Tacalcitol (1,24(OH)2D3, TV-02) inhibits phorbol ester-induced epidermal proliferation and cutaneous inflammation,and induces epidermal differentiation in mice

In this study, we examined the cutaneous effects of tacalcitol [1, 24(R)(OH)₂D₃] on epidermal proliferation, differentiation, and skin inflammation in vivo using hairless mice. Tacalcitol was shown to inhibit epidermal proliferation using TPA-induced ornithine decarboxylase activity and DNA synthesis as indices, and the induction of epidermal differentiation using type I transglutaminase activity as an index. Tacalcitol also displayed an antiinflammatory effect on TPA-induced inflammatory changes histopathologically. These results confirm the clinical efficacy of tacalcitol in psoriasis, and suggest that it may be efficacious in the treatment of other inflammatory skin diseases.     

The comparison between trichloroacetic Acid 50% and co(2) laser in the treatment of cutaneous leishmaniasis scar

Background:

The scars of the cutaneous leishmaniasis and psychological problems of this disease need different interventions for its correction.

Aim:

Our objective in this study was to compare the efficacy of 50% trichloroacetic acid (TCA) solution and CO₂ laser for treatment of the atrophic scars due to leishmaniasis.

Materials and Methods:

This was a randomized clinical trial performed in 92 patients. Patients were randomized into two groups: the first group was treated with 50% TCA solution, once monthly and for a maximum of 5 months, and the second group was treated with CO₂ laser which was performed for only one time. Patients were followed-up at 3 and 6 months after starting the treatment. The improvement of scar was graded by a 6-point scale using digital camera and the collected data were analyzed using SPSS software.

Results:

In this study, 74 females and 18 males were enrolled. The improvement of scar was 48.13% in the TCA group and 44.87% in the CO₂ laser group. This difference was not statically significant (P = 0.55). There was also no significant difference regarding side effects between these two groups.

Conclusion:

The results of our study showed that efficacy of focal with 50% TCA solution is compared with CO₂ laser in treatment of leishmaniasis scar. Because of the low cost and simple application of TCA solution in comparison with CO₂ laser, we suggest use of this treatment for correction of leishmaniasis scar or the atrophic scars.     

Expression of apoptosis regulatory markers in the skin of advanced hepatitis-C virus liver patients

Background:

Hepatitis-C virus (HCV) infection is considered a major worldwide public health problem with a global prevalence. Maintenance of skin homeostasis requires a delicate balance between proliferation, differentiation, and apoptosis. Meanwhile, it is unclear if there is an altered keratinocyte proliferation/apoptosis balance in advanced liver disease with HCV infection.

Aim:

This work aimed to evaluate the epidermal thickness and changes in the expression of apoptosis regulatory markers as well as apoptotic index in skin samples of advanced HCV liver patients compared to normal controls.

Materials and Methods:

Twenty biopsies were taken from apparently normal skin of advanced HCV liver disease patients, as well as five healthy control subjects. These specimens were used for histometric epidermal measurement, immunohistochemical staining of apoptosis regulatory proteins (Bax, Fas, p53, Caspase-3, Bcl-2, Bcl-xL) as well as the TUNEL technique for detection of apoptotic cells.

Results:

The mean epidermal thickness was significantly lower than the control group (P=0.000). There were significant overexpression of pro-apoptotic markers (Bax, Fas, P53, and Caspase-3) in patients (P=0.03, 0.03, 0.003, 0.003 respectively), with increased apoptotic index in HCV liver patients (P=0.002) when compared to normal controls. On the other hand, no statistically significant difference were encountered in the expression of antiapoptotic markers (Bcl-2, Bcl-xL) in HCV patients when compared to normal controls (P=0.5, 0.9, respectively).

Conclusion:

These findings suggest that an alteration in the proliferation/apoptosis balance is present in the skin of HCV liver patients.     

