Clinical Evaluation after Introduction of Stem Cell Supernatant Biocell Shot 65 by Electroporation

Objectives: The objective of this study is clinical evaluation after introduction of stem cell supernatant Biocell Shot 65 by electroporation. Background: There is a clinical report of psoriasis treatment by umbilical cord blood-derived stem cells, in which there was a beneficial result. These clinical results are the result of cord blood-derived cell growth factors. The umbilical cord blood-derived stem cell culture supernatant contains a high amount of TGF-β, PDGA, etc., and promotes wound healing. In addition, we suppose that the supernatant has the esthetic effect of improving skin condition, thus, we planned to make a clinical evaluation. However, it is difficult to set judgement criteria, and human judgement tends to be subjective. Therefore, in this study, as a new clinical evaluator, we used an AI skin diagnostic device with learning function. Methods: Stem cell culture supernatant Biocell Shot 65 was used as an introduction solution. After it was applied to the full faces of four patients, electroporation with BeBe pinocchio DM-5 SUPER DX Plus promoted infiltration deep in the keratinized layer. The patients were all healthy women in their forties. This procedure was performed every two weeks for three months. Wrinkles, fine lines around eyes, stains, pores, and 4V, which is considered as one diagnostic criteria, were evaluated at baseline and after each procedure with the skin diagnostic device HiMirror-Professional. In this study, macroscopic findings were not examined. Results: In all four patients, 4V did not change remarkably. Patient 1 showed improvement after the procedure in wrinkles, fine lines around eyes, stains, and pores. Patient 2 revealed improvement only in fine lines around eyes, but did not show improvement in other items. Patient 3 improved in wrinkles, stains, and pores only after the second procedure, but did not show improvement in the other procedures. Patient 4 improved in all items except 4V after the fourth procedure. In addition, when the mean values of all the patients were plotted and compared before and after each procedure, there was a trend toward improvements after the fifth procedure. Conclusion: In addition to application of supernatant culture to the skin, introduction of the solution to the skin by electroporation might improve stains, wrinkles, and pores. Our evaluation was performed with a facial diagnostic device three months after the start of the procedure.

Lipocalin-2 as a biomarker for diabetic nephropathy

Diabetes is a major global public health issue.The prevalence of type 1 diabetes is comparatively static,as hereditary and genetic causes are involved,while type 2 diabetes(T2D)prevalence is increasing day by day.T2D is associated with chronic complications,including diabetic neuropathy(DN),nephropathy,retinopathy,and other complications like diabetic foot.DN is the main complication of both types of diabetes.DN can be diagnosed by routine laboratory tests,microalbuminuria>300 mg/24 h,and a gradual decrease in glomerular filtration rate.As the appearance of microalbuminuria is a late manifestation,an early marker for renal damage is needed.Lipocalin-2,also known as neutrophil gelatinaseassociated lipocalin(NGAL),is a small protein purified from neutrophil granules and a good marker for kidney disease.NGAL is a transporter protein responsible for many physiological processes,such as inflammation,generation of the immune response,and metabolic homeostasis.NGAL has been reported to depict the early changes in renal damage when urine microalbumin is still undetecable.Therefore,elucidating the role of NGAL in detecting DN and understanding its mechanism can help establish it as a potential early marker for DN.

Tentative New Terminology: Initial Comedonal Phase Preceding Acute Inflammatory Phase of Acne Vulgaris—Importance of Early Treatment

We report a case of a 12-year-old female with closed and open comedo without inflammatory lesions at the first visit. She had been treated with topical adapalene once daily, and closed and open comedo subsided without inflammatory lesions one month after the treatment without any side effects induced by adapalen. The recurrence of comedo had not been observed afterwards. In the Japanese Dermatological Association (JDA) guidelines for the treatment of acne vulgaris, comedonal phase has not been stated. Then we propose the tentative new terminology of a comedonal phase and emphasize its importance in the early initial treatment for comedo to prevent the development of the acute inflammatory phase such as red papules and pustules and formation of acne scars.

