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1.
Arch Dermatol Res ; 316(6): 316, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38822884

ABSTRACT

In the present study, we have formulated a methotrexate (MTX)-loaded microemulsion topical gel employing quality-by-design optimization. The optimized lipid-based microemulsion was incorporated into a 2% carbopol gel. The prepared formulation was characterized for micromeritics, surface charge, surface morphology, conductivity studies, rheology studies, texture analysis/spreadability, drug entrapment, and drug loading studies. The formulation was further evaluated for drug release and release kinetics, cytotoxicity assays, drug permeation and drug retention studies, and dermatokinetics. The developed nanosystem was not only rheologically acceptable but also offered substantial drug entrapment and loading. From drug release studies, it was observed that the nanogel showed higher drug release at pH 5.0 compared to plain MTX, plain gel, and plain microemulsion. The developed system with improved dermatokinetics, nanometric size, higher drug loading, and enhanced efficacy towards A314 squamous epithelial cells offers a huge promise in the topical delivery of methotrexate.


Subject(s)
Drug Liberation , Emulsions , Gels , Methotrexate , Skin Absorption , Methotrexate/administration & dosage , Methotrexate/chemistry , Methotrexate/pharmacokinetics , Humans , Skin Absorption/drug effects , Rheology , Lipids/chemistry , Administration, Cutaneous , Skin/metabolism , Skin/drug effects , Administration, Topical , Drug Delivery Systems/methods , Animals , Particle Size , Drug Carriers/chemistry , Nanogels/chemistry
2.
Arch Dermatol Res ; 316(6): 313, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38822940

ABSTRACT

Female Pattern Hair Loss (FPHL) is a common form of non-scaring hair loss that occurs in adult women. Although several treatments have already been proposed for FPHL, only Topical Minoxidil accumulated an adequate level of evidence. This study aimed to evaluate the therapeutic response of MMP® (intradermal infiltration) of Minoxidil formulation in the frontal-parietal-vertex regions compared with the gold-standard home administration of Minoxidil 5% Capillary Solution. This self-controlled comparative study evaluated 16 FPHL patients, without treatment for at least 6 months, confirmed by trichoscopy with TrichoLAB® software. They received 4 monthly sessions of MMP® with Minoxidil 0,5% on the right side of the scalp (frontal-parietal-vertex areas), followed by occlusion with plastic film for 12 h and prescription of Minoxidil 5% Solution for home use once a day, on both scalp sides, starting 72 h after the procedure. The reassessment trichoscopy was 6 weeks after the last session and they answered a "self-assessment" questionnaire. Treated scalp areas were compared and showed both treatments, in general, were effective, with no difference between them. If they were analyzed separately by treated areas, there were signs of better response in the parietal-vertex regions with treatment by MMP® with Minoxidil, while clinical treatment indicated a better response in the other regions. When patients were divided into more and less advanced cases, a better response in parietal-vertex regions treated by MMP® with Minoxidil in less advanced patients was confirmed. MMP® with Minoxidil showed a better response in the parietal-vertex regions in less advanced FPHL patients. It represents yet another resource to improve quality of life of these suffering patients.


Subject(s)
Alopecia , Minoxidil , Scalp , Humans , Minoxidil/administration & dosage , Female , Alopecia/drug therapy , Pilot Projects , Adult , Middle Aged , Treatment Outcome , Administration, Topical
3.
Carbohydr Polym ; 339: 122250, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-38823917

ABSTRACT

Glycyrrhizae Radix et rhizome/licorice is a precious herb in traditional Chinese medicine (TCM). TCM's polysaccharides are medicinally active. But herbal polysaccharides pose some limitations for topical applications. Therefore, this study aimed to utilize licorice polysaccharide via mesoporous silica nanoparticles (MSN) for anti-acne efficacy in topical delivery. The polysaccharide (GGP) was extracted with a 10 % NaOH solution. Chemical characterization suggested that GGP possesses an Mw of 267.9 kDa, comprised primarily of Glc (54.1 %) and Ara (19.12 %), and probably 1,4-linked Glc as a backbone. Then, MSN and amino-functionalized MSN were synthesized, GGP entrapped, and coated with polydopamine (PDA) to produce nanoparticle cargo. The resulted product exhibited 76 % entrapment efficiency and an in vitro release of 89 % at pH 5, which is usually an acne-prone skin's pH. Moreover, it significantly increased Sebocytes' cellular uptake. GGP effectively acted as an anti-acne agent and preserved its efficacy in synthesized nanoparticles. In vivo, the results showed that a 20 % gel of MSN-NH2-GGP@PDA could mediate an inflammatory response via inhibiting pro-inflammatory cytokines and regulating anti-inflammatory cytokines. The MSN-NH2-GGP@PDA inhibited TLR2-activated-MAPK and NF-κB pathway triggered by heat-killed P. acnes. In conclusion, fabricated MSN entrapped GGP for biomimetic anti-acne efficacy in topical application.


