The effect of electrical stimulation on skin vulnerability to irritants.

PURPOSE: Electrical stimulation (ES) is a widely used technique in the medical field for various purposes. The effect of ES on several skin properties has been investigated; however, its effect on skin vulnerability to irritants remains unknown. This study aimed to investigate the effects of ES application on skin vulnerability to external irritants. MATERIALS AND METHODS: An experimental study on 12 healthy male subjects (Mean ± SD, 22.9 ± 3.6 years) who completed the study. The subjects were free of skin abnormalities in the volar aspect of both forearms. Three areas were allocated to each forearm and marked as areas 1, 2, and A in the treated forearm, and areas 3, 4, and B in the control forearm. ES was applied to the volar aspect of the treated forearm for 30 min three times a week, for 2 weeks. The effect of ES on skin vulnerability was investigated using 5% and 0.5% sodium lauryl sulfate (SLS) patches applied to both treated and control forearms. The skin response to irritants was evaluated using transepidermal water loss (TEWL) and a visual erythema score 24 h after patch removal. RESULTS: Compared to the control forearm, ES increased skin permeability and erythema in response to external irritants (SLS), as measured by the visual analog score (Z = 2.75, p = 0.006) and TEWL (p < 0.05), respectively. CONCLUSIONS: ES escalates skin reactions to low concentrations of irritant substances, such as SLS, in the area between the two electrodes. This emphasizes the use of this substance, and similar irritants should be avoided in areas treated with ES.

Clarithromycin laurate salt: physicochemical properties and pharmacokinetics after oral administration in humans.

OBJECTIVE: To prepare and characterize the physicochemical and pharmacokinetic properties of clarithromycin laurate (CLM-L), a fatty acid salt of clarithromycin (CLM). METHODS: CLM-L was prepared by a simple co-melting process. The formation of CLM-L was confirmed using FTIR, 1H NMR, and 13C NMR. Solubility, intrinsic dissolution rate (IDR), and partitioning properties of CLM-L were determined and compared to those of CLM. Bioavailability of CLM from CLM-L tablets was evaluated in healthy volunteers and compared to immediate release CLM tablets. RESULTS: CLM-L showed lower aqueous solubility, higher partitioning coefficient, and slower dissolution rate. Tablets of CLM-L also showed a significantly slower in vitro release in comparison to CLM tablets. Cmax, Tmax and AUC0→∞ of CLM-L tablets and immediate release CLM tablets did not show a significant difference. However, the AUC0→∞ for the CLM-L tablets tended to be higher than that of CLM tablets at all-time points. CONCLUSION: CLM-L was successfully prepared and its formation was confirmed. CLM-L was more hydrophobic than CLM. It exhibited a slight in vivo absorption enhancement in comparison to CLM. However, its pharmacokinetic behavior was comparable to that of CLM.

Does Salt and Mineral Content of Dead Sea Mud Affect Its Irritation Potential: A Laser Doppler Flowmetry Study.

The aim of the study was to investigate skin microcirculation, flux, and temperature changes induced by the application of Dead Sea mud (DSM) formulas with different mud salts and mineral contents using laser Doppler flowmetry. Instrumental analysis of eight over-the-shelf DSM products and four different samples of nonformulated Dead Sea mud were carried out to determine their contents of various salts and elements, including K, Na, Cl, Mg, Mn, Ca, SO3, SiO2, Al, Br, Fe, Hg, Cr, Co, Ni, Cu, Zn, As, Cd, Pb, and Sr. Three DSM samples with different levels of salts were then used to study the influence of salt content on skin irritation potential using laser Doppler flowmetry. Fifteen healthy nonsmoking females aged 18-45 years participated in the study. Subjects were randomly assigned to either "Salted" mud group (n = 5), "As is" mud group (n = 5), or "Over-the-Shelf" mud group (n = 5). Five circular areas were marked on the ventral aspect of each forearm. One forearm was assigned randomly for mud treatment and the other forearm was untreated. Ten milliliters of mud was applied on the assigned forearm and left for 30 minutes. Two reading protocols were designed and used to study the effects of tested type of mud on skin blood flux and temperature during mud application (protocol 2) as well as before and after mud removal (protocol 1). All types of tested mud were not associated with a significant measurable elevation in skin temperature and skin blood flow. All types of Dead Sea mud did not cause detectable microcirculatory and skin temperature changes regardless of their different mineral and salts contents.