Fractional CO2 Laser Versus Intense Pulsed Light in Treating Striae Distensae

Context:Striae distensae are linear atrophic dermal scars covered with flat atrophic epidermis. They may cause disfigurement, especially in females. Many factors may cause striae distensae such as steroids, obesity, and pregnancy. Although there is no standard treatment for striae; many topical applications, peeling, and light and laser systems have been tried.Aims:To evaluate and compare the efficacy of fractional CO₂ laser with intense pulse light in treating striae distensae.Results:Both groups showed significant improvement after treatments (P < 0.05). Patients treated with fractional CO₂ laser showed significant improvement after the fifth session compared with those treated with ten sessions of intense pulsed light (P < 0.05) in all parameters except in the length of striae (P > 0.05).Conclusions:The current study has provided supportive evidence to the effectiveness of both fractional CO₂ laser and intense pulse light as treatments for striae distensae. Fractional CO₂ laser was found to be more effective in the treatment of striae distensae compared with intense pulse light.     

环氧合酶-2和磷酸化P38丝裂原活化蛋白激酶在扁平苔藓皮损中的表达

目的：检测环氧合酶-2（COX-2）及其上游调控蛋白磷酸化P38丝裂原活化蛋白激酶（p-P38MAPK）在扁平苔藓皮损中的表达，探讨其在发病中的意义。方法：采用免疫组化技术检测20例扁平苔藓皮损标本中COX-2和p-P38MAPK的表达情况，20例正常皮肤组织作为对照。结果：20例扁平苔藓皮损标本中COX-2和p-P38MAPK的积分光密度值（IOD）分别为（8.46±1.79）×10³和（11.54±2.85）×103，均明显高于对照组(3.14±2.35)×103和(6.26±3.12)×10³，差别具有统计学意义（均P＜0.01），同时COX-2与p-P38MAPK的表达强度呈正相关（r=0.62，P＜0.01）。结论：扁平苔藓皮损中COX-2表达上调，可能与上游P38MAPK的活化有关，可能是引起扁平苔藓发病的环节之一。     

Effect of dihomogammalinolenic acid and its 15-lipoxygenase metabolite on eicosanoid metabolism by human mononuclear leukocytes in vitro: selective inhibition of the 5-lipoxygenase pathway

Summary The purpose of the present study was to determine the effect of the n-6 fatty acid, dihomogammalinolenic acid (DGLA, 203, n-6) on arachidonic acid (AA) (C204) metabolism by human peripheral mononuclear leukocytes (HPML). After incubation of HPML with A23187 (5 M) and DGLA, the cyclooxygenase (CO) and lipoxygenase (LO) products were separated and quantified by reversed-phase high-performance liquid chromatography (RP-HPLC) combined with radioimmunoassay. DGLA led to no change in PGE₂ formation, but at similar concentrations there was a dose-dependent decrease in LTB₄ formation (IC₅₀=45.0 M). The inhibition of LTB₄ formation by DGLA was associated with a dosedependent increase in its 15-LO metabolite 15-hydroxyeicosatrienoic acid (15-HETrE) and its CO metabolite prostaglandin E₁ (PGE₁). Incubation of HPLM with 15-HETrE (0–1.5 M) alone did not result in a change in PGE₂ formation, whereas 15-HETrE was a much more potent inhibitor of LTB₄ formation (IC₅₀=0.5 M) than DGLA. These results show that the addition of DGLA to HPML results in a selective inhibition of LTB₄ formation, presumably via its metabolite (15-HETrE).     

The Rate and Pattern of Bcl-2 and Cytokeratin 15 Expression in Trichoepithelioma and Nodular Basal Cell Carcinoma: A Comparative Study

Context:

Histopathological evaluations can differentiate between clinically resembling trichoepithelioma (TE) and basal cell carcinoma (BCC) unless the biopsy specimens are small or superficial. Previous studies used immunohistochemical evaluation for Bcl-2 and cytokeratin 15 (CK15), in attempts to differentiate between these two entities, with heterogeneous findings.