Subject(s)
Acne Vulgaris , Glycyrrhiza , Nanoparticles , Polysaccharides , Silicon Dioxide , Glycyrrhiza/chemistry , Silicon Dioxide/chemistry , Polysaccharides/chemistry , Polysaccharides/pharmacology , Nanoparticles/chemistry , Animals , Porosity , Acne Vulgaris/drug therapy , Mice , Administration, Topical , Humans , Drug Carriers/chemistry , Drug Liberation , Indoles , Polymers
4.
Int Wound J ; 21(6): e14907, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38822706

ABSTRACT

Recent randomised controlled trials (RCTs) have investigated the analgesic activity of sesame oil among patients with limb trauma; nevertheless, their findings are inconsistent. Hence, this review aimed to clarify the impact of topical administration of sesame oil on acute pain of adult outpatients with minor limb trauma. The online databases (e.g., Scopus, PubMed, Web of Science) were searched up to 31 January 2024. The RCTs were included if they compared the effect of applying standard treatments plus topical sesame oil to administering standard treatments alone or with a placebo/sham treatment. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) and the Cochrane Collaboration's risk of bias tool were applied to address the evidence quality and the study's methodological rigour, respectively. Four RCTs had the inclusion criteria, and their findings were pooled in a meta-analysis employing a random-effects approach. According to the pooled analysis, the reduction in mean change of the pain score from baseline to the second/third intervention day was significantly higher in favour of clients who received standard care plus daily massage of the trauma site with sesame oil compared to those who received a control condition (weighted mean difference: -1.10; 95% confidence interval [-1.62, -0.57]; p < 0.001). However, the evidence quality was moderate, and only two studies had good methodological rigour. Hence, more high-quality studies are needed to make a solid evidence-based conclusion about the favourable consequence of topical sesame oil on alleviating acute traumatic limb pain.


Subject(s)
Administration, Topical , Randomized Controlled Trials as Topic , Sesame Oil , Humans , Sesame Oil/therapeutic use , Sesame Oil/administration & dosage , Pain Management/methods , Pain Management/standards , Adult , Female , Male , Analgesics/administration & dosage , Analgesics/therapeutic use , Pain Measurement/methods , Middle Aged , Extremities/injuries
7.
PLoS One ; 19(5): e0303039, 2024.
Article in English | MEDLINE | ID: mdl-38701045

ABSTRACT

The complexity of chronic wounds creates difficulty in effective treatments, leading to prolonged care and significant morbidity. Additionally, these wounds are incredibly prone to bacterial biofilm development, further complicating treatment. The current standard treatment of colonized superficial wounds, debridement with intermittent systemic antibiotics, can lead to systemic side-effects and often fails to directly target the bacterial biofilm. Furthermore, standard of care dressings do not directly provide adequate antimicrobial properties. This study aims to assess the capacity of human-derived collagen hydrogel to provide sustained antibiotic release to disrupt bacterial biofilms and decrease bacterial load while maintaining host cell viability and scaffold integrity. Human collagen harvested from flexor tendons underwent processing to yield a gellable liquid, and subsequently was combined with varying concentrations of gentamicin (50-500 mg/L) or clindamycin (10-100 mg/L). The elution kinetics of antibiotics from the hydrogel were analyzed using liquid chromatography-mass spectrometry. The gel was used to topically treat Methicillin-resistant Staphylococcus aureus (MRSA) and Clostridium perfringens in established Kirby-Bauer and Crystal Violet models to assess the efficacy of bacterial inhibition. 2D mammalian cell monolayers were topically treated, and cell death was quantified to assess cytotoxicity. Bacteria-enhanced in vitro scratch assays were treated with antibiotic-embedded hydrogel and imaged over time to assess cell death and mobility. Collagen hydrogel embedded with antibiotics (cHG+abx) demonstrated sustained antibiotic release for up to 48 hours with successful inhibition of both MRSA and C. perfringens biofilms, while remaining bioactive up to 72 hours. Administration of cHG+abx with antibiotic concentrations up to 100X minimum inhibitory concentration was found to be non-toxic and facilitated mammalian cell migration in an in vitro scratch model. Collagen hydrogel is a promising pharmaceutical delivery vehicle that allows for safe, precise bacterial targeting for effective bacterial inhibition in a pro-regenerative scaffold.


