In Vivo Evaluation of Wound Healing Efficacy of Gel-Based Dressings Loaded with Pycnogenol™ and Ceratothoa oestroides Extracts.

Ceratothoa oestroides and French maritime pine bark (Pycnogenol™) extracts are considered promising therapeutic agents in wound healing. This study explores the healing efficacy of composite dressings containing these extracts, aiming to enhance their stability and effectiveness, utilizing a low-temperature vacuum method for producing Sodium Alginate-Maltodextrin gel dressings. Surgical wounds were inflicted on SKH-hr2 hairless mice. Dressings were loaded with Pycnogenol™ and/or C. oestroides extracts and assessed for their efficacy. Wound healing was primarily evaluated by clinical and histopathological evaluation and secondarily by Antera 3D camera and biophysical measurements. Dressings were stable and did not compromise the therapeutic properties of C. oestroides extract. All interventions were compared to the C. oestroides ointment as a reference product. Most of the wounds treated with the reference formulation and the C. oestrodes dressing had already closed by the 15th day, with histological scores of 7 and 6.5, respectively. In contrast, wounds treated with Pycnogenol™, either alone or in combination with C. oestroides, did not close by the end of the experiment (16th day), with histological scores reaching 15 in both cases. Furthermore, treatment with 5% Pycnogenol™ dressing appeared to induce skin thickening and increase body temperature. The study underscores the wound healing potential of C. oestroides extracts and highlights the need for further research to optimize Pycnogenol™ dosing in topical applications.

Type I Diabetes Mellitus Suppresses Experimental Skin Carcinogenesis.

This study explores the previously uncharted territory of the effects of ultraviolet (UV) radiation on diabetic skin, compared to its well-documented impact on normal skin, particularly focusing on carcinogenesis and aging. Employing hairless SKH-hr2, Type 1 and 2 diabetic, and nondiabetic male mice, the research subjected these to UV radiation thrice weekly for eight months. The investigation included comprehensive assessments of photoaging and photocarcinogenesis in diabetic versus normal skin, measuring factors such as hydration, trans-epidermal water loss, elasticity, skin thickness, melanin, sebum content, stratum corneum exfoliation and body weight, alongside photo documentation. Additionally, oxidative stress and the presence of hydrophilic antioxidants (uric acid and glutathione) in the stratum corneum were evaluated. Histopathological examination post-sacrifice provided insights into the morphological changes. Findings reveal that under UV exposure, Type 1 diabetic skin showed heightened dehydration, thinning, and signs of accelerated aging. Remarkably, Type 1 diabetic mice did not develop squamous cell carcinoma or pigmented nevi, contrary to normal and Type 2 diabetic skin. This unexpected resistance to UV-induced skin cancers in Type 1 diabetic skin prompts a crucial need for further research to uncover the underlying mechanisms providing this resistance.

Octenidine Versus Dispase Gels for Wound Healing After Cryosurgery Treatment in Patients with Basal Cell Carcinoma.

For a specific group of patients with basal cell carcinoma (small, low risk), cryosurgery could be the suggested treatment, which results in the formation of an ulcer in the lesion area. The proteolytic enzymes' contribution to the wound healing is an ongoing research goal. Preclinical animal experiments in the Laboratory of the Pharmaceutical Technology Department of the National and Kapodistrian University of Athens have showed that a dose of 5 U/mL of dispase gel after the formation of tissue rashes, significantly promoted wound healing. Herein, a feasibility study in 16 patients enrolled by the First Department of Dermatology of Andreas Syggros Hospital was designed: 5 U/mL of dispase gel (once every 3 days) versus a drug reference containing octenidine (daily administration). The evaluation of the healing effect, safety, and tolerance was done on days 1 (cryosurgery), 2, 7, 21, and 60. The study end point was considered either the ulcer complete healing or the eighth week since treatment initiation. Wound healing was faster with dispase gel and hemoglobin reduced rapidly after the seventh day. Yet, hydration was higher in the control group. Our non-parametric analysis provides evidence that the dispase gel shows faster healing compared to the reference drug, in humans, meriting further investigation in larger human sample sizes before massive production of the product.

