A Case of Transient Hyperlactatemia Induced by Intravenous Glycerol Administration in a Patient With Brain Trauma.

Elevated lactate levels are associated with a poor prognosis in patients with sepsis and shock. Intravenous glycerol administration is often used in Japan to treat patients with acute stroke or brain trauma, but such treatment can cause elevated lactate levels. We experienced a case of transient hyperlactatemia induced by intravenous glycerol administration in a patient with brain trauma. A 74-year-old woman underwent decompressive craniotomy because of loss of consciousness and brain edema. Glycerol was administered after the operation for management of the brain edema. Although the patient's hemodynamics remained stable, her lactate level decreased and increased repeatedly. We recognized that the elevation in her lactate level was associated with the administration of intravenous glycerol. This case suggests that intravenous glycerol administration can induce transient hyperlactatemia.

Quantitative Investigation on Exposure to Potentially Harmful Excipients by Injection Drug Administration in Children Under 2 Years of Age and Analysis of Association with Adverse Events: A Single-Center, Retrospective Observational Study.

INTRODUCTION: Potentially harmful excipients (PHEs) for children have been reported and the need for information collection has been advocated. However, studies on the actual occurrence of adverse events are limited. This study investigated the quantitative exposure of PHEs via injection and their association with adverse events in children under 2 years of age. MATERIALS AND METHODS: As a single-center observational study, children aged 0-23 months received injectable drugs from April 1, 2018, to March 31, 2023 were included. Information on PHE exposure and adverse events after administration were extracted from medical records. Sodium benzoate, benzyl alcohol, ethanol, glycerol, lactose, polyethylene glycol paraben, polysorbate, propylene glycol, sorbitol, sucrose, sulfite, and thimerosal were selected as PHEs. RESULTS AND DISCUSSION: 6265 cases, 333,694 prescriptions, and 368 drugs (264 ingredients) were analyzed. The median age was 0.63 years (interquartile range [IQR] 0.1-1.1). 72,133 prescriptions, 132 drugs and 99 ingredients contained PHE; 2,961 cases exposed to PHE and 1825 cases exceeding permitted daily exposure. The drug with the highest number of exposure cases was hydroxyzine, and the highest number of prescriptions was heparin (both drugs contain benzyl alcohol). In association between adverse events and PHE exposure, higher doses in cases of adverse event occurrence were found in benzyl alcohol, glycerol, polyethylene glycol, and polysorbate exposed cases. Among thimerosal-exposed cases, "developmental delay" was more frequent in exposed cases, but the causal relationship was unknown. Further investigation is needed to clarify the relationship between adverse events and PHE exposure. Additionally, more precise information on PDE for pediatrics including neonates is necessary.

Rhabdomyolysis aggravates renal iron accumulation and acute kidney injury in a humanized mouse model of sickle cell disease.

Individuals with sickle cell disease (SCD) are at greater risk of rhabdomyolysis, a potentially life-threatening condition resulting from the breakdown of skeletal muscle fibers. Acute kidney injury (AKI) is one of the most severe complications of rhabdomyolysis. Chronic kidney and cardiovascular disease, which account for SCD mortality, are long-term consequences of AKI. Although SCD elevates the risks of rhabdomyolysis-induced sudden death, the mechanisms that underlie rhabdomyolysis-induced AKI in SCD are unclear. In the present study, we show that, unlike their control non-sickling (AA) counterparts, transgenic homozygous SCD (SS; Townes model) mice exhibited 100% mortality 8-24 h after intramuscular glycerol injection. Five hours after glycerol injection, SS mice showed a more significant increase in myoglobinuria and plasma creatine kinase levels than AA mice. Basal plasma heme and kidney tissue iron levels were significantly higher in SS than in AA mice. In contrast to AA, glycerol-induced rhabdomyolysis aggravated these parameters in SS mice. Rhabdomyolysis also amplified oxidative stress in SS compared to AA mice. Glycerol-treated SS mice exhibited worse renal function, exemplified by a reduction in GFR with a corresponding increase in plasma and urinary biomarkers of early AKI and renal tubular damage. The free radical scavenger and Fenton chemistry inhibitor, TEMPOL, ameliorated rhabdomyolysis-induced AKI in the SS mice. These findings demonstrate that oxidative stress driven by renal iron accumulation amplifies rhabdomyolysis-induced AKI in SCD mice.