Subject(s)
Anti-Bacterial Agents , Biofilms , Collagen , Hydrogels , Methicillin-Resistant Staphylococcus aureus , Biofilms/drug effects , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/administration & dosage , Humans , Collagen/chemistry , Hydrogels/chemistry , Methicillin-Resistant Staphylococcus aureus/drug effects , Clindamycin/pharmacology , Clindamycin/administration & dosage , Microbial Sensitivity Tests , Administration, Topical , Gentamicins/pharmacology , Gentamicins/administration & dosage
8.
Adv Exp Med Biol ; 1447: 117-129, 2024.
Article in English | MEDLINE | ID: mdl-38724789

ABSTRACT

With recent advances in topical therapies for atopic dermatitis (AD), steroid-sparing options like calcineurin inhibitors, Janus kinase (JAK) inhibitors, and phosphodiesterase-4 (PDE-4) inhibitors are becoming mainstays in therapy, underscoring the importance of careful selection and usage of topical corticosteroids (TCSs) to minimize side effects. Alongside the necessity of emollient use, these steroid-sparing alternatives offer rapid itch relief and efficacy in improving disease severity. While TCSs still hold a prominent role in AD management, promising novel topical treatments like tapinarof and live biotherapeutics to modulate the skin microbiome are also discussed. Overall, the recent addition of novel topical therapies offers diverse options for AD management and underscores the importance of topical treatments in the management of AD.


Subject(s)
Dermatitis, Atopic , Humans , Dermatitis, Atopic/drug therapy , Dermatitis, Atopic/microbiology , Administration, Topical , Adrenal Cortex Hormones/therapeutic use , Adrenal Cortex Hormones/administration & dosage , Phosphodiesterase 4 Inhibitors/therapeutic use , Administration, Cutaneous , Skin/drug effects , Skin/microbiology , Skin/pathology , Calcineurin Inhibitors/therapeutic use , Calcineurin Inhibitors/administration & dosage , Dermatologic Agents/therapeutic use , Dermatologic Agents/administration & dosage , Dermatologic Agents/adverse effects
9.
Int J Mol Sci ; 25(10)2024 May 15.
Article in English | MEDLINE | ID: mdl-38791412

ABSTRACT

Eczema (atopic dermatitis, AD) is a skin disease characterized by skin barrier dysfunction due to various factors, including genetics, immune system abnormalities, and environmental triggers. Application of emollients and topical drugs such as corticosteroids and calcineurin inhibitors form the mainstay of treatments for this challenging condition. This review aims to summarize the recent advances made in phytochemical-based topical applications to treat AD and the different carriers that are being used. In this review, the clinical efficacy of several plant extracts and bioactive phytochemical compounds in treating AD are discussed. The anti-atopic effects of the herbs are evident through improvements in the Scoring Atopic Dermatitis (SCORAD) index, reduced epidermal thickness, decreased transepidermal water loss, and alleviated itching and dryness in individuals affected by AD as well as in AD mouse models. Histopathological studies and serum analyses conducted in AD mouse models demonstrated a reduction in key inflammatory factors, including thymic stromal lymphopoietin (TSLP), serum immunoglobulin E (IgE), and interleukins (IL). Additionally, there was an observed upregulation of the filaggrin (FLG) gene, which regulates the proteins constituting the stratum corneum, the outermost layer of the epidermis. Carriers play a crucial role in topical drug applications, influencing dose delivery, retention, and bioavailability. This discussion delves into the efficacy of various nanocarriers, including liposomes, ethosomes, nanoemulsions, micelles, nanocrystals, solid-lipid nanoparticles, and polymeric nanoparticles. Consequently, the potential long-term side effects such as atrophy, eruptions, lymphoma, pain, and allergic reactions that are associated with current topical treatments, including emollients, topical corticosteroids, topical calcineurin inhibitors, and crisaborole, can potentially be mitigated through the use of phytochemical-based natural topical treatments.