Ulvan-Based Nanofibrous Patches Enhance Wound Healing of Skin Trauma Resulting from Cryosurgical Treatment of Keloids.

Keloids are skin fibroproliferative disorders, resulting from abnormal healing of deep cutaneous injuries. Cryosurgery, the most common treatment for keloids, causes skin traumas. Even though the clinical practice of cryosurgery has increased, effective wound healing therapy is still lacking. In this investigation, nonwoven nanofibrous patches composed of ulvan, a marine sulfated polysaccharide exhibiting anti-inflammatory and antioxidant activities, and polyethylene oxide (PEO) were fabricated through electrospinning and characterized. Their wound healing efficacy on skin traumas resulting from cryosurgical treatment of keloids was clinically tested and evaluated in comparison to a reference product. Twenty-four volunteer patients undergoing cryosurgery as a treatment of keloids were selected to apply either the ulvan/PEO patch or the reference product for 21 days. The ulvan/PEO patch, 21 days after cryosurgery, showed significant wound healing, elimination of skin inflammation, restoration of biophysical parameters similar to normal values and significant decrease in haemoglobin concentration, skin texture and volume, while no discomfort or adverse reaction was observed. In contrast, the reference product showed inferior performance in all evaluated parameters. The designed ulvan/PEO patch represents the first wound dressing to effectively heal skin trauma after cryosurgical treatment of keloids.

Management of Acute Radiodermatitis in Non-Melanoma Skin Cancer Patients Using Electrospun Nanofibrous Patches Loaded with Pinus halepensis Bark Extract.

Acute radiodermatitis is the most common side effect in non-melanoma skin cancer patients undergoing radiotherapy. Nonetheless, despite the ongoing progress of clinical trials, no effective regimen has been found yet. In this study, a non-woven patch, comprised of electrospun polymeric micro/nanofibers loaded with an aqueous extract of Pinus halepensis bark (PHBE), was fabricated and clinically tested for its efficacy to prevent radiodermatitis. The bioactivity of the PHBE patch was evaluated in comparison with a medical cream indicated for acute radiodermatitis. Twelve volunteer patients were selected and randomly assigned to two groups, applying either the PHBE patch or the reference cream daily. Evaluation of radiation-induced skin reactions was performed during the radiotherapy period and 1 month afterwards according to the Radiation Therapy Oncology Group (RTOG) grading scale, photo-documentation, patient-reported outcomes (Visual Analog Scale, questionnaire), biophysical measurements (hydration, transepidermal water loss, erythema, melanin), and image analysis. In contrast with the reference product, the PHBE patch showed significant anti-inflammatory activity and restored most skin parameters to normal levels 1 month after completion of radiation therapy. No adverse event was reported, indicating that the application of the PHBE patch can be considered as a safe medical device for prophylactic radiodermatitis treatment.

Optimization of psoriasis mouse models.

INTRODUCTION: Psoriasis, is a common, chronic, autoimmune, inflammatory, relapsing disease, which would benefit from reliable and human-relevant animal models to test drugs pre-clinically and to understand their mechanism of action. Because of its ease of use, convenience and low cost, the imiquimod (IMQ)-induced psoriasis-like model is widely utilized; however, it is not known whether all mouse strains are equivalent and if the hairless mouse is appropriate, so that the imiquimod model can be further optimized. METHODS: Under similar experimental conditions, common mouse strains (BALB/c, C57BL/6J, and ApoE) and a new hairless strain (ApoE/SKH-hr2) as well as several inducers (IMQ, IMQ + acetic acid (AcOH) topical and IMQ + AcOH systemic) were compared by clinical, histopathological, biophysical and locomotor activity assessments. RESULTS AND DISCUSSION: The BALB/c mice yielded an optimal psoriasis-like phenotype with IMQ + AcOH topical treatment, and the corresponding phenotypes for the other mouse strains were C57BL/6J moderate and ApoE mild. In contrast, the ApoE/SKH-hr2 mice, as a result of the absence of a Munro abscess in the histopathology analysis, left doubt about the psoriasis-like acquisition. Locomotor activity of BALB/c mice treated with IMQ, IMQ + AcOH topically and IMQ + AcOH systemically showed decreased distance and rearing coverage and increased immobility with all treatments. Hence, the BALB/c mouse strain appears to be an optimal psoriasis-like model when utilizing IMQ + AcOH topical application.

