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Low-fluence, multisession therapy of Nd:YAG laser has been widely used for treating melasma.To evaluate the efficacy and safety of low-fluence Nd:YAG laser toning for melasma using a systematic review and meta-analysis.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.The mean Melasma Area and Severity Index/modified Melasma Area and Severity Index scores for laser toning as monotherapy at4, 4 to8, 8 to12, 12 to24, 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).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.

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.

Purpose: This study investigated the efficacy and safety of selective laser trabeculoplasty (SLT) in Korean patients with medically uncontrolled pseudoexfoliation glaucoma (PEXG).Methods: This retrospective observational study enrolled 43 medically uncontrolled PEXG patients who underwent a 360° SLT and were followed up for at least 12 months after SLT. The intraocular pressure (IOP) before and after SLT at 1 week, 1, 3, 6, and 12 months was evaluated. Treatment success was defined as an IOP reduction of ≥20% from the baseline and an IOP equal to lower than 22 mmHg without additional anti-glaucomatous intervention. Additionally, every follow-up medical record was reviewed to assess any possible side effects of SLT.Results: Based on the Kaplan-Meier survival analysis, the treatment success rate at 12 months after SLT was 41.9% (18 eyes). For the success group at the 12 months follow-up, SLT showed a mean IOP reduction of 10.3 ± 5.0 mmHg (from 25.6 ± 4.4 to 15.2 ± 2.9 mmHg; 39.3%, p < 0.05). Among the 25 eyes that were considered as the treatment failure group, 14 eyes underwent glaucoma filtering surgeries, four eyes received additional SLT, and further intervention and follow-up was refused for seven eyes. During the overall follow-up period, there were no significant adverse events.Conclusions: SLT is a partially effective and safe procedure for lowering IOP in Korean patients with medically refractory PEXG. Therefore, it can be considered as one of the alternative treatment modalities in patients who are at high risk for conventional filtering surgery.

Various topical agents have been used to treat melasma; however, a large-scale evaluation among the currently available treatment is lacking.The aim of this study was to evaluate the efficacy and safety of topical agents for melasma.The MEDLINE, Embase, Web of Science, Cochrane, and Alt-Healthwatch databases were searched in November 2021. Original studies that reported pre- and post-treatment Melasma Area Severity Index (MASI)/modified Melasma Area Severity Index (mMASI) scores and/or adverse effects (AEs) were eligible for inclusion. The main outcome was the efficacy analyzed by the changes in the pre- and post-treatment with standardized mean difference (SMD) of MASI/mMASI scores; the AEs were calculated with incidence proportion by the reported percentage of skin irritations.A total of 45 studies (2359 patients) and 55 studies (4539 patients) met the inclusion criteria for efficacy and AEs, respectively. Hydroquinone (HQ) monotherapy (SMD -1.3, 95% CI [-1.6 to -1.0]), HQ-containing combination therapy (-1.4, [-1.7 to -1.1]), cysteamine (-1.6, [-2.0 to -1.2]), tranexamic acid (-1.5, [-2.0 to -1.1]), azelaic acid (-1.3, [-1.7 to -1.0]), and kojic acid (-0.9, [-1.3 to -0.5]) demonstrated comparable efficacy, while zinc sulfate did not exhibit statistically significant improvement (-1.2, [-2.7 to 0.4]). HQ-containing combination therapy (50.9%) and cysteamine (42.2%) demonstrated the highest incidence of irritation, while azelaic acid (18.7%), kojic acid (5.3%), and tranexamic acid (0.8%) revealed a lower risk.In this meta-analysis, non-HQ agents except zinc sulfate may be considered as an alternative to HQ-containing agents. However, treatment should be guided by patient's tolerance, availability, and physicians' experience.