Subject(s)
Eczema , Filaggrin Proteins , Phytochemicals , Humans , Animals , Phytochemicals/administration & dosage , Phytochemicals/therapeutic use , Phytochemicals/pharmacology , Eczema/drug therapy , Plant Extracts/administration & dosage , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Administration, Topical , Dermatitis, Atopic/drug therapy , Dermatitis, Atopic/pathology
10.
J Wound Care ; 33(Sup5b): S12-S19, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38752846

ABSTRACT

A single centre, non-comparative evaluation was undertaken to observe the clinical results achieved when following best practice for the application of Debrichem. The treatment protocol involved use of this debridement product plus standard of care. The sample comprised 21 patients with complex, non-healing wounds of various aetiologies. One patient dropped out of the evaluation for unknown reasons. Wound types were either venous leg ulcers (n=16) or post-traumatic wounds (n=25). The mean wound duration was 22 months (range: 2 weeks-17 years). Over the 4-week follow-up period, there was a decline in the mean percentage of devitalised tissue present on the wounds, reducing from 69% at baseline to 49% at week 4. Most of the devitalised tissue was slough, for which the mean baseline percentage was 63% compared with an endpoint of 49%. Conversely, the mean percentage of granulation tissue increased from 31% at baseline to 51% at week 4. The mean visual analogue pain score reported during application was 4/10, where 0 represents no pain. However, general wound-related pain scores improved during the follow-up period, with no scores above 2 at week 2, compared with five at baseline. The results indicate that Debrichem is a safe and effective method of debridement that requires minimal training and is single use.


Subject(s)
Debridement , Wound Healing , Humans , Male , Female , Wound Healing/drug effects , Middle Aged , Aged , Debridement/methods , Adult , Aged, 80 and over , Treatment Outcome , Administration, Topical , Varicose Ulcer/therapy , Wounds and Injuries/therapy , Wound Infection
11.
Exp Biol Med (Maywood) ; 249: 10175, 2024.
Article in English | MEDLINE | ID: mdl-38756167

ABSTRACT

Diabetes mellitus is a prevalent disease that is often accompanied by ocular surface abnormalities including delayed epithelial wound healing and decreased corneal sensitivity. The impact of diabetes on the lacrimal functional unit (LFU) and the structures responsible for maintaining tear homeostasis, is not completely known. It has been shown that the Opioid Growth Factor Receptor (OGFr), and its ligand, Opioid Growth Factor (OGF), is dysregulated in the ocular surface of diabetic rats leading to overproduction of the inhibitory growth peptide OGF. The opioid antagonist naltrexone hydrochloride (NTX) blocks the OGF-OGFr pathway, and complete blockade following systemic or topical treatment with NTX restores the rate of re-epithelialization of corneal epithelial wounds, normalizes corneal sensitivity, and reverses dry eye in diabetic animal models. These effects occur rapidly and within days of initiating treatment. The present study was designed to understand mechanisms related to the fast reversal (<5 days) of dry eye by NTX in type 1 diabetes (T1D) by investigating dysregulation of the LFU. The approach involved examination of the morphology of the LFU before and after NTX treatment. Male and female adult Sprague-Dawley rats were rendered hyperglycemic with streptozotocin, and after 6 weeks rats were considered to be a T1D model. Rats received topical NTX twice daily to one eye for 10 days. During the period of treatment, tear production and corneal sensitivity were recorded. On day 11, animals were euthanized and orbital tissues including conjunctiva, eyelids, and lacrimal glands, were removed and processed for histologic examination including immunohistochemistry. Male and female T1D rats had significantly decreased tear production and corneal insensitivity, significantly decreased number and size of lacrimal gland acini, decreased expression of aquaporin-5 (AQP5) protein and decreased goblet cell size. Thus, 10 days of NTX treatment restored tear production and corneal sensitivity to normal values, increased AQP5 expression, and restored the surface area of goblet cells to normal. NTX had no effect on the number of lacrimal gland acini or the number of conjunctival goblet cells. In summary, blockade of the OGF-OGFr pathway with NTX reversed corneal and lacrimal gland complications and restored some components of tear homeostasis confirming the efficacy of topical NTX as a treatment for ocular defects in diabetes.