Effective Skin Care Guidance for Patients with Acne Vulgaris after Standard Treatment

With the introduction of new drugs, the treatment of acne vulgaris has improved dramatically;however, there remains a considerable gap between treatment outcomes and patients’ treatment goals. This study aimed to determine whether dermatologists’ guidance on appropriate skincare for skin symptoms such as post-inflammatory erythema and post-inflammatory hyperpigmentation (PIH), which are not covered by acne treatment, leads to an improvement in patients’ skin condition and patient satisfaction. Japanese women who had completed standard treatment for acne vulgaris and those with mild symptoms not requiring treatment were included in the study. The participants received instructions about skin care at the beginning of the study, which they continued to apply for 6 weeks. At the start and end of the study, participants were examined by a dermatologist;afterward, skin measurements, including skin color, skin surface lipid content, and image analysis by VISIA® Evolution, analysis of stratum corneum obtained from the skin surface, and Skindex-16 questionnaire for assessing quality of life (QOL), were performed. The following showed significant improvements: PIH score, number of inflammatory acne lesions, and number of non-inflammatory acne lesions observed via skin examination;skin surface lipid content and values of L* and a* obtained via instrumental measurement;n number of pore, texture, red spot, and pigmented spot obtained via by image analysis;and degree of multilayer exfoliation and interleukin-1α determined by analysis of epidermal stratum corneum. QOL measurement using Skindex-16 also improved significantly. Appropriate skin care guidance following standard acne vulgaris treatment is helpful in achieving patients’ treatment goals. .

Non-alcoholic fatty liver disease and psoriasis: So far, so near

Psoriasis is a chronic inflammatory immune-mediated skin diseases which is frequently associated to comorbidities. Non-alcoholic fatty liver disease(NAFLD) is defined as an excessive accumulation of triglycerides in hepatocytes and includes a wide spectrum of liver conditions ranging from relatively benign steatosis to non-alcoholic steatohepatitis with fatty infiltration and lobular inflammation and to cirrhosis and endstage liver disease. Actually, psoriasis is considered a systemic diseases associated to comorbidities, as metabolic syndrome and NAFLD is seen the hepatic manifestation of the metabolic syndrome. The possible link between psoriasis, obesity and metabolic syndrome, which are known risk factors for NAFLD has beenrecently documented focusing in the crucial role of the adipose tissue in the development of the inflammatory background sharing by the above entities. According to recent data, patients with psoriasis show a greater prevalence of NAFLD and metabolic syndrome than the general population. Moreover, patients with NAFLD and psoriasis are at higher risk of severe liver fibrosis than those with NAFLD and without psoriasis. The link between these pathological conditions appears to be a chronic low-grade inflammatory status. The aim of this review is to focus on the multiple aspects linking NAFLD and psoriasis, only apparently far diseases.

Immunohistochemical evaluation of vitamin D receptor(VDR) expression in cutaneous melanoma tissues and four VDR gene polymorphisms

Objective:Vitamin D receptor(VDR)mediates vitamin D activity.We examined whether VDR expression in excised melanoma tissues is associated with VDR gene(VDR)polymorphisms.Methods:We evaluated VDR protein expression(by monoclonal antibody immunostaining),melanoma characteristics,and carriage of VDR-Fok I-rs2228570(C>T),VDR-Bsm I-rs1544410(G>A),VDR-ApaI-rs7975232(T>G),and VDR-TaqI-rs731236(T>C)polymorphisms(by restriction fragment length polymorphism).Absence or presence of restriction site was denoted by a capital or lower letter,respectively:"F"and"f"for Fok I,"B"and"b"for Bsm I,"A"and"a"for ApaI,and "T"and"t"for TaqI endonuclease.Seventy-four Italian cutaneous primary melanomas(52.1±12.7 years old)were studied;51.4% were stage Ⅰ,21.6% stage Ⅱ ,13.5% stage Ⅲ,and 13.5% stage Ⅳ melanomas.VDR expression was categorized as follows:100% positive vs.<100%;over the median 20%(high VDR expression)vs.≤20%(low VDR expression);absence vs.presence of VDR-expressing cells.Results:Stage I melanomas,Breslow thickness of<1.00 mm,level II Clark invasion,Aa heterozygous genotype,and AaTT combined genotype were more frequent in melanomas with high vs.low VDR expression.Combined genotypes BbAA,bbAa,AATt,BbAATt,and bbAaTT were more frequent in 100%vs.<100%VDR-expressing cells.Combined genotype AATT was more frequent in melanomas lacking VDR expression(odds ratio=14.5;P=0.025).VDR expression was not associated with metastasis,ulceration,mitosis>1,regression,tumor-infiltrating lymphocytes,tumoral infiltration of vascular tissues,additional skin and non-skin cancers,and melanoma familiarity.Conclusions:We highlighted that VDR polymorphisms can affect VDR expression in excised melanoma cells.Low VDR expression in AATT carriers is a new finding that merits further study.VDR expression possibly poses implications for vitamin D supplementation against melanoma.VDR expression and VDR genotype may become precise medicinal tools for melanoma in the future.

