Skin Structure Research Articles

Ceftobiprole: A therapeutic update.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. The purpose of this therapy update is to highlight new clinical studies comparing ceftobiprole to current therapies and provide evidence for its suggested role in therapeutic management of selected infectious diseases. Antimicrobial resistance continues to be a global health problem, and newer targeted antimicrobials are necessary to combat increasing rates of problematic infections. More specifically, targeted antimicrobials against methicillin-resistant Staphylococcus aureus are needed. Ceftobiprole has been marketed internationally for the treatment of complicated skin and skin structure infections, community-acquired pneumonia, and hospital-acquired pneumonia. While Food and Drug Administration approval was previously pursued for its use in acute bacterial skin and skin structure infections in the US, the Food and Drug Administration issued a complete response letter determining that study data were unreliable and recommended completion of additional studies. In April 2024, ceftobiprole was granted approval for 3 indications in the US based on updated clinical study data. Ceftobiprole is the second fifth-generation cephalosporin to be developed and approved for clinical use. Ceftobiprole has been shown to be safe and effective in treating specific infectious diseases such as bloodstream infections, acute bacterial skin and skin structure infections, and community-acquired bacterial pneumonia. Its use should be considered when targeting infections caused by methicillin-resistant S. aureus where other therapeutic options may be limited. However, additional real-world data on the efficacy of ceftobiprole should be continually monitored as experience in the US increases.

Bridging the Gap: A Systematic Review with Expert Opinion on the Use of Dalbavancin for In-Label and Off-Label Indications in Pediatric Patients

Objectives: The aim of this work was to perform a systematic review assessing the pharmacokinetic/pharmacodynamic (PK/PD) properties of dalbavancin and the clinical use for in-label and off-label indications in pediatric patients. Methods: Two authors independently searched the PubMed-MEDLINE and Scopus databases and clinicaltrials.gov up to 20 November 2024, to retrieve randomized controlled trials (RCTs), observational studies, PK studies, and case series/reports assessing dalbavancin PK/PD properties or the clinical use for both in-label and off-label indications in pediatric patients. Data were independently extracted by the two authors, and the quality of the included studies was independently assessed by means of specific tools according to study design. Clinical success was selected as the primary outcome. Descriptive statistics were used for summarizing the retrieved data. Subgroup analysis according to PK/PD data, as well as in-label and off-label indications, was performed. Results: After screening 206 articles, nine studies were included in the systematic review (one RCT, three PK studies, and five case series/reports; n = 267). Dalbavancin exposure was 30% lower in pediatric patients compared to adults. In acute bacterial skin and skin structure infections (ABSSSIs), the overall clinical success of dalbavancin was 96.1-97.3% and 92.9% in RCT and case series, respectively. Bone and joint infections (60.7%) and central-line-associated bloodstream infections (14.3%) represented the most common dalbavancin off-label indications in pediatric patients. Overall, the clinical success for off-label indications was 92.9%. The rate of adverse events ranged from 7.1% to 10.7%. Conclusions: Our systematic review summarized evidence concerning the PK/PD properties of dalbavancin and its use for in-label or off-label indications in pediatric patients. The available findings suggest that dalbavancin may be a valuable alternative for the management of ABSSSIs and/or off-label indications in pediatric patients according to efficacy and safety data, allowing for a potential minimized duration of hospital stay.

Study on the Effect of Bee Venom and Its Main Component Melittin in Delaying Skin Aging in Mice.

Bee venom (BV) and its main compound melittin (MLT) have antioxidant, anti-inflammatory, and anti-aging activities; however, very little research has been conducted on their effects on skin aging. In this study, a mouse skin aging model induced by D-galactose was constructed via subcutaneous injection into the scruff of the neck, and different doses of BV and MLT were used as interventions. The anti-aging effects and mechanisms of BV and MLT were explored by detecting the skin morphology and structure, and anti-aging-related factors and performing non-targeted metabolomics of mice. BV and MLT improved dermal and epidermal thickness, boosted the collagen fiber content, increased hydroxyproline and hyaluronic acid levels, and enhanced transcript-level expression of IL-10, Col1a1, and Col3a1, while decreasing that of IL-1β. Metabolomic analysis showed that BV and MLT regulated the levels of some metabolites (compared to those in the skin aging control). BV effectively alleviated skin aging by regulating the pentose phosphate pathway, and pathways associated with carbon, galactose, and β-alanine metabolism, whereas MLT regulated pathways related to lipid metabolism, cholesterol metabolism, and atherosclerosis. This study highlights the potential applicability of BV and MLT in skin aging treatments and cosmetic products.

