An alternative pharmacological approach to the detection of anti-androgenic drugs for acne therapy

Both testosterone and dihydrotestosterone may be able to stimulate sebaceous glands, and the glandular function may continue under direct testosterone control in the presence of 5 alpha-reductase blockade. Antagonism of sebaceous gland hypertrophy, induced by exogenous testosterone or dihydrotestosterone, has been studied in the hairless hamster using established and experimental drugs applied topically. The results support the proposition that testosterone plays a direct role in mediating sebaceous gland response. This suggests possibilities for the design of sebum inhibitory drugs with minimal systemic anti-androgenic side effects.     

Activation of the alternative complement pathway by Fonsecaea pedrosoi

The effect of the skin-depigmenting agent hydroquinone (HQ) on 2 melanotic and 3 nonmelanotic cell lines was studied. Significant differences in its effect on DNA and RNA synthesis were observed between cell lines. HQ caused inhibition of cellular metabolism in all cells tested, but the dose that caused 50% inhibition of tritiated thymidine incorporation was approximately 30 times lower for melanotic cells. Tritiated uridine incorporation was found to be 85 times more sensitive to HQ in the melanotic cells. These results suggest that HQ exerts its depigmenting effect by selective action on melanocyte metabolism rather than a specific effect on melanin synthesis. Further, the effects of UV irradiation on this system were investigated and found to be negligible, in spite of the stimulation of in vivo melanin synthesis by UV radiation.     

Activation of the alternative pathway of complement by skin immune deposits

Skin immune deposits at the basement membrane zone have been demonstrated by functional assays to activate complement. This important biologic function has not yet been explored for immune deposits present in other locations mainly because many cytoplasmic structures in the skin have the capacity to activate the complement cascade by the classical pathway. In this study the capacity of immune deposits to activate directly the alternative pathway was examined using a functional guinea pig C3 binding test. This test was devised so as to avoid complement activation by normal cutaneous structures, thus it did not examine the capacity of immune reactants to activate the classical pathway. The main findings were that alternative pathway activation could be demonstrated only when human C3 deposits were seen by direct immunofluorescence, but not all C3 deposits were found to activate the alternative pathway; such activation was restricted to vascular deposits; the phlogistic potential of the immune deposits correlated with serologic evidence of ongoing immune reactions, i.e., hypocomplementemia and circulating immune complexes. It is suggested that this test provides data on one aspect of the phlogistic potential of skin immune deposits not detectable by direct immunofluorescence.     

威灵仙等4种中药抑制黑素生成作用的机制研究

目的：研究威灵仙等4种中药对melan-a小鼠黑素细胞酪氨酸酶（Tyr）活性、Tyr及酪氨酸酶相关蛋白（TRP）基因转录与蛋白表达的影响,对4种中药抑制黑素生成的作用机制进行初步探讨.方法：用中药提取物处理melan-a小鼠黑素细胞后进行黑素含量测定,左旋多巴染色、实时荧光定量反转录（RT）-PCR和Western blot分别测Tyr及TRP-1、TRP-2的mRNA和蛋白表达水平.以熊果苷作为阳性对照.结果：4种中药在20 μg/mL浓度时具有明确的抑制黑素生成的作用,并且都不同程度地抑制Tyr的氧化活性.威灵仙、五倍子可以同时降低Tyr及TRP-1、TRP-2的基因转录和蛋白表达量.而麦冬、白苏叶可以降低Tyr及TRP-1、TRP-2的合成,但是对基因表达无影响.结论：威灵仙及五倍子提取物可以通过抑制Tyr、TRP-1、TRP-2的基因表达及蛋白合成和Tyr的多巴氧化活性这三方面实现其抑制黑素产生的作用;麦冬、白苏叶在基因转录后的酶蛋白水平发挥抑制黑素生成的作用.     

Abnormalities in the alternative pathway of complement in psoriasis

Some of the immunologic aspects of psoriasis suggest that complement may be involved in the pathophysiology of that disease. The purpose of this work was to examine the complement system in more detail in 20 patients with psoriasis. Classical pathway determinations, RCH50 and factor B levels were normal or elevated. Abnormally low properdin levels were seen in 12/20 patients. No patient had a serum properdin value greater than 1 standard deviation above the control mean. Mean C3–C9 consumption after zymosan or cobra venom incubation was also significantly less than normal (P < 0·001). Thus, abnormalities of the complement system are present in psoriasis and seem limited to the alternative pathway.     

