SREBP2 restricts osteoclast differentiation and activity by regulating IRF7 and limits inflammatory bone erosion

Osteoclasts are multinucleated bone-resorbing cells,and their formation is tightly regulated to prevent excessive bone loss.However,the mechanisms by which osteoclast formation is restricted remain incompletely determined.Here,we found that sterol regulatory element binding protein 2(SREBP2)functions as a negative regulator of osteoclast formation and inflammatory bone loss.Cholesterols and SREBP2,a key transcription factor for cholesterol biosynthesis,increased in the late phase of osteoclastogenesis.

止汗研究

讨论了人体排汗和体味产生的机理以及抑制气味的方法。阐明了止汗剂的种类及其作用机理。指出排汗受生理和心理双重作用的影响 。

Efficacy and safety of herbal medicines in treating gastric ulcer:A review

Gastric ulcer is a common disorder of the digestive system.Current therapeutic regimens largely rely on Western medicine.However,numerous studies have demonstrated that herbal medicines can effectively treat gastric ulcer in humans and various animal models via divergent mechanisms.This review updates the efficacy and safety of herbal medicines in treating gastric ulcer,and the mechanisms of their action in humans and animal models.Studies have demonstrated that the efficacy of herbal medicines is comparable or superior to that of drugs such as omeprazole or cimetidine in humans and animal models,and herbal medicines display fewer adverse effects.The mechanisms by which herbal medicines benefit gastric ulcer include stimulation of mucous cell proliferation,anti-oxidation,and inhibition of gastric acid secretion and H(+)/K(+)-ATPase activity.Some herbal medicines also exhibit antimicrobial properties.Utilization of herbal medicines could be a valuable alternative to treat gastric ulcer in humans effectively,with few adverse effects.

Pathogenesis and diagnosis of contact dermatitis:Applications of reflectance confocal microscopy

Contact dermatitis(CD) is the most common professional skin disease, with frequencies ranging from 24 to 170 every 100000 individuals. Approximately 20% of the United States population suffers from CD. CD can be classified according to its origin and severity. ICD stands for irritant CD, whereas ACD means allergic CD. Their clinical presentation includes acute, sub-acute and chronic eczema. Despite their different origin, ICD and ACD often present similar clinical and histologic findings. The current gold standard for diagnosis is patchtesting. However, patch-testing is being questioned in terms of validity and reproducibility, as it relies heavily on the skill of the observer. Real-time reflectance confocal microscopy is a non-invasive imaging technique that bears strong promise for the study of CD, and it enables the evaluation of cellular and subcellular changes over time with similar resolution compared to that of conventional histology.

Identification of Bulge Stem Cells in Mouse and Human Hair Follicles

The skin contains various populaions of stem cells, but its characterization has been hampered by lack of markers and unclear location. The hair follicle has a niche for stem cells called a “bulge” which acts as a reservoir of multipotent stem cells. In the study reported here, an immunohistochemical and immunofluorescence analysis was performed on mouse and human tissues in order to determine the possible presence of stem cells of hair follicle through cytokeratin 15 (CK15), CD34, and CD200 markers identified as crucial to the stem cells and to identify the bulge region. Mouse (n = 7) and human (n = 7) skin samples were used. The expression of proteins was determined by the indirect immunoperoxidase technique and a secondary antibody bound to a fluorochrome. The specificity of staining was evaluated by negative controls. The results revealed that the stem cells associated with CD34 and CD200 antibodies were differentially expressed in the interfollicular epidermis, sebaceous glands, and bulge region, indicating that, in mice, CD34 and, in humans, CD200 are more specific than CK15 in detecting bulge cells. It also suggests that CD34 is specific for mouse bulge cells, while CD200 might have specificity for progenitor cells and partially differentiated cells in humans.

Isolation, Cultivation, and Morphological Characteristics of Hair Follicle Adult Stem Cells in the Bulge Region in Mouse and Human