The human microbiome is a rich environment consisting of bacteria, fungi and other commensal microorganisms of the gut, mucosa and skin. The functional role of the gut microbiome includes facilitation in metabolism of macronutrients, maturation of the immune system, and production of pro- or anti-inflammatory signaling molecules and peptides. The identification of these resident organisms has brought about a new understanding of disease processes. Nevertheless, more questions remain regarding the interactions within the microbiome, its interactions with the host, and its contributions to the pathophysiology of disease. The purpose of this review is to examine the existing medical literature to highlight the role of the gut microbiome in human health, also paying attention to its role in several inflammatory skin diseases, namely atopic dermatitis, psoriasis, and rosacea. (Ann Dermatol 32(4) 265∼272, 2020)

Lasers and energy-based devices (EBD) are popular treatments for skin rejuvenation and resurfacing. Achieving desired outcomes and avoiding complications require understanding the effects of these devices at a histologic level. Currently, no comprehensive review summarizing the histologic effects of laser and energy-based treatments exists.To describe how lasers and EBD alter skin histology and improve the overall understanding of these devices.A PubMed search was conducted for studies with histologic analysis of fractional picosecond laser, fractional radiofrequency microneedling, nonablative lasers, and ablative lasers.Fractional picosecond lasers induce intraepidermal and/or dermal vacuoles from laser-induced optical breakdown. Fractional radiofrequency microneedling delivers thermal energy to the dermis while sparing the epidermis, making it safer for patients with darker skin phototypes. Fractional nonablative lasers induce conical zones of coagulation of the epidermis and upper dermis. Ablative lasers vaporize the stratum corneum down to the dermis. Traditional ablative lasers cause diffuse vaporization while fractional ablative lasers generate columns of tissue ablation.Lasers and EBD are effective for skin resurfacing and rejuvenation and have different mechanisms with disparate targets in the skin. Safe and effective use of devices requires understanding the histologic laser-tissue interaction.

Hovenia dulcis, known as the oriental raisin tree, is used for food supplements and traditional medicine for the liver after alcohol-related symptoms. However, little information exists about the use of its leaves and branches. In this study, we established a method to use the leaves and branches to develop anti-hangover treatment and elucidated the underlying mechanisms. Oxidation-treated leaves (OL) exhibited high antioxidant content comparable to that of the peduncles and showed an anti-hangover effect in male mice. The branch extract (BE) was enriched in the flavonoid catechin, approximately five times more than OL extract. The mixture of OL and BE (OLB) was formulated in a 2:1 ratio with frozen-dried extract weight and was tested for anti-hangover effects and protective properties against binge alcohol-induced liver injury. OLB showed better anti-hangover effect than OL. In addition to this anti-hangover effect, OLB protected the liver from oxidative/nitrosative damage induced by binge alcohol intake.

Fragile X syndrome (FXS) is the most common heritable form of neurodevelopmental disorder, which is caused by the loss of fragile X mental retardation protein (FMRP) expression. Despite the unceasing efforts to develop therapeutic agents against FXS based on the pathophysiological changes observed in animal models of FXS and human patients, therapeutic candidates including mGluR signaling modulators have failed to provide sufficient effects. Based on the recent successful demonstration of an endogenous polyamine, agmatine, to improve the autism-like symptoms in the valproic acid animal model of autism, we investigated the effects of agmatine against FXS symptoms using Fmr1 knockout (KO) mice.We used male Fmr1 KO mice for behavioral tests such as marble burying, open-field test, memory tasks, social interaction tests and startle response to confirm the symptoms of FXS. We also checked the electrophysiological profile of neural activity in agmatine-treated Fmr1 KO mice.Agmatine reversed the compulsion, learning and memory deficits, hyperactivity, aberrant social interaction, and communication deficit in Fmr1 KO mice while it normalized the aberrant LTP and LTD in the hippocampus.The results highlight the potential of agmatine's novel disease-ameliorating effects in FXS, which warrants further studies to ascertain whether these findings translate into clinical effects in FXS patients.

