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1.
Int J Womens Dermatol ; 10(3): e169, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39015748

ABSTRACT

Background: Pigmented lesions such as melanosis have rarely been reported in patients with vulvar lichen sclerosus (VLS) that is typically characterized by hypopigmented lesions. Objective: We aimed to analyze systematically anogenital melanosis in a large cohort of VLS patients. Methods: We analyzed the clinical data of 198 female patients with VLS. The anogenital lesions of all patients were professionally photographed in a standardized position and illumination. Severity classification of architectural findings followed an easy-to-use clinical score. A modified Melasma Area and Severity Index and an image analysis software were used to evaluate the area and intensity of pigmentation. Results: According to the clinical score, 79 (198/39.9%) patients showed grade 1 disease, 78 (198/39.4%) grade 2, 37 (198/18.7%) grade 3, and 4 (198/2%) grade 4 disease. About 111 (56.1%) of the 198 patients had anogenital melanosis with a median modified Melasma Area and Severity Index of 3.6 (0.4-14). Univariate analysis revealed that anogenital melanosis was positively correlated with the use of topical estrogens (P = .0018) and negatively correlated with the use of pulsed high-dose corticosteroids plus low-dose methotrexate (PHDC-LDM, P = .021). On multivariable analysis, the use of topical hormone therapy turned out to be a strong independent predictor for the presence of anogenital melanosis (odds ratio: 4.57, 95% confidence interval: 1.66-12.57, P = .0033), whereas PHDC-LDM use was an independent predictor for the absence of anogenital melanosis (odds ratio: 0.35, 95% confidence interval: 0.15-0.84, P = .018). Limitations: The study includes the retrospective monocentric design. Conclusion: Anogenital melanosis is a very frequent and so far, under-reported clinical finding in VLS patients. It is likely caused by the use of topical estrogens employed for VLS treatment. In contrast, patients with more severe disease and PHDC-LDM treatment appear to develop less likely anogenital melanosis.

2.
Plants (Basel) ; 13(13)2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38999635

ABSTRACT

Prolonged exposure to environmental oxidative stress can result in visible signs of skin aging such as wrinkles, hyperpigmentation, and thinning of the skin. Oryza sativa variety Sang 5 CMU, an inbred rice cultivar from northern Thailand, contains phenolic and flavonoid compounds in its bran and husk portions that are known for their natural antioxidant properties. In this study, we evaluated the cosmetic properties of crude extracts from rice bran and husk of Sang 5 CMU, focusing on antioxidant, anti-inflammatory, anti-melanogenesis, and collagen-regulating properties. Our findings suggest that both extracts possess antioxidant potential against DPPH, ABTS radicals, and metal ions. Additionally, they could downregulate TBARS levels from 125% to 100% of the control, approximately, while increasing the expression of genes related to the NRF2-mediated antioxidant pathway, such as NRF2 and HO-1, in H2O2-induced human fibroblast cells. Notably, rice bran and husk extracts could increase mRNA levels of HO-1 more greatly than the standard L-ascorbic acid, by about 1.29 and 1.07 times, respectively. Furthermore, the crude extracts exhibited anti-inflammatory activity by suppressing nitric oxide production in both mouse macrophage and human fibroblast cells. Specifically, the bran and husk extracts inhibited the gene expression of the inflammatory cytokine IL-6 in LPS-induced inflammation in fibroblasts. Moreover, both extracts demonstrated potential for inhibiting melanin production and intracellular tyrosinase activity in human melanoma cells by decreasing the expression of the transcription factor MITF and the pigmentary genes TYR, TRP-1, and DCT. They also exhibit collagen-stimulating effects by reducing MMP-2 expression in H2O2-induced fibroblasts from 135% to 80% of the control, approximately, and increasing the gene associated with type I collagen production, COL1A1. Overall, the rice bran and husk extracts of Sang 5 CMU showed promise as effective natural ingredients for cosmetic applications.