Subject(s)
Aquaporin 5 , Diabetes Mellitus, Experimental , Lacrimal Apparatus , Naltrexone , Rats, Sprague-Dawley , Tears , Animals , Lacrimal Apparatus/metabolism , Lacrimal Apparatus/drug effects , Lacrimal Apparatus/pathology , Tears/metabolism , Tears/drug effects , Naltrexone/pharmacology , Male , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Experimental/pathology , Rats , Aquaporin 5/metabolism , Administration, Topical , Dry Eye Syndromes/drug therapy , Dry Eye Syndromes/pathology , Dry Eye Syndromes/metabolism
12.
PLoS One ; 19(5): e0302969, 2024.
Article in English | MEDLINE | ID: mdl-38743769

ABSTRACT

BACKGROUND: Synthesizing current evidence on interventions to improve survival outcomes in preterm infants is crucial for informing programs and policies. The objective of this study is to investigate the impact of topical emollient oil application on the weight of preterm infants. METHODS: A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted. To identify relevant studies, comprehensive searches were conducted across multiple databases, including PubMed, Cochrane, Scopus, Clinical trials, ProQuest Central, Epistemonikos, and gray literature sources. The inclusion criteria were based on the PICO (Population, Intervention, Comparison, and Outcomes) format. Study quality was assessed using the Cochrane risk of bias tool for randomized trials (RoB 2.0). Data analysis was performed using StataCrop MP V.17 software, which included evaluating heterogeneity, conducting subgroup analysis, sensitivity analysis, and meta-regression. The findings were reported in accordance with the PRISMA checklist, and the review was registered with PROSPERO (CRD42023413770). RESULTS: Out of the initial pool of 2734 articles, a total of 18 studies involving 1454 preterm neonates were included in the final analysis. Fourteen of these studies provided data that contributed to the calculation of the pooled difference in mean weight gain in preterm neonates. The random effects meta-analysis revealed a significant pooled difference in mean weight gain of 52.15 grams (95% CI: 45.96, 58.35), albeit with high heterogeneity (I2 > 93.24%, p 0.000). Subgroup analyses were conducted, revealing that preterm infants who received massages three times daily with either sunflower oil or coconut oil exhibited greater mean differences in weight gain. Meta-regression analysis indicated that the type of emollient oil, duration of therapy, and frequency of application significantly contributed to the observed heterogeneity. A sensitivity analysis was performed, excluding two outlier studies, resulting in a pooled mean weight difference of 78.57grams (95% CI: 52.46, 104.68). Among the nine studies that reported adverse events, only two mentioned occurrences of rash and accidental slippage in the intervention groups. CONCLUSION: The available evidence suggests that the application of topical emollient oil in preterm neonates is likely to be effective in promoting weight gain, with a moderate-to-high level of certainty. Based on these findings, it is recommended that local policymakers and health planners prioritize the routine use of emollient oils in newborn care for preterm infants. By incorporating emollient oils into standard care protocols, healthcare providers can provide additional support to promote optimal growth and development in preterm infants.


Subject(s)
Emollients , Infant, Premature , Humans , Infant, Newborn , Emollients/administration & dosage , Randomized Controlled Trials as Topic , Administration, Topical , Weight Gain/drug effects
13.
Sci Rep ; 14(1): 10986, 2024 05 14.
Article in English | MEDLINE | ID: mdl-38744994

ABSTRACT

To assess the efficacy and safety of topical insulin (TI) for treating neurotrophic keratopathy (NK) within one-month post-diabetic vitrectomy (DV) compared to conventional non-invasive measures, we conducted this retrospective case-control study including all eyes that developed acute NK (stages 2 and 3) following DV between October 2020 and June 2023. The control group included NK cases managed with preservative-free lubricant eye drops and prophylactic topical antibiotics. In contrast, the study group included NK cases treated with TI [1 unit per drop] four times daily, in addition to the previously mentioned treatment. The primary outcome measure was time to epithelial healing. Secondary outcome measures included any adverse effect of TI or the need for amniotic membrane transplantation (AMT). During the study period, 19 patients with a mean age of 49.3 ± 8.6 years received TI versus 18 controls with a mean age of 52.5 ± 10.7 years. Corneal epithelial healing was significantly faster in the TI-treated group compared to controls, with a mean difference of 12.16 days (95% CI 6.1-18.3, P = 0.001). Survival analysis indicated that the insulin-treated group had 0% and 20% of NK stages 2 and 3, respectively, that failed to achieve corneal epithelial healing, compared to 20% and 66.7% for the control group (P < 0.001). In the control group, two eyes required AMT due to progressive thinning. Additionally, three patients in the control group, progressing to stage 3 NK, were switched to TI, achieving healing after a mean of 14 days. No adverse effects were reported in the TI-treated group. Our study suggests that TI can effectively and safely promote the healing of NK after DV.


