A simple and rapid spectrophotometric method for the determination of trans-chalcone in raw-materialand topical formulation / Método espectrofotométrico simples e rápido paradeterminação de trans-chalcona em matéria-primae em formulação tópica

Trans-chalcone (TC) is a flavonoid precursor characterized by a wide spectrum of action, with anti-inflammatory and antioxidant effects. However, no validated methods are available in official compendia for the analysis of this substance. Thus, the aim of this work was to develop and validate a simple, fast, and reproducible spectrophotometric method for the analysis of TC in raw material, and in topical pharmaceutical formulation containing TC. The established conditions were: methanol as extracting solvent, and detection wavelength of 309 nm by UV spectrophotometer. All tests followed the rules of Resolution RDC 166, 2017. The proposed method was selective. Linearity was demonstrated in the concentration range of 1 to 8 µg/mL (r = 0.999). Repeatability and intermediate precision were confirmed by low relative standard deviation values of 1.53% and 2.70% for TC, and of 1.73% and 2.91% for formulation containing TC. Accuracy, evaluated through recovery test, was adequate, with minimum of 98.24% and maximum of 100.23% of recovery. It was observed that the small deliberate modifications done did not interfere with the results, demonstrating the method is robust. The results showed that the method was considered suitable for the intended purpose, inexpensive, easy to apply, selective, linear, precise, accurate, and robust for the determination TC, and pharmaceutical formulation containing TC. Thus, the method developed satisfies the need for an analytical method for the determination of TC, and topical formulation containing TC, being effective, innovative and able to aid in the development of the pharmaceutical field.

Trans-chalcona (TC) é um precursor de flavonoides caracterizado por um amplo espectro de ação, como efeitos anti-inflamatórios e antioxidantes. No entanto, não há método validado disponível em compêndio oficial para análise deste composto. Então, o objetivo deste trabalho foi desenvolver e validar um método espectrofotométrico, simples, rápido e reprodutível para análise de TC em matéria-prima, e em formulação farmacêutica tópica contendo TC. As condições estabelecidas foram: metanol como o solvente de extração, e detecção no comprimento de onda de 309 nm por espectrofotometria no UV. Todos os testes seguiram as normas da RDC 166, 2017. O método proposto foi seletivo. A linearidade foi demonstrada na faixa de concentração de 1 a 8 µg/mL (r = 0.999). A repetibilidade e a precisão intermediária foram confirmadas pelos valores baixos de desvio padrão relativo de 1,53% e 2,70% para a TC, e de 1,73% e 2,91% para a formulação contendo TC. A exatidão, avaliada por meio de testes de recuperação, foi adequada, com mínimo de 98,24% e máximo de 100,04% de recuperação. Observou-se que pequenas modificações no método não interferiram nos resultados, demonstrando que o método é robusto. Os resultados demonstraram que o método foi adequado para a finalidade pretendida, barato, de fácil aplicação, seletivo, linear, preciso, exato e robusto para determinação de TC, e de formulação contendo TC. Então o método desenvolvido satisfaz as necessidades de um método analítico para determinação de TC, e de formulação tópica contendo TC, e é eficaz, inovador e pode contribuir para o desenvolvimento da área farmacêutica.

Kaempferia galanga L. alleviates the expression of COX-2 and NF-kappaB-p65 in the oral mucosa ulcer of Wistar rats and exhibits no irritation toward the vascular membrane of chicken eggs and the skin of albino rabbits.

