Short Caco-2 model for evaluation of drug permeability: A sodium valerate-assisted approach.

The human colorectal adenocarcinoma cell line Caco-2, widely used for studying intestinal drug permeability, is typically grown on permeable filter supports and matures in 21 days with frequent media changes. The process is labor-intensive, prone to contamination, and has low throughput, contributing to the overall high utilization cost. Efforts to establish a low-cost, high-throughput, and short-duration model have encountered obstacles, such as weaker tight junctions causing monolayer leaks, incomplete differentiation resulting in low transporter expression, intricate and challenging protocols, and cytotoxicity, limiting the usability. Hence, this study aimed to develop a low-cost, efficient, and short-duration model by addressing the aforementioned concerns by customizing the media and finding a safe differentiation inducer. We generated a new rapid model using sodium valerate, which demonstrated sufficient transporter activity, improved monolayer integrity, and higher levels of differentiation markers than the 21-day model. Furthermore, this model exhibited consistent and reliable results when used to evaluate drug permeability over multiple days of repeated use. This study demonstrates the potential of a sodium valerate-assisted abbreviated model for drug permeability assessment with economic and practical advantages.

Histological Assessment of the Effectiveness of Microneedling Device-Assisted Filler Delivery.

BACKGROUND: Microneedling is used to enhance transcutaneous drug delivery. However, the extent to which microneedling devices impact filler delivery and whether this varies by filler type, microneedling device type, and treatment sequence is not known. OBJECTIVE: To histologically assess and quantify the delivery of commonly used fillers through microneedling, using both a microneedling pen and a microneedling roller. In addition, the authors investigated whether there is a variation in filler delivery based on the sequence of microneedling in relation to topical filler application. METHODS: Ex vivo human abdominal skin samples were subjected to microneedling pen or microneedling roller treatment. Black tissue marking ink, hyaluronic acid, poly-l-lactic acid, or undiluted calcium hydroxyapatite was topically applied before or immediately after microneedling treatment. RESULTS: Histological evaluation revealed a notable presence of black ink within channels formed by both microneedling treatments (15.5%-98.1%), whereas there was limited presence of the various filler types tested (0%-6.6%) in all settings. Topical application before microneedling treatment led to relatively higher filler/ink deposition within the channels formed by the microneedling treatments compared with topical application after microneedling. CONCLUSION: Transcutaneous delivery of fillers was not significantly helped by microneedling treatment, whereas the microneedling devices demonstrated effective delivery of an aqueous solution.

Laser-Assisted and Device-Assisted Filler Delivery: A Histologic Evaluation.

BACKGROUND: Lasers and devices are used to enhance transcutaneous delivery of fillers. However, little has been published on the histologic findings of this form of laser/device-assisted delivery to determine the optimal devices and fillers. OBJECTIVE: To objectively evaluate the histological effects of laser-assisted and device-assisted filler delivery. METHODS: Ex vivo human abdominoplasty skin samples were treated with fractional CO 2 laser (ECO 2 , 120 µm tip, 120 mJ), fractional radiofrequency microneedling (FRMN, Genius, 1.5 mm, 20 mJ/pin), and microneedling (2.0 mm). Immediately after poly- l -lactic acid (PLLA), hyaluronic acid gel, calcium hydroxylapatite, and black tissue marking dye were topically applied. After treatment, biopsies were collected for histologic evaluation. RESULTS: Histology revealed that PLLA and black dye were found in greatest abundance, hyaluronic acid was found to a lesser extent, and calcium hydroxylapatite was least found within channels created by fractional CO 2 laser. Microneedling was effective only at delivering black dye, whereas FRMN failed to show significant channel formation or delivery of the studied products. CONCLUSION: Among the devices and fillers studied, fractional CO 2 laser and PLLA proved to be the most effective combination for laser/device-assisted filler delivery. Neither microneedling nor FRMN was effective as devices to enhance filler delivery.

Merkel Cell Hyperplasia Versus Intraepidermal Merkel Cell Carcinoma: A Comparative Study of 2 Cases.

ABSTRACT: Intraepidermal Merkel cell hyperplasia and Merkel cell carcinoma represent 2 histologically similar-appearing diagnoses with significant differences regarding prognosis and management. We present 1 case of each diagnosis to highlight characteristic histopathologic and immunohistochemical features. Our case of Merkel cell hyperplasia was identified by its small intraepidermal nest of monomorphic cells without atypia or mitoses, which demonstrated cytoplasmic, rather than perinuclear dot, patterning on CK20 staining. This can be contrasted with our case of intraepidermal Merkel cell carcinoma, which, despite a lack of dermal extension, demonstrated large nests of pleomorphic cells with frequent mitoses and apoptoses. The diagnosis was further confirmed by immunohistochemistry because CK20 staining showed classic perinuclear dot patterning. By presenting both diagnoses in parallel, this comparison aims to underscore crucial histopathologic and immunohistochemical similarities and differences.