Aims:

This study intended to compare the rate and patterns of Bcl-2 and CK15 expressions between specimens of TE and nodular BCC.

Settings and Design:

Case-series including formalin-fixed, paraffin-embedded cutaneous biopsies.

Subjects and Methods:

Twenty-two BCC and 12 TE specimens were stained for Bcl-2 and CK15 and examined microscopically. The rate and patterns of expressions were compared between the two groups.

Statistical Analysis Used:

Statistical analysis was performed using the statistical software (SPSS version 16.0; SPSS Inc., Chicago, IL, USA), Pearson Chi-square, or Fisher''s exact tests, wherever appropriate.

Results:

The two groups were comparable for the expression rate and patterns of Bcl-2 (86.4%: 5 central, 14 diffuse in BCC vs. 83.3%: 2 central, 8 diffuse in TE; P = 0.59 and 0.54 for rate and pattern, respectively). The rate of CK15 expression was significantly higher in TE specimens (66.7%: 4 central, 3 diffuse, 1 peripheral vs. 4.5%: 1 central; P < 0.001). The positive likelihood ratio in distinguishing the two neoplasms was 14.7 (95% confidence interval: 2.1-103.7).

Conclusions:

CK15 but not Bcl-2 staining may help in differentiating between BCC and TE even in BCCs with follicular differentiation.     

Comparing the effectiveness of fractional CO2 laser and the combination therapy with micro-needling and topical 10% trichloroacetic acid to remove infra-orbital dark circles in Tehran women

Background: Infra orbital dark circles are now recognized as being a cosmetic problem that should be considered in treatment issue. The present study aimed to assess and compare the clinical efficiency of the combination of micro-needling and 10% trichloroacetic acid (TCA) cream as well as carbon dioxide laser in the management of infra-orbital dark circles. Methods: This randomized clinical trial was performed on women aged 28–62 years who complained of infra-orbital dark circles. The patients were randomly assigned to be treated with micro-needling combined with 10% TCA cream topically or CO₂ laser. The treatment period in each group included three sessions with an interval of one month between sessions. The assessment was based on both subjective and objective methods. Results: the mean of ΔE (the difference in the intensity of darkening at infra-orbital points and other points of the face) was significantly higher in the laser group than in the other group in all sessions. The patients who were treated with laser were found to have a higher level of satisfaction in the fifth visit when compared to those who received the other treatment method. Conclusion: Regarding clinical effectiveness and the patients’ compliance, fractional CO₂ laser was more preferred in the combination therapy with micro-needling and topical TCA for removing infra-orbital dark circles.     

Changes of membrane fluidity and Na+, K+-ATPase activity during cellular differentiation in the guinea pig epidermis

Summary The dynamic properties of plasma membrane in epidermal cells were determined by means of electron spin resonance using two kinds of doxyl stearic acid spin labeling agents: 5-DSA and 12-DSA. 5-DSA and 12-DSA are stearic acid analogues with a nitroxide radical ring at the 5th and 12th carbon positions, and these motions reflect molecular motion of lipid bilayer surrounding the hydrophilic region and the hydrophobic region, respectively. Guinea pig epidermal cells were separated into three regions of keratinocytes by Percoll density gradient centrifugation; the upper, middle, and lower epidermal cells. The order parameter S values for 5-DSA and 12-DSA incorporated into the isolated keratinocytes increased, suggesting a decrease in the plasma membrane fluidity, as cells approached the upper epidermal cell layer. The Na⁺, K⁺-ATPase activity as a plasma membrane-bound enzyme was determined in each epidermal cell region, and was found to decrease gradually as the cells approached the upper layer. Accordingly, the differentiation of epidermal cells in the keratinization process was found to be assiciated with a decrease in plasma membrane fluidity and with a decline of Na⁺, K⁺-ATPase activity.     