The future approach for the management of acute bacterial skin and skin structure infections.

To discuss the new available options for the treatment of acute bacterial skin and skin structure infections (ABSSSIs) and how to implement in the clinical practice innovative approaches for their management. The availability of long-acting antibiotics, including dalbavancin and oritavancin, changed the approach to patients with ABSSSI. Direct discharge from the emergency department and early discharge from the hospital should be considered in patients with ABSSSI. Despite limited data about different bactericidal properties, the choice between dalbavancin and oritavacin is usually based on patients' characteristics and comorbidities. Delafloxacin and omadacycline are other options and have the advantage to be available for both intravenous and oral formulations, allowing a sequential therapy and switch from intravenous to oral treatment in clinically stable patients. Further studies should elucidate the profile of patients who may beneficiate from these drugs. Early discharge from the hospital should be considered in patients with ABSSSI at a high risk of methicillin-resistant Staphylococcus aureus and in vulnerable patients for which hospitalization may have detrimental consequences. In elderly individuals, patients with diabetes mellitus, oncological people who need for continuing their healthcare pathway, this approach may reduce complications and costs related to hospitalization.

Establishing an animal model for post-inflammatory hyperpigmentation following fractional CO2 laser application.

Post-inflammatory hyperpigmentation (PIH) is a common cosmetic concern, often leading to significant psychological distress for the patients. With the widespread application of lasers including ablative fractional resurfacing (AFR) with a 10,600nm CO2 laser, PIH caused by lasers is becoming increasingly common. But due to the absence of an appropriate animal research model, our understanding of pathophysiological mechanisms and preventive strategies for PIH remains limited. This study aimed to establish an animal model to investigate PIH following AFR CO2 laser application, focusing on the dynamic changes in melanin, inflammatory cytokines, growth factors, and skin structures as PIH developed. We employed pigmented guinea pigs as our experimental subjects and conducted our research in two phases. In the first phase, we utilized three modes of AFR CO2 laser to identify which laser mode could induce PIH by monitoring dynamic melanin changes. In the second phase, the laser mode that most reliably induced PIH was applied to re-establish the PIH model. Pathophysiological changes during PIH progression were investigated through histopathological observations, real-time quantitative polymerase chain reaction, and two-photon microscopy. We successfully established a replicable animal model for PIH following AFR CO2 laser application. We observed a significant increase in inflammatory cytokines and growth factors within the skin tissue by the second week, with stable pigmentation becoming apparent by the third week. Our research provides a promising animal model for understanding and further investigating the mechanisms of PIH after laser procedures. V (animal study).

Ceftobiprole activity against multidrug-resistant Staphylococcus aureus clinical isolates collected in the United States from 2016 through 2022.