Background Vitamin D status is associated with muscle strength and maintenance of muscle fibers. However, which serum vitamin D biomarker better reflects sarcopenia remains unclear. The aim of this study was to investigate associations between various serum vitamin D biomarkers (total 25‐hydroxy vitamin D [25(OH)D], bioavailable 25(OH)D, 24,25‐dihydroxyvitamin D [24,25(OH)2D], and vitamin D metabolite ratio [VMR]) and sarcopenia. Methods The data for 83 hip fracture patients were finally included in the analysis. Sarcopenia was defined according to the Asia Working Group for Sarcopenia (AWGS) criteria. Measurements of 24,25(OH)2D and 25(OH)D were made using solid‐phase extraction (SPE) and subsequent liquid chromatography‐tandem mass spectrometry (LC‐MS/MS). Vitamin D binding protein (VDBP) concentration was measured using an enzyme‐linked immunosorbent assay. The VMR was calculated by dividing serum 24,25(OH)2D by serum 25(OH)D and then multiplying by 100. Based on total 25(OH)D, VDBP, and albumin concentrations, bioavailable 25(OH)D concentrations were calculated using the equations from the other previous studies. Results Bioavailable 25(OH)D levels were significantly (p = 0.030) decreased in the sarcopenia group compared with the non‐sarcopenia group. Results of ROC analysis for the diagnosis of sarcopenia using serum level of bioavailable of 25(OH)D revealed that the cutoff point for bioavailable 25(OH)D was 1.70 ng/ml (AUC = 0.649, p, We demonstrated that bioavailable 25(OH)D was associated with sarcopenia among the various serum vitamin D biomarkers. Bioavailable vitamin D might be helpful for assessing the risk of sarcopenia.

Over the past decades, the production and use of hazardous chemicals has increased worldwide, and the incidence of neurological diseases is increasing proportionately. Among these chemicals, Bis(2-ethylhexyl) phthalate (DEHP) is the most common member of the phthalate family used as a plasticizer. The present study assessed the consequences of daily DEHP ingestion and its effects on brain functions related to depressive-like behaviors. Adolescent C57BL/6 male mice ingested different concentrations of DEHP in their diet (2, 20, and 200 mg/kg of diet), and behavioral changes in anxiety, despair, anhedonia, and sociality were investigated. DEHP exposure evoked depressive-like behaviors in a dose-dependent manner for each symptom. The levels of corticosterone and reactive oxygen species/reactive nitrogen species increased in DEHP-exposed groups, suggesting chronic stress-like responses. In the medial prefrontal cortex (mPFC), glutamate and glutamine were decreased, and glutamine synthetase showed lower activity compared to the control group, suggesting imbalanced glutamatergic signaling. Measuring the spontaneous excitatory postsynaptic current of glutamatergic neurons, we found that DEHP ingestion resulted in hypoactive glutamatergic signaling in the mPFC.

Background For ethnic skin, laser surgery for pigmented lesions presents a special challenge due to the increased risk of postprocedural complications-erythema, blistering, and postinflammatory dyspigmentation. Aims To describe the treatment of ephelides in Asian skin treated with a picosecond 785-nm laser. Patients/methods The first patient with ephelides on the cheeks and nose was treated with a picosecond 785-nm laser with the treatment parameter of 1.2 J/cm2 and 3-mm spot size. The second patient with ephelides on the cheeks was treated with a picosecond 785-nm laser with the treatment parameter of 1.3 J/cm2 and 3-mm spot size. Results After a single laser session, both patients achieved appreciable improvement without any complications. Conclusion This is the first case series demonstrating the efficacy and safety of the picosecond 785-nm laser for the treatment of ephelides in Asian skin.

Keloids are benign fibroproliferative growths that occur from an abnormal response to skin injury and can be disfiguring, functionally impairing, and have dramatic impacts on quality of life. Furthermore, treatment is notoriously challenging, and the rate of recurrence is high. Various treatment modalities have been proposed for keloids including occlusive dressings, compression therapy, silicone sheeting, intralesional corticosteroid injections, cryotherapy, surgical removal, pulsed dye laser, radiation, imiquimod cream, intralesional verapamil, 5-fluorouracil, bleomycin, and interferon-α2b injections.1, 2 Laser-assisted drug delivery is an evolving new treatment modality with many possible applications, including keloids and hypertrophic scars. Here we present a case of refractory keloids treated with laser-assisted drug delivery using fractional ablative laser followed by a combined treatment of topical application and intralesional injection of steroid suspension.