Subject(s)
Corneal Diseases , Insulin , Vitrectomy , Humans , Middle Aged , Male , Female , Insulin/administration & dosage , Retrospective Studies , Vitrectomy/methods , Case-Control Studies , Adult , Corneal Diseases/drug therapy , Corneal Diseases/surgery , Diabetic Retinopathy/drug therapy , Wound Healing/drug effects , Administration, Topical , Aged , Treatment Outcome
14.
J Biomed Opt ; 29(5): 050501, 2024 May.
Article in English | MEDLINE | ID: mdl-38774711

ABSTRACT

Significance: Fiber-optic microendoscopy is a promising approach to noninvasively visualize epithelial nuclear morphometry for early cancer and precancer detection. However, the broader clinical application of this approach is limited by a lack of topical contrast agents available for in vivo use. Aim: The aim of this study was to evaluate the ability to image nuclear morphometry in vivo with a novel fiber-optic microendoscope used together with topical application of methylene blue (MB), a dye with FDA approval for use in chromoendoscopy in the gastrointestinal tract. Approach: The low-cost, high-resolution microendoscope implements scanning darkfield imaging without complex optomechanical components by leveraging programmable illumination and the rolling shutter of the image sensor. We validate the integration of our system and MB staining for visualizing epithelial cell nuclei by performing ex vivo imaging on fresh animal specimens and in vivo imaging on healthy volunteers. Results: The results indicate that scanning darkfield imaging significantly reduces specular reflection and resolves epithelial nuclei with enhanced image contrast and spatial resolution compared to non-scanning widefield imaging. The image quality of darkfield images with MB staining is comparable to that of fluorescence images with proflavine staining. Conclusions: Our approach enables real-time microscopic evaluation of nuclear patterns and has the potential to be a powerful noninvasive tool for early cancer detection.


Subject(s)
Methylene Blue , Methylene Blue/chemistry , Animals , Humans , Cell Nucleus , Fiber Optic Technology/instrumentation , Equipment Design , Endoscopy/methods , Endoscopy/instrumentation , Administration, Topical
15.
Acta Ortop Mex ; 38(2): 73-81, 2024.
Article in Spanish | MEDLINE | ID: mdl-38782471

ABSTRACT

INTRODUCTION: surgical site infections (SSI) remain a significant cause of morbidity and mortality and one of the most representative causes of nosocomial infections. The use of intrawound vancomycin in lumbar spine surgery is a potential prophylactic measure against SSI; however, evidence regarding its efficacy is contradictory. Our study was designed to research if intrawound vancomycin significantly prevents SSI in lumbar spine surgery. MATERIAL AND METHODS: this is a randomized, double-blinded, controlled clinical trial; 233 patients who underwent lumbar spine surgery, were randomly assigned to a group in which intrawound vancomycin was instilled in the incision before closure (109), or to a control group (114). The main outcome is the presence of SSI; we determined its prevalence and searched for difference between groups for association between SSI and independent variables. RESULTS: global SSI prevalence was 1.8%, in the experimental group was 0.9%, in the control group was 2.6%. There was no significant difference between these values, p = 0.622. The relative risk of SSI in the experimental group was 0.35 (95% CI 0.037-3.30), that of the control group was 2.87 (95% CI 0.30-27.16). The number needed to treat is 58.3. We did not find a significant association between the independent variables studied and the appearance of SSI. CONCLUSIONS: we did not find a significant difference in the prevalence of SSI between groups nor a significant association between SSI and independent variables.


