BACKGROUND: Alpha hydroxy acids (AHAs) are known to diminish corneocyte cohesion at the innermost levels of the stratum corneum and have been used in the treatment of various disorders of keratinization. However, their effect on skin barrier function and their irritant potential is not fully understood. OBJECTIVE: Our study was done to evaluate the skin irritancy of AHAs in normal human skin. METHODS: Patches with 1%, 5% and 10% solutions of lactic acid (LA) and glycolic acid (GA) were applied to the volar forearm of 20 healthy volunteers for 24 hours using large Finn chambers with filter paper. Visual scores, erythema (E-) index and transepidermal water loss (TEWL) were measured at 30 min, 24 h and 48 h after removal of the patches. RESULTS: The results are summarized as follows. 1. Visual scores were 0.1+/-0.3 (1%), 0.5+/-0.6 (5%) and 1.1+/-0.8 (10%) at 24 h after removal of LA, and were 0.2+/-0.4 (1%), 0.6+/-0.6 (5%) and 1.0+/-0.7 (10%) at 24 h after removal of GA. They were increased in proportion to the concentrations and there were significant differences in skin responses between the control and each concentration of the solutions. 2. E-indices were 9.1+/-2.1 (control), 8.8+/-1.8 (1%), 9.0+/-2.6 (5%) and 10.5+/-3.9 (10%) at 24 h after removal of LA, and were 9.4+/-1.8 (control), 9.3+/-2.3 (1%), 10.0+/-3.0 (5%) and 11.1+/-3.5 (10%) at 24 h after removal of GA. They were not increased in the patch areas of 1% and 5% solutions in both the LA and GA group, but were significantly increased in the patch areas of 10% solutions in both the LA and GA group. 3. TEWL values were 7.3+/-2.3 (control), 8.3+/-4.0 (1%), 9.8+/-4.5 (5%) and 16.7+/-9.1 (10%) at 24 h after removal of LA, and were 8.1+/-3.2 (control), 7.8+/-3.8 (1%), 8.6+/-3.0 (5%) and 10.9+/-4.1 (10%) at 24 h after removal of GA. They were not increased in the patch areas of 1% LA, 1% GA and 5% LA, but there were high significant differences between the controls and 10% solutions of both LA and GA. CONCLUSION: Visual scores were increased in all concentrations of AHAs tested, but the increase in E-index and TEWL values were not significant or minimal in 1% and 5% solutions of AHAs. These findings suggest that AHAs could be classified as non-corrosive irritants.
Erythema ; Forearm ; Healthy Volunteers ; Humans* ; Hydroxy Acids* ; Irritants ; Lactic Acid ; Skin*

Animals ; Hydroxy Acids ; toxicity ; Lacquer ; toxicity ; Mice ; Mice, Inbred ICR ; Superoxide Dismutase ; metabolism

Photoaging skin occurs as a result of long-term exposure to ultraviolet radiation. In contrast to intrinsic aging, skin changes of photoaging can be reversed by the topical use of skin care products. Several skin care products have now undergone sufficient evaluation and have a well-defined role in our practice. Retin-A and alpha hydroxy acids have a significant number of data available for evaluation; data for Vitamin C and antioxidants are still emerging. We conducted clinical trial to compare the anti-photoaging effects of Rein-A and Vitamin C in 25 women volunteers. Each formulation wes applied daily to the randomly assigned hemifaces over the 8-month study period. Comparative evaluations of anti-photoaging effects were made using subject self-appraisal questionnares, plastic surgeon's assessment, ultraviolet revelations, and histologic examinations. Subject self-appraisal and plastic surgeon's assessment showed predominance of Retin-A over Vitamin C. But both Retin-A and Vitamin C provided objective and subjective improvement in photodamaged facial skin and no significant difference was found between Retin-A and Vitamin C in histologic examinations.
Antioxidants ; Ascorbic Acid* ; Diagnostic Self Evaluation ; Female ; Humans ; Hydroxy Acids ; Skin Aging ; Skin Care ; Skin* ; Tretinoin* ; Vitamins* ; Volunteers

OBJECTIVETo assess the effect of postconditioning on cardiac protection of rat hearts suffered from long-term hypothermic preservation.