Protective effect of citronellol in rhabdomyolysis-induced acute kidney injury in mice.

Acute kidney injury (AKI) is a serious pathophysiological event consequent to rhabdomyolysis. Inflammatory mechanisms play a role in the development of rhabdomyolysis-induced AKI. Citronellol (CT) is a naturally occurring monoterpene in essential oils of aromatic plant species. In this study, we explored the protective effects of citronellol on AKI resulting from glycerol-induced rhabdomyolysis. Rhabdomyolysis was induced by a single intramuscular injection of glycerol 50% (10mg/kg) in the thigh caudal muscle. Four groups of mice were assigned, including a control group, a group administered with glycerol to induce AKI as a model, a group treated with glycerol plus 50mg/kg CT, and a group treated with glycerol plus 100mg/kg CT. The renal function of mice from all groups was evaluated using kidney histopathological changes and kidney injury molecule-1 (KIM-1). Myoglobin levels were measured to detect rhabdomyolysis. Apoptosis was evaluated by renal cleaved caspase-3 and BAX levels. Both doses of citronellol (50mg/kg and 100mg/kg) significantly reduced KIM-1 mRNA expression and myoglobin levels compared to the glycerol group. In addition, citronellol resulted in lower cleaved caspase-3 and BAX in the renal tissue, indicating that citronellol exerted an anti-apoptotic effect in AKI. Citronellol showed a reno-protective effect against rhabdomyolysis-induced AKI, which may be attributed to its anti-apoptotic effects.

Emu Oil and zinc monoglycerolate independently reduce disease severity in a rat model of ulcerative colitis.

Ulcerative colitis is characterized by colonic inflammation. Previously, Emu Oil protected the intestine against experimentally-induced inflammatory intestinal disorders. Zinc monoglycerolate (ZMG) polymer, formed by heating zinc oxide with glycerol, demonstrated anti-inflammatory and wound healing properties. We aimed to determine whether ZMG, alone or in combination with Emu Oil, could reduce acute colitis severity in rats. Male Sprague Dawley rats (n = 8/group) were orally-administered either vehicle, ZMG, Emu Oil (EO) or ZMG combined with EO (ZMG/EO) daily. Rats were provided ad libitum access to drinking water (Groups 1-4) or dextran sulphate sodium (DSS; 2%w/v; Groups 5-8) throughout the trial (days 0-5) before euthanasia on day 6. Disease activity index, crypt depth, degranulated mast cells (DMCs) and myeloperoxidase (MPO) activity were assessed. p < 0.05 was considered significant. DSS increased disease severity (days 3-6) compared to normal controls (p < 0.05). Importantly, in DSS-administered rats, ZMG/EO (day 3) and ZMG (day 6) reduced disease activity index compared to controls (p < 0.05). Following DSS consumption, distal colonic crypts lengthened (p < 0.01), occurring to a greater extent with EO compared to ZMG and ZMG/EO (p < 0.001). DSS increased colonic DMC numbers compared to normal controls (p < 0.001); an effect decreased only by EO (p < 0.05). Colonic MPO activity increased following DSS consumption (p < 0.05); notably, ZMG, EO and ZMG/EO treatments decreased MPO activity compared to DSS controls (p < 0.001). EO, ZMG and ZMG/EO did not impact any parameter in normal animals. Emu Oil and ZMG independently decreased selected indicators of colitic disease severity in rats; however, the combination did not reveal any additional benefit.

Post-injury Inhibition of Endothelin-1 Dependent Renal Vasoregulation Mitigates Rhabdomyolysis-Induced Acute Kidney Injury.