Ceftobiprole was recently approved by the United States (US) Food and Drug Administration (FDA) for the treatment of adult patients with Staphylococcus aureus bacteremia, including right-side endocarditis, acute bacterial skin and skin structure infections, and community-acquired bacterial pneumonia in adults and pediatrics. Ceftobiprole is an advanced-generation cephalosporin approved in many countries for the treatment of adults with community-acquired pneumonia and hospital-acquired pneumonia, excluding ventilator-associated pneumonia. We evaluated the activities of ceftobiprole and comparators against methicillin-resistant S. aureus (MRSA) and multidrug-resistant (MDR) S. aureus clinical isolates. A total of 19,764 S. aureus isolates were collected from patients with various infection types at 37 US medical centers from 2016 to 2022. Susceptibility testing was performed by broth microdilution according to Clinical and Laboratory Standard Institutes (CLSI) standards. Isolates were categorized as MDR if they were nonsusceptible by CLSI criteria to ≥3 antimicrobials. Ceftobiprole was highly active against MRSA (n = 8,184; MIC50/90, 1/2 mg/L; 99.3% susceptible [S]) and MDR (n = 2,789; MIC50/90, 1/2 mg/L; 98.1%S) isolates and retained activity against 87.3% of ceftaroline-nonsusceptible isolates (n = 433; MIC50/90, 2/4 mg/L). Ceftobiprole demonstrated greater susceptibility rates than ceftaroline against all resistant subsets. Ceftobiprole was highly active against isolates nonsusceptible to clindamycin (98.0%S), daptomycin (100.0%S), doxycycline (98.2%S), erythromycin (99.5%S), gentamicin (98.1%S), levofloxacin (99.1%S), tetracycline (99.1%S), tigecycline (100.0%S), and trimethoprim-sulfamethoxazole (99.4%S) and isolates with decreased susceptibility to vancomycin (98.3%S).

Using Dalbavancin for the Treatment of Acute Bacterial Skin and Skin Structure Infections (ABSSSIs) in Obese Patients: A Real-Life, Single-Center Observational Study.

Background/Objectives: Obesity is an established risk factor for several infective conditions, including Acute Bacterial Skin and Skin Structure Infections (ABSSSIs), with a rising trend in their incidence expected in this population. Although numerous antibiotics are available for the prevention and treatment of ABSSSIs, their characterization in obese patients is not a regulatory mandate, highlighting a knowledge gap in this field. Dalbavancin (DAL) is the first approved long-acting antibiotic for the treatment of ABSSSIs. The aim of the study was to describe the clinical effectiveness of DAL in the treatment of ABSSSI, with or without concomitant osteoarticular infections (OAIs), in obese patients compared with non-obese patients. Furthermore, we compared the effectiveness of DAL and intravenous standard of care (SOC) regimens in a subgroup of obese patients with ABSSSI. Results: Overall, 45 subjects treated with DAL (12 obese and 33 non-obese) and 8 obese subjects treated with SOC regimens (1:1 ratio) were included. Obese patients treated with DAL had a similar clinical resolution to non-obese patients. However, obese patients tended to have a better cure rate in ABSSSI than OAI. The subgroup of obese patients with ABSSSI had a high clinical resolution, which was comparable to that of SOC. DAL was overall highly tolerated in obese patients. Methods: Over a three-year period, hospitalized subjects with ABSSSI who were treated with DAL were included. Patients were further divided into two groups according to the presence/absence of obesity (BMI ≥ 30 kg/m2). Furthermore, obese patients treated with DAL were compared with obese patients treated with SOC (1:1 ratio). Conclusions: In our real-world study, DAL confirmed its high effectiveness in the treatment of ABSSSI, including in a difficult-to-treat population such as obese patients.

Lipidomic and Instrumental Evaluation of a Melatonin-Based In & Out Strategy Versus Topical Treatment in Skin Aging: A Randomized Prospective Trial.