Treatment of ocular rosacea: comparative study of topical cyclosporine and oral doxycycline

AIM: To compare the effectiveness of topical cyclosporine A emulsion with that of oral doxycycline for rosacea associated ocular changes and dry eye complaints.METHODS: One hundred and ten patients with rosacea were screened. Thirty-eight patients having rosacea associated eyelid and ocular surface changes and dry eye complaints were included in the study. Patients were randomly divided into two groups: nineteen patients were given topical cyclosporine twice daily and nineteen patients were given oral doxycycline 100 mg twice daily for the first month and once daily for the following two months. Symptom and sign scores, ocular surface disease index questionnarie and tear function tests were evaluated at baseline and monthly for 3mo. Three months after results were compared with that of baseline.RESULTS: Mean values of symptom, eyelid sign and corneal/conjunctival sign scores of each treatment group at baseline and 3mo after treatments were compared and both drugs were found to be effective on rosacea associated ocular changes(P 【0.001). Cyclosporine was more effective in symptomatic relief and in the treatment of eyelid signs(P =0.01). There was statistically significant increase in the mean Schirmer score with anesthesia and tear break up time scores in the cyclosporine treatment group compared to the doxycycline treatment group(P 【0.05).CONCLUSION: Cyclosporine as a topical drug can be used in the treatment of rosacea associated ocular complications because it is more effective than doxycycline. In addition ocular rosacea as a chronic disease requires long term treatment and doxycycline has various side effects limiting its long term usage.

Bsm I(rs1544410) and Fok I(rs2228570) vitamin D receptor polymorphisms, smoking, and body mass index as risk factors of cutaneous malignant melanoma in northeast Italy

Objective:To investigate whether vitamin D receptor gene(VDR)Bsm I-rs1544410 and Fok I-rs2228570 polymorphisms,smoking duration,and body mass index(BMI)are risk factors for cutaneous melanoma,especially metastatic melanoma.Methods:We studied 120 cutaneous melanoma cases[68 stage I and II non-metastatic melanoma(NMet M)patients,plus 52Stage III and IV metastatic melanoma(Met M)patients],and 120 matching healthy controls from northeast Italy.VDR polymorphisms were measured by restriction fragment length polymorphism analysis.Absence or presence of Bsm I and Fok I restriction sites was denoted by"B"and"F"or by"b"and"f,"respectively.Results:VDR-Bsm I bb genotype was more frequent among Met M(32.7%)than among NMet M cases(13.2%),with odds ratio(OR)=3.18.Comparison of all melanoma patients vs healthy controls showed that the following biomarkers were at risk:≥20 years of smoking(OR=2.43);≥20 years of smoking combined with bb(OR=4.78),Bb+bb(OR=2.30),Ff(OR=3.04),and Ff+ff(OR=3.08);obesity(BMI>30Conclusions:Risk factors for cutaneous Met M include two VDR polymorphisms combined with smoking duration and obesity.Results suggest gene-environment implications in melanoma susceptibility and severity.Future studies in larger cohorts and in subjects with different genetic background are warranted to extend our findings.