The global incidence of recurrent aphthous stomatitis in 2018 reached 5-66 % of the population, while in Indonesia 8 %. Moreover, the prevalence of oral mucosal fibrosis and recurrent aphthous stomatitis among male doctors and nurses in China was 21.24 % and 24.27 %, respectively. Our previous study has shown that the ethanol extract of Kaempferia galanga L. rhizome (EKGR) revealed an accelerated wound-healing effect in the oral mucosa ulcer of Wistar rats. This study aims to explore the effects of EKGR on the expression of NF-kappaB-p65 and COX-2 in the tongue tissue of male Wistar rats by Western blot analysis and immunohistochemistry technique, its safety towards the vascular membrane of the egg chorioallantoic membrane, and its single-dose application on the skin of male rabbits. The rats were randomly assigned into 7 groups: the normal control; the negative control; the positive control (treated with triamcinolone acetonide); and 4 treatment groups of EKGR (0.5 %; 1 %; 2 %; 4 %). Western blot and immunohistochemistry methods were used to measure the expression of NF-kappaB-p65 and COX-2. The hen's egg test-chorioallantoic membrane assay was employed to predict the safety of EKGR towards the vascular membrane. Moreover, the effect of 200 mg/kg BW EKGR application on the dorsal skin of male albino rabbits was also evaluated. EKGR inhibits the expression of NF-kappaB-p65 and COX-2 as proven by WB and IHC results. In the HET-CAM assay, all concentrations of EKGR do not induce irritation responses, which elicits the safety of EKGR. The administration of EKGR causes mild irritation to the dorsal skin of male rabbits but does not induce erythema and edema, no significant changes in BW, no toxic effects on organ macroscopic examination or histopathology, and does not induce abnormalities in the hematological profile of male albino rabbits. EKGR has confirmed its anti-inflammatory activity by suppressing the expression of COX-2 and NF-kappaB-p65 in the oral mucosa ulcer of Wistar rats. EKGR is safe as it does not exhibit irritating potential and harmful effects.

Development and Evaluation of Methotrexate and Baicalin-Loaded Nanolipid Carriers for Psoriasis Treatment.

Objectives: Psoriasis is a chronic inflammatory, T-lymphocyte immune-mediated skin disease. In this study, skin-permeating nanolipid carriers (NLCs) of Methotrexate (MTX) and Baicalin (BL) were formulated. This further gave formulation of nano-lipid encapsulated carriers for dual-drug delivery of the hydrophilic and hydrophobic drugs through the liposomal gel. Materials and Methods: Optimization of the formulation of NLCs was performed and characterized by determining their particle size, drug permeation, skin irritation, drug loading capacity, stability, in vitro drug release behavior, and in vitro cellular viability. Ex vivo skin permeation and in vivo psoriatic efficiency were also evaluated and compared. Results: Results revealed that the amount of MTX permeating the skin was 2.4 to 4.4 fold greater for dual-drug s than for single NLCs. The optimized dual-drug loaded NLCs had an average particle size (150.20 ± 3.57 nm) and polydispersity index (0.301 ± 0.01) and high entrapment (86.32 ± 2.78% w/w). The MTX nanoparticles exhibit a positive Zeta potential of 38.6 mV. The psoriasis area and severity index scoring showed the lowest skin erythema, skin thickness and scaling. MTX-BL NLCs were inhibited the expression of inflammatory cytokines (tumor necrosis factor-alpha, and interleukin-17) . Conclusion: It can be concluded that newer targeting strategies for NLCs for dual-drug delivery of nano-lipid carriers could be administered topically for the treatment of psoriasis.

Successful utilization of topical trametinib for neurofibromatosis type I-associated plexiform neurofibroma.

An 11-year-old female with neurofibromatosis type 1 (NF-1) and history of optic glioma presented with a progressive cutaneous plexiform neurofibroma of the breast. The lesion was treated with topical application of a mitogen-activated protein kinase inhibitor, trametinib, resulting in stable, non-progression cutaneous plexiform neurofibroma for greater than 2 years. This case demonstrates the potential application of topical trametinib for NF1-associated superficial cutaneous plexiform neurofibroma without the toxicities associated with systemic treatment.

Topical Anti-Inflammatory Treatments for Eczema: A Cochrane Systematic Review and Network Meta-Analysis.