INTRODUCCIÓN: las infecciones postoperatorias del sitio quirúrgico son una importante causa de morbimortalidad y una de las formas más comunes de infecciones nosocomiales. La aplicación de vancomicina al terminar una intervención de columna lumbar es una potencial práctica profiláctica de infecciones del sitio quirúrgico (ISQ). La evidencia que sostiene su uso es controversial. Nuestro estudio investiga si la aplicación de vancomicina disminuye en forma significativa la prevalencia de ISQ. MATERIAL Y MÉTODOS: ensayo clínico aleatorizado, controlado, cegado; 223 pacientes intervenidos de la columna lumbar fueron aleatoriamente asignados a un grupo experimental de 109 pacientes en quienes se colocó vancomicina y a un grupo control de 114 pacientes que no recibió vancomicina. El principal desenlace del estudio es la aparición de ISQ; se estudió la prevalencia de ISQ en ambos grupos y se buscó si existe diferencia significativa. Se analizó la existencia de factores predictores de ISQ. RESULTADOS: la prevalencia global de infección fue 1.8%; en el grupo experimenta 0.09% y en el grupo control 2.6%. No hubo diferencia significativa entre estas cifras, p = 0.622. El riesgo relativo de ISQ en el grupo experimental fue 0.35 (IC95% 0.037-3.30), el del grupo control fue 2.87 (IC95% 0.30-27.16). El número necesario para tratar es 58.3. No encontramos asociación significativa entre las variables independientes estudiadas y la aparición de ISQ. CONCLUSIONES: no encontramos evidencia suficiente de que la aplicación de vancomicina disminuya significativamente la prevalencia de ISQ ni asociación significativa de ISQ con las variables independientes estudiadas.


Subject(s)
Administration, Topical , Anti-Bacterial Agents , Lumbar Vertebrae , Surgical Wound Infection , Vancomycin , Humans , Surgical Wound Infection/prevention & control , Surgical Wound Infection/epidemiology , Male , Female , Vancomycin/administration & dosage , Vancomycin/therapeutic use , Middle Aged , Double-Blind Method , Lumbar Vertebrae/surgery , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/therapeutic use , Aged , Adult
16.
Exp Dermatol ; 33(5): e15099, 2024 May.
Article in English | MEDLINE | ID: mdl-38794814

ABSTRACT

Suitable human models for the development and characterization of topical compounds for inflammatory skin diseases such as atopic dermatitis are not readily available to date. We describe here the development of a translational model involving healthy human skin mimicking major aspects of AD and its application for the characterization of topical Janus kinase inhibitors. Full thickness human abdominal skin obtained from plastic surgery stimulated in vitro with IL4 and IL13 shows molecular features of AD. This is evidenced by STAT6 phosphorylation assessed by immunohistochemistry and analysis of skin lysates. Broad transcriptome changes assessed by AmpliSeq followed by gene set variation analysis showed a consistent upregulation of gene signatures characterizing AD in this model. Topical application of experimental formulations of compounds targeting the JAK pathway to full thickness skin normalizes the molecular features of AD induced by IL4 and IL13 stimulation. The inhibitory effects of topical JAK inhibitors on molecular features of AD are supported by pharmacokinetic analysis. The model described here is suited for the characterization of topical compounds for AD and has the potential to be extended to other inflammatory skin diseases and pathophysiological pathways.


Subject(s)
Dermatitis, Atopic , Janus Kinase Inhibitors , Skin , Humans , Dermatitis, Atopic/drug therapy , Skin/metabolism , Skin/drug effects , Janus Kinase Inhibitors/pharmacology , STAT6 Transcription Factor/metabolism , Interleukin-4/metabolism , Interleukin-13/metabolism , Phosphorylation , Transcriptome , Models, Biological , Pyrimidines/pharmacology , Administration, Topical , Piperidines
17.
BMJ Paediatr Open ; 8(1)2024 May 23.
Article in English | MEDLINE | ID: mdl-38782481

