Effect of palmitic acid on neutrophil functions in vitro

BACKGROUND: It has been shown that in acne comedones the proportion of linoleic acid is markedly decreased, while palmitic acid is significantly increased. We previously reported that the decreased proportion of linoleic acid, which markedly suppresses neutrophil reactive oxygen species (ROS) generation and phagocytosis, contribute to the worsening of acne inflammation. The aim of this study was to examine the effect of palmitic acid on neutrophil functions in vitro. METHODS: We investigated the effect of palmitic acid on inflammatory parameters such as neutrophil chemotaxis, phagocytosis, and ROS generation. Reactive oxygen species generation in a cell-free, xanthine-xanthine oxidase system was also assessed. The species examined were superoxide radical anion (O2-), hydrogen peroxide (H2O2), and hydroxyl radical (OH.). RESULTS: Palmitic acid significantly decreased H2O2 generation both by neutrophils and in the xanthine-xanthine oxidase system, while neutrophil chemotaxis and phagocytosis as well as O2- and OH. generation by both systems were not markedly affected in the presence of palmitic acid. CONCLUSIONS: The present study suggests that palmitic acid may be involved in the pathogenesis of acne inflammation from a standpoint of oxidative tissue injury.     

Suppressive effects of linoleic acid on neutrophil oxygen metabolism and phagocytosis

On the basis of recent reports that the proportion of linoleic acid (C18:2Cis 9,12), a free fatty acid, is markedly decreased in acne comedones and that tetracycline is effective against acne comedones by acting directly as an antioxidant on infiltrating neutrophils, we investigated the effect of linoleic acid on several inflammatory parameters of neutrophils, including neutrophil chemotaxis, phagocytosis, and generation of reactive oxygen species (ROS). Linoleic acid significantly decreased phagocytosis and the generation of O2-, H2O2, and OH.by neutrophils, whereas it did not significantly inhibit neutrophil chemotaxis or decrease the ROS levels generated in a cell-free, xanthine-xanthine oxidase system. The present study seems to suggest that decreased levels of linoleic acid in acne comedones contribute, in part, to the worsening of acne inflammation by the failure of low levels of linoleic acid to suppress neutrophil phagocytosis and ROS generation.     

Effects of cepharanthin on neutrophil chemotaxis, phagocytosis, and reactive oxygen species generation.

The effects of cepharanthin on inflammatory parameters such as neutrophil chemotaxis, phagocytosis and reactive oxygen species (ROS) generation, were examined. Cepharanthin significantly decreased the levels of O2-, H2O2, and OH. generated by neutrophils. H2O2 and OH. generated in a cell-free, xanthine-xanthine oxidase system were also reduced in the presence of cepharanthin. However, the drug did not affect neutrophil chemotaxis or phagocytosis. The present study indicates that cepharanthin is an effective ROS scavenger, exerting its anti-inflammatory action by reducing the potent ROS species excessively generated in tissues and organs, especially at the sites of inflammation.     

Anti-oxidant effects of gold compounds

The anti-oxidant efficacy, in vitro, of the gold compounds auranofin (AF) and gold sodium thiomalate (GST) was examined by studying their effects on the generation of reactive oxygen species (ROS) using zymosan-stimulated polymorphonuclear leukocytes (PMNs) and a cell-free, xanthine-xanthine oxidase system. The oxygen species investigated were the superoxide radical anion (O2-), hydrogen peroxide (H2O2) and the hydroxyl radical (OH.). AF had an inhibitory effect on ROS production by PMNs. In particular, OH. generation was significantly suppressed in a dose-dependent fashion. AF did not inhibit ROS production in the cell-free system. GST produced only a small degree of inhibition at higher concentrations. These findings suggest that AF may play an important role in the inhibition of respiratory bursts and the generation of inflammatory reaction products. Since the products of the respiratory burst, especially potent oxidants such as OH. and H2O2, are thought to be important inflammatory mediators, it is postulated that the blockade of toxic ROS generation by AF affects rheumatoid as well as dermatological inflammation and tissue damage.     