Skin Tolerance of Three Types of Dead Sea Mud on Healthy Skin: A Short-Term Study.

Dead Sea mud (DSM) is commonly used by patients with various skin conditions because of its contents of healing elements. No study was published to show whether DSM application weakens or strengthens skin barrier function. In this study, we investigated the impact of 30-minute single application of various types of DSM ("As Is" mud, mud with extra Dead Sea salt, and over-the-shelf mud) on the barrier function of normal skin. The influence of 30-minute application of various types of DSM was investigated noninvasively on skin barrier properties of healthy female adult volunteers (n = 75) on predetermined circular areas. Skin hydration, transepidermal water loss (TEWL), erythema and melanin levels, and skin pH were measured directly, 30 minutes, and 60 minutes after mud removal. Thirty-minute single application of DSM was well tolerated with short-lived moisturizing effects, which was enhanced by the presence of humectant ingredients, and with no negative impact on barrier integrity, pH, and erythema and melanin levels.

Effect of formulation variables on the physical properties and stability of Dead Sea mud masks.

The physical stability of Dead Sea mud mask formulations under different conditions and their rheological properties were evaluated as a function of the type and level of thickeners, level of the humectant, incorporation of ethanol, and mode of mud treatment. Formulations were evaluated in terms of visual appearance, pH, moisture content, spreadability, extrudability, separation, rate of drying at 32 degrees C, and rheological properties. Prepared mud formulations and over-the-shelf products showed viscoplastic shear thinning behavior; satisfactory rheological behavior was observed with formulations containing a total concentration of thickeners less than 10% (w/w). Casson and Herschel-Bulkley models were found the most suitable to describe the rheological data of the prepared formulations. Thickener incorporation decreased phase separation and improved formulation stability. Bentonite incorporation in the mud prevented color changes during stability studies while glycerin improved spreadability. Addition of 5% (w/w) ethanol improved mud extrudability, slightly increased percent separation, accelerated drying at 32 degrees C, and decreased viscosity and yield stress values. Different mud treatment techniques did not cause a clear behavioral change in the final mud preparation. B10G and K5B5G were labeled as "best formulas" based on having satisfactory physical and aesthetic criteria investigated in this study, while other formulations failed in one or more of the tests we have performed.

Eco-friendly solvent bar microextraction based on a natural deep eutectic solvent and multivariate optimization for simultaneous determination of spironolactone and canrenone in urine and plasma samples.

Simultaneous measurement of spironolactone and canrenone in urine and plasma provides valuable insight into renal function, and therapeutic efficacy and can be utilized to identify potential health risks and ensure patient safety throughout treatment. By adopting greener methods to analyze these compounds, significant reductions in the environmental impact of such studies can be achieved. For this purpose, a sensitive and eco-friendly solvent bar microextraction method using natural deep eutectic solvent (NDE) followed by high-performance liquid chromatography-diode array detection (HPLC-DAD) was developed to determine spironolactone and canrenone in urine and plasma samples. The extraction solvents were synthesized using NDE-based terpenoids containing menthol and camphor in various ratios. The extraction efficiency percentage (EE%) of both drugs was measured using response surface methodology (RSM) based on central composite design (CCD), and 29 extraction tests were conducted to determine the optimum conditions. Although all parameters were found to be significant, the extraction and elution times were critical for isolating the target analytes. Under optimized conditions, the linear dynamic ranges for spironolactone (SPI)/canrenone (CAN) were 11.7-104/13.1-104 µg L-1 and 21.7-104/24.6-104 µg L-1 in urine and plasma samples, respectively with R2 ≥ 0.993. The ranges of intra-/interprecision (relative standard deviation (RSD) %, n = 5) were 1.31-9.17%/ 2.4-11% with extraction recovery ≥ 88.6% for both drugs. The comparison findings with previously published methods confirmed that the developed NDE-solvent bar microextraction (SBME)-HPLC-DAD method for spironolactone and canrenone analysis displayed confident sensitivity, feasible operation, and simple analysis. Furthermore, the method's applicability and effectiveness were proven by successfully analyzing spironolactone and its metabolite canrenone in patients' urine and plasma samples.