3.
Front Oncol ; 14: 1396819, 2024.
Article in English | MEDLINE | ID: mdl-38974235

ABSTRACT

Background: Currently, there is no standard treatment for relapsed/refractory NK/T-cell lymphoma (NKTCL). Liposomal mitoxantrone (Lipo-MIT) showed good anti-tumor effect in patients with NKTCL, breaking the limitation of natural resistance of NKTCL to anthracyclines. To further improve the efficacy, we tried a combination therapy based on Lipo-MIT in patients with relapsed/refractory NKTCL. Methods: 12 patients with relapsed/refractory NKTCL were enrolled in this retrospective study, all of whom had previously received pegaspargase-based treatments. The salvage treatment was a combination regimen based on Lipo-MIT. The efficacy was evaluated after every two cycles. Results: 11 patients had stage IV NKTCL, and all but one patients had an NRI score of ≥3. The median previous lines of treatment was two (range, 1-4), and five patients were refractory to their last line of treatment. The best response rates were as follows: complete response (CR) in five (41.7%) patients, partial response in five (41.7%) patients, stable disease in one (8.3%) patient, and progressive disease in one (8.3%) patient. At a median follow-up of four months (range, 2-14), seven patients died, with a median PFS of five months and a median OS of seven months. The six-month PFS and OS rate was 44.4% and 52.1%, respectively. All patients had suffered from side effects, among which myelosuppression was most reported. Nine patients had grade three or more myelosuppression, and the median recovery time from myelosuppression was 14 days (2-35 days). Five patients had obvious skin hyperpigmentation, and the CR rate was significantly higher compared with those without skin hyperpigmentation (80% vs. 14.3%, p=0.023). Other side effects included liver insufficiency (N=4), coagulation dysfunction (N=4), acute pancreatitis (N=2), and immunotherapy-related adverse effects (irAEs, N=2). Conclusion: Combination therapy based on Lipo-MIT has a high remission rate for relapsed/refractory NKTCL, but the duration of remission needs to be further extended. Lipo-MIT has obvious myelosuppression toxicity, and active supportive therapy should be given when combined with other cytotoxic drugs.

4.
HCA Healthc J Med ; 5(2): 103-111, 2024.
Article in English | MEDLINE | ID: mdl-38984232

ABSTRACT

Description Atopic dermatitis is a chronic inflammatory skin disorder classically affecting flexural areas of the body. It is present in children and adults, including those with darker skin pigmentation. Chronic lesions are hyperpigmented plaques that are dry, cracked, and/or scaly often with lichenification. Differential diagnoses include psoriasis, seborrheic dermatitis, ichthyosis, and pityriasis rosea. This article will showcase clinical images with varying presentations of chronic atopic dermatitis in a range of age groups and skin colors according to the Fitzpatrick scale.

5.
J Am Acad Dermatol ; 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38980249

ABSTRACT

The rising global popularity of cosmetic and corrective tattoos has concurrently led to an increased demand for their removal. While in the past, methods like surgical excision, chemical destruction, and dermabrasion were employed, lasers have emerged as a reliable and effective tool for tattoo removal. Increasing technological options and combination treatment strategies have raised the importance of understanding the various approaches to laser tattoo removal along with their respective clinical impact. This CME aims to describe the multifaceted aspects of laser tattoo removal, including the method selection, application principles, and safety considerations. Furthermore, it addresses the factors considered when selecting the most suitable laser to achieve optimal treatment outcomes.