In patients with rhabdomyolysis, the overwhelming release of myoglobin into the circulation is the primary cause of kidney injury. Myoglobin causes direct kidney injury as well as severe renal vasoconstriction. An increase in renal vascular resistance (RVR) results in renal blood flow (RBF) and glomerular filtration rate (GFR) reduction, tubular injury, and acute kidney injury (AKI). The mechanisms that underlie rhabdomyolysis-induced AKI are not fully understood but may involve the local production of vasoactive mediators in the kidney. Studies have shown that myoglobin stimulates endothelin-1 (ET-1) production in glomerular mesangial cells. Circulating ET-1 is also increased in rats subjected to glycerol-induced rhabdomyolysis. However, the upstream mechanisms of ET-1 production and downstream effectors of ET-1 actions in rhabdomyolysis-induced AKI remain unclear. Vasoactive ET-1 is generated by ET converting enzyme 1 (ECE-1)-induced proteolytic processing of inactive big ET to biologically active peptides. The downstream ion channel effectors of ET-1-induced vasoregulation include the transient receptor potential cation channel, subfamily C member 3 (TRPC3). This study demonstrates that glycerol-induced rhabdomyolysis in Wistar rats promotes ECE-1-dependent ET-1 production, RVR increase, GFR decrease, and AKI. Rhabdomyolysis-induced increases in RVR and AKI in the rats were attenuated by post-injury pharmacological inhibition of ECE-1, ET receptors, and TRPC3 channels. CRISPR/Cas9-mediated knockout of TRPC3 channels attenuated ET-1-induced renal vascular reactivity and rhabdomyolysis-induced AKI. These findings suggest that ECE-1-driven ET-1 production and downstream activation of TRPC3-dependent renal vasoconstriction contribute to rhabdomyolysis-induced AKI. Hence, post-injury inhibition of ET-1-mediated renal vasoregulation may provide therapeutic targets for rhabdomyolysis-induced AKI.

Effect of glycerin on immediate cutaneous reactions of histamine (positive) and phosphate-buffered saline (negative) controls in intradermal skin testing of healthy dogs: A randomised, blinded study.

BACKGROUND: Glycerinated allergen extracts contain 50% glycerin, an excellent preservative. While glycerin is a recognised irritant in humans, the utility of glycerinated extracts for intradermal testing has not been validated in dogs. HYPOTHESIS/OBJECTIVE: To determine and compare the effects of glycerin on immediate cutaneous reactions to intradermal injections of histamine and saline in healthy dogs. ANIMALS: Eight healthy laboratory beagles. MATERIALS AND METHODS: The study was designed as a randomised, blinded study. Intradermal injections of histamine (positive control) and saline (negative control) in aqueous and glycerinated (50%) forms were performed on the right thorax. Global wheal scores (GWS) at 20 min were evaluated by two independent investigators blinded to the interventions. RESULTS: There were no wheal and flare reactions observed after the intradermal injections of phenolated saline. By contrast, 50% glycerosaline injections induced erythema and induration in all dogs. Global wheal scores were significantly higher in aqueous histamine (Friedman test, p < 0.0001) and 50% glycerinated histamine (Friedman test, p = 0.0084) compared to phenolated saline controls. Interestingly, only aqueous histamine (Friedman test, p = 0.01) had significantly higher GWS than 50% glycerosaline injections, while no significant difference in GWS between 50% glycerinated histamine and 50% glycerosaline groups was observed (Friedman test, p = 0.59). CONCLUSION AND CLINICAL RELEVANCE: This study demonstrates that intradermal injection of 50% glycerosaline induces erythema and induration skin reactions in healthy dogs that can mimic positive reactions to allergenic extracts. Further dilutions of glycerinated positive and negative control solutions need to be optimised for intradermal testing in dogs.

The main e-cigarette component vegetable glycerin enhances neutrophil migration and fibrosis in endotoxin-induced lung injury via p38 MAPK activation.