Skin contains various populations of stem cells (SCs). Among these are hair follicle stem cells (HFSCs) in the bulge region. The behavior of HFSCs deserves to be widely studied due to the benefits to be derived from their identification, isolation, and amplification. Skin samples of newborn mice (n = 32) and human adults (n = 10) were used, and the bulge region was isolated and cultured. The isolation and characterization of cells were conducted through immunocytochemistry and immunofluorescence, using mainly CD34 and CD200 monoclonal antibodies. Initially, cells grew slowly from the explant around the bulge region, accruing cells with different morphology in both mouse and human, latter being mostly polygonal;the mouse cells reaching confluence faster (5 to 7 days) than the human (12 to 15 days). It was possible to isolate into subcultures cells with small size (10 - 13 μm diameter), round-shape, scant cytoplasm, central prominent nucleus and with nucleolus, which formed colonies, maintaining their phenotype in a high proportion (77% - 83% and 91% in mouse and human, respectively), without showing changes in their morphology during almost 7 months in the mouse cells, and a month and a half in the human. These results demonstrate that the selection, the isolation, and the conditioned mediums allowed population increases of bulge cells and indicate that cultured cells may retain their sternness in that they maintained their phenotypic characteristics, expressed specific markers for SCs, and showed a high proliferative capacity for long periods. Hair follicles, in mice and humans, are important repositories of multipotent stem cells, due to their tendency to differentiate into keratinocytes. Human HFSCs, obtained by depilation, preserve their potential for proliferation and prove to be easily accessible. This suggests that the bulge cells may present an alternative source of autologous stem cells for tissue engineering and regenerative medicine.

Evolution of Post-Surgical Scars Treated with Pure Rosehip Seed Oil

The rosehip seed oil (RHO), obtained from different plant species of the genus Rosa, is one of the compounds used empirically for cosmetic improvement of skin scarring. Despite its widespread use in clinical practice, there are few studies evaluating the activity of this compound on the clinical course of cutaneous scars. The aim of this study was to determine the effect of Repavar&reg?rosehip oil on improvement of post-surgical skin scars. One comparative, single-center, prospective clinical trial was carried out in 108 patients undergoing cutaneous surgery procedures in the Dermatology Service of University Hospital of Gran Canaria Dr. Negrín (Spain). Subjective parameters (erythema, discoloration, atrophy and hypertrophy) were evaluated at 6 and 12 weeks on 76 adults who treated scars with pure RHO twice a day (test group), 32 patients with not treatment (control group), and completed the study. Lesser degree of erythema was observed at 6 and 12 weeks in treated-patients compared with the control group and decreased discoloration and atrophy at 12 weeks, with statistically significant differences in all cases (p < 0.05). This study demonstrates that the RHO Repavar&reg?is useful for cosmetic improvement on erythema, discoloration and atrophyof post-surgical skin scars, getting a better overall evolution and appearance thereof.

良性对称性脂肪过多症(劳-邦综合征)

A 37-year-old woman with a personal history of appendicectomy, cholecystectomy, left oophorectomy secondary to an ovarian cyst complication, nephritic colic with repeated episodes of pyelonephritis, alcoholic hepatopathy, Raynaud’ s phenomenon and bilateral exophthalmos showed an increase in volume in the root of the upper limbs and in the base of the neck over a period of 4 years, painful to the touch and of a soft consistency. She presented with a pseudo- athletic appearance (Fig. 1) produced by an increase in the volume at the root of the upper limbs, upper back and the back of the neck (Fig. 2). The lesions produced a pulling sensation and were associated with paresthesia, hyperesthesia, and a moderate loss of strength in both arms. A biopsy taken from the upper third of the right arm showed a diffuse proliferation of the subcutaneous adipose tissue, which appeared normal, and extended between the collagen fibers, reaching in some cases into the most superficial zones of the reticular dermis (Fig. 3). Laboratory evaluation revealed a chronic anemia, leukopenia with moderate lymphopenia, increased erythrocyte sedimentation rate, elevation of enzymes of hepatic function, decrease in total proteins, and increase in ferritin, all in the context of hepatopathy. Antinuclear antibodies and the hormonal profile were normal. Abdominal and gynecologic echography revealed a right ovarian cyst of no clinical relevance. Cranial nuclear magnetic resonance (NMR) revealed an increase in the periorbital fat responsible for bilateral exophthalmos.

普通人群对非黑素性皮肤癌和光化性角化病的认知和态度

Background: The incidence of nonmelanoma skin cancer (NMSC) has dramatically increased worldwide. In areas of high incidence this will place a significant burden on the health system. Objectives: To establish the awareness, knowledge and attitudes of the general public to NMSC and provide an overview on their level of understanding and knowledge of preventative measures. Methods: Two thousand and one hundred Caucasian and Hispanicindividuals,aged 40-75 years,fromthe UK, Italy, Germany, Spain, France, the USA and Australia were randomly selected to participate in this market research survey. In a structured telephone interview lasting approximately 10 min, respondents answered questions on NMSC, specifically actinic keratosis (AK) and basal cell carcinoma (BCC). Results: Overall, 6%of respondents had been diagnosed with NMSC, of which the incidence was highest in Australia and the USA.The frequency of skin cancer detection examinations was also greater within these populations. Countries with a high incidence of NSMC had greater awareness of the condition, with more awareness of BCC than AK. The majority of respondents believed there was a correlation between skin cancer and sun exposure, however, a minority of respondents associated skin cancer with ‘moderate’tanning. Overall, 86%of respondents claimed that they always took precautions against ultraviolet exposure when in the sun, but only 26%applied sunscreen most or all of the time when they were exposed to the sun for more than 1 h. In most of the countries, outside workers reported lower sunscreen use than other respondents. Conclusion: Nonmelanoma skin cancer awareness and prevention behaviors varied significantly among the countries studied. Improved population-specific documentation of skin cancer knowledge and prevention behaviors will facilitate the development and assessment of public health campaigns.