This study aimed to evaluate the efficacy of a novel "In & Out" strategy, combining topical and oral melatonin supplementation, in managing skin aging compared to topical treatment alone. A randomized, prospective study was conducted on 39 healthy females aged 55-69 years. Participants were divided into two groups: one received both the topical formula and oral melatonin supplementation (Group A), while the other received a topical melatonin-based formula (Group B). Clinical evaluations included lipidomic analysis, skin moisturization, and wrinkle depth analysis at baseline and after 84 days. The addition of oral melatonin supplementation to the topical regimen led to improvements in the skin's lipid profile and moisturization levels. These findings suggest that combining topical and oral melatonin may provide a more comprehensive approach to managing skin aging by addressing both local and systemic factors. Background/Objectives: With age, the endogenous antioxidant capacity of the skin decreases, including melatonin (Mel) synthesis. Skin aging is also associated with alterations in epidermal lipids, particularly a reduction in triglycerides and ceramides, which are essential for maintaining skin structure and hydration. The administration of exogenous melatonin could, therefore, be an effective anti-aging strategy. While some data suggest that melatonin may positively influence the lipid profile, specific data on its effects on skin aging are lacking. This study aimed to evaluate the anti-aging effects of an "In & Out" regimen consisting of a Mel-based cream and dietary supplement in comparison with topical treatment alone, focusing on clinical and lipidomic changes involved in skin homeostasis. Results: A statistically significant variation was observed in both groups compared to baseline (T0) in terms of moisturization (+23.6% in Group A, +18.3% in Group B) and wrinkle depth (-18.5% in Group A, -9.4% in Group B, p < 0.05). Both groups showed improvements in the lipid content of the skin, which typically decreases with age. The "In & Out" strategy resulted in a statistically significant increase in triacylglycerols and ceramides, key lipids that exhibit water-holding properties. Conclusions: The "In & Out" melatonin-based regimen demonstrated greater efficacy in clinical improvement and positive lipid profile modifications compared to topical treatment alone, highlighting its potential as a comprehensive anti-aging strategy.

Development and evaluation of a polymer material-based formulation for non-surgical nasolabial fold reduction.

Currently, nasolabial folds are mainly removed by invasive procedures, resulting in long-lasting changes, as non-surgical user-implementable alternatives are scarce and inefficient. For example, the use of coating films for this purpose has thus far faced substantial difficulties because such films should combine the antithetical properties of shrinkability and flexibility. Herein, we challenge this status quo by identifying a polymer that simultaneously exhibits shrinkability and flexibility and using this polymer to develop a cosmetic formulation for immediate and non-invasive nasolabial fold removal. The developed formulation, namely a solution of norbornene/tris(trimethylsiloxy)silylnorbornene copolymer in disiloxane, was tested on a group of Japanese women using visual evaluation, three-dimensional shape analysis and ultrasonography. The polymer film obtained upon drying the formulation was subjected to shrinkage and flexibility tests, and its synchronization with the skin was examined using optical microscopy. The free volume of the polymer films was evaluated using positron annihilation measurements and molecular dynamics simulations. Upon application, the liquid formulation rapidly dries to produce a skin-synchronized polymer film that exhibits significant drying-induced shrinkage without cracking, thereby exerting a lift-up effect and inducing changes in the internal skin structure to efficiently reduce the nasolabial fold, providing a feeling of rejuvenation. On average, the proposed treatment decreases the nasolabial fold depth by 1 mm, increases the opening angle of the nasolabial fold by 11.5° and reduces the hypodermis thickness by 0.2 mm. Our results facilitate the development of cosmetic products targeting the nasolabial fold and inspire further research in this field.

Microneedles as a Promising Technology for Disease Monitoring and Drug Delivery: A Review.

The delivery of molecules, such as DNA, RNA, peptides, and certain hydrophilic drugs, across the epidermal barrier poses a significant obstacle. Microneedle technology has emerged as a prominent area of focus in biomedical research because of its ability to deliver a wide range of biomolecules, vaccines, medicines, and other substances through the skin. Microneedles (MNs) form microchannels by disrupting the skin's structure, which compromises its barrier function, and facilitating the easy penetration of drugs into the skin. These devices enhance the administration of many therapeutic substances to the skin, enhancing their stability. Transcutaneous delivery of medications using a microneedle patch offers advantages over conventional drug administration methods. Microneedles containing active substances can be stimulated by different internal and external factors to result in the regulated release of the substances. To achieve efficient drug administration to the desired location, it is necessary to consider the design of needles with appropriate optimized characteristics. The choice of materials for developing and manufacturing these devices is vital in determining the pharmacodynamics and pharmacokinetics of drug delivery. This article provides the most recent update and overview of the numerous microneedle systems that utilize different activators to stimulate the release of active components from the microneedles. Further, it discusses the materials utilized for producing microneedles and the design strategies important in managing the release of drugs. An explanation of the commonly employed fabrication techniques in biomedical applications and electronics, particularly for integrated microneedle drug delivery systems, is discussed. To successfully implement microneedle technology in clinical settings, it is essential to comprehensively assess several factors, such as biocompatibility, drug stability, safety, and production cost. Finally, an in-depth review of these criteria and the difficulties and potential future direction of microneedles in delivering drugs and monitoring diseases is explored.