We investigated the effects of vegetable glycerin (VG), a main e-cigarette constituent, on endotoxin-induced acute lung injury (ALI). Mice received intratracheal administration of 30% VG in phosphate buffered saline (PBS) vehicle or only PBS (control) for 4 days. On Day 5, mice received an intratracheal instillation of lipopolysaccharide (LPS) (LPS group and VG + LPS group) or PBS (VG group and control group). Lung histopathology, expression of chemokine receptors, and regulatory signaling were analyzed 24 h after the Day 5 treatment. VG significantly increased ALI-associated histopathological and fibrotic changes in both the VG group and LPS-induced ALI mice (VG + LPS group). Immunohistochemistry (IHC) and western blot analyses revealed that VG administration resulted in upregulation of neutrophil markers [lymphocyte antigen 6 complex locus G6D (Ly6G) and myeloperoxidase (MPO)] as well as upregulation of the expression of transforming growth factor-ß (TGF-ß), a central mediator of fibrogenesis, in the lungs of both VG and VG + LPS groups. VG enhanced the expression of adhesion molecules [very late antigen 4 (VLA-4) and vascular cell adhesion molecule 1 (VCAM-1)] and increased activation of p38 mitogen-activated protein kinase (p38 MAPK) to prompt neutrophil recruitment in the lungs of mice with ALI. Intraperitoneal administration of a p38 inhibitor attenuated these histopathological changes significantly as well as VG-induced upregulation in expression of Ly6G, MPO, VLA-4, VCAM-1, TGF-ß, and collagen-1 in mice with ALI. In conclusion, VG enhances neutrophil chemotaxis and fibrosis and it amplifies the inflammatory response associated with LPS-induced ALI in the lungs via enhancement of p38 MAPK activity.

EGFR mediated the renal cell apoptosis in rhabdomyolysis-induced model via upregulation of autophagy.

AIMS: Rhabdomyolysis is a life-threatening condition. One of the most common complications of rhabdomyolysis is acute kidney injury (AKI), and 10 % of all AKI patients present with rhabdomyolysis. EGFR is associated with different types of AKI. However, the function and regulatory mechanism of EGFR in rhabdomyolysis-induced AKI model remain unknown. Here, we performed the experiments to explore the role of EGFR in this model. MAIN METHODS: We used proximal tubule-specific Atg7 knockout mice and Wa-2 mice to establish animal models. Then, the samples were collected for pathology assay and IB detection. In vitro, the BUMPT cells treated with myoglobin were collected for the detection of apoptosis and autophagy. IB detection were processed for the analysis of protein expressions, FCM analysis for the cell apoptosis, GFP-LC3 transfection and immunofluorescent for autophagy. KEY FINDINGS: EGFR promotes autophagy to mediate rhabdomyolysis-induced AKI via STAT3/Atg7 axis, and gefitinib is a potential therapeutic option for AKI. Here, we demonstrated that EGFR was activated by myoglobin and glycerol both in vitro and in vivo, respectively. Genetic or pharmacological inhibition of EGFR ameliorated myoglobin and glycerol-induced renal cell apoptosis. Mechanistically, EGFR mediated autophagy induction via STAT3/Atg7 axis, thereby resulting in kidney cell apoptosis. Furthermore, Wa-2 mice or gefitinib treatment prevented the progression of rhabdomyolysis-induced AKI as well as renal cell apoptosis and autophagy via inhibiting STAT3/Atg7 axis. SIGNIFICANCE: Researchers can use this finding to better study the function and regulatory mechanism of EGFR in RM-induced AKI model. And gefitinib represents a potential target for treatment of AKI.

Rhabdomyolysis-induced acute kidney injury and concomitant apoptosis induction via ROS-mediated ER stress is efficaciously counteracted by epigallocatechin gallate.