Influence of Omega-3 Fatty Acid-Rich Fish Oils on Hyperlipidemia: Effect of Eel, Sardine, Trout, and Cod Oils on Hyperlipidemic Mice.

Dyslipidemia is one of the most important cardiovascular disease (CVD) risk factors. Polyunsaturated fatty acids (FAs), and especially omega-3 FAs, could significantly contribute to the management of dyslipidemia and the prevention of CVD. The anti-hyperlipidemic effect of selected fish oils (eel, sardine, trout, cod liver) was comparatively evaluated in a high fat diet (HFD)-fed mouse model. At the end of 30 days on the HFD, all animals were hyperlipidemic and were switched to a diet consisting of 90% standard rodent chow plus 10% of oil from eel, sardine, cod liver, or trout. At the end of 60 days on these diets, blood glucose, total blood cholesterol, triglycerides (TGs), and high density lipoprotein (HDL) were quantitated. All diets, except sardine and standard rodent chow, showed statistically significant decreases in blood glucose from day 30 to 90. Total blood cholesterol decreased in all diets except the HFD group, which was continued on this diet until the end of the study. Eel and cod liver oil diets showed significant decreases in TGs. All dietary groups showed a decrease in HDL, but only the trout and standard chow groups exhibited statistically significant decreases. The fish oils tested here for effects on hyperlipidemia vary in per cent of omega-3 FAs and omega-6/-3 FA ratios as determined by gas chromatography Overall, smoked eel was the best source of omega-3 FA, with a balance of omega-6 FA, that ameliorated HFD-induced mixed hyperlipidemia.

Protective Effects of Pinus halepensis Bark Extract and Nicotine on Cigarette Smoke-induced Oxidative Stress in Keratinocytes.

BACKGROUND/AIM: Cigarette smoke (CS) is a major environmental health threat. The oxidative stress induced by CS on keratinocytes and the possible protective effect of nicotine, its receptor inhibitors, and Pinus halepensis bark extract in relation to known antioxidants were investigated. MATERIALS AND METHODS: Primary mouse keratinocytes were exposed to cigarette smoke in the presence and absence of Pinus halepensis bark extract (1 µg/ml), rutin (50 µM) and ascorbic acid (250 µM), nicotine (1 µM) with or without mecamylamine (5 µM) and α-bungarotoxin (0.1 µM). Keratinocyte viability and oxidative stress were evaluated by MTT and fluorescence assays. RESULTS: Pinus halepensis bark extract decreased the oxidative stress and increased the viability of keratinocytes, and moreover, these effects were more pronounced compared to the mixture of rutin and L-ascorbic acid. Nicotine significantly enhanced the viability potentiation of the beneficial effect induced by Pinus halepensis bark extract. Mecamylamine and α-bungarotoxin showed no specific effect. CONCLUSION: Pinus halepensis bark extract in combination with nicotine may successfully reverse skin damage induced by cigarette smoke.

Ointments containing Ceratothoa oestroides extract: Evaluation of their healing potential in the treatment of diabetic foot ulcers.