OBJECTIVE: Eczema is the most burdensome skin condition worldwide and topical anti-inflammatory treatments are commonly used to control symptoms. The relative effectiveness and safety of different topical anti-inflammatory treatments is uncertain. DESIGN: Network meta-analysis performed within a Cochrane systematic review to compare and statistically rank efficacy and safety of topical anti-inflammatory eczema treatments. DATA SOURCES: Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase and trial registries to June 2023. ELIGIBILITY CRITERIA FOR SELECTED TRIALS: Included trials were within-participant or between-participant randomised controlled trials. Participants had eczema that was not clinically infected and was not contact dermatitis, seborrheic eczema or hand eczema. Interventions were topical anti-inflammatory treatments but not complementary treatments, antibiotics alone, wet wraps, phototherapy or systemic treatments. Comparators were no treatment/vehicle or another topical anti-inflammatory. RESULTS: We identified 291 trials (45,846 participants), mainly in high-income countries. Most were industry-funded with median 3 weeks treatment duration. Risk of bias assessed using the Cochrane Risk of Bias 2.0 tool was high in 89% of trials, mainly due to risk of selective reporting. Network meta-analysis of binary outcomes ranked potent and/or very potent topical steroids, tacrolimus 0.1% and ruxolitinib 1.5% among the most effective treatments for improving patient-reported symptoms (40 trials, all low confidence) and clinician-reported signs (32 trials, all moderate confidence). For investigator global assessment, the Janus kinas inhibitors ruxolitinib 1.5%, delgocitinib 0.5% or 0.25%, very potent/potent topical steroids and tacrolimus 0.1% were ranked as most effective (140 trials, all moderate confidence). Continuous outcome data were mixed. Local application site reactions were most common with tacrolimus 0.1% (moderate confidence) and crisaborole 2% (high confidence) and least common with topical steroids (moderate confidence). Skin thinning was not increased with short-term use of any topical steroid potency (low confidence) but skin thinning was reported in 6/2044 (0.3%) participants treated with longer-term (6-60 months) topical steroids. CONCLUSION: Potent topical steroids, Janus kinase inhibitors and tacrolimus 0.1% were consistently ranked as among the most effective topical anti-inflammatory treatments for eczema.

Bcl-2 knockdown by multifunctional lipid nanoparticle and its influence in apoptosis pathway regarding cutaneous melanoma: in vitro and ex vivo studies.

Multifunctional therapies have emerged as innovative strategies in cancer treatment. In this research article, we proposed a nanostructured lipid carrier (NLC) designed for the topical treatment of cutaneous melanoma, which simultaneously delivers 5-FU and Bcl-2 siRNA. The characterized nanoparticles exhibited a diameter of 259 ± 9 nm and a polydispersion index of 0.2, indicating a uniform size distribution. The NLCs were primarily localized in the epidermis, effectively minimizing the systemic release of 5-FU across skin layers. The ex vivo skin model revealed the formation of a protective lipid film, decreasing the desquamation process of the stratum corneum which can be associated to an effect of increasing permeation. In vitro assays demonstrated that A375 melanoma cells exhibited a higher sensitivity to the treatment compared to non-cancerous cells, reflecting the expected difference in their metabolic rates. The uptake of NLC by A375 cells reached approximately 90% within 4 h. The efficacy of Bcl-2 knockdown was thoroughly assessed using ELISA, Western blot, and qRT-PCR analyses, revealing a significant knockdown and synergistic action of the NLC formulation containing 5-FU and Bcl-2 siRNA (at low concentration --100 pM). Notably, the silencing of Bcl-2 mRNA also impacted other members of the Bcl-2 protein family, including Mcl-1, Bcl-xl, BAX, and BAK. The observed modulation of these proteins strongly indicated the activation of the apoptosis pathway, suggesting a successful inhibition of melanoma growth and prevention of its in vitro spread.

Safety and efficacy of a picosecond 755-nm alexandrite laser combined with topical tranexamic acid in the treatment of melasma.

BACKGROUND: The picosecond 755-nm alexandrite laser and topical tranexamic acid (TA) have shown promise in treating melasma. AIM: This aim of this study was to evaluate the efficacy and safety of combining to a picosecond 755-nm alexandrite laser combined with topical TA for melasma treatment. PATIENTS AND METHODS: Forty-eight patients' facial halves with bilateral symmetrical melasma were randomized to receive either topical TA and picosecond laser treatment or laser monotherapy. All patients received three consecutive picosecond laser treatment sessions at 4-week intervals, and additional one side facial received topical TA treatment twice daily until 4 weeks after the third treatments. Efficacy was assessed using the Modified Melasma Area and Severity Index (mMASI) score, VISIA (Canfield, USA) red area feature counts, and average pore volume as measured by Antera 3D®. Patient satisfaction was evaluated through questionnaires. RESULTS: Thirty-five patients completed the study. Post-treatment, mMASI scores and VISIA red area feature counts were lower in combination therapy halves and laser monotherapy halves, and average melanin level was lower in the combination therapy halves (p < 0.05). Comparisons between the combination therapy halves and laser monotherapy halves after the third treatment revealed significant differences in mMASI scores, melanin levels, and VISIA red area feature counts (p < 0.05). After treatment, patient satisfaction rates in the combination therapy halves and monotherapy halves was 71.4% and 54.3%, respectively (p < 0.05). No obvious adverse effects were observed in the combination therapy halves; whereas, 10.42% (5/48) of participants in the laser monotherapy halves experienced temporary pigmentation, which resolved within 3 months. CONCLUSION: The picosecond 755-nm alexandrite laser, when used independently and in combination with topical TA, has been proven to be effective in the improvement of melasma. However, the combined treatment approach showed a more pronounced improvement in melasma symptoms, with higher patient satisfaction, and was associated with a lower incidence of adverse effects. These findings strongly support that integrating topical TA with picosecond laser therapy as a superior therapeutic strategy for melasma management. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR2200057771.