Vagarious successful treatment of recalcitrant warts in combination with CO2 laser and imiquimod 5% cream

Abstract

Background. Imiquimod 5% cream is widely regarded as a safe and effective option when treating recalcitrant warts, owing to the ointment's negligible side effects. However, our observations highlighted case of a patient incurring severe adverse reactions due to application of the cream, although the treatment proved successful in curing recalcitrant warts which had developed on the external auditory canal and external ear. Methods. All lesions were entirely removed with short-pulsed CO₂ laser. As soon as the wound-healing process was completed, imiquimod 5% cream was self-applied on the healing wounds once daily for 5 days per week in a total of 2 weeks. Results. The patient appeared normal after the CO₂ laser treatment and experienced severe redness, itching, exudation, and incrustation after a 2-week imiquimod 5% cream therapy. All lesions showed no recurrence during the 12-month followed-up process. Conclusions. We concluded that a feasible treatment modality to cure recalcitrant cutaneous warts is in combination of CO₂ laser and imiquimod. Immunoenhancement plays an important role in the treatment of recalcitrant warts.     

Efficacy and Safety of Terbinafine Hydrochloride 1% Cream vs. Sertaconazole Nitrate 2% Cream in Tinea Corporis and Tinea Cruris: A Comparative Therapeutic Trial

Context:

To the best of our knowledge, till date no study comparing the efficacy and safety of terbinafine hydrochloride 1% cream and sertaconazole nitrate 2% cream has been done in localized tinea corporis and tinea cruris.

Aims:

This clinical trial was carried out to study and compare the efficacy of topical terbinafine hydrochloride 1% cream and sertaconazole nitrate 2% cream in localized tinea corporis and tinea cruris and to know the adverse effects of these antifungal creams.

Settings and Design:

In this prospective, single blind, randomized control trial with two arms, patient were randomized into two groups Group A (treatment with terbinafine cream) and Group B (treatment with sertaconazole cream). A total of 38 patients were enrolled for the study, 20 patients in group A and 18 patients in group B. But five patients of group A and three patients of group B were lost for follow-ups. Therefore sample size was of 30 patients with 15 patients in group A and group B each.

Materials and Methods:

Patients in group A and B were treated with twice daily topical 1% terbinafine hydrochloride and 2% sertaconazole nitrate cream respectively for a total duration of three weeks. Clinical improvement in signs and symptoms of each clinical parameter, namely itching, erythema, papules, pustules, vesicles, and scaling were graded weekly and clinical cure was assessed. KOH mount and culture was done weekly up to 3 weeks to access mycological cure. Fungal culture was done on Sabouraud''s dextrose agar with chloramphenicol and cycloheximide.

Statistical Analysis Used:

Statistical analysis was done using students paired and unpaired t-tests from the data obtained.

Results:

Comparison between Group A and Group B for complete cure (clinical and mycological) showed that at the end of 3 weeks both terbinafine and sertaconazole groups had 100% complete cure. When the two groups were compared for complete cure, at the end of 1^st and 2^nd week, statistically non-significant results were observed (P = 0.461 and P = 0.679 respectively). However, at the end of 2^nd week, complete cure rate for terbinafine was 80% as compared to 73.35% for sertaconazole with no statistical significance. In both Group A and Group B, clinically significant local side effects like erythema, swelling, stinging sensation, or increased itching were not noticed. A majority of our patients in both the group showed Trichophyton rubrum followed by Trichophyton mentagrophytes growth on culture. In Group A, 11 patients showed growth of T. rubrum, 2 patients showed growth of T. mentagrophytes, and 1 patient had only KOH test positive. In Group B, 10 patients revealed growth of T. rubrum, followed by growth of T. mentagrophytes in 3 and Microsporum canis in 2 patients. The therapeutic response is more or less same in infection with different species.