METHODSThe Langendorff model of isolated rat heart was used. After 30 min of stabilization, the hearts were stored in 4 degrees C Celsior solution for 3 or 5 h followed by 60 min of reperfusion. Postconditioning was initiated by 3 cycles of 30 s ischemia followed by 30 s reperfusion at the beginning of subsequent persistent reperfusion. The recovery of cardiac contractile function and arrhythmia score were observed.

RESULTS(1) Compared with control group, postconditioning increased the recovery of heart rate (HR), left ventricular systolic pressure (LVDP), maximal rise/fall rate of ventricular pressure (dP/dt(max)) and coronary flow (CF) and rate-pressure product (RPP) during reperfusion after 3 h of hypothermic preservation. However, left ventricular end-diastolic pressure (LVEDP) and the cardiac arrhythmia score during the first 10 min of reperfusion was significantly lower in 3 h postconditioning group than that in 3 h control group. (2) The rat hearts treated by postconditioning with 5-HD(100 micromol/L) abolished the amelioration of contract function induced by postconditioning. And it could also increase the cardiac arrhythmia score. (3) Compared with 5 h control group, the HR, LVDP,dP/dt(max), CF, LVEDP, RPP and the cardiac arrhythmia score were not significantly different in postconditioning treated hearts during reperfusion after 5 h of hypothermic preservation.

CONCLUSIONPostconditioning could provide the cardiac protection on 3 h hypothermic preserved rat hearts,but not on 5 h hypothermic preserved rat hearts. The cardiac protection effect might be partly associated with activation of selective mitochondrial ATP-sensitive potassium channel.

Animals ; Cryopreservation ; Decanoic Acids ; pharmacology ; Heart ; Hydroxy Acids ; pharmacology ; In Vitro Techniques ; Ischemic Preconditioning, Myocardial ; methods ; Male ; Myocardial Reperfusion Injury ; prevention & control ; Organ Preservation ; Rats ; Rats, Sprague-Dawley

BACKGROUND: The injury by a nerve ligation produces a mechanical allodynia. The antiallodynic effect resulted from intrathecal administration of the adenosine analogues has been well known. ATP-sensitive potassium channel blockers have been known to reverse the effect of some antinociceptive drugs in animal and human studies. Therefore, the present study is to assess the relationship between antiallodynic effect of N6-(R)-phenylisopropyl adenosine (R-PIA) and mitochondrial ATP-sensitive potassium (mKATP) channel in a neuropathic pain model. METHODS: Allodynia was induced in male Sprague Dawley rats by the tight ligation of the left lumbar 5th and 6th spinal nerves. We tested the mechanical allodynia by pricking von Frey filaments to the left hind paw and assessed withdrawal thresholds of paw with up-down method. For the estimation of the antiallodynic effect of R-PIA, R-PIA (0.5, 1 and 2microgram) or saline were administered intrathecally.To investigate the reversal effect on antiallodynic effect of R-PIA, variable amounts of 5-hydroxydecanoate (5-HD, 20, 30 and 40 mg), mKATP channel blocker were administered intraperitoneally at 5 min prior to the intrathecal injection of 2microgram of R-PIA, and the degree of allodynia was assessed. RESULTS: The paw withdrawal threshold was gradually increased with increased dose of R-PIA and reached the maximum level with 2microgram R-PIA (P < 0.05). The increase of paw withdrawal threshold with 2microgram R-PIA was significantly reversed dose-dependently by intraperitoneal pretreatment of 20, 30 and 40 mg/kg 5-HD (P < 0.05). CONCLUSIONS: In our results, intraperitoneal injection of 5-HD before intrathecal injection of R-PIA had reversed the antiallodynic effect of R-PIA. This results suggest that the mechanism of mechanical antiallodynia induced by intrathecal injection of R-PIA may relate with the mK(ATP) channel in a rat model of nerve ligation injury.
Adenosine ; Animals ; Decanoic Acids ; Humans ; Hydroxy Acids ; Hyperalgesia ; Injections, Intraperitoneal ; Injections, Spinal ; Ligation ; Male ; Neuralgia ; Polymethacrylic Acids ; Potassium ; Potassium Channel Blockers ; Rats ; Rats, Sprague-Dawley ; Receptors, Purinergic P1 ; Spinal Nerves