Oral Patch/Film for Drug Delivery-Current Status and Future Prospects.

In recent years, there has been extensive research into drug delivery systems aimed at enhancing drug utilization while minimizing drug toxicities. Among these systems, oral patches/films have garnered significant attention due to their convenience, noninvasive administration, ability to bypass hepatic first-pass metabolism, thereby enhancing drug bioavailability, and their potential to ensure good compliance, particularly among special patient populations. In this review, from the perspective of the anatomical characteristics of the oral cavity and the advantages and difficulties of oral drug delivery, we illustrate the design ideas, manufacturing techniques, research methodologies, and the essential attributes of an ideal oral patch/film. Furthermore, the applications of oral patches/films in both localized and systemic drug delivery were discussed. Finally, we offer insights into the future prospects of the oral patch/film, aiming to provide valuable reference for the advancement of oral localized drug delivery systems.

Vulvar Paget's disease: a population-based cancer registry descriptive study.

BACKGROUND: Although vulvar Paget's Disease (VPD) is a rare skin cancer associated with an excellent prognosis, high recurrence rates are associated with impaired quality of life. OBJECTIVES: Our objective was to investigate the epidemiological and clinical features of VPD diagnosed in a French administrative area (Franche Comté). METHODS: This retrospective study investigated clinical, histologic, therapeutic and follow-up data of patients with VPD diagnosed between 1981 and 2021, including data from the Doubs cancer registry. RESULTS: Among the 21 patients included (19 intra-epithelial and 2 invasive VPD), the median time to diagnosis was 24 months [0-110 months], with a median age of 72 years [38-88 years]. An associated cancer was present in 6 patients (29%). At 5 years of follow-up, the recurrence rate was 26%, but then increased to 42% after a median follow-up of 145 months [31-503 months]. Among the 14 patients first surgically treated, incomplete resection (positive margins) was observed in all patients (100%), associated with a postoperative recurrence rate of 86% which was much higher than the rate observed in patients first topically treated (20%). Postoperative adjuvant therapy (surgical revision, laser, imiquimod) significantly increased the recurrence-free survival (p < 0.001). CONCLUSIONS: Postoperative recurrence of VPD is frequent, mainly after 5 years, proving the importance of prolonged follow-up. Recurrence-free survival was significantly higher after postoperative adjuvant treatment.

Topical dorzolamide for macular holes: A randomised, double-blind, placebo-controlled trial.

BACKGROUND: To assess topical dorzolamide as medical therapy for idiopathic full-thickness macular holes (FTMHs). METHODS: Randomised, double-blinded, placebo-controlled, single-centre clinical trial involving 32 patients with idiopathic small FTMHs (<400 µm $$ \upmu \mathrm{m} $$ ). Participants in both arms used topical dorzolamide 2% or saline thrice daily for 8 weeks with monthly OCT. Those with persisting FTMH underwent vitrectomy with ILM peel and gas tamponade. The primary outcome was the rate of FTMH closure at the end of treatment. RESULTS: Between 6 March 2020 and 16 June 2023, 32 eligible patients were enrolled: 16 participants in each arm. All participants in both groups were included in the final analysis. At the final visit, 3 of 16 (18.8%) patients in both the topical dorzolamide and placebo group demonstrated closure. There was no statistically significant difference in the proportion of FTMH closure between the control and treatment group (p = 1.00), nor statistically significant difference in the mean change in best corrected visual acuity (BCVA; p = 0.909). There was no difference in the change in FTMH diameter between groups (p = 0.225). No serious adverse events were reported in either group. CONCLUSION: Topical dorzolamide was safe but not superior to placebo in the functional and anatomical outcomes of FTMH.

Quality by design driven development of lipid nanoparticles for cutaneous targeting: a preliminary approach.

