Epidemiology of herpes simplex diseases]

The epidemiological principle of the herpes simplex virus (HSV) infections is to have the affected host survive, to persist in it and thus to make it to be a life long starting point for new infection chains. There is an accurately tuned correlation between virus and host organism, in which the persistence of the virus as a latent infection in the ganglion cells of sensory neurones is of central importance. In this state the virus cannot be attacked by the defensive power of the body. When changing from latency in the ganglion cell to activity in the periphery it utilizes the nerve conduction. It has not yet been cleared which factors are responsible for the change-over from the productive, cytocide infection to the latent infection, how the latency is being stabilized and how the reactivation to the herpes recidivans takes place. The organ and tissue specifity of both the HSV types 1 and 2 seems to be bound to the entire pathogenetic complex so that inspite of occasional reverse infections HSV type 1 remains epidemiologically the facial virus type and HSV type 2 the genital one. Apparent and inapparent rimary infections and relapes lead to numerous uncontrolled contacts so that the rate of infection is 50% until the age of puberty and 80% in middle-age adults. The contamination with the mainly venerically transmitted HSV type 2 starts with the age of puberty and reaches abt. 10 to 15% of our population. In patients suffering from cervix carcinoma antibodies against herpes simplex virus type 2 are more frequently demonstrated. Comparative examinations have shown that an increased exposition cannot be the sole cause for this prevalence. The kind of relationship between herpes genitalis and cervix carcinoma remains, however, unclear.     

Indications and action mechanisms of phototherapy

Recently phototherapy has become one of the most commonly used modalities for the treatment of a variety of skin diseases, although the action mechanisms have not been fully understood. The inhibitory effect of UVR on DNA synthesis may be one of the actions for proliferating skin diseases. However, phototherapy is also used for the treatment of allergic or autoimmune diseases. It has been confirmed that the skin is an important immunologic organ whose constitutive cells are all involved in immunologic reactions. We have investigated the effects of PUVA and UVB radiation on the immunocompetent cells, including Langerhans cells, T lymphocytes, mast cells, endothelial cells and natural killer cells. Exposure to UVR inhibits contact sensitization to haptens applied not only to the irradiated skin area but also to the non-irradiated distant skin when the exposure dose is relatively high and/or the application skin area is large. In addition, hapten-specific tolerance develops by the generation of suppressor T cells. Phototherapy is also useful for immediate type hypersensitivity such as urticaria. Action mode in the case may be the inhibitory effects of UVR on histamine release from mast cells. The results obtained from these experiments suggest that phototherapy exerts its anti-allergic and anti-inflammatory effects through immunosuppression.     

Minoxidil: mechanisms of action on hair growth

We have known for over 30 years that minoxidil stimulates hair growth, yet our understanding of its mechanism of action on the hair follicle is very limited. In animal studies, topical minoxidil shortens telogen, causing premature entry of resting hair follicles into anagen, and it probably has a similar action in humans. Minoxidil may also cause prolongation of anagen and increases hair follicle size. Orally administered minoxidil lowers blood pressure by relaxing vascular smooth muscle through the action of its sulphated metabolite, minoxidil sulphate, as an opener of sarcolemmal KATP channels. There is some evidence that the stimulatory effect of minoxidil on hair growth is also due to the opening of potassium channels by minoxidil sulphate, but this idea has been difficult to prove and to date there has been no clear demonstration that KATP channels are expressed in the hair follicle. A number of in vitro effects of minoxidil have been described in monocultures of various skin and hair follicle cell types including stimulation of cell proliferation, inhibition of collagen synthesis, and stimulation of vascular endothelial growth factor and prostaglandin synthesis. Some or all of these effects may be relevant to hair growth, but the application of results obtained in cell culture studies to the complex biology of the hair follicle is uncertain. In this article we review the current state of knowledge on the mode of action of minoxidil on hair growth and indicate lines of future research.     

Molecular mechanisms of VEGF-A action during tissue repair

Vascular endothelial growth factor-A (VEGF-A) is a crucial mediator of vascular hyperpermeability, angiogenesis, and inflammation, processes intimately involved in tissue repair. Although much emphasis has been placed on understanding the synthesis and stability of VEGF-A mRNA, relatively little attention has been given to the study of the stability and processing of VEGF-A proteins themselves. In recent years, several studies indicated that VEGF-A protein activity is highly controlled through interaction with angiogenic or non-angiogenic mediators. We analyzed mechanisms that might control extracellular VEGF-A processing during wound repair. First, our studies provide evidence that VEGF-A protein is a target of proteases present in the microenvironment of human chronic non-healing wounds. Serine proteases, in particular plasmin cleave VEGF165 and digested VEGF fragments, showed decreased mitogenic activity. Inactivation of the plasmin cleavage site Arg110/Ala111 preserved the structural integrity and increased the angiogenic potency of VEGF165 when tested in an impaired healing mouse model. Secondly, we identified significantly increased levels of the potent VEGF-A inhibitor, the soluble form of the VEGF receptor VEGFR-1 (sVEGFR-1) in non-healing wounds when compared to healing wounds. Wound closure in healing and non-healing wounds correlated significantly with a decline in sVEGFR-1 levels. These observations support the concept that VEGF-A and VEGF-A receptors are important mediators in tissue repair. Further, our data provide mechanisms how VEGF-A-mediated interactions are disturbed during impaired healing.     

Secondary autoimmune diseases in herpes gestationis (pemphigoid gestationis).