Rhabdomyolysis induced acute kidney injury (RIAKI) is a life-threatening condition responsible for approximately 19-58% of AKI cases worldwide. We performed an intramuscular injection of glycerol (10 mL/kg) in male wistar rats to induce AKI. Epigallocatechin gallate (EGCG) was administered for 3 consecutive days to evaluate its protective effects. We observed significant downregulation in serum creatinine, blood urea nitrogen (BUN) and LDH at different time points on EGCG treatment groups in a dose-dependent manner. Similarly, H&E staining also revealed that EGCG was able to reduce the formation of damaged tubules and tubular necrosis which was prominently spread throughout the kidney tissue of glycerol treatment group. Concomitantly, we observed upregulated inflammation, ER stress and elevated oxidative stress in the glycerol treated group only, which was significantly normalized upon EGCG treatment in both in vitro and in vivo studies. The occurrence of apoptosis in kidney tubules was found to be relatively higher in glycerol treated group and H2O2 treated HEK-293 cells. The results obtained after EGCG treatment revealed a significant decrease in apoptotic cell population, which was further validated by immunofluorescence staining against p53 and comet assay in HEK-293 cells and p53 IHC in kidney tissues. Western blotting also revealed a systemic downregulation of intrinsic mitochondrial apoptotic pathway markers such as bax, bcl-2, pro and cleaved caspase 3, caspase 9 and PARP1. Additionally, the results for flow cytometry analysis and TUNEL assay corroborated apoptotic equilibrium. Conclusively, we reckon EGCG as a multi-therapeutic natural product that can be used the for treatment of AKI.

Gallic Acid Improves Therapeutic Effects of Mesenchymal Stem Cells Derived from Adipose Tissue in Acute Renal Injury Following Rhabdomyolysis Induced by Glycerol.

Acute kidney injury (AKI) is identified by a progressive reduction in the glomerular filtration rate (GFR) and retention of nitrogenous waste products. Traumatic and nontraumatic rhabdomyolysis is recently considered the main cause of AKI. According to several studies, stem cell treatment is a promising therapeutic strategy for many types of disorders including AKI. The main limitation of mesenchymal stem cells (MSCs) therapy is reducing cell survival in response to oxidative stress products in injured organ areas. Gallic acid (GA) as a well-known antioxidant has been reported to confer potent-free radical scavenging and anti-inflammatory properties. Therefore, the aim of the current study was to assess the influence of MSCs and GA in acute renal injury following rhabdomyolysis induced by glycerol. A total of 70 healthy rats were divided into seven groups (10 in each group): control, AKI (glycerol, intramuscular), cell therapy (AKI + intravenous injection of mesenchymal stem cells derived from adipose tissue (AMCs), AKI + AMCs + GA (50, 100, and 200 mg/kg, intraperitoneally, 3 days a week for 3 consecutive weeks), and positive control group (the most effective dose of gallic acid). After the treatment, rats were sacrificed; blood, urine, and kidney tissues were collected; and qualitative and quantitative parameters (including blood urea nitrogen (BUN), creatine kinase (CK), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), aspartate transaminase (SGOT), oxidative stress markers kidney function parameters) and histopathological indexes were assayed. Our results revealed that co-treatment of AMCs plus GA into AKI rats decreased BUN and creatinine and ameliorated kidney injury parameters after 3 weeks. Improved oxidative stress markers such as decreased MDA and increased SOD and CAT were significant in the GA + AMCs group compared to the AMCs alone in AKI rats. Also, the histopathological appearances of AKI rats including renal tubule cavity expansion and renal tubular epithelial cell edema, and interstitial inflammation, were alleviated using GA + AMCs treatment compared to the control. The obtained results of the current study documented that antioxidants could make mesenchymal stem cells more resistant to the condition in which they are supposed to be transplanted and probably improve the efficacy of stem cell therapy in AKI patients.

Effect of chitosan and curcumin nanoparticles against skeletal muscle fibrosis at early regenerative stage of glycerol-injured rat muscles.