Fungal infections are the fourth common cause of infection affecting around 50 million populations across the globe. Dermatophytes contribute to the majority of superficial fungal infections. Clotrimazole (CTZ), an imidazole derivative is widely preferred for the treatment of topical fungal infections. Conventional topical formulations enable effective penetration of CTZ into the stratum corneum, however, its low solubility results in poor dermal bioavailability, and variable drug levels limit the efficacy. The aim was to increase dermal bioavailability and sustain drug release, thereby potentially enhancing drug retention and reducing its side effects. This work evaluated the CTZ loaded solid lipid nanoparticles (SLN) consisting of precirol and polysorbate-80 developed using high pressure homogenization and optimized with QbD approach. Prior to release studies, CTZ-SLNs were characterized by different analytical techniques. The laser diffractometry and field emission scanning electron microscopy indicated that SLNs were spherical in shape with mean diameter of 450 ± 3.45 nm. DSC and XRD results revealed that the drug remained molecularly dispersed in the lipid matrix. The CTZ-SLNs showed no physicochemical instability during 6 months of storage at different temperatures. Further, the Carbopol with its pseudoplastic behavior showed a crucial role in forming homogenous and stable network for imbibing the CTZ-SLN dispersion for effective retention in skin. As examined, in-vitro drug release was sustained up to 24 h while ex-vivo skin retention and drug permeation studies showed the highest accumulation and lowest permeation with nanogel in comparison to pure drug and Candid® cream. Further, the in-vivo antifungal efficacy of nanogel suggested once-a-day application for 10 days, supported by histopathological analysis for complete eradication infection. In summary, the findings suggest, that nanogel-loaded with CTZ-SLNs has great potential for the management of fungal infections caused by Candida albicans.

Essential Oil Components Incorporated Emulsion Hydrogels for Eradicating Dermatophytosis Caused by Pathogenic Fungi Trichophyton mentagrophytes and Microsporum canis.

Dermatophytosis is a prevalent fungal infection and public health burden, majorly caused by the attack of zoophilic fungi genera of Trichophyton and Microsporum. Among them, T. mentagrophytes and M. canis are the dominating pathogens that cause dermatophytosis in humans. Though anti-fungal treatments are available, the widespread drug resistance and minimal efficacy of conventional therapies cause recurring infections. In addition, prolonged anti-fungal medications induce several systemic side effects, including hepatotoxicity and leucopenia. The anti-dermatophytic formulation of biocompatible essential oil components (EOCs) is attractive due to their highly potent anti-dermatophytic action. Herein, two EOCs, Eugenol (EU) and Isoeugenol (IU), incorporated emulsion hydrogel (EOCs-EHG) synthesized from hydroxypropylmethyl cellulose and poly(ethylene glycol) methyl ether methacrylate. The cytocompatibility of the hydrogels is confirmed by treating them with fibroblast and keratinocyte cell lines. The EOCs-EHG demonstrated pH and temperature-responsive sustained release of entrapped EOCs and inhibited fungal spore germination. T. mentagrophytes and M. canis biofilms are eradicated at a minimal inhibitory concentration of 2 µg mL-1 each of EU and IU. The in vivo anti-dermatophytic activity of EOCs-EHG is confirmed in dermatophyte-infected Wistar albino rat models. The topical application of EOCs-EHG demonstrated complete infection eradication and facilitated skin regeneration, emphasizing the therapeutic potential of EOCs-EHG against dermatophytosis.

Common consumer residual insecticides lack efficacy against insecticide-susceptible and resistant populations of the German cockroach (Blattodea: Ectobiidae).

The German cockroach, Blattella germanica (L.) (Blattodea: Ectobiidae), is a ubiquitous pest in affordable housing. They represent a major threat to human health due to their contribution of asthma-exacerbating allergens and the potential to transfer pathogenic microorganisms indoors. Despite well-documented pyrethroid resistance, pyrethroid-based broadcast residual insecticide products are often used by residents to control cockroaches in their homes. Additionally, there is little empirical independent testing of these products. Thus, it remains unclear how effective these commonly used do-it-yourself products are at controlling German cockroaches. This study represents a comprehensive examination of the efficacy of these products with direct, limited, and continuous exposure assays on a variety of common household surfaces on field populations of cockroaches with varying levels of pyrethroid resistance. While most products performed well when applied directly to test insects, mortality was substantially lower across all surfaces with limited exposure (30 min). In continuous exposure assays on a nonporous surface, products took at least 24 hr to cause 100% mortality in a field population, with some products taking up to 5 d to achieve 100% mortality. The findings of this study demonstrate a lack of residual efficacy from common pyrethroid-based consumer-use pesticides products. Given that it is not feasible to find and treat every cockroach in a home directly, the residuality of spray-based formulations is critical for products designed to control German cockroaches. Without residual efficacy, as shown in the consumer aerosol and spray products tested, we expect these products to add little to no value to cockroach control.