Caffeine as an Active Molecule in Cosmetic Products for Hair Loss: Its Mechanisms of Action in the Context of Hair Physiology and Pathology.

Caffeine has recently attracted attention as a potential remedy for hair loss. In the present review, we look into the molecule's possible mechanisms of action and pharmacodynamics. At the molecular level, it appears that the physiological effects of caffeine are mainly due to the molecule's interaction with adenosine pathways which leads to an increase in cAMP level and the stimulation of metabolic activity in the hair follicle. Moreover, caffeine also acts as an antioxidant and may prevent degenerative processes. While the intact stratum corneum seems virtually impenetrable to caffeine and a range of physical and chemical methods have been proposed to facilitate its penetration, hair follicles seem to be both a main entry route into the skin and target structures for caffeine at the same time. Caffeine readily forms bonds with water and other molecules which may influence its bioavailability and should be taken into account when engineering future hair products. The results of clinical studies published so far seem promising; however, the majority of the studies of caffeine-based hair loss products offer a very low level of evidence due to considerable flaws in study designs. Nevertheless, the metabolic activity of caffeine and its ability to enter and accumulate in the hair follicles combined with the results of available clinical trials seem to indicate that caffeine could indeed prove as an effective and safe option in the management of hair loss.

Fruit Acid Inhibits UV-Induced Skin Aging via PI3K/Akt and NF-κB Pathway Inhibition.

Ultraviolet (UV) radiation-induced photoaging is a multifaceted biological process. Fruit acids have shown promise in combating photoaging. This study aims to investigate the mechanisms underlying the protective effects of fruit acids on UV-induced skin photoaging. Initially, we induced skin photoaging in rats through UV irradiation. Subsequently, the model group received glycolic acid treatment. The reparative effects of glycolic acid on skin tissue morphology and structure were assessed using Hematoxylin-eosin (HE) staining. The influence of glycolic acid on oxidative stress indicators (Superoxide Dismutase (SOD), Glutathione Peroxidase (GSH-Px), Malondialdehyde (MDA), Catalase (CAT)) and levels of cellular inflammatory factors (Interleukin-6 (IL-6), Tumor Necrosis Factor-alpha (TNF-α), IL-1β, Interferon-gamma (IFN-γ)) in photoaged skin was evaluated via Enzyme-Linked Immunosorbent Assay (ELISA). Additionally, alterations in collagen expression and levels of proteins associated with the Phosphoinositide 3-kinase/Protein Kinase B (PI3K/Akt) and Nuclear Factor kappa B (NF-κB) signaling pathways were determined through Western blot analysis. Compared to the model group, the fruit group exhibited a decrease in the thickness of the skin epidermal keratinization layer, an increase in dermal thickness, and more vigorous cortical secretion. Moreover, compared with the model group, the fruit group showed significant increases in SOD activity, CAT, GSH-Px, Collagen I, Collagen III, Collagen VII, and elastin. Conversely, levels of MDA, IL-6, IL-1β, IFN-γ, and TNF-α were lower in the fruit acid group than in the model group. Additionally, fruit acid treatment inhibited the phosphorylation levels of PI3K, Akt, and p65 induced by UV. Fruit acid demonstrates the ability to diminish the oxidative stress and inflammatory responses in skin photoaging rat models, thereby facilitating collagen recovery and ameliorating symptoms of skin photoaging. Its potential mechanism may entail the inhibition of the activation of the PI3K/Akt and NF-κB signaling pathways.

Vanillin and IGF1-loaded dual-layer multifunctional wound dressing with micro-nanofibrous structure for full-thickness wound healing acceleration.