Background CD90 fibroblasts have been described arising from and replacing the homeostatic CD34 network in scleroderma, but have not been specifically examined in other forms of cutaneous fibrosis. Objectives To address expression, timelines, and spatial relationships of CD90, CD34, and smooth muscle actin (SMA) expressing fibroblasts in scars and to examine for the presence of a CD34-to-CD90 transition. Methods One hundred and seventeen scars (reparative/hypertrophic/keloidal) were evaluated for CD90, CD34, and SMA expression. Double-staining immunohistochemistry for CD90/CD34 was performed to identify CD90/CD34 transitioning cells, confirmed by double-color immunofluorescence. In addition, some scars were double-stained with CD90/SMA, CD90/procollagen-1, or SMA/procollagen-1 to evaluate spatial relationships and active collagen synthesis. Expression was graded as diffuse, minority, and negative. Results Most scars demonstrate a CD90/CD34 pattern, and dual CD90/CD34 fibroblasts were observed in 91% of scars. In reparative scars, CD90 expression reverses to a CD34/CD90 state with maturation. Pathologic scars exhibit prolonged CD90 expression. Both CD90 and SMA fibroblasts collagenize scars, although CD90 fibroblasts are more prevalent. Conclusions CD90 fibroblasts likely arise from the resting CD34 fibroblastic network. Actively collagenizing scar fibroblasts exhibit a CD90/CD34 phenotype, which is prolonged in pathologic scars. CD90 fibroblasts are likely important players in cutaneous scarring.

Emerging evidence has shown the low levels of glutamate (Glu) and glutamine (Gln) and the hypoactivity in the cortex of patients with depression. The hypoactivity is closely related with low frequency of glutamatergic signaling that is affected by the levels of Glu and Gln. Thus, we hypothesized that there might be a causality among low levels of Glu and Gln, hypoactive glutamatergic neurotransmissions, and depressive behaviors. Here, we found low Glu and Gln levels and low frequency of spontaneous excitatory postsynaptic current (sEPSC) of glutamatergic neurons in the medial prefrontal cortex (mPFC) of chronic immobilization stress (CIS)-induced depressed mice. The depressed mice also showed hypoactive Gln synthetase (GS). Inhibition of GS by methionine sulfoximine (MSO) decreased Glu and Gln levels and increased depressive behaviors with low frequency of sEPSC in the mPFC, indicating that Glu and Gln decrements cause hypoactive glutamatergic neurotransmissions and depressive behaviors. Both Glu and Gln could increase sEPSC of glutamatergic neurons in the mPFC on slice patch, but only Gln overcame MSO to increase sEPSC, suggesting that exogenous Gln would recover CIS-induced low frequency of sEPSC caused by hypoactive GS and act as an antidepressant. Expectedly, Gln supplementation showed antidepressant effects against CIS; it increased glutamatergic neurotransmissions with Glu and Gln increment in the mPFC and attenuated depressive behaviors. Moreover, selective glutamatergic activation in the mPFC by optogenetics decreased depressive behavior. In conclusion, depressive behaviors evoked by chronic stress were due to hypoactive glutamatergic neurons in the mPFC caused by low levels of Glu and Gln, and exogenous Gln can be used as an alternative antidepressant to increase glutamatergic neurotransmission.

DHP107 is a novel lipid-based oral paclitaxel formulation for the treatment of various cancers. In the present study, to increase the treatment effect of DHP107, we aimed to improve this formulation. We optimized the paclitaxel content in DHP107 formulation, evaluated its antitumor activity, and compared its activity with that of the intravenous paclitaxel formulation, Taxol®, in various mouse cancer models. The oral bioavailability of paclitaxel increased dose-dependently up to 50 mg/kg. However, the paclitaxel absorption from the DHP107 formulations containing ≥1.5% (w/v) paclitaxel decreased with the increase in DHP107 dose as paclitaxel was crystallized when exposed to water. Therefore, the optimized DHP107 formulation containing 1% (w/v) paclitaxel was selected, and it exhibited similar antitumor activity as Taxol®. However, the DHP107 showed a better survival rate with low toxicity than that of Taxol®. The concentration of paclitaxel in the tumor tissues of mice in the DHP107 was also higher than that in Taxol®. The optimized DHP107 formulation might reduce the possible toxic effects of the formulation, with antitumor activities similar to those of intravenous paclitaxel Taxol®, by enhancing the distribution to tumor tissues. Furthermore, it might be beneficial to use DHP107 for patients with hypersensitivity reactions to intravenous Taxol®.