BACKGROUND: Alpha hydroxy acid containing products are now widely used as cosmetics or skin protectives because it is believed to have a favorable effect against the aging process of skin. OBJECTIVE: The study aimed to find the effects of AHAs (glycolic acid, lactic acid) on the skin of hairless mice. METHODS: Glycolic acid (10 %, pH 3.9), lactic acid (10 %, pH 6.0) and vehicle control were applied topically to the back skin of hairless mice for two weeks. The thickness of the skin was measured by histometric analysis in addition to Masson-trichrome staining, immunohistochemical staining for TGF-beta and a Northern blot assay for pro α-l(I) collagen mRNA. RESULTS: The change of the skin after topical treatment showed decreased mean epidermal thickness in the AHAs treated group, but the thickness of the dermis increased greatly compare to the controls (glycolic acid > lactic acid > control). Staining with Massontrichrome and TGF-beta showed a relatively increased expression in the AHAs treated specimens. These effects were correlated to the increased expression of pro a-1(I) collagen mR- NA from glycolic acid treated skin. CONCLUSION: It is suggested that the favorable effects of AHAs treatment are achieved by increased dermal thickness associated with prominent collagen synthesis.
Aging ; Animals ; Blotting, Northern ; Collagen ; Dermis ; Hydrogen-Ion Concentration ; Hydroxy Acids* ; Lactic Acid ; Mice ; Mice, Hairless* ; RNA, Messenger ; Skin* ; Transforming Growth Factor beta

BACKGROUND: Users of cosmetics and skin care products often report adverse reactions ranging from itching, stinging and dryness to intense inflammatory responses such as erythema, wheals and rashes. Sensitive skin has been described as a skin type showing higher reactivity than normal skin, and it develops exaggerated reactions when exposed to internal stimulants and external irritants. The alpha hydroxy acids (AHAs), naturally occurring organic acids which include lactic acid, glycolic acid, citric acid, malic acid and tartaric acid are all kinds of noncorrosive irritants. The lactic acid sting test is widely accepted as a marker of sensitive skin and is employed for the selection of subjects experiencing invisible sensory irritation. OBJECTIVE: This study was performed to compare the results of sting tests conducted on the sensitive and nonsensitive skin group which had been exposed to various kinds of AHAs. METHOD: A total of 50 individuals (25 individuals with a sensitive skin group and 25 individuals with a nonsensitive skin group) were selected by the method of self-assessment questionnaires relating to sensitive skin. The subjects were tested on the face with 2 variables of 5 AHA types ( with or without Hilltop chamber occlusion), at 2 weeks intervals, for a total of 10 times. RESULTS: The positive response rate of stinging in the sensitive skin group was higher than that in the nonsensitive skin group for all tests except the glycolic acid sting test using Hilltop chamber (p<0.05). The mean value of sting scores in the sensitive skin group was higher than that in the nonsensitive skin group for all tests (p<0.05). CONCLUSION: Sting tests using various kinds of AHAs are a useful method in determining sensitive skin.
Bites and Stings* ; Citric Acid ; Dental Calculus ; Erythema ; Exanthema ; Hydroxy Acids* ; Irritants ; Lactic Acid ; Patient Selection ; Pruritus ; Self-Assessment ; Skin Care ; Skin* ; Surveys and Questionnaires

