitment. TLR4 and JAK inhibitors were used to investigate mechanistic avenues of bacterial response inhibition. GNAs, especially F. nucleatum, stimulated vastly higher CXCL8, IL17C, CCL20, IL6, TNF and IL36γ transcription in normal skin keratinocytes than the GPs S. epidermidis and S. aureus. Using RNAseq, we found that F. nucleatum (and Prevotella) strongly induced the IL-17 pathway in keratinocytes and overlapped with transcriptome profiles of HS patient clinical samples. Bacteria were juxtaposed to activated keratinocytes invivo, and F. nucleatum strongly recruited murine neutrophil and macrophage migration. Both the TLR4 and pan-JAK inhibitors reduced cytokine production. Detailed transcriptomic profiling of healthy skin keratinocytes exposed to GNAs prevalent in HS revealed a potent, extensive inflammatory response vastly stronger than GPs. GNAs stimulated HS-relevant genes, including many genes in the IL-17 response pathway, and were significantly associated with HS tissue transcriptomes. The close association of activated keratinocytes with bacteria in HS lesions and innate infiltration in murine skin cemented GNA pathogenic potential. These novel mechanistic insights could drive future targeted therapies.

Efficacy and Tolerability of a Hyaluronic Acid-Based Extracellular Matrix for Labia Majora Rejuvenation and Augmentation: A Pilot Study.

A new injectable solution containing low-molecular-weight hyaluronic acid (HA) and a specific amino acid mixture was formulated with proper aesthetic performance for the main signs of facial skin photoaging. The present study aimed to investigate its new application for rejuvenating and augmenting labia majora using clinical and biometric assessments. Three sessions of intradermal injections were performed using 3 ml of test extracellular matrix (ECM) for 10 eligible post-menopause female subjects (age 53.6 ± 7.93 years). The effectiveness of the intervention was assessed by an independent physician using before-and-after pictures based on the physician's global assessment score. Objective biophysical skin assessments, including skin hydration, skin erythema, and melanin index, as well as elasticity parameters including firmness (R0), gross elasticity (R2), and net elasticity (R5), were also performed before the first injection and then on the 2nd and 12th weeks after the last session. Patients' satisfaction and all reported or observed adverse events were documented. At week 12, all the subjects reported an aesthetic improvement of 25% or more in rejuvenation and sagging of the labia major area. A statistically significant improvement was also detected in R0 and R5 at week 12 (p-values 0.005 and 0.022, respectively). Patient satisfaction surveys revealed a median score of 8 at both follow-up visits. The results showed a new indication of the tested HA ECM for providing a beneficial, durable, rejuvenating effect on the labia majora with a good safety profile.

A comparison of the effectiveness of intralesional tranexamic acid against platelet-rich plasma in the treatment of melasma

Background: Melasma, derived from the Greek word "melas" meaning "black", manifests as an acquired, more or less symmetrical hypermelanosis of sun-exposed skin. This study aimed to compare and evaluate the efficacy and safety of intradermal injection of tranexamic acid and platelet-rich plasma in treating various types of melasma. Methods: Conducted from June 2022 to December 2023 at the outpatient department of dermatology, Sri Lakshmi Narayana institute of medical sciences, Puducherry, this split-face prospective study involved 40 melasma cases. Tranexamic acid (4 mg/ml) was intradermally injected into the right side of the face, while PRP was injected into the left side. Improvement was assessed using the modified Melasma area severity index (MASI) grading system and dermoscopy, measuring disease severity and percentage of improvement before and after therapy on both sides of the face. Results: The study comprised predominantly females (80%) aged 20 to 30 years (50%), followed by those aged 30 to 40 years (35%). Most cases (93%) exhibited a gradual onset, with centrofacial (52.5%) and malar (37.5%) patterns being predominant. Mixed pattern (67.5%) was common. Pre-treatment mean MASI scores for tranexamic acid and PRP sides were 7.54 and 6.92, respectively, with post-treatment scores of 4.6 and 2.83, respectively. Conclusions: Intradermal PRP demonstrated significantly superior efficacy over intradermal tranexamic acid in managing melasma, particularly in the longer term. Thus, PRP, coupled with good compliance, may substantially reduce the disease burden compared to conventional tranexamic acid treatment.