Long-term exposure changes the environmentally relevant bis(2-ethylhexyl) phthalate to be a neuro-hazardous substance disrupting neural homeostasis in emotional and cognitive functions.

Bis(2-ethylhexyl) phthalate (DEHP) is the most used member of the phthalate class of compounds. Extensive use of this plasticizer allows daily exposure to humans via various routes. A positive relationship between DEHP exposure and neurobehavioral disorders is suspected. But, there are insufficient data on the harmfulness of neurobehavioral disorders caused by DEHP exposure, particularly at daily exposure levels. In this study, we assessed the consequences of daily DEHP ingestion (2 and 20 mg/kg diets) in male mice for at least 100 days and examined its effects on neuronal functions associated with neurobehavioral disorders, such as depression and cognitive decline. We found the marked depressive behaviors and reduced learning and memory function in the DEHP-ingestion groups, and that biomarkers related to chronic stress were increased in plasma and brain tissues. Long-term DEHP ingestion induced collapse of glutamate (Glu) and glutamine (Gln) homeostasis as a result of disruption of the Glu-Gln cycle in the medial prefrontal cortex and hippocampus. The reduced glutamatergic neurotransmission activity caused by DEHP ingestion was demonstrated using an electrophysiological method. This study revealed that long-term exposure to DEHP is hazardous and can cause neurobehavioral disorders, even at daily exposure levels.

24,25-Dihydroxy Vitamin D and Vitamin D Metabolite Ratio as Biomarkers of Vitamin D in Chronic Kidney Disease.

The appropriate management of vitamin D deficiency and hyperparathyroidism is essential to prevent metabolic bone disorder (MBD) and cardiovascular diseases in chronic kidney disease (CKD). Recently, the 24,25-dihydroxyvitamin D [24,25(OH)2D] and vitamin D metabolite ratio (VMR), i.e., the ratio of 24,25(OH)2D to 25-hydroxyvitamin D [25(OH)D], have emerged as biomarkers of vitamin D level. We analyzed the usefulness of vitamin D biomarkers for the evaluation of MBD in patients with CKD. We analyzed blood and urine samples from 208 outpatients with CKD stage G2-G5. 25(OH)D showed a poor correlation with the estimated glomerular filtration rate (eGFR). Conversely, the 24,25(OH)2D level and VMR were significantly correlated with eGFR and the intact parathyroid hormone level. In conclusion, 24,25(OH)2D and VMR have the potential to be vitamin D biomarkers for the detection of MBD in CKD patients.

Efficacy and Safety of Low Fluence Nd:YAG Laser Treatment in Melasma: A Meta-Analysis and Systematic Review.

BACKGROUND: Low-fluence, multisession therapy of Nd:YAG laser has been widely used for treating melasma. OBJECTIVE: To evaluate the efficacy and safety of low-fluence Nd:YAG laser toning for melasma using a systematic review and meta-analysis. METHODS: The PubMed, Web of Science, Embase, and Cochrane Library databases were searched till December 2020. A total of 50 studies (1,772 patients) and 66 studies were selected for the evaluation of the efficacy and complications, retrospectively. RESULTS: The mean Melasma Area and Severity Index/modified Melasma Area and Severity Index scores for laser toning as monotherapy at <4, 4 to <8, 8 to <12, 12 to <24, and ≥24 weeks after treatment compared with that at pretreatment were -0.51, -0.91, -0.97, -0.92, 0.01 SD, whereas those as combination therapy were -1.64, -1.26, -0.94, not available, -1.45 SD, respectively. An increase in light value and a decrease in relative lightness index have remained up to 8 weeks after laser toning. Complications including hypopigmentation/leukoderma, postinflammatory hyperpigmentation, and recurrence were noted. The incidence of hypopigmentation/leukoderma correlated with the number of laser sessions (p = .036). CONCLUSION: Low-fluence Nd:YAG laser toning as combination therapy has shown better efficacy than monotherapy and the efficacy seems to diminish with time. This study suggests the positive correlation of hypopigmentation/leukoderma with the number of laser sessions.