Multifunctional dual-layer wound dressings hold significant promise for comprehensive full-thickness wound management by closely mimicking the native skin structure and features. Herein, we employed an innovative approach utilizing electrospinning techniques to develop a dual-layer dressing comprising a microfibrous Ecoflex®-Vanillin (Ex-Vnil) top layer (TL) and a nanofibrous Soluplus®-Insulin-like growth factor-1 (Sol-IGF1) bottom layer (BL). The tensile properties of dual-layer wound dressings were within the standard range for use in skin tissue regeneration. The TL exhibited hydrophobic properties with a contact angle value of 92.4° and significant antibacterial activity, mimicking the epidermis of the skin, thereby preventing fluid and bacterial penetration. Moreover, the dual-layer wound dressing demonstrated standard water vapour transmission rate, with 91.2% release of IGF1 and 66.8% release of Vnil within 5days. Notably, the fabricated dual-layer dressing promoted cell behaviour and exhibited a significant angiogenesis effect and accelerated healing of full-thickness wound, achieving 96.4% closure after 14days, attributed to reduced inflammation, early blood vessel formation, and enhanced collagen density. Our findings underscore the potential of the fabricated dual-layer dressing as an innovative solution in full-thickness wound care.

Nanoparticles' Perspective in Skin Tissue Engineering: Current Concepts and Future Outlook.

Nanotechnology seems to provide solutions to the unresolved complications in skin tissue engineering. According to the broad function of nanoparticles, this review article is intended to build a perspective for future success in skin tissue engineering. In the present review, recent studies were reviewed, and essential benefits and challenging issues regarding the application of nanoparticles in skin tissue engineering were summarized. Previous studies indicated that nanoparticles can play essential roles in the improvement of engineered skin. Bio-inspired design of an engineered skin structure first needs to understand the native tissue and mimic that in laboratory conditions. Moreover, a fundamental comprehension of the nanoparticles and their related effects on the final structure can guide researchers in recruiting appropriate nanoparticles. Attention to essential details, including the designation of nanoparticle type according to the scaffold, how to prepare the nanoparticles, and what concentration to use, is critical for the application of nanoparticles to become a reality. In conclusion, nanoparticles were applied to promote scaffold characteristics and angiogenesis, improve cell behavior, provide antimicrobial conditions, and cell tracking.

Enzyme-assisted Rosa davurica mitigates UV-induced skin photodamage by modulating apoptosis through Nrf2/ARE and MAPK/NF-κB pathways.

Exposure to UV irradiation results in abnormal, extensive apoptosis of skin cells. This excessive cell death can promote inflammation and alter the microenvironment, increasing the risk of skin cancer. Despite extensive research, few materials are effective at simultaneously protecting against both UVA and UVB irradiation. This study aims to develop dual-action material using enzyme-assisted extraction of Rosa davurica Pall (RD) to prevent skin photodamage caused by UVA and UVB irradiation. Three different enzymes were used to assist the extraction of RD, followed by an analysis of the changes in active component levels. Skin photodamage models were established by exposing Normal Human Dermal Fibroblasts (NHDF) and HaCaT cells to UVA and UVB irradiation. The impact of enzyme-assisted extracted RD (ERD) on Reactive Oxygen Species (ROS) production and cell apoptosis was assessed using Flow Cytometry. The effects of ERDs on inflammatory cytokines were measured using ELISA, and RT-PCR was used to evaluate its impact on apoptotic gene expression in photodamaged cells. Furthermore, the impact of ERDs on the Nuclear factor erythroid 2-related factor 2 (Nrf2)/Antioxidant response element (ARE) and Mitogen-activated protein kinases (MAPK)/Nuclear factor-κB (NF-κB) signaling pathways was assessed through Western blot analysis. Finally, the impact of ERDs on full-thickness artificial skin tissue after UV irradiation was assessed using hematoxylin and eosin (H&E) staining. Furthermore, leveraging the experimental results, network pharmacology was utilized to explore the potential of ERDs in preventing skin cancer. Enzyme-assisted extraction enhanced the bioactive components of RD. ERDs effectively reduced ROS levels and suppressed the secretion of Tumor necrosis factor (TNF)-α, Interleukin (IL)-1β, and IL-6 by modulating the Nrf2/ARE and inhibiting the MAPK/NF-κB signaling pathways. This mechanism promoted the expression of the anti-apoptotic gene Bcl-2 and decreased the activity of proapoptotic genes BAX, caspase-3, and caspase-9, thereby countering UV-induced apoptosis. Additionally, staining results demonstrated that ERDs effectively repaired UV-induced photodamage and maintained the integrity of skin structure. ERDs provides comprehensive protection against photodamage induced by UVA and UVB irradiation, demonstrating its potential as an effective photoprotective material and possibly in preventing skin cancer.