伴鱼鳞病的中性脂质贮存异常的发病机制和屏障功能障碍(Chanarin-Dorfman综合征)

Neutral lipid storage disease with ichthyosis (NLSDI; Chanarin-Dorfman syndrome) is an ichthyosiform syndrome, often associated with mutations in a lipid hydrolase, CGI-58. The presence of oil red O-positive, neutral lipid droplets in tissue biopsies, and/or in leukocytes on blood smears, coupled with a constellation of multisystem abnormalities and a pruritic ichthyosiform erythroderma, are together diagnostic of NLSDI. We investigated the pathogenesis of the ichthyosiform erythroderma in patients from three unrelated kindreds with a clinical diagnosis of NLSDI. Basal permeability barrier function and stratum corneum (SC) integrity were abnormal, but barrier recovery rates were faster than normal, as in atopic dermatitis. The basal barrier abnormality was linked to the secretion of lipid micro-inclusions, first segregated within lamellar bodies (LB), which then form a non-lamellar phase within the SC interstices, shown by combined ruthenium tetroxide post-fixation and lipid-retaining resin-white embedding. With colloidal lanthanum nitrate perfusion, excess water/solute movement was restricted to the SC interstices, and further localized to non-lamellar domains. Phase separation of excess stored lipid provides a unifying pathogenic mechanism not only for NLSDI, but also in several other inherited ichthyosiform disorders of lipid metabolism, such as recessive X-linked ichthyosis and type 2 Gaucher’s disease.

从伊拉克战场返回肯塔基州坎贝尔堡的军人中的皮肤利什曼病引起对其诊断和治疗方法的重视

Background:Cutaneous leishmaniasis (CL), rare in the first Gulf War, is common in American troops serving in Operation Iraqi Freedom. Awareness of the clinical features and treatment options of CL would benefit clinicians who may encounter soldiers, as well as civilians, returning from the Middle East with skin lesions. Objective:Our purpose was to describe our clinical experience in treating soldiers with CL. Methods:From December 2003 through June 2004, approximately 360 of an estimated 20,000 soldiers returning from a year long deployment in Iraq with skin lesions suspected of being CL were examined by dermatologists. We summarized CL diagnoses, laboratory evaluations, and treatments, including localized heat therapy (ThermoMed model 1.8; ThermoSurgery Technologies, Inc, Phoenix,Ariz),oralfluconazole,cryotherapy,anditraconazole. Results:Among 237 soldiers diagnosed with CL, 181 had one or more laboratory confirmations, most by Giemsa-stained lesion smears and polymerase chain reaction (PCR). PCR was positive for all 122 smear-positive and 26 biopsy-positive lesions and all 34 smear negative and all 3 biopsy-negative cases. Primary outpatient treatments, including ThermoMed (n=26), oral fluconazole (n=15), cryotherapy (n=4), and itraconazole (n=2), were safe and tolerable. Treatment failure occurred in 2 fluconazole recipients and was suspected in 1 ThermoMed and 2 fluconazole recipients. Seventy-two soldiers elected no treatment. Limitation:This was a retrospective study. Conclusion:Approximately 1%of Ft Campbell troops returning from Iraq were diagnosed with CL, most by laboratory confirmation. PCR appeared to be the most useful diagnostic technique. Among out patient treatments,Thermo Medandcry other apyhad favorable safety and efficacy profiles.