INTRODUCTION: Chitosan and curcumin are natural products that have a wide range of beneficial effects including wound healing. However, their high molecular weight and poor water solubility limit their applications. AIMS: Therefore, the current study aims to evaluate the effects of chitosan (Cs) and curcumin (Cn) nanoparticles (NPs) on fibrosis and regeneration of glycerol-injured muscle. METHODS: Muscle injury was induced by intramuscular injection of glycerol into the tibialis anterior muscle of rats. Cs-NPs and Cn-NPs were administered at different doses intraperitoneally after injury. Injured muscles were collected at day 7 after injury, and muscle fibrosis and regeneration were assessed. RESULTS: The present results revealed that Cs-NPs and Cn-NPs treatment significantly decreased fibrosis index and increased the average myotube diameter with shifting of the distribution of myotube diameters towards larger diameters in a dose-dependent manner. Immunohistochemical analysis revealed that Cs-NPs and Cn-NPs treatment significantly decreased the number of CD-68+ cells and Col-1+ area. Results showed that Cn-NPs had a higher protective effect, in the form of attenuating muscle fibrosis and inflammation, and enhancing muscle regeneration, than that of Cs-NPs. CONCLUSIONS: To our knowledge, this is the first study to document the effects of Cs-NPs in injured muscles. The results of study might be a novel approach to attenuate muscle fibrosis in humans using curcumin and chitosan nanoparticles.

A Prospective, Randomized, Double-Blind, Vehicle-Controlled Study Evaluating the Efficacy, Safety, and Patient Satisfaction of Tretinoin 0.05% Lotion for Chest Rejuvenation.

BACKGROUND: There is increasing interest in non-invasive options for chest rejuvenation with minimal to no downtime. Topical retinoids have long been used to correct photoaging due to their ability to promote epidermal hyperplasia, matrix metalloproteinase inhibition, collagen synthesis, and dispersion of melanin granules. Topical retinoid use is often limited by the ensuing irritation that occurs with initial use and resolves after about one month. Vehicle of delivery is a key factor to consider in order to minimize irritation and increase patient satisfaction. Micronized tretinoin 0.05% suspended in a polymer emulsion of hydrating ingredients (sodium hyaluronate, soluble collagen, and glycerin) is designed to aid in reducing irritation while ensuring uniform drug delivery. OBJECTIVE: The primary objective of our study is to evaluate the safety, efficacy, and patient satisfaction of tretinoin 0.05% lotion for nonprocedural photorejuvenation of the chest. RESULTS: A total of 29 patients completed the trial, average age of 54.42 years (37-66 years old), Fitzpatrick II-IV skin types. Both the active and vehicle groups showed 30-40% improvement at day 180 according to the blinded evaluator mean percent improvement. Investigator global aesthetic improvement scale also trended towards improvement in both groups, with most patients exhibiting "improvement." Both the active and vehicle groups showed a significant change over time according to the nine-point photodamage and wrinkling scale, P<0.001 and P=0.007 (single factor ANOVA), respectively. The Fabi Bolton Wrinkle Scale also demonstrated improvement from screening to day 180; however, there was no statistical significance at any time point. At day 90, the active group had statistically significantly more erythema than the vehicle group (P<0.001), although both groups were only mild. At day 180, erythema decreased in both groups with the active group being similar to the vehicle group, 0.50±0.73 versus 0.09±0.30, respectively. Subjects in both the active and vehicle groups were equally satisfied at day 180, (2.38±1.15 in the active group versus 2.30±1.16 in the treatment group), with most subjects feeling "satisfied" with their results by day 180. This was also reflected in the subject global aesthetic improvement scale with most subjects noting noticeable improvement in the appearance of their chest from day 30 to day 180. CONCLUSION: Tretinoin 0.05% lotion delivered in a proprietary blend of hydrating ingredients offers a safe and efficacious option that has minimal downtime for patients seeking non-procedural photo-rejuvenation of the chest. The proprietary vehicle, containing hyaluronic acid, glycerin, and collagen, was crucial in minimizing irritation and producing at least a one-point improvement according to the 9 point photodamage scale and 30-40% improvement in photodamage as noted by the blinded evaluator percent improvement score in both the vehicle and active groups. J Drugs Dermatol. 2022;21(6):645-652. doi:10.36849/JDD.6658.

Ozonized glycerin (OG)-based cosmetic products lighten age spots on human facial skin.