BACKGROUND AND OBJECTIVES: It is known that various inflammatory mediators released from the eosinophils and mast cells play important roles in the pathogenesis of nasal polyp. Among those mediators, the arachidonic acid has particular importance as a precursor of other mediators. By assaying the tissue concentration of the6-keto-PGF(1alpha), leukotrienes (LTs), and hydroxyeicosatetraenoic acids (HETE) in the nasal polyp, we aimed to investigate the role of arachidonic acid metabolite in the pathogenesis of antrochoanal polyp and nasal polyp associated with chronic paranasal sinusitis. MATERIALS AND METHODS:Three turbinate tissues taken during the septoplasty were served as the control. The experimental group consisted of 3 antrochoanal polyps and 7 inflammatory polyps. The tissue level of the 6-keto-PGF(1alpha), LTC(4), LTD(4), LTE(4), 15-HETE, and 12-HETE were measured using high performance liquid chromatography. RESULTS: The level of 6-keto-PGF(1alpha), LTC4, 15-HETE, 12-HETE were significantly lower in antrochoanal polyp than in the control turbinate. In the inflammatory polyp, the levels of 6-keto-PGF(1alpha) and LTC(4) were lower than the control. However, in the inflammatory polyp, LTD(4) and LTE(4) were detectable, which were not detected in the control turbinate and antrochoanal polyp. CONCLUSION: The results of this study indicate that the decreased arachidonic acid metabolism may underlie the pathogenesis of the antrochoanal polyp. However, in the pathogenesis of inflammatory polyp, the increased production of LTD(4) and LTE(4) may have an important role.
12-Hydroxy-5,8,10,14-eicosatetraenoic Acid ; Arachidonic Acid* ; Chromatography, Liquid ; Eosinophils ; Hydroxyeicosatetraenoic Acids ; Leukotriene C4 ; Leukotrienes ; Mast Cells ; Metabolism ; Nasal Polyps* ; Polyps* ; Sinusitis* ; Turbinates

This study aims to explore the effects of arachidonic acid lipoxygenase metabolism in vascular calcification. We used 5/6 nephrectomy and high-phosphorus feeding to establish a model of vascular calcification in mice. Six weeks after nephrectomy surgery, vascular calcium content was measured, and Alizarin Red S and Von Kossa staining were applied to detect calcium deposition in aortic arch. Control aortas and calcified aortas were collected for mass spectrometry detection of arachidonic acid metabolites, and active molecules in lipoxygenase pathway were analyzed. Real-time quantitative PCR was used to detect changes in the expression of lipoxygenase in calcified aortas. Lipoxygenase inhibitor was used to clarify the effect of lipoxygenase metabolic pathways on vascular calcification. The results showed that 6 weeks after nephrectomy surgery, the aortic calcium content of the surgery group was significantly higher than that of the sham group (P < 0.05). Alizarin Red S staining and Von Kossa staining showed obvious calcium deposition in aortic arch from surgery group, indicating formation of vascular calcification. Nine arachidonic acid lipoxygenase metabolites were quantitated using liquid chromatography/mass spectrometry (LC-MS) analysis. The content of multiple metabolites (12-HETE, 11-HETE, 15-HETE, etc.) was significantly increased in calcified aortas, and the most abundant and up-regulated metabolite was 12-HETE. Furthermore, we examined the mRNA levels of metabolic enzymes that produce 12-HETE in calcified blood vessels and found the expression of arachidonate lipoxygenase-15 (Alox15) was increased. Blocking Alox15/12-HETE by Alox15 specific inhibitor PD146176 significantly decreased the plasma 12-HETE content, promoted calcium deposition in aortic arch and increased vascular calcium content. These results suggest that the metabolism of arachidonic acid lipoxygenase is activated in calcified aorta, and the Alox15/12-HETE signaling pathway may play a protective role in vascular calcification.
12-Hydroxy-5,8,10,14-eicosatetraenoic Acid ; Animals ; Arachidonate 12-Lipoxygenase ; Arachidonate 15-Lipoxygenase/metabolism* ; Arachidonic Acid ; Hydroxyeicosatetraenoic Acids ; Lipoxygenase/metabolism* ; Mice ; Signal Transduction ; Vascular Calcification