Anti-Bacterial Activity of Green Synthesised Silver and Zinc Oxide Nanoparticles against Propionibacterium acnes.

Propionibacterium acnes plays a critical role in the development of acne vulgaris. There has been a rise in the number of patients carrying P. acnes strains that are resistant to antibiotics. Thus, alternative anti-microbial agents are required. Zinc oxide (ZnO-NPs) and silver (Ag-NPs) nanoparticles can be used against several antibiotic-resistant bacteria. The impact of Ag-NPs and ZnO-NPs against two clinical strains of P. acnes, P1 and P2, and a reference strain, NCTC747, were investigated in this research. A chemical approach for the green synthesis of Ag-NPs and ZnO-NPs from Peganum harmala was employed. The microtiter plate method was used to examine the effects of NPs on bacterial growth, biofilm development, and biofilm eradication. A broth microdilution process was performed in order to determine minimal inhibitory (MIC) concentrations. Ag-NPs and ZnO-NPs had a spherical shape and average dimensions of 10 and 50 nm, respectively. MIC values for all P. acnes strains for Ag-NPs and ZnO-NPs were 125 µg/mL and 250 µg/mL, respectively. Ag-NP and ZnO-NP concentrations of 3.9- 62.5 µg/mL and 15-62.5 µg/mL significantly inhibited the growth and biofilm formation of all P. acnes strains, respectively. ZnO-NP concentrations of 15-62.5 µg/mL significantly inhibited the growth of NCTC747 and P2 strains. The growth of P1 was impacted by concentrations of 31.25 µg/mL and 62.5 µg/mL. Biofilm formation in the NCTC747 strain was diminished by a ZnO-NP concentration of 15 µg/mL. The clinical strains of P. acnes were only affected by ZnO-NP titres of more than 31.25 µg/mL. Established P. acne biofilm biomass was significantly reduced in all strains at a Ag-NP and ZnO-NP concentration of 62.5 µg/mL. The findings demonstrated that Ag-NPs and ZnO-NPs exert an anti-bacterial effect against P. acnes. Further research is required to determine their potential utility as a treatment option for acne.

Cosmeceutical formulations of pro-vitamin E phosphate: In-vitro release testing and dermal penetration into excised human skin.