A new therapeutic approach to treat psoriasis by inhibition of fatty acid oxidation by Etomoxir

Background The dogma in psoriasis is that due to pathogen‐induced inflammatory responses, an autoreactive immune response is induced that leads to tissue destruction. However, this model might be too simplistic. Literature data suggest that the expression of enzymes crucial for fatty acid oxidation is upregulated in the skin of patients with psoriasis compared with healthy individuals. Objectives To examine the influence of fatty acid oxidation on psoriasis with regard to expression and activity of the key enzyme in fatty acid oxidation, carnitine palmitoyltransferase‐1 (CPT‐1) and the effect of the CPT‐1 inhibitor, Etomoxir. Methods Experiments were performed with homogenates of lesional and healthy skin, fibroblast cultures and a model of human psoriatic skin transplanted on immune‐deficient BNX mice. Results CPT‐1 was highly active in lesional skin. Etomoxir was able to block CPT‐1 activity in skin, implying that this antagonist may have the potential to suppress psoriasis when administered topically. In the mouse model, Etomoxir had an antipsoriatic effect that was at least as good as that of betamethasone, as evidenced by reduction of epidermal thickness, keratinocyte proliferation and differentiation. Conclusions We conclude that fatty acid metabolism and in particular CPT‐1 may be an excellent target for treatment of psoriasis.     

Activation of components of the alternative pathway of complement by Propionibacterium acnes cell wall carbohydrate

The trichloroacetic acid (TCA) extractable molecules in Propionibacterium acnes cell wall were tested for the ability to activate the alternative pathway of complement in human serum treated with ethyleneglycol-bis (beta-aminoethyl ether) N,N-tetracetic acid (EGTA). The extracted molecules failed to consume hemolytic activity against antibody-coated sheep erythrocytes but gave a dose-dependent consumption of rabbit erythrocyte (RE) lytic activity. Similarly, the extract produced significant cleavage of Factor B, but failed to cleave C3, as detected by immunoelectrophoresis. Adsorption of the extracted material to sheep erythrocytes did not render the cells susceptible to lysis via the alternative pathway. Sephadex G-25 chromatography yielded several fractions which were able to consume RE lytic activity from EGTA-treated serum. These fractions were analyzed and found to contain glucose, mannose, and galactose. No teichoic acid or protein was detected. The alternative pathway activator in P. acnes is thus a nonteichoic acid cell wall carbohydrate which, in its extractable form is capable of activating only alternative pathway reactants prior to C3.     

An approach to cutaneous changes caused by hematologic malignancies

Most hematologic malignancies can present with or later develop cutaneous lesions. The proper diagnosis of such patients through the evaluation of their cutaneous lesions is complicated both by the confusing variety of clinical findings and by the shifting classifications of hematologic malignancies in the face of evolving knowledge. The spectrum of T-cell malignancies continues to increase and now includes several disorders formerly attributed to B-cells or macrophages. The cutaneous findings of malignant and malignant behaving hematologic disorders are grouped by the presumed cellular etiology and by the clinical subset of tumor. Clinical and histopathologic features unique to individual disorders are emphasized, as well as those features that may be shared by otherwise quite dissimilar malignancies.     

Activation of the alternative complement pathway by 405 nm light in serum from porphyric rat

Sera from hexachlorobenzene-induced porphyric rats were examined for evidence of complement activation. The serum irradiated in vitro with 405 nm light resulted in a dose-dependent diminution of the total hemolytic activity of the complement. Further, such irradiated serum showed immunoelectrophoretical C3 conversion and chemotactic activity for rat polymorphonuclear leukocytes, and caused increased vascular permeability in vivo. C3 conversion was not induced in serum chelated with EDTA, but occurred in serum chelated with Mg++-EGTA. By sephadex G-75 chromatography, the irradiated serum had potent chemotactic activity eluted near the cytochrome C marker. These studies indicate that the irradiation of porphyric rat serum with 405 nm light induces activation of the complement system via the alternative pathway, with the resultant development of anaphylatoxin.     

Stratum corneum activation of complement through the antibody-independent alternative pathway

We provide evidence that stratum corneum (SC) activates complement through the alternative pathway to generate C5a anaphylatoxin. By immunofluorescence studies it was shown that in addition to circulating IgG autoantibody, there were anti-SC antibodies of IgM and IgA classes in the sera from normal individuals. However, all the titers were significantly lower than the level of C3 deposition between corneocytes. By contrast, no C1q deposition occurred. Immunoelectrophoretically the orthokeratotic SC homogenates were found to induce the conversion of C3 from native C3 to C3b in fresh human serum even when the classic pathway was blocked by Ca2+-chelation. Enzyme immunoassay showed that factor B split product, Bb, was generated by the SC homogenates in the Ca2+-chelated serum. Radioimmunoassay for C5a also demonstrated that the SC homogenates could generate C5a anaphylatoxin in serum to an extent similar to that in non-treated serum when restricted to the alternative pathway activation; neutrophil chemotactic activity was generated in Ca2+-chelated serum at levels comparable to that generated in non-treated fresh serum. We separated the SC samples into a cornified envelope and soluble and keratin fractions. The cornified envelope was more effective in activating complement. This activity resided in heat-stable and non-lipid substances of corneocytes. Our hypothesis is that when the SC comes in contact with serum, it activates complement mainly through the alternative pathway to induce chemotactic C5a anaphylatoxin. Hence, inflammation in normal individuals after a traumatic injury to the skin or rupture of acne comedones, or epidermal cysts and possibly the formation of subcorneal sterile pustules noted in several dermatoses are explainable through this mechanism.     