6.
Lasers Surg Med ; 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39010642

ABSTRACT

OBJECTIVES: Iatrogenic cutaneous siderosis is a well-recognized dermatologic complication after parenteral iron infusion. The condition manifests as discrete, hyperpigmented patches near the site of injection. Most cases do not resolve spontaneously, leading to significant aesthetic and psychological distress to patients. A recent case of iatrogenic cutaneous siderosis at our institution prompted a systematic review of the efficacy of energy-based devices previously reported in the treatment of this condition. METHODS: PubMed and Cochrane databases were searched for all peer-reviewed articles published using the following search terms: "iron OR heme OR hemosiderosis OR siderosis" and "hyperpigmentation OR staining OR tattoo." Articles reporting on energy-based devices in the treatment of iron-induced hyperpigmentation were included. RESULTS: A total of seven articles and 54 total patients were included in this review. All patients, including the patient treated at our institution, were female, with an average age of 44 years. Hyperpigmentation was most commonly associated with intravenous iron infusion (48/54, 89%), on the arm or forearm (44/54, 81%), and used for the treatment of underlying iron deficiency anemia (54/54, 100%). The application of six different nanosecond or picosecond quality-switched laser systems was reported in the treatment of cutaneous siderosis, with wavelengths ranging from 532 to 1064 nm. Spot sizes varied between 2 and 7 mm, with energy fluences spanning 0.5-40 J/cm2 depending on both the device and spot size. Outcomes were measured after an average of 5.4 laser treatments and 10.4 months, with over half of all reported patients experiencing complete clearance (27/50, 54%). Our patient received treatment in three test areas with picosecond alexandrite 785 nm, nanosecond Nd:YAG 532 nm, and picosecond Nd:YAG 532 nm devices. The nanosecond Nd:YAG 532 nm treated area demonstrated the greatest improvement, and the entire arm was subsequently treated with this device. CONCLUSIONS: Despite the often intractable nature of iatrogenic cutaneous siderosis, laser surgery is a reasonable and safe treatment modality for patients seeking cosmetic improvement of this dyschromia. Dermatologists should be aware of this entity and the efficacy of the energy-based devices currently in our armamentarium. A combination approach may need to be utilized with different wavelengths and pulsed widths to target iron pigment in both dermal and subcutaneous layers.

7.
BMC Med Genomics ; 17(1): 178, 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38965556

ABSTRACT

BACKGROUND: The SLC29A3 gene, which encodes a nucleoside transporter protein, is primarily located in intracellular membranes. The mutations in this gene can give rise to various clinical manifestations, including H syndrome, dysosteosclerosis, Faisalabad histiocytosis, and pigmented hypertrichosis with insulin-dependent diabetes. The aim of this study is to present two Iranian patients with H syndrome and to describe a novel start-loss mutation in SLC29A3 gene. METHODS: In this study, we employed whole-exome sequencing (WES) as a method to identify genetic variations that contribute to the development of H syndrome in a 16-year-old girl and her 8-year-old brother. These siblings were part of an Iranian family with consanguineous parents. To confirmed the pathogenicity of the identified variant, we utilized in-silico tools and cross-referenced various databases to confirm its novelty. Additionally, we conducted a co-segregation study and verified the presence of the variant in the parents of the affected patients through Sanger sequencing. RESULTS: In our study, we identified a novel start-loss mutation (c.2T > A, p.Met1Lys) in the SLC29A3 gene, which was found in both of two patients. Co-segregation analysis using Sanger sequencing confirmed that this variant was inherited from the parents. To evaluate the potential pathogenicity and novelty of this mutation, we consulted various databases. Additionally, we employed bioinformatics tools to predict the three-dimensional structure of the mutant SLC29A3 protein. These analyses were conducted with the aim of providing valuable insights into the functional implications of the identified mutation on the structure and function of the SLC29A3 protein. CONCLUSION: Our study contributes to the expanding body of evidence supporting the association between mutations in the SLC29A3 gene and H syndrome. The molecular analysis of diseases related to SLC29A3 is crucial in understanding the range of variability and raising awareness of H syndrome, with the ultimate goal of facilitating early diagnosis and appropriate treatment. The discovery of this novel biallelic variant in the probands further underscores the significance of utilizing genetic testing approaches, such as WES, as dependable diagnostic tools for individuals with this particular condition.