Long-term exposure to solar radiation can lead to skin damage such as photoageing, and photocarcinogenesis. This can be prevented by topically applying α-tocopherol phosphate (α-TP). The major challenge is that a significant amount of α-TP needs to reach viable skin layers for effective photoprotection. This study aims to develop candidate formulations of α-TP (gel-like, solution, lotion, and gel), and investigate formulation characteristics' effect on membrane diffusion and human skin permeation. All the formulations developed in the study had an appealing appearance and no signs of separation. All formulations had low viscosity and high spreadability except the gel. The flux of α-TP through the polyethersulfone membrane was the highest for lotion (6.63 ±â€¯0.86 mg/cm2/h), followed by control gel-like (6.14 ±â€¯1.76 mg/cm2/h), solution (4.65 ±â€¯0.86 mg/cm2/h), and gel (1.02 ±â€¯0.22 mg/cm2/h). The flux of α-TP through the human skin membrane was numerically higher for lotion compared to the gel-like (328.6 vs.175.2 µg/cm2/h). The lotion delivered 3-fold and 5-fold higher α-TP in viable skin layers at 3 h and 24 h, respectively, compared to that of the gel-like. The low skin membrane penetration rate and deposition of α-TP in viable skin layers were observed for the solution and gel. Our study demonstrated that dermal penetration of α-TP was influenced by characteristics of formulation such as formulation type, pH, and viscosity. The α-TP in the lotion scavenged higher DPPH free radicals compared to that of gel-like (almost 73% vs. 46%). The IC50 of α-TP in lotion was significantly lower than that of gel-like (397.2 vs. 626.0 µg/mL). The preservative challenge test specifications were fulfilled by Geogard 221 and suggested that the combination of benzyl alcohol and Dehydroacetic Acid effectively preserved 2% α-TP lotion. This result confirms the suitability of the α-TP cosmeceutical lotion formulation employed in the present work for effective photoprotection.

The impact of biosynthesized ZnO nanoparticles from Olea europaea (Common Olive) on Pseudomonas aeruginosa growth and biofilm formation.

There is a limitation in the range of effectual antibiotics due to the Pseudomonas aeruginosa (PA) infection due to its innate antimicrobial resistance. Researchers have therefore been concentrating their efforts to discover advanced and cost effective antibacterial agents among the ever-increasing PA bacterial resistance strains. It has been discovered that various nanoparticles can be employed as antimicrobial agents. Here, we evaluated the antibacterial properties of the Zinc Oxide nanoparticles (ZnO NPs), which was biosynthesized, being examined on six hospital strains of PA alongside a reference strain (ATCC 27853). A chemical approach was applied to biosynthesize the ZnO NPs from Olea europaea was performed, and confirmed by using X-ray diffraction and Scanning Electron Microscopes. The nanoparticles then applied their antibacterial properties to examine them against six clinically isolated PA strains alongside the reference strain. This process tested for the results of the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC). The Growth, biofilm formation and eradication were analyzed. The influence of the differentiating degrees ZnO NPs in regard to Quorom sensing gene expression were further examined. The ZnO NPs exhibited a crystalline size and diameter (Dc) of 40-60 nm and both the MIC and MBC tests revealed positive outcomes of concentrations of 3 and 6 mg/ml for each PA strain, respectively. At sub inhibitory concentration, The ZnO NPs were found to significantly inhibit the growth and biofilm formation of all PA strains and decreases in the biomass and metabolic behavior of PA established biofilms; these decreases varied depending on the dosage. At ZnO NPs concentrations of 900 µg/ml, the expression of majority of quorum sensing genes of all strains were significantly reduced, at ZnO NPs concentrations of 300 µg/ml, few genes were significantly impacted. In conclusion, the treatment of PA and could be other antibiotic resistant bacteria can therefore be approached by using ZnO NPs as it has been uncovered that they withhold advanced antibacterial properties.

The efficacy of biosynthesized silver nanoparticles against Pseudomonas aeruginosa isolates from cystic fibrosis patients.