Efficacy and safety of oral silymarin in comparison with oral doxycycline and their combination therapy in the treatment of acne vulgaris

Two factors of oxidative stress and inflammatory processes are implicated in pathogenesis of acne vulgaris. Silymarin has antioxidant and anti‐inflammatory activities. This study was done to evaluate the effect of oral silymarin in the treatment of acne vulgaris compared to doxycycline and also their combination therapy. This randomized controlled trial was performed on 60 patients with acne vulgaris were divided into three groups of 20 patients, including: Silymarin (Group 1), Doxycycline (Group 2), and both compounds (Group 3). The patients' response was monitored every month and the lesions were evaluated using photography and two methods of Global Acne Grading system (GAGS) and Acne Severity Index (ASI). According to the results, the response to silymarin was not significantly different with doxycycline in the GAGS index (p = .260), but was lower in the ASI (p = .021). In this study, the synergistic effects of silymarin and doxycycline combination have been investigated in comparison with doxycycline. Although the improvement was more favorable in combination group, there was no statistically significant difference (p = .9 in ASI and p = .5 in GAGS). The results of our study suggest that although the silymarin monotherapy is not as effective as doxycycline for the treatment of acne vulgaris, it can be a therapeutic option.     

A comparison of doxycycline and minocycline in the treatment of acne vulgaris

A 12–week, observer-blind, study compared doxycycline (50 mg daily) with minocycline (50 mg twice daily) in the treatment of acne vulgaris in 4.1 patients. The analysis of data on 34 patients completing the study (15 receiving doxycycline and 19 receiving minocycline) showed both treatments to be equally effective, although the use of doxycycline had the advantage of it being a once-daily treatment regime. Doxycycline, with minimal side effects, can be recommended for the treatment of acne vulgaris.     

Treatment of acne vulgaris. A comparison of doxycycline versus minocycline

In the course of a randomized, comparative, clinical study, 50 patients with acne vulgaris received systemic treatment with a single daily dose of 50 mg doxycycline or two daily doses of 50 mg minocycline. At the completion of the 12-week treatment, cure or improvement of acne was found in 78% of the patients in the doxycycline group compared to 82% in the minocycline group. The rate of unsatisfactory therapeutic results was 22% in the doxycycline group and 18% in the group of patients treated with minocycline. The results showed no significant difference between the clinical efficacy of treating acne vulgaris with doxycycline at a daily dose of 50 mg and 100 mg of minocycline daily, a fact which has already been demonstrated by earlier studies.     

Increased hydrogen peroxide generation by neutrophils from patients with acne inflammation

BACKGROUND: Reactive oxygen species generated by neutrophils are closely correlated with the pathogenesis of a variety of inflammatory skin diseases. The aim of this study was to investigate the possible role of reactive oxygen species generated by neutrophils in the mediation of acne inflammation. METHODS: Bacterial phagocytotic stimuli, mediated by opsonin activity, were applied to whole blood, and neutrophil hydrogen peroxide production was measured. RESULTS: Patients with acne inflammation showed a significantly increased level of hydrogen peroxide produced by neutrophils compared to patients with acne comedones and healthy controls. There were no marked differences in the level of hydrogen peroxide produced by neutrophils between patients with acne comedones and healthy controls. In addition, patients with acne inflammation treated by oral administration of minocycline hydrochloride, a drug that inhibits hydrogen peroxide generation by neutrophils, showed a significant decrease in the ability of neutrophils to produce hydrogen peroxide in accordance with a decrease in the inflammatory activity of acne lesions. CONCLUSIONS: The present study seems to suggest that acne inflammation is mediated in part by hydrogen peroxide generation by neutrophils.     