Subject(s)
Consanguinity , Nucleoside Transport Proteins , Pedigree , Humans , Female , Nucleoside Transport Proteins/genetics , Male , Adolescent , Child , Mutation , Histiocytosis/genetics , Histiocytosis/pathology , Computer Simulation , Hypertrichosis/genetics , Exome Sequencing , Contracture , Hearing Loss, Sensorineural
8.
Exp Dermatol ; 33(7): e15138, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39005203

ABSTRACT

Seborrheic keratosis (SK) is a common benign tumour, often associated with hyperpigmentation. To investigate the mechanism of melanin accumulation in SK, we have conducted comprehensive gene expression and histological analyses. We obtained five pairs of skin samples, including non-lesional and SK samples, from the backs of three male Japanese participants aged 40-59 years. To examine melanocytes and keratinocytes in SK, three pairs of skin samples were separated by laser capture microdissection into the basal layer and the other layer in the epidermis. We performed a comprehensive gene expression analysis to identify differentially expressed genes between non-lesional and SK skin, followed by gene ontology and pathway analysis. We found abnormal morphogenesis and cell proliferation in the basal layer, along with increased immune response and impaired cell differentiation and metabolism in the other layer of SK. We focused on cell proliferation and differentiation, as these are directly associated with melanin accumulation. Immunohistochemical analyses of Ki67, keratin 10, and keratin 14 demonstrated the decreases in the proliferation and early differentiation of the epidermis. Contrarily, no significant changes were observed in terminal differentiation markers, filaggrin and loricrin. Although the number of melanocytes was higher in SK than in non-lesional skin, melanogenic activity showed no difference. These results indicated that melanin accumulation in SK is caused by delayed melanin excretion due to reduced turnover around the basal and spinous layers of the epidermis and melanin production due to an increased number of melanocytes. Our findings provide new insights for therapeutic approaches in SK.


Subject(s)
Cell Differentiation , Cell Proliferation , Filaggrin Proteins , Keratinocytes , Keratosis, Seborrheic , Melanins , Melanocytes , Humans , Melanocytes/metabolism , Melanocytes/pathology , Keratosis, Seborrheic/metabolism , Keratosis, Seborrheic/pathology , Male , Melanins/metabolism , Middle Aged , Keratinocytes/metabolism , Adult , Epidermis/metabolism , Epidermis/pathology , Membrane Proteins
9.
Int J Mol Sci ; 25(13)2024 Jul 03.
Article in English | MEDLINE | ID: mdl-39000417

ABSTRACT

Metabolites resulting from the bacterial fermentation of dietary fibers, such as short-chain fatty acids, especially butyrate, play important roles in maintaining gut health and regulating various biological effects in the skin. However, butyrate is underutilized due to its unpleasant odor. To circumvent this organoleptic unfavorable property, phenylalanine butyramide (PBA), a butyrate precursor, has been synthesized and is currently available on the market. We evaluated the inhibition of mushroom tyrosinase by butyrate and PBA through in vitro assays, finding IC50 values of 34.7 mM and 120.3 mM, respectively. Docking calculations using a homology model of human tyrosinase identified a putative binding mode of PBA into the catalytic site. The anti-aging and anti-spot efficacy of topical PBA was evaluated in a randomized, double-blind, parallel-arm, placebo-controlled clinical trial involving 43 women affected by photo-damage. The results of this study showed that PBA significantly improved skin conditions compared to the placebo and was well tolerated. Specifically, PBA demonstrated strong skin depigmenting activity on both UV and brown spots (UV: -12.7% and -9.9%, Bs: -20.8% and -17.7% after 15 and 30 days, respectively, p < 0.001). Moreover, PBA brightened and lightened the skin (ITA°: +12% and 13% after 15 and 30 days, respectively, p < 0.001). Finally, PBA significantly improved skin elasticity (Ua/Uf: +12.4% and +32.3% after 15 and 30 days, respectively, p < 0.001) and firmness (Uf: -3.2% and -14.9% after 15 and 30 days, respectively, p < 0.01).