Enhancing Tranexamic Acid Penetration through AQP-3 Protein Triggering via ZIF-8 Encapsulation for Melasma and Rosacea Therapy.

The systemic use of tranexamic acid (TA) as an oral drug can bring adverse reactions, while intradermal injection leads to pain and a risk of infection. Moreover, it is difficult for highly hydrophilic TA to penetrate the skin barrier that contains lots of hydrophobic lipid compounds, which poses enormous restrictions on its topical application. Current transdermal TA delivery strategies are suffering from low drug load rates, plus their synthesis complexity, time-consumption, etc. adding to the difficulty of TA topical application in clinical therapeutics. To increase the penetration of TA, a novel approach using TA-loaded ZIF-8 (TA@ZIF-8) is developed. The encapsulation efficiency of TA@ZIF-8 reaches ≈25% through physical adsorption and chemical bonding of TA indicates by theoretical simulation and the improved TA penetration is elevated through activating the aquaporin-3 (AQP-3) protein. Additionally, in vivo and in vitro experiments demonstrate the preponderance of TA@ZIF-8 for penetration ability and the advantages in intracellular uptake, minor cytotoxicity, and inhibition of melanogenesis and inflammatory factors. Moreover, clinical trials demonstrate the safety and efficacy of TA@ZIF-8 in the treatment of melasma and rosacea. This work presents a potential topical application of TA, free from the safety concerns associated with systemic drug administration.

Upregulated miR-374a-5p drives psoriasis pathogenesis through WIF1 downregulation and Wnt5a/NF-κB activation

BackgroundPsoriasis is a chronic, inflammatory skin disease. MicroRNAs (miRNAs) are an abundant class of non-coding RNA molecules. Recent studies have shown that multiple miRNAs are abnormally expressed in patients with psoriasis. The upregulation of miR-374a-5p has been associated with psoriasis severity. However, the specific role of miR-374a-5p in the pathogenesis of psoriasis remain unclear. MethodsqRT-PCR was employed to validate the expression of miR-374a-5p in psoriatic lesions and in a psoriasis-like cell model constructed using a mixture of M5 (IL-17A, IL-22, OSM, IL-1α, and TNF-α). HaCaT cells were transfected with miR-374a-5p mimic/inhibitor, and assays including EdU, CCK-8, and flow cytometry were conducted to evaluate the effect of miR-374a-5p on cell proliferation. The expression of inflammatory cytokines IL-1β, IL-6, IL-8, and TNF-α was verified by qRT-PCR. Bioinformatics analysis and dual-luciferase reporter gene assay were performed to detect the downstream target genes and upstream transcription factors of miR-374a-5p, followed by validation of their expression through qRT-PCR and Western blotting. A psoriasis-like mouse model was established using imiquimod cream topical application. The psoriasis area and severity index scoring, hematoxylin-eosin histology staining, and Ki67 immunohistochemistry were employed to validate the effect of miR-374a-5p on the psoriatic inflammation phenotype after intradermal injection of miR-374a-5p agomir/NC. Additionally, the expression of pathway-related molecules and inflammatory factors such as IL-1β, IL-17a, and TNF-α was verified by immunohistochemistry. ResultsUpregulation of miR-374a-5p was observed in psoriatic lesions and the psoriasis-like cell model. In vitro experiments demonstrated that miR-374a-5p not only promoted the proliferation of HaCaT cells but also upregulated the expression of inflammatory cytokines, including IL-1β, IL-6, IL-8, and TNF-α. Furthermore, miR-374a-5p promoted skin inflammation and epidermal thickening in the Imiquimod-induced psoriasis-like mouse model. Mechanistic studies revealed that miR-374a-5p led to downregulation of WIF1, thereby activating the Wnt5a/NF-κB signaling pathway. The transcription factor p65 encoded by RELA, as a subunit of NF-κB, further upregulated the expression of miR-374a-5p upon activation. This positive feedback loop promoted keratinocyte proliferation and abnormal inflammation, thereby facilitating the development of psoriasis. ConclusionOur findings elucidate the role of miR-374a-5p upregulation in the pathogenesis of psoriasis through inhibition of WIF1 and activation of the Wnt5a/NF-κB pathway, providing new potential therapeutic targets for psoriasis.