Effects of subantimicrobial-dose doxycycline in the treatment of moderate acne

OBJECTIVE: To determine if treatment with subantimicrobial-dose (SD) doxycycline hyclate (20-mg tablets taken twice daily) improved clinical outcome, had any detectable effect on skin flora, led to overgrowth or colonization of skin by opportunistic pathogens, or resulted in an increase in antibiotic resistance by the surface skin microflora in patients with moderate acne compared with placebo. DESIGN: Multicenter, double-blind, randomized, placebo-controlled, parallel-group trial. SETTING: Two university-based clinics. SUBJECTS: Adults (N = 51) with moderate facial acne. INTERVENTIONS: Patients were randomized to receive SD doxycycline (Periostat; CollaGenex Pharmaceuticals Inc, Newtown, Pa) or placebo twice daily for 6 months. MAIN EFFICACY OUTCOMES: Primary: changes from baseline in numbers of inflammatory, noninflammatory, and total lesions. Secondary: changes from baseline of individual counts of papules, pustules, and nodules and global assessments of clinical improvement by patient and physician. RESULTS: Forty patients completed 6 months of treatment. At 6 months, the SD doxycycline group had a significantly greater percent reduction in the number of comedones (P<.01), inflammatory and noninflammatory lesions combined (P<.01), and total inflammatory lesions (P<.05) than did the placebo group. They also had significantly greater improvement according to the clinician's global assessment (P =.03). There were no significant differences in microbial counts between groups and no evidence of change in antibiotic susceptibility or colonization by potential pathogens. The treatment was well tolerated. CONCLUSIONS: Twice-daily SD doxycycline treatment significantly reduced the number of inflammatory and noninflammatory lesions in patients with moderate facial acne, was well tolerated, had no detectable antimicrobial effect on the skin flora, and did not result in any increase in the number or severity of resistant organisms.     

Effects of date seed oil on normal human skin in vitro

Oxidative stress has been implicated in various skin diseases through the generation of reactive oxygen species and the depletion of endogenous antioxidant systems. The administration of antioxidants or free radical scavengers is reportedly helpful, notably in order to enhance the healing process. We investigated the protective effect of one new natural product:"date seed oil: DSO" against hydrogen peroxide (H(2)O(2))-induced oxidative stress, in terms of lipid peroxidation, depletion of endogenous antioxidant defense enzymes such as glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT), one day after a 2 h exposure to H(2)O(2), using human skin organ culture as an in vitro model. In the investigated model system, DSO has significant protective effect, by inhibition of damage caused by H(2)O(2), endowing a radical scavenging ability. Treatment of skin with DSO inhibited H(2)O(2)-induced lipid peroxidation. In addition, this oil inhibited H(2)O(2)-induced depletion of antioxidant defense components, such as superoxide dismutase and catalase. We conclude that DSO could be useful in the attenuation of H(2)O(2)-induced oxidative stress-mediated skin diseases in human skin, possibly due to antioxidant properties.     

Comparison of efficacy of azithromycin vs. doxycycline in the treatment of acne vulgaris

Acne vulgaris is a common inflammatory disorder of the skin. Oral antibiotics are known to be effective in its treatment. A randomized, investigator-blinded study was performed to compare the efficacy of azithromycin with doxycycline. Fifty-one patients were randomized to receive either azithromycin 500 mg/day on 3 consecutive days per week in the first, on 2 consecutive days per week in the second, and on 1 day per week in the third month. The other group was given doxycycline twice a day for the first month and once a day for the second and third months. Clinical assessment was made at baseline, at the end of first, second, third, and post-treatment first and second months. Side effects were recorded. Statistically significant improvement for the facial lesions were obtained with both drugs. Neither drug was shown to be more effective than the other. The beneficial effect continued until 2 months after treatment. In the azithromycin group three patients had diarrohea, while photosensitivity was seen in two patients using doxycycline. This study indicates that azithromycin is at least as effective as doxycycline in the treatment of acne.     