BACKGROUND: Herpes gestationis (HG) is an autoimmune disease of the skin that occurs exclusively in association with pregnancy (or trophoblastic disease). It is associated with the HLA-DR3 and -DR4 antigens that are also associated with several other autoimmune diseases. HG has previously been reported in association with Graves' disease. OBJECTIVE: Our purpose was to determine the frequency of other autoimmune disease(s) in patients with a history of HG. METHODS: Seventy-five patients with a history of HG were studied for the frequency of other autoimmune diseases. RESULTS: We found an increased frequency of Graves' disease in patients with a history of HG. Those with HG have an increased risk for the development of other autoantibodies. There is an increased frequency of autoimmune diseases in the family members of patients with HG. CONCLUSION: Secondary autoimmune disease in HG is unusual, but does occur. The most frequent is Graves' disease.     

Thalidomide: dermatological indications, mechanisms of action and side-effects

Thalidomide was first introduced in the 1950s as a sedative but was quickly removed from the market after it was linked to cases of severe birth defects. However, it has since made a remarkable comeback for the U.S. Food and Drug Administration‐approved use in the treatment of erythema nodosum leprosum. Further, it has shown its effectiveness in unresponsive dermatological conditions such as actinic prurigo, adult Langerhans cell histiocytosis, aphthous stomatitis, Behçet's syndrome, graft‐versus‐host disease, cutaneous sarcoidosis, erythema multiforme, Jessner–Kanof lymphocytic infiltration of the skin, Kaposi sarcoma, lichen planus, lupus erythematosus, melanoma, prurigo nodularis, pyoderma gangrenosum and uraemic pruritus. This article reviews the history, pharmacology, mechanism of action, clinical uses and adverse effects of thalidomide.     

皮肤微生物群在玫瑰痤疮发病中的作用及机制研究进展

【摘要】 皮肤微生物群在玫瑰痤疮发病中的作用尚未明确,本文综述了目前报道的与玫瑰痤疮发病可能相关的重要皮肤微生物群,包括蠕形螨、Bacillus oleronius、痤疮丙酸杆菌、Corynebacterium kroppenstedtii等,并进一步探讨其潜在的作用机制。     

Retinoids: therapeutic applications and mechanisms of action in cutaneous T-cell lymphoma

Retinoids, natural and synthetic derivatives of vitamin A, are biological regulators of differentiation, proliferation, apoptosis, and immune response. Retinoic-acid-receptor-selective retinoids (all-trans retinoic acid, 13-cis-retinoic acid, and the synthetic analogs isotretinoin, etretinate and acitretin) have been used for years as monotherapy and/or in combination for treatment of cutaneous T-cell lymphoma (CTCL). Orally administered bexarotene, the first synthetic highly selective retinoid-X-receptor retinoid to be approved by the FDA for CTCL, was shown to be active against the cutaneous manifestations of all stages of CTCL. The topical gel formulation was also effective for early cutaneous manifestations of CTCL or as an adjunct to systemic or phototherapy. Bexarotene treatment induces apoptosis of CTCL cells with down-regulation of its receptors and of survivin, an inhibitor of apoptosis. Identification of new receptor subtype-selective retinoids, combination of various receptor-selective retinoids or other agents, and a new drug delivery system may improve the clinical efficacy of retinoids in the future.     

Propranolol for infantile haemangiomas: insights into the molecular mechanisms of action

Infantile haemangiomas (IH) are the most common benign tumours of infancy. Although most IH are innocuous and 85–90% regress spontaneously, some may become life‐ or function‐threatening and require immediate treatment. Previous standard therapeutic options include physical measures (laser surgery, cryosurgery) and systemic corticosteroids, in severe cases also vincristine, α‐interferon or cyclophosphamide, all bearing the risk of serious side‐effects. Oral propranolol is a very recent therapeutic option for complicated IH with impressive efficacy and generally good tolerance. The effects of propranolol on IH were discovered by chance, and very little is known about its mechanisms of action in IH. Here we present a summary of current knowledge of how propranolol interferes with endothelial cells, vascular tone, angiogenesis and apoptosis. Early, intermediate and long‐term effects of propranolol on IH can be attributed to three different pharmacological targets. Early effects (brightening of the haemangioma surface within 1–3 days after start of therapy) are attributable to vasoconstriction due to decreased release of nitric oxide. Intermediate effects are due to the blocking of proangiogenic signals (vascular endothelial growth factor, basic fibroblast growth factor, matrix metalloproteinase 2/9) and result in growth arrest. Long‐term effects of propranolol are characterized by induction of apoptosis in proliferating endothelial cells, and result in tumour regression.     

Recurrent genital herpes in a population attending a clinic for sexually transmitted diseases.

Patients with recurrent genital herpes attending a sexually transmitted disease clinic were studied and transmission of the infection was elucidated by evaluating serostatus in their partners. Of 84 patients attending for recurrent genital herpes, 94% had a herpes simplex virus type 2 (HSV-2) infection and only 6% (5 patients) a type 1 infection. The mean age of the patients was 36 years and the duration of their infection was up to 37 years (median 4 years). In most patients the number of recurrences had not decreased between the first year and the last year. About half had experienced a more severe first episode infection. Of the patients, 64% were not aware of asymptomatic shedding and the risk of sexual transmission without clinical symptoms. Of 67 steady partners of patients with genital HSV-2, 15% had a history of genital herpes. By HSV serology, HSV-2 antibodies (indicating subclinical genital herpes) were demonstrated in more than half of the partners. The duration of the relationship or condom use did not seem to influence the frequency of transmission to the partner, which may indicate an individual susceptibility for acquiring a genital HSV-2 infection. Eleven per cent of the patients were on suppressive antiviral therapy, while 39% had no experience of antiviral therapy. Type-specific HSV serology was found to be of value in counselling partners of patients with genital herpes.