Ketone bodies can be increased in the blood under certain physiological conditions, but their role under such conditions remains to be clarified. In the present study, we found the increment and usage of β-hydroxybutyrate (BHB) in the prefrontal cortex (PFC) during acute stress. BHB levels increased in the blood and PFC after 30-min acute immobilization stress, and BHB dehydrogenase 1 increased in the PFC simultaneously, but not in the hippocampus. Moreover, increased levels of acetyl-CoA, pyruvate carboxylase, and glutamate dehydrogenase 1 were found in the PFC, implicating the metabolism of increased BHB in the brain. Thus, we checked the levels of glutamate, glutamine, and GABA and found increased levels of glutamate and glutamine in the stressed group compared with that in the control group in the PFC. Exogenous administration of BHB enhanced struggling behaviors under stressful conditions. Our results suggest that the metabolism of BHB from peripheral blood in the PFC may contribute to acute stress responses to escape stressful conditions.

Background and objectives The aim of this study is to histologically characterize the wound healing process of in vivo human skin treated with 1064- and 532-nm microlens array (MLA)-type picosecond lasers. Study design/materials and methods Three patients (Fitzpatrick skin types II-IV), who were undergoing future cosmetic abdominoplasties, were treated with 1064- and 532-nm MLA-type lasers under different fluence settings. Treatments were performed 2 weeks, 1 week, and immediately prior to surgery. Skin samples were harvested from the resected tissue with 8 mm punch biopsies immediately after the abdominoplasties were performed. Results The study demonstrates that intraepidermal vacuoles, created from tissue damage induced by the laser, are histologically resolved within 1 week without persistent damage to the dermoepidermal junction or vasculature. After 2 weeks, all foci of microscopic epidermal necrotic debris had either resolved or migrated to more superficial levels in the stratum corneum. There was no evidence of persistent vascular damage, increased melanophages, or accumulation of melanin in the dermis at 2 weeks. Furthermore, the 1064-nm picosecond laser with the high fluence setting demonstrated the capacity to fractionally ablate the epidermis and induce multifocal fibrosis in the papillary dermis in lighter skin types. Conclusion This is the first study to demonstrate the wound healing profile of in vivo human skin after treatment with the picosecond 1064- and 532-nm MLA-type lasers. It shows that laser-induced tissue damage is histologically resolved within 2 weeks, clinically reflecting a favorable safety profile and short downtime. The study also shows that the picosecond laser can be used to induce either fractional ablative or non-ablative effects, depending on the fluence settings used. Lasers Surg. Med. © 2021 Wiley Periodicals LLC.

Importance Despite several recent reports on the elevated risk of bullous pemphigoid in patients with type 2 diabetes treated with dipeptidyl peptidase–4 (DPP-4) inhibitors, evidence on the absolute risk and comparative safety against other antidiabetics is limited. Objective To characterize the incidence rate of bullous pemphigoid associated with DPP-4 inhibitor use compared with second-generation sulfonylureas. Design, Setting, and Participants This cohort study used data from 2 large commercial insurance claims databases (Optum Clinformatics Data Mart from October 17, 2006, to December 31, 2018, and IBM MarketScan Research Database from October 17, 2006, to December 31, 2017) and Medicare data from January 1, 2006, to December 31, 2016. Patients with type 2 diabetes who initiated treatment with DPP-4 inhibitors or second-generation sulfonylurea were included. Main Outcomes and Measures The primary outcome of the study was bullous pemphigoid, identified using diagnosis codes. After 1:1 propensity score matching, the incidence rates of bullous pemphigoid and the hazard ratios (HRs) with 95% CIs comparing patients who initiated DPP-4 inhibitor and second-generation sulfonylurea therapy were estimated. Subgroup analyses by age, sex, race, and individual DPP-4 agents were performed. The results from each database were pooled using inverse-variance fixed-effects meta-analysis. Results A total of 1 664 880 patients who initiated DPP-4 inhibitors (51.0% female; mean [SD] age, 63.9 [9.7] years) and sulfonylurea (50.4% female; mean [SD] age, 63.9 [9.9] years) were included. The incidence rate of bullous pemphigoid per 1000 person-years was 0.42 in the DPP-4 inhibitor group vs 0.31 in the sulfonylurea group (HR, 1.42; 95% CI, 1.17-1.72). Higher rates per 1000 person-years for DPP-4 inhibitor vs sulfonylurea groups were seen in those who were 65 years or older (0.79 vs 0.49; HR, 1.62; 95% CI, 1.32-1.99), white (0.93 vs 0.54; HR, 1.70; 95% CI, 1.30-2.24), and treated with linagliptin (1.20 vs 0.55; HR, 1.68; 95% CI, 1.16-2.43). Conclusions and Relevance This study found that patients who initiated DPP-4 inhibitor therapy had higher risk of bullous pemphigoid than those who initiated second-generation sulfonylurea therapy. Clinicians should be aware of this rare adverse effect of DPP-4 inhibitors in subgroups of patients who are older, white, and linagliptin users.