Diabetic foot ulceration is a common and severe complication of diabetes, causing substantial social, medical, and economic burdens. Treatment of foot ulcers remains challenging, thus requiring increasing awareness and more efficient management. This study investigates the efficacy of ointments, containing as main active ingredient the olive oil extract of the marine isopod Ceratothoa oestroides, in the treatment of patients with diabetic foot ulcers. Fifty-two patients were allocated into four treatment groups either receiving therapy with an ointment containing extract of C. oestroides or extract of C. oestroides and eosin or extract of C. oestroides and cefaclor or no treatment. Patients were monitored for a period of 135 days by evaluation of transepidermal water loss, skin hydration, planimetry, photo-documentation, and clinical condition. Treatment with the extract of C. oestroides demonstrated significant healing properties that became evident after 45 days of treatment and resulted in complete ulcer healing in 61% of the patients. A significant improvement in transepidermal water loss (p < 0.001), skin hydration levels (p < 0.001), and wound area (p < 0.001) was observed in all patients. Similar efficacy was demonstrated for the combination of C. oestroides extract with eosin treatment (p < 0.001). On the contrary, the combination of C. oestroides extract with cefaclor antibiotic agent completely inhibited the healing properties of the isopod extract and did not improve water loss, skin hydration, or wound area. An important factor for C. oestroides extract healing properties is its selective activity against Gram negative bacteria. Ointments containing C. oestroides extract alone or combined with the antimicrobial agent eosin emerges as an effective regimen for the treatment of diabetic foot ulcers.

In Vivo Evaluation of the Anti-Inflammatory Activity of Electrospun Micro/Nanofibrous Patches Loaded with Pinus halepensis Bark Extract on Hairless Mice Skin.

Skin inflammation is the most common symptom in dermatological diseases. It is usually treated by topically applied products, such as creams, gels and lotions. Skin dressings offer a promising alternative as they are endowed with more controlled administration conditions. In this study, the anti-inflammatory activity of electrospun alginate micro/nanofibrous dressings loaded with the aqueous extract of Pinus halepensis bark (PHBE) was evaluated in vivo in mice. The upper back skin of SKH-1 female hairless mice was exposed to a single dose of ultraviolet radiation (3 MEDs) and the inflamed area was treated daily by the direct application of a nanofibrous patch. The condition of the skin was evaluated primarily on the basis of clinical observation, photo-documentation and histopathological assessment, while measurements of the erythema, hydration, transepidermal water loss (TEWL) and sebum production were also taken into account. The results showed that the topical application of alginate micro/nanofibrous dressings loaded with PHBE on UV-inflamed skin significantly attenuated inflammation damage, reducing the healing period. Increase of the loading dose of PHBE resulted in a proportional reduction of the extent, the density and the depth of skin inflammation. With the steadily increasing interest of the skin dressing industry towards nanofibrous matrices, electrospun nonwovens could serve as ideal candidates for the development of multifunctional anti-inflammatory care systems.

Efficacy of a Ceratothoa oestroides Olive Oil Extract in Patients With Chronic Ulcers: A Pilot Study.

Chronic wounds unresponsive to existing treatments constitute a serious disease burden. Factors that contribute to the pathogenesis of chronic ulcers include oxidative stress, comorbid microbial infections, and the type of immune system response. Preclinically, and in a case study, a formulation containing a Ceratothoa oestroides olive oil extract promoted wound healing. Patients with chronic venous and pressure ulcers, clinically assessed as being unresponsive to healing agents, were treated for 3 months with an ointment containing the C oestroides extract combined with antibiotic and/or antiseptic agents chosen according to the type of bacterial infection. Treatment evaluation was performed using the Bates-Jensen criteria with +WoundDesk and MOWA cell phone applications. After 3 months of treatment, C oestroides resulted in an average decrease of 36% in the Bates-Jensen score of ulcers (P < .000), with the decrease being significant from the first month (P < .007). The combined use of topically applied antibiotics and antiseptics efficiently controlled microbial ulcer infection and facilitated wound healing. In relation to other factors such as initial wound size, chronicity appeared to be an important prognostic factor regarding the extent of wound healing. Future clinical investigations assessing the wound healing efficacy of the C oestroides olive oil extract are warranted.