Conclusions:

The newer fungistatic drug sertaconazole nitrate 2% cream was as effective as terbinafine hydrochloride 1% cream which is one of the fungicidal drugs, though terbinafine hydrochloride 1% cream has higher rates of complete cure at the end of 2 weeks as compared to sertaconazole nitrate 2% cream. Both the drugs showed good tolerability with no adverse effects.     

A systematic review of comparative studies of CO2 and erbium:YAG lasers in resurfacing facial rhytides (wrinkles)

Background: Laser resurfacing is used to minimize wrinkles, solar scars and sequelae of acne. Objective: Purpose of the systematic review was to compare resurfacing outcomes of CO₂ laser and erbium: yttrium aluminium garnet (erb:YAG) laser therapies. Materials and methods: Medline, Cochrane Library, EMBASE and Google Scholar databases were searched until 9 April 2015 using the following terms: laser, carbon dioxide/CO₂, facial wrinkles, rhytides and erbium-doped yttrium aluminium garnet/erbium:YAG/Er:YAG. Two-armed controlled split faced studies that compared CO₂ laser and erbium:YAG laser in patients with mild-to-moderate facial wrinkles or rhytides were included. Results: The pooled data in this study and findings of other studies support the greater efficacy with the CO₂ laser in improving facial wrinkles, but the erb:YAG laser was associated with a better complication profile compared with the CO₂ laser. Except one case of hypopigmentation, other complications (i.e., erythema, hyperpigmentation and crusting) and their rates were reported by studies examining both lasers. Conclusion: In general, the CO₂ laser appeared to be more efficacious then the erb:YAG laser in treating facial wrinkles. Both lasers treatments were well tolerated.     

The clinical effectiveness and cost-effectiveness of fractional CO2 laser in acne scars and skin rejuvenation: A meta-analysis and economic evaluation

Introduction: Fractional CO₂ has many indications in medicine including in treatment of acne scars and rejuvenation. The aim of this study was to evaluate the safety, efficacy, and cost-effectiveness of Fractional CO₂ Laser in comparison with other methods of rejuvenation and acne scar treatment. Materials and Methods: Several databases including Medline, OVID, EMBASE, CINHAL, SCOPUS, Web of science, CRD, and Cochrane were searched. After conducting the search and evaluation of selected publications, critical appraisal was done and eligible studies were accepted for inclusion in the systematic review. Results and Discussion: From 2667 identified publications two of the trials were eligible. The effectiveness and complications of Fractional CO₂ laser were comparable with Er:YAG but Fractional CO₂ laser was 14.7% (p = 0.01) more effective than Q-Switched ND:YAG laser. Cost affectivity of this method was the same as other alternative lasers. In conclusion Fractional CO₂ laser is an effective and safe method for curing of several kinds of skin diseases. Nevertheless there was not sufficient evidence to support its advantage. This device has equal or lower price in comparison to competent technologies except for the non- fractional ablative CO₂ laser that has the same or lower price and comparable effects.     

Congenital melanocytic nevus on the lower eyelid treated with continuous wave and superpulsed CO2 laser followed by erbium laser

There are several therapeutic options to treat congenital melanocytic nevi. The motivations for the treatment of small- to medium-sized congenital nevi located on the face or other sensitive areas are frequently cosmetic. The choice of therapy depends on the operator’s expertise and on the likelihood of improved cosmesis. We report a case of a medium-sized congenital nevi located on the lower eyelid, successfully treated with a combination of ablative lasers with a single surgical procedure. We achieved an excellent clinical and cosmetic result. No scarring, distortion, or recurrence were observed.     

SHARPIN regulates mitochondria-dependent apoptosis in keratinocytes

Background

The chronic proliferative dermatitis mutation (CPDM) in mice, due to Sharpin deficiency (Sharpin^cpdm), is a multisystem disorder characterized by peripheral blood eosinophilia and eosinophil infiltration of affected tissues including the skin, bone marrow, spleen, lung, heart, and other organs. The epidermis has numerous apoptotic keratinocytes which increase with age, coalesce, form vesicles, and rupture causing ulceration.