The objective of this paper was to investigate the effect and mechanism of mitochondrial ATP-sensitive K(+) (MitoK(ATP)) channel on the proliferation of airway smooth muscle cells (ASMCs) in asthmic rats. Thirty-six Sprague-Dawley (SD) rats were randomly assigned into 2 groups (18 in each): (1) Asthma group: the asthmic rat model was established by ovalbumin (OVA) sensitization and excitation; (2) Normal group: rats were subjected to inhalation of equal amount of normal saline. The rat ASMCs were isolated from fresh lung tissues and cultured respectively as follows: (1) CONTROL GROUP: normal ASMCs were cultured under normoxia for 24 h; (2) Diazoxide group: normal ASMCs were cultured under normoxia for 24 h with diazoxide (an opener of MitoK(ATP) channel); (3) 5-HD group: normal ASMCs were cultured under normoxia for 24 h with 5-hydroxydecanoate (5-HD) (an antagonist of MitoK(ATP) channel); (4) Asthma group: Asthmic ASMCs were cultured under normoxia for 24 h; (5) Asthma + diazoxide group: Asthmic ASMCs were cultured under normoxia with diazoxide for 24 h; (6) Asthma + 5-HD group: Asthmic ASMCs were cultured under normoxia with 5-HD for 24 h. The mitochondrial membrane potential (ΔΨm) was detected using Rhodamine 123 (R-123). The level of reactive oxygen species (ROS) was detected by DCF fluorescence. The expression of nuclear factor-kappa B (NF-κB) mRNA was examined by RT-PCR. The proliferation and apoptosis of rat ASMCs were examined respectively by MTT colorimetric assay and cell cycle analysis. The results were as follows. (1) After exposure to diazoxide for 24 h, the R-123 fluorescence intensity, the ROS level, NF-κB mRNA expression and the MTT absorbance value (A value) in normal ASMCs were significantly increased, and the apoptosis of rat ASMCs was significantly decreased compared to the control group (P<0.05). However, there was no significant changes in those indices after the normal ASMCs had been exposed to 5-HD for 24 h. (2) In Asthma and Asthma + diazoxide groups, the R-123 fluorescence intensity, ROS level and the MTT A value were markedly increased, and the apoptosis was markedly decreased compared to control group (P<0.05). These changes were more obvious in Asthma + diazoxide group than those in Asthma group (P<0.05). 5-HD partly weakened the effect of asthma on the R-123 fluorescence intensity, ROS level and the MTT A value and the apoptosis of rat ASMCs (P<0.05). R-123 fluorescence intensity and NF-κB mRNA expression were positively correlated with ROS level. NF-κB mRNA expression was positively correlated with the MTT A value and negatively correlated with the apoptosis of rat ASMCs. All the results suggest that the opening of MitoK(ATP) channel followed by a depolarization of ΔΨm contributes to the increase in ROS level and NF-κB mRNA expression in rat ASMCs and to the unbalance between cell proliferation and apoptosis of ASMCs induced by asthma. This might be a mechanism of the development of airway remodeling in asthma.
Airway Remodeling ; Animals ; Apoptosis ; Asthma ; physiopathology ; Cell Proliferation ; Cells, Cultured ; Decanoic Acids ; pharmacology ; Diazoxide ; pharmacology ; Hydroxy Acids ; pharmacology ; Lung ; cytology ; Membrane Potential, Mitochondrial ; Myocytes, Smooth Muscle ; metabolism ; Potassium Channels ; metabolism ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species ; metabolism