The high antibiotic resistance of Pseudomonas aeruginosa (PA) makes it critical to develop alternative antimicrobial agents that are effective and affordable. One of the many applications of silver nanoparticles (Ag NPs) is their use as an antimicrobial agent against bacteria resistant to common antibiotics. The key purpose of this research was to assess the antibacterial and antibiofilm effectiveness of biosynthesized Ag NPs against six biofilm-forming clinically isolated strains of PA and one reference strain (ATCC 27853). Ag NPs were biosynthesized using a seed extract of Peganum harmala as a reducing agent. Ag NPs were characterized by Ultraviolet-visible (UV-Vis) spectroscopy and scanning transmission electron microscopy (STEM). The effect of Ag NPs on biofilm formation and eradication was examined through micro-titer plate assays, and the minimal inhibitory (MIC) and minimum bactericidal (MBC) concentrations determined. In addition, real-time polymerase chain reactions (RT-PCR) were performed to examine the effects of Ag NPs on the expression of seven PA biofilm-encoding genes (LasR, LasI, LssB, rhIR, rhII, pqsA and pqsR). The biosynthesized Ag NPs were spherically-shaped with a mean diameter of 11 nm. The MIC for each PA strain was 15.6 µg/ml, while the MBC was 31.25 µg/ml. All PA strains exposed to Ag NPs at sub-inhibitory concentrations (0.22-7.5 µg/ml) showed significant inhibitory effects on growth and biofilm formation. Biomass and biofilm metabolism were reduced dependent on Ag NP concentration. The expression of the quorum-sensing genes of all strains were significantly reduced at an Ag NP concentration of 7.5 µg/ml. The results demonstrate the extensive in-vitro antibacterial and antibiofilm performance of Ag NPs and their potential in the treatment of PA infection. It is recommended that future studies examine the possible synergy between Ag NPs and antibiotics.

Preparation and evaluation of ascorbyl glucoside and ascorbic acid solid in oil nanodispersions for corneal epithelial wound healing.

The objective of this study was to develop and evaluate an effective topical formulation to promote corneal epithelial wound healing. Ascorbyl glucoside (AA-2G), a stable prodrug of AA, was formulated in solid in oil (S/O) nanodispersions by emulsifying AA-2G solutions in cyclohexane using Span 85 as an emulsifying agent and freeze-drying emulsions to produce AA-2G - surfactant complex. The complexes were then dispersed in castor oil to produce S/O nanodispersions which were evaluated in terms of their particle size, polydispersity index, encapsulation efficiency, morphology, physical stability as well as the transcorneal permeation and accumulation of AA-2G. The same preparation procedure was used to prepare S/O nanodispersions of AA. S/O nanodispersions of AA and AA-2G were formulated into oily drops that were tested for efficacy in promoting wound healing after corneal epithelial depredation. AA-2G was loaded efficiently in S/O nanodispersions (EE > 99%) in the form of spherical nanoparticles. S/O nanodispersions were physically stable and resulted in improved permeation (18x) and accumulation (7x) of AA-2G in transcorneal diffusion experiments in comparison to AA-2G solutions. Oily eye drops of AA-2G and AA showed no irritation and significant improvement in epithelial healing in vivo in comparison to AA-2G and AA solutions.

The cutaneous effects of long-term use of Dead Sea mud on healthy skin: a 4-week study.

PURPOSE: To investigate the effects of various types of Dead Sea mud (DSM) on skin barrier properties over a period of four weeks. METHODS: The effects of a 4-week application of three types of DSM (as is mud, mud with extra Dead Sea salt, and over the shelf mud) on the barrier properties of normal skin were investigated. Preparations were applied onto forearms of healthy volunteers every other day for 4 weeks, and skin hydration, transepidermal water loss (TEWL), melanin, erythema level, skin pH, skin elasticity, dermal thickness, and collagen content were measured at predefined circular areas on subjects' forearms at baseline, week 1, week 2, and week 4 during the treatment phase and on week 5 following a 1-week regression period in which no mud was applied. RESULTS: The use of DSM for 4 weeks was well tolerated with no noticeable changes in TEWL, skin pH, melanin, and erythema levels. A slight firming effect was observed in the forearms treated with salted DSM. Skin hydration was not significantly affected by any type of DSM. However, a slight drying effect of "as is" and "salted" DSM and slight hydration effect of "over the shelf" DSM were observed. This effect could be attributed to the content of DSM rather than to disruption of skin integrity as confirmed by TEWL values. CONCLUSION: Long-term use of all types of DSM did not compromise the barrier integrity of the skin. This provides dermatologists with needed information on safety of DSM and lack of skin disruption activity upon long-term use.