慢性肾脏病患者铁剂应用的争议：来自改善全球肾脏病预后组织(KDIGO)会议的结论

慢性肾脏病和终末期肾病患者常需补铁治疗。但近年来铁剂的使用逐年增加,带来了铁超载、氧化应激和超敏反应等新问题,并可能促进感染的发生,其使用的安全性受到关注。为此,改善全球肾脏病预后组织(KDIGO)召开专家组会议,全面评估铁剂使用的利和弊,并且提供合理使用方案以减轻急性反应及其他毒副作用。

Gut microbiota and nutrient interactions with skin in psoriasis:A comprehensive review of animal and human studies

The intestinal tract(i.e.,the gut),is where the body’s nutrients are absorbed,and is simultaneously inhabited by numerous microbes.An increasing body of literature suggests a crucial role for the gut microbiome in modulating systemic inflammatory disease.Psoriasis is a chronic systemic inflammatory disease and its pathogenesis is related to the interaction between genetic susceptibility,immune response and environmental triggers.The omics era has allowed physicians to assess different aspects of psoriasis pathogenesis such as the microbiome,infectome,and autoinfectome.Furthermore,diet appears to play an important role in modulating disease activity,perhaps by influencing gut microbes.Given these observations,we aimed to summarize the current knowledge regarding skin-microbiome-gut-nutrients and psoriasis.

巨大环状皮肤肌纤维瘤

A 74-year-old lady presented with a painful giant annular abdominal plaque for a duration of 2 years. The plaque developed from a cholecystectomy scar and extended peripherally around it. The patient had had a cholecystectomy for gallstones 10 years previously. She was a diabetic on oral hypoglycaemic agents and had no history of radiotherapy. Physical examination showed a tender well-demarcated annular erythermatous keloid-like plaque, measuring 13 cm × 15 cm, surrounding a cholecystectomy scar. Another smaller oval plaque, measuring 3 cm× 2 cm, was found on the left side of the abdomen (Fig. 1). The initial clinical diagnosis was dermatofibrosarcoma protuberan (DFSP).Adeep incisional biopsy including subcutaneous fatwas performed under local anesthesia for pathological examination. Histologically, there was a plaque-like lesion involving the upper reticular dermis but not extending to the subcutaneous fat. The lesion showed proliferation of spindle-shaped cells arranged in intersecting fascicles and appeared parallel to the skin surface. Only a vague storiform pattern was seen at the edges. The cells had relatively uniform elongated nuclei and mitosis was not seen. The overlying epidermis showed mild hyperplasia with pigmentation of the basal layer (Fig. 2). Smoothmuscle actinwas positive (Fig. 3), desminwas negative and CD34 was negative. The final diagnosis was dermatomyofibroma (DMF). Extra-abdominal fibromatosis was unlikely because broad elongated fascicles among collagenous stroma were not evident, while intersecting fascicles parallel to the skin surface were typical of DMF. The smaller plaque on her left abdomen was excised and gave similar histological and staining results. The giant annular plaque was not excised as the patient refused further surgery. She has since been closely monitored.

孟鲁司特治疗中重度成人异位性皮炎的随机、双盲、安慰剂对照研究

In a randomized,double-blind,placebo-controlled 4-week trial, 59 patients with moderate to severe atopic dermatitis were treated orally with 10 mg of the leukotriene antagonist montelukast. Forty-seven patients completed the study. No difference in efficacy was seen among patients who received montelukast and the group given a placebo.

When the skin meets the bowel: About a case

Ulcerative colitis (UC) is a chronic relapsing inflammatory disease of the colorectal region which may be complicated by extraintestinal manifestations, as cutaneous involvement. Immune dysregulation resulting in a lymphocyte mediated destructive process has been suggested as a possible pathogenetic link between gut and skin-related manifestations. The authors describe an atypical clinical aspect of lichen ruber planus in a patient affected by vitiligo, alopecia areata and ulcerative colitis.