Pharmacokinetic/pharmacodynamic analysis of tedizolid phosphate against Staphylococcus aureus and Streptococcus pneumoniae in children, adolescents, and adults by Monte Carlo simulation

The objective of this study was to investigate the cumulative fraction of response of various dosage regimens of tedizolid phosphate against Staphylococcus aureus and Streptococcus pneumoniae in children, adolescents, and adults. Monte Carlo simulations (MCSs) were performed using previously published pharmacokinetic parameters and pharmacodynamic data to evaluate the efficacy of the simulated dosage strategies in terms of area under the concentration-time curve/minimum inhibitory concentration targets of tedizolid. According to the results of the MCSs, currently approved dosage regimens of tedizolid phosphate were effective in the treatment of acute bacterial skin and skin structure infections (ABSSSIs) caused by methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) including vancomycin intermediate, heterogeneous vancomycin intermediate, and daptomycin-non-susceptible MRSA in adult and pediatric patients aged 12 years and older. However, high-dose regimens of tedizolid phosphate should be the preferred option to optimize efficacy against ABSSSIs caused by linezolid-resistant MRSA, particularly cfr-mediated isolates. Furthermore, the dosage regimens of 3 and 4 mg/kg/day of tedizolid phosphate were appropriate to treat ABSSSIs caused by MSSA and MRSA in children aged 2 to 6 and 6 to 12 years, respectively. Moreover, approved dosage regimens of tedizolid phosphate for patients older than 12 years may be sufficient against Streptococcus pneumoniae pneumonia but insufficient for Staphylococcus aureus pneumonia. For neutropenic patients, almost all the simulated regimens of tedizolid phosphate were ineffective against Staphylococcus aureus and Streptococcus pneumoniae. These pharmacokinetics/pharmacodynamics-based simulations rationalize and optimize the dosage regimens of tedizolid phosphate against Staphylococcus aureus and Streptococcus pneumoniae in children, adolescents, and adults.

Effects of Cryolipolysis on Subcutaneous Adipose Tissue of Adult Women: Immunohistochemical Analysis

BACKGROUND: The skin, the largest organ in the human body, is composed of complex layers that include subcutaneous adipose tissue. Understanding the characteristics of this skin structure is essential to optimize therapeutic interventions, such as cryolipolysis, aiming for more effective and personalized results. OBJECTIVE: To evaluate the immunohistochemical effects of skin tissue in adult women undergoing cryolipolysis. MATERIALS AND METHODS: We carried out an experimental and blind study with immunohistochemical analysis in women with localized abdominal fat, categorized based on the constitution of the skin as flaccid or firm according to the Investigator Assessment Skin Laxity Scoring System scale. Participants were randomized before undergoing the cryolipolysis procedure. Forty-five days after the procedure, they underwent abdominoplasty, with collection of biological material. We evaluated the inflammatory markers EBF-1, TNF-alpha, and CD68, as well as Caspase 3, cleaved Caspase 3, apoptotic BCL2, Ki-67 for fibroblast proliferation, and FIS1 for mitochondrial proliferation. RESULTS: Six women were included, divided into two groups; three women with loose and three with firm skin. We observed that after cryolipolysis, the group with flaccid skin showed higher expression of the Casp3, TNF-alpha, BCL2, and FIS1 markers compared to those with firm skin. CONCLUSION: Cryolipolysis may act differently according to tissue morphology, suggesting that its apoptotic response is more pronounced in the group with flaccid skin.