Small Molecule Topical Ophthalmic Formulation Development-Data Driven Trends & Perspectives from Commercially Available Products in the US.

Topical ophthalmic drug product development is a niche research domain as the drug formulations need to be designed to perform in the unique ocular physiological conditions. The most common array of small molecule drug formulations intended for topical ophthalmic administration include solutions, suspensions, emulsions, gels, and ointments. The formulation components such as excipients and container closure are unique to serve the needs of topical ophthalmic delivery compared to other parenteral products. The selection of appropriate formulation platform, excipients, and container closure for delivery of drugs by topical ophthalmic route is influenced by a combination of factors like physicochemical properties of the drug molecule, intended dose, pharmacological indication as well as the market trends influenced by the patient population. In this review, data from literature and packaging inserts of 118 reference listed topical ophthalmic medications marketed in the US are collected and analyzed to identify trends that would serve as a guidance for topical ophthalmic formulation development for small molecule drugs. Specifically, the topics reviewed include current landscape of the available small molecule topical ophthalmic drug products in the US, physicochemical properties of the active pharmaceutical ingredients (APIs), formulation platforms, excipients, and container closure systems.

Pain perception enhancement in consecutive second-eye phacoemulsification cataract surgeries under topical anesthesia.

Cataract is the main cause of visual impairment and blindness worldwide while the only effective cure for cataract is still surgery. Consecutive phacoemulsification under topical anesthesia has been the routine procedure for cataract surgery. However, patients often grumbled that they felt more painful during the second-eye surgery compared to the first-eye surgery. The intraoperative pain experience has negative influence on satisfaction and willingness for second-eye cataract surgery of patients with bilateral cataracts. Intraoperative ocular pain is a complicated process induced by the nociceptors activation in the peripheral nervous system. Immunological, neuropsychological, and pharmacological factors work together in the enhancement of intraoperative pain. Accumulating published literatures have focused on the pain enhancement during the second-eye phacoemulsification surgeries. In this review, we searched PubMed database for articles associated with pain perception differences between consecutive cataract surgeries published up to Feb. 1, 2024. We summarized the recent research progress in mechanisms and interventions for pain perception enhancement in consecutive second-eye phacoemulsification cataract surgeries. This review aimed to provide novel insights into strategies for improving patients' intraoperative experience in second-eye cataract surgeries.

Preservatives and ocular surface disease: A review.

Ocular surface disease (OSD) is a complex condition that can cause a range of symptoms (e.g, dryness, irritation, and pain) and can significantly impact the quality of life of affected individuals. Iatrogenic OSD, a common finding in patients with glaucoma who receive chronic therapy with topical ocular antihypertensive drugs containing preservatives such as benzalkonium chloride (BAK), has been linked to damage to the ocular surface barrier, corneal epithelial cells, nerves, conjunctival goblet cells, and trabecular meshwork. Chronic BAK exposure activates inflammatory pathways and worsens symptoms, compromising the success of subsequent filtration surgery in an exposure-dependent manner. In eyes being treated for glaucoma, symptomatic treatment of OSD may provide some relief, but addressing the root cause of the OSD often necessitates reducing or, ideally, eliminating BAK toxicity. Strategies to decrease BAK exposure in patients with glaucoma encompass the use of preservative-free formulations or drugs with alternative and less toxic preservatives such as SofZia®, Polyquad, potassium sorbate, or Purite®. Though the benefits of these alternative preservatives are largely unproven, they might be considered when financial constraints prevent the use of preservative-free versions. For patients receiving multiple topical preserved drugs, the best practice is to switch to nonpreserved equivalents wherever feasible, regardless of OSD severity. Furthermore, nonpharmacological approaches, including laser or incisional procedures, should be considered. This review explores the effects of BAK on the ocular surface and reviews strategies for minimizing or eliminating BAK exposure in patients with glaucoma in order to significantly improve their quality of life and prevent complications associated with chronic exposure to BAK.