ABSTRACT

OBJECTIVE: To develop evidence-based guidance for topical steroid use in paediatric eosinophilic oesophagitis (pEoE) in the UK for both induction and maintenance treatment. METHODS: A systematic literature review using Cochrane guidance was carried out by the British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN) Eosinophilic Oesophagitis (EoE) Working Group (WG) and research leads to determine the evidence base for preparation, dosing and duration of use of swallowed topical steroid (STS) formulations in EoE. Seven themes relating to pEoE were reviewed by the WG, alongside the Cochrane review this formed the evidence base for consensus recommendations for pEoE in the UK. We provide an overview of practical considerations including treatment regimen and dosing. Oral viscous budesonide (OVB) and, if agreed by local regulatory committees, orodispersible budesonide (budesonide 1 mg tablets) were selected for ease of use and with most improvement in histology. A practical 'how to prepare and use' OVB appendix is included. Side effects identified included candidiasis and adrenal gland suppression. The use of oral systemic steroids in strictures is discussed briefly. RESULTS: 2638 citations were identified and 18 randomised controlled trials were included. Evidence exists for the use of STS for induction and maintenance therapy in EoE, especially regarding histological improvement. Using the Appraisal of Guidelines, Research and Evaluation criteria, dosing of steroids by age (0.5 mg two times per day <10 years and 1 mg two times per day ≥10 years) for induction of at least 3 months was suggested based on evidence and practical consideration. Once histological remission is achieved, maintenance dosing of steroids appears to reduce the frequency and severity of relapse, as such a maintenance weaning regimen is proposed. CONCLUSION: A practical, evidence-based flow chart and guidance recommendations with consensus from the EoE WG and education and research representatives of BSPGHAN were developed with detailed practical considerations for use in the UK.


Subject(s)
Budesonide , Eosinophilic Esophagitis , Humans , Eosinophilic Esophagitis/drug therapy , Child , Budesonide/administration & dosage , Budesonide/therapeutic use , Administration, Topical , Evidence-Based Medicine , Glucocorticoids/administration & dosage , Glucocorticoids/therapeutic use , United Kingdom , Administration, Oral
19.
Curr Pharm Des ; 30(7): 489-518, 2024.
Article in English | MEDLINE | ID: mdl-38757691

ABSTRACT

Topical drug delivery holds immense significance in dermatological treatments due to its non-invasive nature and direct application to the target site. Organogels, a promising class of topical drug delivery systems, have acquired substantial attention for enhancing drug delivery efficiency. This review article aims to explore the advantages of organogels, including enhanced drug solubility, controlled release, improved skin penetration, non-greasy formulations, and ease of application. The mechanism of organogel permeation into the skin is discussed, along with formulation strategies, which encompass the selection of gelling agents, cogelling agents, and additives while considering the influence of temperature and pH on gel formation. Various types of organogelators and organogels and their properties, such as viscoelasticity, non-birefringence, thermal stability, and optical clarity, are presented. Moreover, the biomedical applications of organogels in targeting skin cancer, anti-inflammatory drug delivery, and antifungal drug delivery are discussed. Characterization parameters, biocompatibility, safety considerations, and future directions in optimizing skin permeation, ensuring long-term stability, addressing regulatory challenges, and exploring potential combination therapies are thoroughly examined. Overall, this review highlights the immense potential of organogels in redefining topical drug delivery and their significant impact on the field of dermatological treatments, thus paving the way for exciting prospects in the domain.


Subject(s)
Drug Delivery Systems , Gels , Gels/chemistry , Humans , Administration, Topical , Animals , Administration, Cutaneous , Skin Absorption/drug effects
20.
Pediatr Surg Int ; 40(1): 132, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38739164

ABSTRACT

Local estrogen therapy has been explored as an alternative to conventional testosterone therapy in children requiring urethroplasty for hypospadias. Our objective is to evaluate if preoperative estrogen stimulation reduces post-urethroplasty complications and enhances penile dimensions. A systematic search was conducted on various databases, selecting only randomized controlled trials (RCTs) that tested estrogen on hypospadias patients under 18 years. Articles underwent sorting following PRISMA guidelines and bias risk was assessed using the JBI clinical appraisal tool for RCTs. Out of 607 screened records, 10 underwent full-text review, and 4 randomized controlled trials (RCTs) were selected for analysis. The total patient cohort across studies was 387 with 174 in the estrogen group. All studies utilized topical estrogen, but in different formulations and timings. Prudence is necessary for interpreting results due to variations in formulation, timing, and hypospadias type across studies. Limited by a small number of studies and outcome presentation non-uniformity, the review suggests no change in penile dimensions or postoperative complications with topical estrogen. Further research is needed to explore wound-healing properties of estrogen in hypospadias through animal and human studies.Registration and protocol: Registered in Prospero CRD42024502183.


Subject(s)
Administration, Topical , Estrogens , Hypospadias , Child , Humans , Male , Estrogens/administration & dosage , Estrogens/therapeutic use , Hypospadias/surgery , Postoperative Complications/prevention & control , Preoperative Care/methods , Randomized Controlled Trials as Topic , Urethra/surgery , Urologic Surgical Procedures, Male/methods
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