An approach to initial examination of the nail

A systematic method of examining nail disorders is important. A patient questionnaire (sample provided) and a basic method of categorizing various problems are helpful tools. Thorough investigation usually yields a diagnosis.     

An approach to the treatment of anogenital pruritus

The anogenital area is a common location for pruritic complaints. Specific terms for chronic itch in this location have included pruritus vulvae, pruritus ani, lichen simplex chronicus, and neurodermatitis. A male counterpart to pruritus vulvae, pruritus scroti, is less common. Acute anogenital pruritus is usually caused by infections or contact dermatitis. In chronic pruritus, inflammatory dermatoses and malignancies must be ruled out. In idiopathic anogenital pruritus or neurodermatitis, the skin findings should be limited to lichenification and excoriations. Skin findings may be entirely absent. When treating anogenital pruritus, topic irritants and potential sensitizers must be eliminated. Cleansing and toilet habits must be addressed. A short course of a high-potency topical steroid should bring moderate to complete relief. Sedating antihistamines may limit nighttime symptoms. In some patients, psychotropic agents are required to achieve adequate sedation. Antidepressants may be required in patients refractory to treatment or with underlying psychiatric disorders.     

An approach to the treatment of psychogenic parasitosis

Background Patients with psychogenic parasitosis typically seek help from nonpsychiatric physicians and can be difficult and time-consuming to treat. Pimozide has been promoted as the treatment of choice but is not indicated for every patient presenting with this symptom. Our purpose was to develop a realistic treatment protocol for the nonpsychiatric physician faced with these patients.
Methods Using what is known about this problem through review of the literature and our own experience with 20 patients, a practical treatment strategy is suggested.
Results It is proposed that dermatologists and primary care professionals seeing these patients determine (1) whether or not the patient's belief in infestation is shakable and (2) whether or not the patient is depressed, in order to chose a therapeutic plan.
Conclusions Dermatologists and psychiatrists can work together to develop treatment protocols that minimize risk and maximize therapy for patients with psychogenic parasitosis.     

An anatomic approach to the rejuvenation of the neck

The neck is a difficult but important area in rejuvenation of the face. Discussed are the major anatomic landmarks for neck surgery, the aging process of the neck, and the most commonly used treatments presently available for rejuvenation of the neck and their complications.     

Activation of the alternative pathway of complement in psoriatic lesional skin

The complement system may play an important role in the inflammatory reaction of psoriasis. While the classical pathway of the complement has been shown to be activated in psoriasis, there have been few reports on the involvement of the alternative pathway in the inflammatory reactions in psoriasis. Complement fragments, C4d and Bb, are released at the time of the classical and alternative pathway activation, respectively. The presence of the C4d or Bb fragment, therefore, denotes a preceding complement activation through the classical and/or alternative pathway. In the present study, we have measured the levels of C4d and Bb in psoriatic scale extracts using enzyme immunoassay techniques. The scales of these dermatoses contained higher levels of C4d and Bb detectable by enzyme immunoassay than those in the stratum corneum of noninflammatory skin. These results suggest that the alternative as well as the classical pathway of complement are activated in psoriatic lesional skin.     

An alternative approach for Mohs surgery using a combination of a flexible blade and the traditional scalpel

Background Mohs surgery is a specialized surgical and pathological technique used for the removal of high‐risk neoplasms. Previous reports show the ability of using a flexible blade for Mohs surgery. Method We utilized a technique combining the traditional #15 blade and scalpel with a flexible blade to perform excisions for Mohs surgery. Discussion The use of the flexible blade alone in Mohs may yield jagged tissue peripheral edges after cutting on the cryostat. The classic technique with a scalpel excision often results in a deeper cut than desired, resulting in a larger defect. We modified both the traditional Mohs technique and the flexible blade by combining both. We have performed this method in approximately over 100 cases on the scalp, face and ears, preserving tissue, minimizing bleeding and avoiding alopecia.