Striae gravidarum as a predictor of spontaneous preterm delivery: A case control study

Background/Aims: The association between striae gravidarum (SG) and preterm delivery may be postulated because of sharing similar poor organization of extracellular matrix in both skin and cervix. Our goal was to compare the frequency of striae gravidarum in women who gave preterm birth and women who gave term birth. Methods: A case-control study was conducted in women who gave preterm birth (n = 66) and age matched women who gave term birth (n = 68). Cases and controls were recruited from puerperal women consequently seen at delivery wards of perinatology unit. All women underwent dermatologic examination in terms of SG blindly to theirs gestational weeks of delivery. The frequency of SG was compared in all groups. Results: The frequency of SG was 63.6% in women with preterm birth and 54.4% in women with term birth (p = 0.278). SG is five times more common in late preterm group than in women with term group, but this difference was not statistically significant [(p = 0.227, OR: 5.02, CI 95% (0.5 - 44.0)]. The rate of preventive cream usage was not statistically different in women with SG and without SG (p = 0.245). Conclusions: It seems that there was no statistically significant association between the risk of preterm labor and the presence of striae gravidarum. Larger prospective observational studies are needed to state expressly the probable clinical association between the presence of SG and preterm delivery.

<i>Momordica charantia</i>Ameliorates Atopic Dermatitis by Inhibiting the Expression of Inducible Nitric Oxidase Synthase in NC/Nga Mice

Introduction: Momordica charantia (MC) has been reported to possess various beneficial effects. Improvement in natural aging of the skin has been observed with the use of MC. However, few studies have detailed the effects of MC on atopic dermatitis (AD). Therefore, in this study, we investigated the effects of MC on the skin symptoms of AD. Methods: Specific pathogen-free and conventional NC/Nga mice were orally administered a 50 mg/kg/day dose of MC every day for 2 weeks. Results: The expression levels of lipopolysaccharide (LPS), inducible nitric oxidase synthase (iNOS), and prostaglandin E2 (PGE2) remarkably increased in AD, but were suppressed by MC administration. As a result, the degradation of filaggrin by PGE2 was suppressed. Furthermore, in AD, iNOS induced macrophage type 1 and increased NO levels. In contrast, due to suppression of iNOS with MC administration, macrophages shifted to type 2 and an increase in L-ornithine was observed, which subsequently promoted filaggrin synthesis. Conclusions: These findings indicate that the AD-like skin symptoms were decelerated by MC via the regulation of the LPS/iNOS/PGE2/filaggrin and LPS/iNOS/Arginase 1/L-ornithine/ filaggrin signaling pathways.

Comparison of the Melatonin Receptor Agonist Ramelteon and the Non-Benzodiazepine Hypnotic Zolpidem for Nocturia

To examine the efficacy of the melatonin receptor agonist ramelteon for nocturia, it was compared with zolpidem, a conventional non-benzodiazepine hypnotic. A total of 50 patients with nocturia (32 urinations/night) were enrolled. Subjects assigned odd numbers or even numbers were respectively prescribed 8 mg of ramelteon (n = 27;mean age: 75 years) or 5 mg of zolpidem (n = 23;mean age: 73 years) once a day before sleeping for 4 weeks. The daytime and nighttime frequencies of urination, as well as the results of global self-assessment by the patients, were compared between the two groups before and after 4 weeks of treatment. Both ramelteon and zolpidem caused a significant decrease of nocturia to about once per night after 4 weeks. The global self-assessment rating at 4 weeks was “good” or “fair” for more patients in the zolpidem group than in the ramelteon group, while the rating was “excellent” or “no change” for more patients in the ramelteon group. There were no serious adverse events in either group. Ramelteon was safe and effective for nocturia, achieving similar results to zolpidem. However, responders and non-responders to ramelteon were more clearly distinguished. Ramelteon might be effective for patients with sleep disturbance and nocturia because of low melatonin levels. Therefore, as diagnostic therapy for identification of nocturia caused by sleep disturbance and melatonin deficiency, ramelteon should be administered to patients who do not respond to alpha-1 antagonists and/or anticholinergic agents.

Evaluation of the Efficacy and Safety for Atopic Dry Skin of a Medicinal Moisturizing Lotion (Mentholatum AP Soft Medicinal Moisture Lotion) Prepared by a High-Pressure Emulsification Method

In order to evaluate the efficacy and safety of Mentholatumò AP Soft Lotion (APA), which is a Vaseline-based preparation that has been converted to nanoparticles by high-pressure emulsification technology, we conducted a study of 4-week continuous use on the atopic dry skin of patients with minor to moderate atopic dermatitis (AD). The results showed that improvements in the skin findings (dryness and scaling) and itching were observed beginning one week after starting to apply APA and that the symptoms had almost completely resolved at 3 to 4 weeks after the start of application. In addition, a significant increase in the degree of high-frequency conductivity, which is an indicator of the amount of moisture in the stratum corneum, and significant decrease in transepidermal water loss (TEWL) were observed, and improvements in skin functions were observed. The results for overall degree of improvement showed “improvement” or better in 100% of the subjects, and no side effects were observed in any of the cases. Based on the above results, it was concluded that APA is a preparation that has excellent efficacy and safety as skin care for atopic dry skin, in which reduced stratum corneum function is observed in the skin, and as a supplemental method of treatment of AD or treatment method to maintain remissions.