体内反射共聚焦显微镜诊断过敏性接触性皮炎的敏感性和特异性的先导性研究

The validity, reproducibility, and specificity of patch-testi-ng in the diagnosis of allergic contact dermatitis (ACD) have repeatedly been addressed. In vivo reflectance confocal microscopy (RCM) has been used for real-time evaluation of the histopathologic features of ACD. This pilot study was designed to determine the sensitivity and specificity of RCM in diagnosing ACD in reference to patch-testing. Sixteen participants were patch tested with allergens and control substances. Clinical scoring, digital photography, and RCM evaluation were performed at 72 hours, and RCM images were subjected to blinded evaluation. RCM evaluation parameters included stratum corneum (SC) disruption, parakeratosis, stratum spinosum (SS) and stratum granulosum (SG) spongiosis, and exocytosis. Overall, there was high specificity for all RCM features, ranging from 95.8% to 100% . Sensitivity ranged from 51.9% to 96.3% . Significant parameters with high sensitivity and specificity included spongiosis and exocytosis at the level of SS. Logistic regression analysis was performed on significant variables; P values were determined by χ 2 analysis. RCM is a promising noninvasive technology for the evaluation of ACD. SC changes are not helpful in the diagnosis of ACD, although the presence of SG spongiosis and SS spongiosis shows high sensitivity in diagnosingACD. Larger sensitivity and specificity studies are needed and the identification of ACD has to be based In addition, individual allergens have to be subjected to further evaluations in order to demonstrate the applicability of our findings for other contact allergens. I on a defined diagnostic algorithm. A limitation of this study is the small sample size; larger sensitivity and specificity studies are needed to confirm these findings. In addition, individual allergens have to be subjected to further evaluations in order to demonstrate the applicability of our findings for other contact allergens. In that regard, RCM may be considered as an adjunctive tool, rather than a substitute, to clinical evaluation.

面部痣细胞痣的浅表切除法

Background. Tangential excision (shaving) is an effective surgical technique for the excision of nevocellular nevi on the trunk, limbs, and scalp. There are few studies on the application of this technique to lesions on the face. Aims. To demonstrate the technique of tangential excision for the removal of nevocellular nevi on the face and to evaluate the cosmetic results, recurrence index, and possible complications. Methods. Two hundred and fifteen patients with multiple nevocellular nevi on different aesthetic units of the face (total of 225 lesions) were selected. All the lesions were removed by tangential excision. The patients returned for postsurgical evaluation at 30, 60, and 90 days. Results. The results were evaluated in relation to the skin type, sex, age, and histologic type of the lesions. An excellent result was achieved in 90.7%, good in 8.4%and poor in 0.9%, with a low index of complications. For comparison, the face was divided into seven aesthetic units. Conclusion. Tangential excision is an alternative surgical technique for the treatment of nevi. It is simple, fast, and efficient, has low risks and low cost for the patient, and yields excellent results when used for cosmetic purposes.

1例美国旅游者的皮肤盘尾丝虫病

A case report of cutaneous onchocercias acquired during travels to Africa is presented. The salient epidemiologic, clinical, diagnostic, and therapeutic aspects are reviewed. Clinical and laboratory differences between onchocerciasis patients who are inhabitants of endemic areas and those who are occasional visitors to such areas are discussed. Parasitic infections, including onchocerciasis, should be considered in the differential diagnosis of pruritic eruptions in patients with a history of foreign travel to Africa, Central and South America.

HLA antigens in individuals with down syndrome and alopecia areata

AIM: To describe human leukocyte antigen(HLA) alleles in individuals with Down syndrome and alopecia areata. METHODS: A cross-sectional study was conducted, which evaluated 109 individuals. Ten with down syndrome(DS) and alopecia areata(AA), ten with DS without AA and ten with AA without DS, and their fami-lies. The individuals were matched by gender and age. The following data were computed: gender, age, ethnic group, karyotype, clinical presentation and family history of alopecia areata. Descriptive analysis: measures of central tendency and frequency distribution. Inferential analysis: Fisher's exact test to compare categorical data between the three groups and Kruskal-Wallis ANOVA test for numerical data.RESULTS: Seventy per cent of evaluated individuals in the DS and AA group were male; presented mean age of 18.6(SD ± 7.2) years and 70% were Caucasian. We observed involvement of the scalp, with a single lesion in 10% and multiple in 90% of subjects. It was observed that there is no significant difference in the frequency distributions of the alleles HLA loci A, B, C, DRB1 and DQB1 of subjects studied. However, according to Fisher's exact test, there is a trend(P = 0.089) of DS group to present higher proportions of HLA-A 36 and HLA-B 15 than the AA group and AA and DS group.CONCLUSION: There was a tendency for the DS group, to present proportion of HLA-A 36 and HLA-B 15 higher than the AA group and group of individuals with AA and DS. However, there was no significant difference in the frequency distribution of the alleles.