Objective

To clarify the molecular pathways involved in the keratinocyte apoptosis caused by loss of function of SHARPIN in mice.

Method

10-week-old Sharpin^cpdm and wildtype mice were used for experiments. Ultrastructural changes of skin were evaluated by transmission electron microscopy. Cross points of mitochondrial pathway were analyzed by in vitro and in vivo cellular and molecular assays.

Results

77.5% skin cells in Sharpin^cpdm mice were functionally apoptotic and dead cells, compared to only 18.1% unhealthy skin cells in wildtype mice, indicated by annexin-V/propidium iodide FACS analysis. Mitochondria in keratinocytes were disrupted containing prominent electron dense inclusions and membrane potential depolarization, accompanied by a shift in protein expression between the anti-apoptotic BCL2 and pro-apoptotic BAX proteins. Enzymatic activities of caspases 9 and 3, but not 8, were markedly increased in Sharpin^cpdm keratinocytes. Caspase-3 was cleaved in most cells in skin of 10-week-old mutant mice.

Conclusion

The present results indicated that keratinocyte apoptosis in Sharpin^cpdm mice was regulated by an intrinsic caspase-dependent mitochondria pathway.     

Combination treatment of CO2 fractional laser,pulsed dye laser,and triamcinolone acetonide injection for refractory keloid scars on the upper back

Abstract

Keloids and hypertrophic scars are common lesions, which typically present as a cosmetic concern; however, they also can cause significant pruritus and pain. These lesions pose as a particular therapeutic challenge among clinicians due to a lack of complete knowledge of the formation of keloids and hypertrophic scars. Multiple treatments are widely accepted, yet all have shown limited benefit. In this case, we describe the treatment combination of the Affirm CO₂ fractional laser (10 600 nm, Cynosure), Cynergy Pulsed dye laser (585 nm, Cynosure), and triamcinolone acetonide injection for keloids refractory to solitary treatments of triamcinolone acetonide injection and other laser modalities.     

环氧合酶-2反义寡核苷酸对Colo-16细胞增殖及环氧合酶-2表达的影响

目的　研究环氧合酶（COX）-2反义寡核苷酸（AsODN）对人皮肤鳞状细胞癌细胞株Colo-16细胞体外增殖的抑制作用及COX-2表达的影响。方法　人工合成COX-2 AsODN,利用脂质体将不同浓度（50,100,200,400 nmol/L）反义寡核苷酸转染入Colo-16细胞,免疫荧光显微镜观察转染情况;采用噻唑蓝（MTT）法检测Colo-16细胞的增殖情况;Western印迹及半定量逆转录PCR检测Colo-16细胞COX-2蛋白和mRNA表达水平。结果 不同浓度的COX-2 AsODN对Colo-16细胞体外增殖均具有抑制作用（P < 0.05）,400 nmol/L反义组在48 h抑制率最高,达60.3%;COX-2 AsODN转染Colo-16细胞后,COX-2蛋白和mRNA表达明显下调,50、100、200、400 nmol/L组COX-2蛋白灰度值分别为0.763 ± 0.070、0.600 ± 0.065、0.430 ± 0.074、0.251 ± 0.045,与阴性对照组相比差异均有统计学意义（P < 0.05）;COX-2 mRNA表达量随COX-2 AsODN浓度的增加而减少,50、100、200、400 nmol/L组COX-2 mRNA灰度值分别是0.778 ± 0.025、0.602 ± 0.041、0.417 ± 0.031、0.297 ± 0.051,各组间COX-2 mRNA表达差异有统计学意义（F = 132.48,P < 0.01）。结论 COX-2 AsODN对Colo-16细胞的体外增殖有抑制作用,并能下调COX-2蛋白及其mRNA在Colo-16细胞中的表达,提示COX-2 AsODN有潜在治疗皮肤鳞状细胞癌的作用。