Development of Dioctyl Phthalate@Fe3O4 Nanocomposite Reinforced Hollow Fiber Solid/ Liquid Phase Microextraction Followed by HPLC-DAD for the Determination of Atorvastatin and Gemfibrozil in Human Urine.

BACKGROUND: The desirable levels of lipids, especially in patients with coronary artery disease, might not be achievable with a single lipid-lowering drug; thus, combination therapy using atorvastatin and gemfibrozil seems to be a promising approach. However, the potential for drugdrug interaction needs to be taken into consideration, and the combination (atorvastatin and gemfibrozil) is recommended only when other options for reducing lipids have been exhausted. OBJECTIVES: Many studies are conducted for the determination of atorvastatin or gemfibrozil in biological fluids and tablets; however, the simultaneous determination of the two drugs in complex biological matrices is limited. Consequently, the development of a sensitive method for simultaneous determination of atorvastatin and gemfibrozil in urine samples is urgently needed to make sure that the doses of both medications are given to patients correctly to prevent the risk of side effects outcomes associated with the adverse drug-drug interaction. METHODS: A synthesized nanocomposite sorbent, dioctyl phthalate coated on the surface of magnetite (DOP@Fe3O4), was reinforced and immobilized into the pores of 2.5 cm segment hollow fiber microtube via ultrasonication, and the lumen of the microtube was filled with 1-octanol as an organic solvent with two ends heat-sealed. The prepared (DOP@Fe3O4-HF-SLPME) device was directly immersed into 10 mL of a sample solution containing atorvastatin and gemfibrozil with agitation. Subsequently, the microextraction device was transferred to HPLC-micro-vial containing an appropriate solvent, and the selected analytes were desorbed under ultrasonication prior to HPLCDAD analysis. The main factors influencing the adsorption and desorption process of the selected drugs have been optimized. RESULTS: The DOP@Fe3O4-HF-SLPME combined with the HPLC-DAD method was analytically evaluated for the simultaneous determination of atorvastatin and gemfibrozil in human urine samples using the optimized conditions. In spiked urine samples, the method showed a good linearity R2˃ 0.998, RSD from 1.41- 5.33%, and the limits of detection/ quantification (LOD/ LOQ) were 0.11/ 0.36 and 0.73/ 2.42 µg L-1 for atorvastatin and gemfibrozil, respectively. The enrichment factors of atorvastatin and gemfibrozil were 83.4 and 101.2, with extraction recoveries of 80.9% and 99.0%, respectively. The developed method demonstrated comparable results against referenced methods and a satisfactory result for determining the selected drugs in the patient's urine samples. CONCLUSION: The DOP@Fe3O4-HF-SLPME followed by HPLC-DAD was proved to be an efficient, sensitive, and cost-effective biopharmaceutical analysis method for trace levels of atorvastatin and gemfibrozil in the biological fluid matrix.

Effects of thermal curing conditions on drug release from polyvinyl acetate-polyvinyl pyrrolidone matrices.

This study aimed to investigate the effects of dry and humid heat curing on the physical and drug release properties of polyvinyl acetate-polyvinyl pyrrolidone matrices. Both conditions resulted in increased tablet hardness; tablets stored under humid conditions showed high plasticity and deformed during hardness testing. Release from the matrices was dependent on the filler's type and level. Release profiles showed significant changes, as a result of exposure to thermal stress, none of the fillers used stabilized matrices against these changes. Density of neat polymeric compacts increased upon exposure to heat; the effect of humid heat was more evident than dry heat. Thermograms of samples cured under dry heat did not show changes, while those of samples stored under high humidity showed significant enlargement of the dehydration endotherm masking the glass transition of polyvinyl acetate. The change of the physical and release properties of matrices could be explained by the hygroscopic nature of polyvinyl pyrrolidone causing water uptake; absorbed water then acts as a plasticizer of polyvinyl acetate promoting plastic flow, deformation, and coalescence of particles, and altering the matrices internal structure. Results suggest that humid heat is more effective as a curing environment than dry heat for polyvinyl acetate-polyvinyl pyrrolidone matrices.