BACKGROUND: Few cosmetic ingredients are shown to be able to safely remove or lighten facial dark spots once they have formed. OG has been reported to possess oxidation power and exhibit various biological activities such as antibacterial, antiviral, and wound healing promotion. AIMS: This study aimed to clarify the effects of OG on human skin, especially on age spots on the face. METHODS: OG formulations (80 and 800 ppm) were mixed with synthetic melanin in vitro for 4 weeks and then assessed for its ability to degrade the melanin. OG also investigated its effect on gene expression of keratinocyte differentiation markers in vitro to explore the cell maturation. In clinical study for the evaluation of effects of OG formulations on age spots on facial skin, 48 women were measured for the melanin content of them by a Mexameter at 4 and 8 weeks after daily twice application of OG formulations. Adverse events were monitored during the study. RESULTS: Both OG formulations showed direct melanin degradation in a time-dependent manner, with significant effects observed as early as 6 h. OG formulation at 800 ppm showed higher activity than OG formulation at 80 ppm, and the amount of melanin was decreased by about 40% on Day 14 of the mixing reaction. Differentiation marker studies using human keratinocytes showed that the gene expression of involucrin and serine palmitoyltransferase was upregulated by OG, which was almost equivalent concentration to OG formulation 80 ppm, suggesting that OGs can enhance turnover of the skin epidermis. In clinical study, OG formulations 80 and 800 ppm showed larger decreases in melanin contents at 8 weeks compared with those at 4 weeks and their mean values of △melanin index were -16.7 and -15.2, respectively. Statistically significant differences were detected against respective controls. Number of subjects with a decrease in melanin index from baseline to 4 or 8 weeks increased in both OG formulations 80 and 800 ppm, especially prominent at 8 weeks. There were no adverse events related to treatments of OG 80 and 800 ppm during the study. CONCLUSION: The result indicated that applications of OG formulations are safe and effective in lightening age spots on the facial skin.

Skin biophysical assessments of four types of soaps by forearm in-use test.

BACKGROUND: While soaps are the most commonly used cleansing agents for human skin, they also damage the epidermal barrier and potentially increase the risk of disorders such as contact dermatitis. AIMS: This study set out to compare the potential skin irritancy of four types of soaps and their effects on the skin barrier function and biophysical parameters. METHODS: In a nonblinded comparative study, three types of soaps (alkaline, creamy, and glycerin soaps), and a syndet were applied to four different groups of 15 healthy subjects. Subjects washed their left forearm with the respective soap at home at least four times a day for seven days. Biophysical skin parameters, including transepidermal water loss (TEWL), erythema, friction, and pH, were measured at various time points using the Cutometer® MPA 580. RESULTS: After the first wash, a significant increase in TEWL was observed for all groups compared to the pre-intervention period. For the alkaline soap, a substantial increase in pH was observed at all time points compared to the baseline. Syndet, the only acidic soap in this study, showed a significant decrease in pH at the last time compared to all time points. The mean value of erythema was significantly higher in alkaline soap users than glycerin and creamy soap users. CONCLUSION: Our study showed that alkaline-based soaps could cause erythema and increase TEWL and skin pH due to their strong cleansing action, and the addition of compounds such as glycerin can modify these effects. A newer generation of soap containing a mild surfactant such as syndets causes less skin damage.

Formaldehyde in Electronic Cigarette Liquid (Aerosolized Liquid).

BACKGROUND: Aerosolized liquid (e-liquid) of electronic cigarettes can be toxic. Beyond the solvent (propylene glycol, vegetable glycerin) and nicotine, little is known about the liquid composition. Formaldehyde, a carcinogen and source of contact dermatitis, has been reported in the vaporized e-liquid, but no studies have assessed the actual e-liquid. OBJECTIVE: The aim of the study was to evaluate e-liquid products for the presence of formaldehyde. METHODS: Sixteen e-liquid products were purchased and analyzed for the release of formaldehyde using the chromotropic acid method of detection. RESULTS: Of the 16 e-liquids purchased, 4 (25%) were positive for the presence of formaldehyde; 2 were flavored and 2 were nonflavored. All positive e-liquids were in pods or disposable electronic cigarette devices, and 2 were purchased from local vape shops. The average nicotine content in the positive e-liquids was 3.85% versus 4.03% in the negative e-liquids. CONCLUSIONS: The e-liquid products contain toxic chemicals not declared on product labels, as shown in this study with 25.0% of e-liquids containing formaldehyde. All positive e-liquids were within pods or disposable devices. Continued analysis of e-liquids and increased product regulation are needed.