Anti-inflammatory actions of benzoyl peroxide: effects on the generation of reactive oxygen species by leucocytes and the activity of protein kinase C and calmodulin

Summary For many years, benzoyl peroxide has been used as a topical treatment for acne. Although the drug has been shown to interfere with a variety of pathways, believed to be of importance in the aetiopathogenesis of acne, its mechanism of action is thought to be principally antibacterial. Recent circumstantial evidence suggests that protein kinase C might serve as an additional pharmacological target of benzoyl peroxide. In the present study, we investigated the effects of benzoyl peroxide on the release of reactive oxygen species, regulated by protein kinase C and calmodulin, from human neutrophils, a potentially important step in acne inflammation. Micromolar drug concentrations were found to inhibit the release of reactive oxygen species, but there was marked drug-induced cytotoxicity in neutrophils. However, when tested in cell-free assays, benzoyl peroxide displayed marginal inhibition of protein kinase C, but failed to antagonize calmodulin, further investigations on its mechanism of action revealed non-specific interference with nucleotide binding sites. Therefore, the data presented here indicate that, in contrast with our previous findings with tetracycline derivatives, the clinical anti-inflammatory activity of benzoyl peroxide is unlikely to be mediated by protein kinase C or calmodulin. The differential interaction of drugs with protein kinase C and calmodulin might help to explain their different clinical usefulness in various degrees of acne severity.     

Azithromycin monthly pulse vs daily doxycycline in the treatment of acne vulgaris

Acne vulgaris is a common skin disease seen primarily in adolescent and young adults. As the treatment involves long term therapy with antibiotics, an agent with a long half life can be very useful in increasing the compliance. To evaluate the role of a monthly dose of azithromycin and compare it with daily doxycycline, we conducted this randomized comparative study. Sixty patients with moderate to severe acne were randomly assigned to two treatment groups, A & B. Patients in group A received 100 mg doxycycline daily in addition to topical 0.05% tretinoin cream, whereas patients in group B were given 500 mg azithromycin once a day for four days per month along with 0.05% topical tretinoin for a total of 12 weeks. Of the 60 patients, 22 in group A and 28 in group B were evaluated. The monthly dose of azithromycin was found to be as effective as daily doxycycline on a pure protocol basis and statistically significantly better than doxycycline by intention to treat analysis.     

The effect of treatment with 13-cis-retinoic acid on the metabolic burst of peripheral blood neutrophils from patients with acne

The N-formylmethionyl-leucyl-phenylalanine (f-MLP)-induced metabolic burst activity of peripheral blood neutrophils isolated from acne patients undergoing treatment with 13-cis-retinoic acid at a dose of 1.0 mg/kg/day was investigated using a luminol-enhanced chemiluminescence assay. The mean and median chemiluminescence response were significantly greater (P less than 0.05) in patients receiving 13-cis-retinoic acid than in untreated acne patients or age-matched controls. Pre-incubation of neutrophils with 13-cis-retinoic acid (10 nmol/l) did not affect the chemiluminescence response to formyl peptide. A sequential study over 20 weeks in seven patients demonstrated that chemiluminescence peaked after 2-8 weeks of treatment. In three patients this was accompanied by a worsening of their acne. These studies suggest that, in the initial phase, treatment with 13-cis-retinoic acid may exacerbate, through pro-inflammatory priming of neutrophils, certain neutrophil-mediated inflammatory processes in acne.     

Oral doxycycline for the treatment of chronic leg ulceration

This pilot study investigated oral doxycycline as an adjunct to compression therapy for non-healing venous leg ulcers. Ten patients received doxycycline 20 mg twice daily (low-dose doxycycline) and ten patients received doxycycline 100 mg twice daily (high-dose doxycycline). Utilising a pre-test post-test study design, ulcer area was measured and wound fluid was collected before and after 4 weeks of treatment. In the high-dose doxycycline group, the reduction in median ulcer area was 48% (p = 0.1) and there was a significant reduction in wound fluid total matrix metalloprotease-1 (p = 0.02). These effects were not observed with low-dose doxycycline. There were no significant changes in wound fluid tumour necrosis factor-α or quantitative bacteriology following treatment with low-dose or high-dose doxycycline. There was no significant relationship between change in ulcer area and matrix metalloprotease-1, -8 or -9 activities in wound fluid at the end of treatment. Median wound fluid doxycycline concentrations after 4 weeks of treatment were 0.2 mg/L(0.45 lM) and 2.3 mg/L (5.18 lM) [DOSAGE ERROR CORRECTED] in the low-dose and high-dose groups, respectively, which are lower than that previously shown to inhibit matrix metalloproteases and tumour necrosis factor-α. Our study suggests that doxycycline 100 mg twice daily may improve the healing rate of recalcitrant leg ulcers, however the mechanism remains unclear.     