Local Therapy and Reconstruction in Penile Cancer: A Review.

Local therapy for penile cancer provides robust survival and can preserve the penis functionally and cosmetically. Interventions must target the appropriate clinical stage. We reviewed studies regarding the primary therapy in penile cancer, from topical therapy to radical penectomy, and reconstructive techniques. Topical therapy (5-FU or Imiquimod) provides a robust oncologic response in patients with Ta or Tis disease. Multiple laser therapies are available for localized patients and those with low-grade T1 disease. There is a non-trivial risk of progression and nodal metastases in poorly selected patients. Wide local excision provides an oncologically sound option in patient with up to T1 disease; less evidence exists for Mohs microsurgery in the setting of penile cancer. Increasingly aggressive approaches include glansectomy and partial/radical penectomy, which provide 5- and 10-year cancer-specific survival rates of over 80%. Meticulous reconstruction is necessary for the durable function of the remaining penis. Preservation of voiding and sexual function occurs via penile skin grafting, glans resurfacing, creation of a functional penile stump, and phalloplasty with a penile implant. Perineal urethrostomy provides an alternative in pathology demanding extensive partial or radical penectomy, and a durable option for seated voiding. Clinical suspicion and timely diagnosis are paramount in terms of management as less-invasive options for earlier-stage disease develop.

Calcipotriol/Betamethasone Dipropionate for the Treatment of Psoriasis: Mechanism of Action and Evidence of Efficacy and Safety versus Topical Corticosteroids.

The combined treatment with calcipotriol (Cal) and betamethasone dipropionate (BDP) has emerged as the leading anti-psoriatic topical treatment. Fixed-dose Cal/BDP is available in different formulations, including ointment, gel, foam, and cream. This review examines the mechanism of action of Cal/BDP underlying its therapeutic effect and compiles the evidence regarding its efficacy and safety compared to monotherapy with topical corticosteroids. The dual-action of Cal/BDP targets the inflammatory pathways and abnormal keratinocyte proliferation, both of them fundamental mechanisms of psoriasis pathogenesis. A large number of randomized, double-blind studies support Cal/BDP superiority over topical corticosteroids, demonstrating its broad efficacy across several degrees of psoriasis severity and its capability to provide early significant clinical improvements. This increased efficacy is achieved without negative effects on the safety profile, since the incidence of adverse effects reported with Cal/BDP is usually similar to that of BDP and even lower than that of Cal alone. The combination therapy rapid onset of action, coupled with a simplified dosing regimen, has been identified as crucial for improving long-term adherence and patient outcomes. In conclusion, Cal/BDP is confirmed as a versatile, effective, and convenient option for the patient in psoriasis management.

Effectiveness of low to moderate potency topical corticosteroids for phimosis resolution in children: results of a network meta-analysis.

PURPOSE: The use of topical corticosteroids (TCSs) has become an efficient, less-invasive treatment for phimosis. Whether any significant difference in efficacy exists between TCSs based on their potency is unclear. METHODS: Electronic databases were searched up to March 2024 for randomised controlled trials (RCTs) comparing the use of any type or concentration of TCSs with placebo or no treatment in boys with any degree of physician diagnosed phimosis. A random-effects network meta-analysis (NMA) using a consistency model within a frequentist approach was employed. The primary outcome was partial or complete resolution of phimosis reported as a pooled risk ratio (RR) with 95% CI. Relative ranking was assessed with surface under the cumulative ranking curve (SUCRA) probabilities. RESULTS: Seventeen RCTs, containing 2057 participants were identified. NMA suggested that, compared with control, the high (RR 3.19 (95% CI 1.42 to 7.16), moderate (RR 2.68 (95% CI 1.87 to 3.83) and low (RR 3.05 (95% CI 1.63 to 5.71) potency TCSs statistically significantly increased complete or partial clinical resolution of phimosis. The SUCRA plot revealed that high potency (SUCRA = 0.76) was ranked first followed by low and moderate TCSs. When we assessed comparative efficacy among TCSs based on potency, none of the classes were superior to others. The certainty of the evidence for an effect of moderate potent TCSs was that of moderate GRADE quality. CONCLUSION: Moderate to low potency TCSs are of comparable therapeutic effect in the treatment of phimosis to that of highly potent formulations. More high-quality RCTs are warranted.