Community Pharmacy Practice During COVID-19 Pandemic: A Perspective From the Middle East.

The coronavirus disease 2019 (COVID-19) pandemic poses serious challenges to pharmaceutical care services, and innovative responses by community pharmacists and regulatory bodies are needed. The experience in Jordan, located in the Middle East, is shared in this article in light of available international guidelines to provide insight into the efforts made by the pharmacists to safely maintain pharmaceutical services during the current pandemic. In addition, unique roles played by community pharmacists in other countries are discussed to shed light on the important role of community pharmacists in this outbreak.

Modulation of buspirone HCl release from hypromellose matrices using chitosan succinate: implications for pH-independent release.

Chitosan succinate (CS) was synthesized through the acylation of chitosan with succinic anhydride. The interaction of CS with buspirone HCl (BUSP) was evaluated using dialysis experiments and shown to result in complex with a stability constant of 2.26 mM and a capacity of 0.0362 micromol BUSP/mg CS. The extent of complexation upon dry and wet mixing of CS and BUSP was determined quantitatively using differential scanning calorimetry. The extent of the interaction was highest in wet mixtures and was found to be dependent on the pH of the granulation liquid. CS was incorporated in BUSP-containing hypromellose (HPMC) tablets using dry mixing and wet granulation with BUSP. Tablet dissolution was tested in 0.1N HCl and phosphate buffer, pH 6.8. According to f(2) and mean dissolution time results, the similarity of profiles increased as CS content increased with the highest f(2) value observed when CS was wet granulated with BUSP. Dissolution was also tested in deionized water and 5% NaCl; where increased ionic strength resulted in faster dissolution suggesting an ion exchange involvement in drug release. CS was proved effective in modulating BUSP release from HPMC matrices for pH-independent release through ionic complex formation.

Effects of the genetic variants of organic cation transporters 1 and 3 on the pharmacokinetics of metformin in Jordanians.

BACKGROUND: Human response to the antidiabetic metformin is influenced by some factors, such as genetic variants in the SLC22A genes. This study aimed to determine the frequency of main SLC22A1 and SLC22A3 genetic variants and their influence on metformin pharmacokinetics among healthy unrelated Arab Jordanians. PATIENTS AND METHODS: The SLC22A1 and SLC22A3 genes were genotyped by DNA sequencing of exons 1, 3, 7, and 9 in the SLC22A1 gene and exons 6, 7, and 9 in the SLC22A3 gene. Then, a clinical pharmacokinetic study was conducted on 26 healthy volunteers. The pharmacokinetic parameters were calculated using non-compartmental model analysis. The study was an open-label, randomized study with single 1000 mg metformin administration. RESULTS: Results showed that volunteers with SLC22A3 rs8187722 variant had higher (χ2, p<0.05) metformin Cmax and AUC values than the wild SLC22A3 volunteers, whereas T½ and Kel were not affected. In addition, volunteers with the heterozygote SLC22A3 rs2292334 variant had significantly higher (χ2, p<0.05) metformin Cmax and AUC and lower Kel values than the wild-type SLC22A3 genotype. CONCLUSIONS: The SLC22A3 rs8187722 and rs2292334 genetic variants affected metformin pharmacokinetics among a clinical sample of Jordanians. The findings may increase our understanding of the inter-individual and inter-ethnic variations in metformin response.

Comparative efficacy and safety of deoxyarbutin, a new tyrosinase-inhibiting agent.