Stimulation of the Protective Response to Actinomycetoma by Nocardia brasiliensis in Mice Treated with Candida albicans Antigens

Actinomycetoma is a chronic subcutaneous lesion caused by the pathogenic bacterium Nocardia (N.) brasiliensis. Yeast antigens of Candida (C.) albicans increase the interferon (IFN)-γ and TCD4+ cells levels that enhance the phagocytic killing of N. brasiliensis, able to survive inside phagocytes and to grow in clustered colonies that form grains. The aim of this work was to test the effect of a crude protein extract of C. albicans on the levels of IFN-γ producing TCD4+ cells and on the outcome of actinomycetoma lesion. Five BALB/c mice with N. brasiliensis infection at left hind footpad were treated four times every other day with C. albicans crude protein extract (CPE). Five uninfected mice treated with CPE or infected mice treated with sterile phosphate-saline buffer were included as positive and negative control groups, respectively. Footpad thickness was recorded in all groups. Once the treatments were finished, single cell suspensions from blood and spleen were prepared for assessing the amount (%) of IFN-γ producing TCD4+ cells by cytofluorometry;presence of TCD4+ and IFN-γ in footpad sections was detected by immunofluorescence and immunohistochemistry, respectively. By comparison with the negative control group, infected mice treated with CPE had lower footpad thickness, higher percentage of blood and spleen IFN-γ producing TCD4+ cells as well as in situ presence of IFN-γ and TCD4+ cells. These findings showed that CPE from C. albicans displayed an immunoadjuvant activity that enhanced the presence of IFN-γ producing TCD4+ cells and IFN-γ for the resolution of N. brasiliensis actinomycetoma in mice.

Detection of β-Glucuronidase Activity within Actinomadura madurae Grains of Human Actinomycetoma

Actinomycetoma syndrome by Actinomadura (A.) madurae is characterized by a subcutaneous chronic lesion that affects fascia, muscle and bone. A. madurae produces colonies that form grains of less than 1 mm in diameter. Grains are surrounded and infiltrated by neutrophils involved in the grain disruption by enzymes like β-glucuronidase released after the neutrophil degranulation. The aim of this work was to evaluate the polysaccharide degradation of grains treated with β-glucuronidase and to detect the presence and activity of β-glucuronidase within the A. madurae grains. Actinomadura madura grains from patients infected were processed to quantify the total content of polysaccharide with the phenol-sulfuric acid reaction. Grains were treated with β-glucuronidase at different conditions to evaluate the optimal polysaccharide degradation. Grains were analyzed to detect the enzyme by using anti-human β-glucuronidase antibody while enzymatic activity was assessed by evaluating the release of reduced sugars and by in situ enzymatic activity. Optimal degradation of polysaccharide in the grains treated with β-glucuronidase was found with 300 units/ml of enzyme and 24 hr of incubation at 37°C. Presence and activity of β-glucuronidase enzyme within the grains were detected. Results suggested that β-glucuronidase present within A. madurae grain resulted from degranulated neutrophils surrounding and/or infiltrated within the grain.

不同肤色个体表皮角质形成细胞Caspase14表达的研究

目的探讨不同肤色人群角质形成细胞中Caspase14表达变化，明确黑素细胞和（或）黑素对其表达的影响。方法以Western印迹检测不同肤色个体原代角质形成细胞Caspase14的表达。取体外培养不同肤色的2代角质形成细胞，分别加入不同肤色的黑素细胞在分化培养基下共同培养24h，以不加黑素细胞组为对照，Western印迹检测Caspase14的表达。结果浅、深肤色个体包皮原代角质形成细胞Cas—pase14的表达存在显著差异，深肤色者（FitzpatrickIV／V）原代角质形成细胞中Caspase14的表达显著高于浅肤色者（FitzpatrickI／II）（P〈0．01）；深、浅肤色个体的角质形成细胞在与不同肤色个体的黑素细胞在分化培养基中共培养后24h后，检测发现，与对照组相比，浅肤色个体角质形成细胞Caspase14表达的增加，差异无统计学意义（P〉0．05），而深肤色个体角质形成细胞Caspase14的表达则显著上调（P〈0．05）。结论深肤色个体角质形成细胞Caspase14表达显著高于浅肤色个体者。黑素细胞显著增加深肤色者角质形成细胞中Caspase14水平的表达。

Herbal Medicines Prevent the Development of Atopic Dermatitis by Multiple Mechanisms

Atopic dermatitis(AD) is among the most common skin disorders in humans. Although a variety of regimens are available for the treatment of AD, preventive approaches are limited. Recent studies have demonstrated that certain naturally-occurring herbal medicines are effective in preventing the development of AD via divergent mechanisms, such as inhibiting cytokine and chemokine expression, IgE production, inflammatory cell infiltration, histamine release, and/or enhancement of epidermal permeability barrier function. Yet, they exhibit few adverse effects. Since herbal medicines are widely available, inexpensive and generally safe, they could represent an ideal approach for preventing the development of AD, in both highly developed and developing countries.