Photodynamic therapy with topical aminolevulinic acid

Photodynamic therapy(PDT) is a relatively new therapy in dermatology that uses the topical application of a porphyrin derivative to selectively destroy a cutaneous target. The action is implemented by the application of a specific light frequency. The ability of porphyrin to selectively target tumor tissue has been known since the 1960 s. In the late 1970 s, the underlying mechanism was defined, and Dougherty's discovery of the first chromophore led to the production and commercialization of Photofrin. Many other chromophores that can act as photosensitizers have been studied since then, with aminolevulinic acid currently the most commonly used chromophore in clinical practice. PDT is simple, minimally invasive and can be administered on an outpatient basis. The efficacy of PDT has been proven for actinic keratosis, Bowen's disease and basal cell carcinoma; another of its well-known applications is the treatment of photoaging. Indications for its use are continuously increasing, and promising results are reported for various skin diseases. In this paper we report the mechanism of action of PDT with aminolevulinic acid, the literature concerning the most common diseases treated with PDT and the subsequent level of evidence.

High dose niacin in the treatment of acne vulgaris:a pilot study

Introduction Acne patients are frequently associated with abnormal lipid profile. It may be useful to apply high doseof niacin that regulates the lipid profile along with acne treatment. There is no report about high dose of niacin in treatment ofacne. Objective To evaluate the therapeutic effect and safety of high-dose niacin in acne vulgaris. Methods Acne patientswere randomly allocated to two treatment groups. Both groups were treated orally with the tablets for 12 weeks; the niacingroup at an increasing dose of niacin tablet: 2000 mg (40 mg/kg/d). The control group (nicotinamide group) at a dose ofnicotinamide tablet: 600 mg (10 mg/kg/d). All patients were asked not to consume certain foods such as milk and alcohol.A high-protein, low-fat and low-glycemic-load diet was recommended in both groups. Results A total of 108 patients werefinished the study. Niacin group: 56 patients; control group: 52 patients. After 12 weeks of treatment, niacin and nicotinamidecaused improvement in acne patients. Percentage Improvement in the niacin group (82.37±7.837) %was significantly higherthan in the nicotinamide group (63.19±10.18)%, P <0.01. The number of successful cases in the niacin group was significantlyhigher than in the nicotinamide group after 12 weeks of treatment, (χ2 = 10.55, P <0.01). Conclusions High dose niacin canreally do it work in treatment of acne vulgaris. The therapeutic effcct of High dose of niacin in treatment of acne vulgaris ismore effective than nicotinamide.

A Novel Vehicle Formulation for Treatment of Inflammatory Skin Diseases

Objective: To test the efficacy of a new topical vehicle formulation containing cetirizine in emu oil in treating inflammatory skin conditions. Methods: A single blind half body comparative study of patients with psoriasis, atopic and stasis dermatitis were all treated with midpotency topical steroid (desoximethasone) in propylene glycol base, desoximethasone and cetirizine in propylene glycol base, desoximethasone in emu oil base and desoximethasone with cetirizine dissolved in emu oil. Results: Based on patients’ ranking of creams’ efficacy, and supported by photographic data and investigators’ clinical assessment, results clearly indicated that desoximethasone and cetirizine in emu base was statistically more efficacious than either desoximethasone alone or with cetirizine in neutral propylene glycol base or desoximethasone in emu oil base (without cetirizine). Conclusions: Cetirizine and emu oil, having inherent anti-inflammatory and other beneficial properties synergistically, and by different biochemical pathways, enhance and magnify each other’s pharmaceutical effects that are useful in treatment of skin inflammatory diseases.