Herbal drugs are widely used for the auxiliary treatment of diseases. The pharmacokinetics of a drug may be altered when it is coadministered with herbal drugs that can affect drug absorption. The effects of herbal drugs on absorption must be evaluated. In this study, we investigated the effects of Rumex acetosa (R. acetosa) extract on fexofenadine absorption. Fexofenadine was selected as a model drug that is a substrate of P-glycoprotein (P-gp) and organic anion transporting polypeptide 1A2 (OATP1A2). Emodine&mdash, the major component of R. acetosa extract&mdash, showed P-gp inhibition in vitro and in vivo. Uptake of fexofenadine via OATP1A2 was inhibited by R. acetosa extract in OATP1A2 transfected cells. A pharmacokinetic study showed that the area under the plasma concentration&ndash, time curve (AUC) of fexofenadine was smaller in the R. acetosa extract coadministered group than in the control group. R. acetosa extract also decreased aqueous solubility of fexofenadine HCl. The results of this study suggest that R. acetosa extract could inhibit the absorption of certain drugs via intervention in the aqueous solubility and the drug transporters. Therefore, R. acetosa extract may cause drug interactions when coadministered with substrates of drug transporters and poorly water-soluble drugs, although further clinical studies are needed.

Herbal drugs are widely used for the auxiliary treatment of diseases. The pharmacokinetics of a drug may be altered when it is coadministered with herbal drugs that can affect drug absorption. The effects of herbal drugs on absorption must be evaluated. In this study, we investigated the effects of Rumex acetosa (R. acetosa) extract on fexofenadine absorption. Fexofenadine was selected as a model drug that is a substrate of P-glycoprotein (P-gp) and organic anion transporting polypeptide 1A2 (OATP1A2). Emodine—the major component of R. acetosa extract—showed P-gp inhibition in vitro and in vivo. Uptake of fexofenadine via OATP1A2 was inhibited by R. acetosa extract in OATP1A2 transfected cells. A pharmacokinetic study showed that the area under the plasma concentration–time curve (AUC) of fexofenadine was smaller in the R. acetosa extract coadministered group than in the control group. R. acetosa extract also decreased aqueous solubility of fexofenadine HCl. The results of this study suggest that R. acetosa extract could inhibit the absorption of certain drugs via intervention in the aqueous solubility and the drug transporters. Therefore, R. acetosa extract may cause drug interactions when coadministered with substrates of drug transporters and poorly water-soluble drugs, although further clinical studies are needed.

Background: Chemical reconstruction of skin scars (CROSS) applies a high strength acid focally to treat atrophic scars. Although this method has gained popularity over the past two decades, no standardized treatment guideline exists for CROSS method in the treatment of atrophic scars. Aims: The purpose of this comprehensive review is to evaluate the indications, detailed techniques, efficacy and safety of CROSS method. Materials and methods: An extensive literature review was conducted to identify articles relating to CROSS method for atrophic scars from 2002 to 2018. Results: The literature search yielded 19 articles meeting criteria. CROSS method has been used for the treatment of acne scars, varicella scars, enlarged pores and depressed surgical scars. In studies using the quantile grading scale for acne scars, 60-100% of patients showed >25% improvement. In two studies for varicella scars, 83-100% of patients showed >25% improvement. CROSS method seems to be effective specifically for ice-pick scars. It is well tolerated and safe in Fitzpatrick skin phototypes I-V. Most reported complications are temporary and include post-inflammatory dyspigmentation, erythema, pain, pruritus, infection and widening of scars. Conclusion: This literature review suggests that CROSS method is a safe and effective treatment for atrophic scars, especially ice-pick scars, in skin types I-V. However, current published works have several limitations, including small sample sizes, lack of control group, different concentrations of acid, different frequency of treatments and follow-up periods. Larger, randomized, controlled studies are needed to elucidate the optimal treatment protocol of CROSS method.