Inhibitory effect of azelaic acid on neutrophil functions: a possible cause for its efficacy in treating pathogenetically unrelated diseases

Summary It has been shown that acne, hyperpigmentation and lentigo malignant are more or less related pathogenetically to reactive oxygen species (ROS). It has recently been reported that azelaic acid is effective in treating these conditions and that it possesses anti-enzymatic and anti-mitochondrial activity, including cytochrome-P₄₅₀ reductase and 5-reductase in microsomal preparations with nicotinamide adenine dinucleotide phosphate (NADPH). We therefore investigated the effects of azelaic acid on human neutrophil functions, such as chemotaxis, phagocytosis and ROS generation. ROS generation in a cell-free system was also assessed. The results revealed that neutrophil chemotaxis and phagocytosis as well as ROS generated in a xanthine — xanthine-oxidase system were not significantly changed in the presence of azelaic acid. However, azelaic acid markedly decreased O ₂ ^– and OH generated by neutrophils. It may be concluded that the reported clinical effectiveness of azelaic acid is partly due to its inhibitory action on neutrophil-generated ROS, leading to a reduction both in oxidative tissue injury at sites of inflammation and in melanin formation.     

Comparison of efficacy of azithromycin vs. doxycycline in the treatment of rosacea: a randomized open clinical trial

Background Rosacea is a common inflammatory disorder of the skin. Systemic antibiotics currently used in the treatment of rosacea are sometimes associated with uncomfortable side effects. Therefore, a need for an effective agent with few side effects and good patient compliance exists. Azithromycin, a macrolide antibiotic with prolonged mode of action, has recently been found to be an effective alternative in the treatment of inflammatory acne. Methods For evaluation of the efficacy of azithromycin in the treatment of rosacea, we planned a randomized, open, clinical trial study to compare the efficacy of azithromycin with doxycycline in the treatment of this disease. Sixty‐seven patients were randomized to receive either azithromycin 500 mg thrice weekly (on Monday, Wednesday, and Saturday) in the first, 250 mg thrice weekly (on Monday, Wednesday, and Saturday) in the second, and 250 mg twice weekly (on Tuesday, and Saturday) in the third month. The other group was given doxycycline 100 mg/day for the three months. Clinical assessment was made at baseline, at the end of first, second, third, and 2 months after treatment. Side affects were recorded. The limitation of this study is that there was no blindness. Results Statistically significant improvement was obtained with both drugs. Neither drug was shown to be more effective than the other. In the azithromycin group four patients had diarrhea, while epigastric burning was seen in two patients using doxycycline. Conclusion This study indicates that azithromycin is at least as effective as doxycycline in the treatment of rosacea.     

Severe drug hypersensitivity reaction in a young woman treated with doxycycline

Doxycycline is a commonly prescribed medication for the management of acne vulgaris. Severe adverse reactions to this medication are uncommon. We describe an unusual case of a 20-year-old female who experienced a life-threatening hypersensitivity reaction, including fever, lymphadenopathy, hepatitis, nephritis and severe pneumonitis with respiratory failure following oral administration of doxycycline for facial acne.     

The treatment of acne vulgaris with low dosage doxycycline

Doxycycline hyclate 20 mg bid is an effective maintenance dosage in patients with inflammatory acne. Twelve subjects aged 14 to 36, both men and women, completed a 16-week study to demonstrate the effectiveness of submicrobial dosing of doxycycline hyclate. Seventeen subjects were screened, and three withdrew before receiving any medication. The subjects received doxycycline hyclate 100 mg daily for eight weeks. One subject withdrew due to unrelated side effects. Eleven subjects had a 50% reduction of lesions at eight weeks, which qualified them to enter the second eight-week phase of the study. This group received either doxycycline hyclate 20 mg bid or placebo. The six subjects receiving doxycycline hyclate 20 mg bid maintained their improvement, while the placebo group did not.