Subject(s)
Monophenol Monooxygenase , Phenylalanine , Skin Aging , Skin Pigmentation , Adult , Female , Humans , Middle Aged , Agaricales/enzymology , Butyrates/chemistry , Butyrates/pharmacology , Double-Blind Method , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/chemistry , Molecular Docking Simulation , Monophenol Monooxygenase/antagonists & inhibitors , Phenylalanine/chemistry , Phenylalanine/analogs & derivatives , Phenylalanine/pharmacology , Skin Aging/drug effects , Skin Pigmentation/drug effects
10.
Indian J Otolaryngol Head Neck Surg ; 76(3): 2820-2823, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38883473

ABSTRACT

A case of congenital hemifacial hypertrophy is described. This rare condition is more prevalent in males, and it is characterized by facial asymmetry. Sometimes, Hemifacial hypertrophy can lead to obstruction of the respiratory airway which may prove lethal. Here we made an attempt to present a complicated female case of true congenital hemifacial hypertrophy with its clinical, radiological presentation and surgical treatment. No single theory for hemifacial hypertrophy explains the etiology adequately. A 19-month-old female child was referred to our hospital with difficulty in breathing. She had Hemifacial hypertrophy presents with neck swelling, enlarged ear pinna with hyperpigmentation, and hypertrichosis. Radiological imaging was done, and it was diagnosed as congenital hemifacial hypertrophy. A mass obstructing the oropharynx with tonsillar enlargement was noted. Transoral endoscopic coablator-assisted excision of the oropharyngeal mass with tonsillar excision was done and the airway was secured. The neck fatty mass was excised externally. Follow-up was done for two years. Congenital Hemifacial hypertrophy is a rare congenital condition and has a good prognosis. Generally, Hemifacial hypertrophy presents with neck swelling, enlarged ear pinna with hyperpigmentation, and hypertrichosis. sometimes when presented with respiratory obstruction it can prove fatal which can be managed by securing the airway immediately. Here this case was managed with endoscopic surgical excision of obstruction and no further complications were noted. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-024-04525-x.

12.
Skin Res Technol ; 30(6): e13793, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38899793

ABSTRACT

BACKGROUND: To evaluate the efficacy and safety of stromal vascular fraction (SVF), platelet rich plasma (PRP), and 1064-nm Q-switched Nd:YAG laser in reducing nanofat treated dark circles and wrinkles under the eyes. METHOD: This study was a single-blinded randomized clinical trial conducted on patients with suborbital darkening under the eyes that randomly divided into control and case groups. In the control group, 15 patients were treated with one session of nanofat injection only, and five patients of each intervention groups received one session of nanofat+SVF injection, nanofat+PRP injection, and nanofat injection+Nd:YAG laser, respectively. Assessments methods were (1) evaluation of the degree of darkness and repair under the eyes by a blinded dermatologist based on clinical photographs, (2) investigating patient satisfaction, (3) using biometric variables for color, thickness, and density of the skin (only 3 months after the treatment), and (4) recording the possible adverse effects. CONCLUSION: In terms of the extent of reduction in the intensity of darkness under the eyes, the combined treatment of nanofat injection together with SVF, PRP, and Nd:YAG laser had a much greater therapeutic effect than nanofat injection alone. In all three groups of combined treatments, patients were 100% satisfied. In terms of biometric variables, amount of changes in colorimeter, complete and dermal thickness, complete and dermal density, between the different groups was statistically significant. The use of combined treatments including nanofat with SVF injection, PRP, and 1064 Q-switched Nd:YAG laser may be more effective than nanofat alone, in reducing infraorbital dark circles and wrinkles.