Using Green Biosynthesized Lycopene-Coated Selenium Nanoparticles to Rescue Renal Damage in Glycerol-Induced Acute Kidney Injury in Rats.

PURPOSE: Selenium nanoparticles (SeNPs) have recently gained much attention in nanomedicine applications owing to their unique biological properties. Biosynthesis of SeNPs using nutraceuticals as lycopene (LYC) maximizes their stability and bioactivities. In this context, this study aimed to elucidate the renoprotective activity of SeNPs coated with LYC (LYC-SeNPs) in the acute kidney injury (AKI) model. METHODS: Rats were divided into six groups: control, AKI (glycerol-treated), AKI+sodium selenite (Na2SeO3; 0.5 mg/kg), AKI+LYC (10 mg/kg), AKI+LYC-SeNPs (0.5 mg/kg) and treated for 14 days. RESULTS: Glycerol treatment evoked significant increases in rhabdomyolysis-related markers (creatine kinase and LDH). Furthermore, relative kidney weight, Kim-1, neutrophil gelatinase-associated lipocalin (NGAL), serum urea, and creatinine in the AKI group were elevated. Glycerol-injected rats displayed declines in reduced glutathione level, and superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase activities, paralleled with downregulations in Nfe2l2 and Hmox-1 expressions and high renal MDA and NO contents. Glycerol-induced renal inflammation was evident by rises in TNF-α, IL-1ß, IL-6, and upregulated Nos2 expression. Also, apoptotic (elevated caspase-3, Bax, and cytochrome-c with lowered Bcl-2) and necroptotic (elevated Pipk3 expression) changes were reported in damaged renal tissue. Co-treatment with Na2SeO3, LYC, or LYC-SeNPs restored the biochemical, molecular, and histological alterations in AKI. In comparison with Na2SeO3 or LYC treatment, LYC-SeNPs had the best nephroprotective profile. CONCLUSION: Our findings authentically revealed that LYC-SeNPs co-administration could be a prospective candidate against AKI-mediated renal damage via antioxidant, anti-inflammatory, anti-apoptotic and anti-necroptotic activities.

Comparative efficacy and safety of glycerol versus mannitol in patients with cerebral oedema and elevated intracranial pressure: A systematic review and meta-analysis.

WHAT IS KNOWN AND OBJECTIVE: Glycerol is thought to be superior to mannitol in the treatment of cerebral oedema and elevated intracranial pressure (ICP), particularly with safety concerns. However, the current evidence remains insufficient. Therefore, we aimed to compare the efficacy and safety of glycerol versus mannitol in this meta-analysis. METHODS: PubMed, EMBASE, Web of Science, CENTRAL, China National Knowledge Infrastructure, Wanfang Database, Chongqing VIP information, ClinicalTrials.gov, and the reference lists of relevant articles were searched for randomized controlled trials comparing glycerol and mannitol in patients with brain oedema and elevated ICP. Two investigators independently identified the articles, assessed the study quality and extracted data. Data analyses were performed using RevMan software. RESULTS AND DISCUSSION: Thirty trials involving 3144 patients met our inclusion criteria. Pooled data indicated that glycerol and mannitol had comparable effectiveness in controlling cerebral oedema (RR, 1.00; 95% CI, 0.97 to 1.03; p = .97), but the risks of acute kidney injury and electrolyte disturbances were significantly lower with glycerol (RR, 0.21; 95% CI, 0.16 to 0.27 and RR, 0.23; 95% CI, 0.17 to 0.30, respectively) than mannitol. Moreover, there seemed to be a lower probability of rebound ICP after the withdrawal of glycerol. Neither haemolysis nor elevated blood glucose levels were observed in the glycerol group. WHAT IS NEW AND CONCLUSION: Regarding the balance between efficacy and safety, glycerol could be an effective and more tolerable alternative therapy for cerebral oedema and elevated ICP than mannitol, especially for high-risk populations of renal failure.