The Effect of Human Adipose Stem Cell-Conditioned Medium (hASC-CM) in Photoaged Skin.

Background: Ultraviolet (UV) exposure causes direct and indirect damages to skin structures. Human adipose stem cell-conditioned medium (hASC-CM) is a collection of several soluble factors, such as cytokines, chemokines, and Growth Factors (GF), secreted by almost all living cells in the extracellular space which support wound healing and skin rejuvenation. Objective: To determine the effects of human adipose stem cell-conditioned medium (hASC-CM) in photoaged skin and evaluate photoaging improvement after treatment. Methods: An experimental randomized controlled trial was performed, involving 64 photoaged subjects at the Dermato-Venereology Outpatient Clinic of Jemursari Islamic Hospital Surabaya from March to June 2022. The subjects were divided into the hASC-CM group and vehiculum (control) group. Patients' transepidermal water loss value, skin tone, and Glogau score in weeks 0, 4, and 8 were evaluated. The data were then analyzed using Mann-Whitney test (p<0.05). Results: All subjects had Glogau scale of III (89.6%) with mean ± SD (3.121 ± 0.329). hASC-CM group showed higher improvements in the pore, wrinkle, spot polarized, spot UV parameters and skin tone compared to vehiculum group(p<0.05). Conclusions: hASC-CM effectively improved all parameters observed. The limitation of this research was on the lack of long-term follow-up after treatment. This research had received an ethical permit from The Ethical Committee Board of Jemursari Islamic Hospital Surabaya under letter 006/KEPK-RSISJS/II/2022.

EXOSOMES FOR FACIAL REPAIR, REGENERATION AND REJUVENATION: COMPARISON BETWEEN DIFFERENT COMMERCIAL PRODUCTS

Exosomes have been studied as a potential therapeutic option for improving skin texture. The mode of action of exosomes for skin texture likely involves several mechanisms, including stimulation of collagen production, promotion of skin cell proliferation reduction of oxidative stress regulation of inflammatory and antioxidant responses extracellular matrix remodeling, which is important for maintaining skin structure and function. Aim of this study is to compare the in vitro effects of some commercial products that use new technologies containing plant derived nanovesicles from Rosa damascena callus, Centella asiaticacallus, Euphorbia supina stem and exosomes from bovine colostrum passively loaded with growth factors and cytokines purified from bovine colostrum, for facial repair, regeneration and rejuvenation.Of all the products tested, only product containing exosomes purified from colostrum gave very encouraging results in terms of effects on proliferation, cell viability and wound repair. The other products tested gave results comparable to the untreated samples.

Beneficial Impacts of Chokeberry and Tart Cherry Based Dietary Supplements Consumption on Cellulite Reduction.

Cellulite is an aesthetically distressing skin condition occurring in 80-90% of females and manifesting as dimples and depressions, producing an uneven surface to the skin. Our aim was to evaluate the effect of combined oral consumption of two dietary supplements based on chokeberry and tart cherry juices over a period of 32 days on cellulite reduction. Twenty women aged 21-49 with a cellulite grade of 1-2 according to the Nurnberger-Muller scale were participating in the study. Ultrasonography was applied to analyze the skin structure in addition to biochemical and anthropometric parameters, which were measured before starting the treatment and after 32 days. A reduction in the thickness of the dermis with subcutaneous fat tissue, subcutaneous fat tissue alone, epidermis, and dermis with epidermis (15.02, 14.34, 21.98, and 20.94%, respectively) was noticed, while the length of the fascicles was reduced by 35.93%. Out of 20 subjects, 11 (57.9%) had edema of the dermis at the beginning of the study, which was not recorded at the end of the study. Moreover, a statistically significant increase in the tissue doppler (TD) signals was recorded in all subjects treated with two dietary supplements, indicating a better blood supply. Changes in anthropometric and biochemical parameters were not recorded. Creatinine, urea, ALT, and AST values, as indicators of kidney and liver function, remained at normal reference levels, pointing out the product's safety. The positive effect of chokeberry and tart cherry juice-based dietary supplements consumption in cellulite condition could be connected with microcirculation improvements.