Subject(s)
Cosmetic Techniques , Lasers, Solid-State , Platelet-Rich Plasma , Skin Aging , Humans , Female , Lasers, Solid-State/therapeutic use , Middle Aged , Single-Blind Method , Adult , Cosmetic Techniques/instrumentation , Treatment Outcome , Male , Patient Satisfaction
13.
Eur J Dermatol ; 34(2): 139-143, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38907543

ABSTRACT

Diffuse hyperpigmentation with guttate hypopigmentation (DHGH) is a new acquired pigmentary disorder. Only a few cases have previously been reported in the Chinese population, in Chinese. To summarise the clinical, dermoscopic, and histopathological findings of DHGH in the English literature, to improve the recognition and management of this condition. This was a retrospective study to summarise the clinical, dermoscopic, and pathological findings of nine cases of DHGH. All nine patients with DHGH were female. The age at onset varied from 6 to 24 years (median 17 years). Patients were generally in good health without systemic disease. The lesions were often generalised to the trunk and extremities without any discomfort. Typical lesions were characterised by multiple uniform hypopigmented spots, 2-5 mm in diameter, irregularly distributed over diffuse hyperpigmentation. Dermoscopy revealed multiple blurred patchy areas of brownish pigmentation, sparse linear and dotted vessels, and perifollicular pigmentation on a white to bright white background, surrounded by brown hyperpigmentation. Histopathological findings included mild abnormal pigment of the epidermis, focal vacuolar degeneration of the basal cells, mild pigment incontinence and perivascular lymphocytic infiltration in the dermis. DHGH is a new entity with distinctive clinical manifestations that differ from those of other known pigmentary disorders. So far, DHGH has only been reported in the Chinese population. It may not be uncommon and has not received much attention due to the few reports. The aetiology and pathogenesis of DHGH are still unknown and require further investigation.


Subject(s)
Hyperpigmentation , Hypopigmentation , Humans , Female , Hyperpigmentation/pathology , Hypopigmentation/pathology , Retrospective Studies , Adolescent , Young Adult , Child , Dermoscopy , Adult
14.
Cureus ; 16(5): e59565, 2024 May.
Article in English | MEDLINE | ID: mdl-38826967

ABSTRACT

Terra firma-forme dermatosis is an acquired and idiopathic disorder with an underestimated incidence. It is characterized by brownish skin pigmentation, forming asymptomatic plaques that give a soiled skin appearance. Soap and water have a minor effect; however, friction with 70% ethyl or isopropyl alcohol immediately eliminates plaques to a normal skin appearance, thus being the ideal method for diagnosis and treatment. The lack of familiarity with this disease possibly contributes to an alarming underdiagnosis. In this report, the authors present a case of terra firma-forme occurring in a 14-year-old Mexican patient who presented with a heart-shaped pigmented lesion in the pubic area.

15.
J Family Med Prim Care ; 13(4): 1563-1565, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38827700

ABSTRACT

This case report explores a rare manifestation of Becker's nevus, where the patient exhibited an unusual dermatomal distribution featuring a hyperpigmented, irregular patch with associated hypertrichosis on the T4 segment. While Becker's nevus is a well-known dermatological condition typically observed in the upper back region, instances of dermatomal distribution are exceptionally uncommon. This case presents a unique occurrence of segmental Becker's nevus, highlighting the atypical presentation of this condition.

16.
17.
Article in English | MEDLINE | ID: mdl-38912718

ABSTRACT

17α­hydroxylase/17,20­lyase deficiency (17OHD) is a rare form of congenital adrenal hyperplasia that causes decreased cortisol and sex steroid levels and leads to high production of adrenocorticotropic hormone (ACTH). Although affected patients have absolute cortisol deficiency, they do not show clinical signs of cortisol deficiency or hyperpigmentation. These patients most commonly present with delayed puberty and amenorrhea at late pubertal age. Impaired production of sex steroids leads to ambiguous or female external genitalia in affected 46, XY individuals. In this report, we describe a patient with 17OHD who presented with hyperpigmentation and hypergonodotropic hypogonadism while receiving chemotherapy.