Several tyrosinase inhibitors have been developed and utilized to ameliorate various cutaneous hyperpigmentary disorders and complexion discolorations. Deoxyarbutin (dA) (i.e., 4-[(tetrahydro-2H-pyran-2-yl)oxy]phenol), designed using quantitative structure-activity relationships (QSAR), demonstrates effective inhibition of mushroom tyrosinase and skin-lightening capability (1). However, its comparative safety, effectiveness, and reversibility to other known tyrosinase inhibitors in human melanocytes had not been determined. The effect of dA was assessed in cultured human skin cells, on xenographs, and with a clinical trial. Using cultured human melanocytes, the maximum concentration of dA that allowed 95% viability was fourfold greater than for hydroquinone (HQ), indicating that dA is less cytotoxic/cytostatic than HQ. The viability of cultured human keratinocytes and fibroblasts was also less compromised by increasing concentrations of dA as opposed to HQ. At the maximum concentration allowing normal cellular viability, dA effectively inhibited tyrosinase activity and melanin content in human melanocytes, whereas HQ was marginally inhibitory. Upon removal of dA, tyrosinase activity and melanin content was normalized within five days. Topical application of dA on human xenografts resulted in a gradual and visually apparent skin lightening effect during an eight-week period. In a clinical trial, dA facilitated fading of pre-tanned skin to a statistically significant greater extent than either HQ or no treatment. These results demonstrate that dA is a potentially safe, effective, and reversible tyrosinase inhibitor.

Women's perceptions of the benefits and risks of skin-lightening creams in two South African communities.

BACKGROUND: Skin-lightening products are commonly used by black communities in South Africa and worldwide. This practice has deep historical and cultural roots and is associated with adverse cutaneous effects. METHODS: A cross-sectional survey of 579 African and Indian women aged 18-70 years was conducted in two large public hospitals in Durban, South Africa. RESULTS: There were 292 Africans and 287 Indians included in the survey sample. Of these 32.3% had used skin-lightening products (60% of Africans and 40% of Indians). Most of those who had used skin lighteners (85 of Africans and 76% of Indians) claimed awareness of the adverse effects of the products, although this did not appear to inform knowledge of the product, how it was used, nor the decision to use the product. Most users (90%) expressed satisfaction with results achieved but 32% reported adverse events. CONCLUSION: Skin-lightening products are used by a third of African and Indian women in South Africa Cultural and historical perceptions equating a fairer skin with social advantage are pervasive and strongly reinforced by the media. There is a poor understanding of the risks associated with the use of these products. Public education campaigns are required to teach consumers about these risks and the importance of concomitant use of sunscreens with these products.

Short-term and long-term effects of electrical stimulation on skin properties.

BACKGROUND: Electrical stimulation (ES) has been used in treating different medical conditions; however, not much is known about the effect of this application on skin properties. The purpose of this study was to investigate the short-term and long-term effects of ES on biophysical properties of the skin. METHODS: A pretest-posttest control design was used in the study. Thirteen men (N = 13, age (M ± SD), 19 ± 5.6 years) were free of skin abnormality on the volar aspect of both forearms. Four areas were allocated and marked with a layout template of two circles 2 cm in diameter and 2 cm apart. Areas 1 and 2 were allocated on the experimental forearm and area 3 and 4 on the control forearm. ES was applied for 15 minutes with two rubber electrodes 8 cm apart surrounding areas 1 and 2 on the experimental forearm three times a week for 2 weeks. Skin properties including transepidermal water loss (TEWL), melanin content, erythema, elasticity and pH were measured pre-ES, during ES and post-ES, and after 2 weeks of applying ES to find out the short-term and long-term effects on skin. RESULTS: The TEWL was increased during ES at 7, 15 and 15-minutes post-ES compared with the baseline (p < 0.01) and to the control forearm (p = 0.04) measurements, and no increase have been noticed of TEWL on the control forearm (p = 0.11). Also, we found no difference in the other skin properties (p > 0.05) on both forearms, and there were no long-term effects (p > 0.05) in any tested variable. CONCLUSION: Electrical stimulation caused temporary increase in TEWL with no effects on other skin properties.