18.
Am J Ophthalmol ; 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38944135

ABSTRACT

PURPOSE: The association between the total macular burden of hyperreflective foci (HRF) in eyes with intermediate AMD (iAMD) and the onset of persistent choroidal hypertransmission defects (hyperTDs) was studied using swept-source optical coherence tomography (SS-OCT). DESIGN: Post hoc subgroup analysis of a prospective study. METHODS: A retrospective review of iAMD eyes from subjects enrolled in a prospective SS-OCT study was performed. All eyes underwent 6×6 mm SS-OCT angiography (SS-OCTA) imaging at baseline and follow-up visits. En face sub-retinal pigment epithelium (subRPE) slabs with segmentation boundaries positioned 64-400 µm beneath Bruch's membrane (BM) were used to identify persistent choroidal hyperTDs. None of the eyes had persistent hyperTDs at baseline. The same subRPE slab was used to identify choroidal hypotransmission defects (hypoTDs) attributable to HRF located either intraretinally (iHRF) or along the RPE (rpeHRF) based on corresponding B-scans. A semiautomated algorithm was used by two independent graders to validate and refine the HRF outlines. The HRF area and the drusen volume within a 5mm fovea-centered circle were measured at each visit. RESULTS: The median follow-up time for the 171 eyes from 121 patients included in this study was 59.1 months (95%CI: 52.0-67.8 months). Of these, 149 eyes (87%) had HRF, and 82 (48%) developed at least one persistent hyperTD during the follow-up. Although univariable Cox regression analyses showed that both drusen volume and total HRF area were associated with the onset of the first persistent hyperTD, multivariable analysis showed that the area of total HRF was the sole significant predictor for the onset of hyperTDs (P<0.001). ROC analysis identified an HRF area ≥ 0.07 mm² to predict the onset of persistent hyperTDs within one year with an area under the curve (AUC) of 0.661 (0.570-0.753), corresponding to a sensitivity of 55% and a specificity of 74% (P<0.001). CONCLUSIONS: The total macular burden of HRF, which includes both the HRF along the RPE and within the retina, is an important predictor of disease progression from iAMD to the onset of persistent hyperTDs and should serve as a key OCT biomarker to select iAMD patients at high-risk for disease progression in future clinical trials.

19.
Bioorg Chem ; 150: 107533, 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38878750

ABSTRACT

Hyperpigmentation disorders may result from inappropriate melanin deposition and/or excessive melanin synthesis. They are classified mainly as aesthetic problems, but they can significantly affect human health by decreasing self-esteem. There are available only limited treatment options for hyperpigmentation disorder, among others, cosmetic products applied topically. Depigmenting ingredients were found to be ineffective and characterized by various side effects. As a result, many efforts are made to discover novel, potent, and safe melanogenesis inhibitors for possible use in topical cosmetic depigmenting formulations. Cinnamic acid derivatives constitute a widely tested group for that purpose. This article reports research in the group of N-alkyl cinnamamide derivatives (un)substituted in phenyl ring. Among tested series, (E)-3-(4-chlorophenyl)-N-(5-hydroxypentyl)acrylamide (compound 21) showed the most promising inhibitory properties in mushroom tyrosinase assay (IC50 = 36.98 ± 1.07 µM for monophenolase activity, IC50 = 146.71 ± 16.82 µM for diphenolase activity) and melanin production inhibition in B16F10 mouse melanoma cell line at concentration 6.25 µM resulting probably from decreasing of Tyr, Mitf, Tyrp-1, and Tyrp-2 genes expression. This compound also showed melanin production inhibitory properties in pigmented reconstructed human epidermis when used in 1 % and 2 % solutions in 50 % PEG400. In vitro evaluation of its safety profile showed no cytotoxicity to human keratinocytes HaCaT, human skin fibroblasts BJ, and human primary epidermal melanocytes HEMa, no mutagenicity in the Ames test, no genotoxicity in micronucleus test, no phototoxicity, as well as no skin irritation potential tested in PEG400 solution. This compound was also shown to penetrate across the epidermis to reach the possible site of action. The performed research led to classify (E)-3-(4-chlorophenyl)-N-(5-hydroxypentyl)acrylamide as a novel potential depigmenting cosmetic ingredient.

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