Search

Aims Previous studies have shown that ultraviolet light can lead to the release of nitric oxide from the skin and decrease blood pressure. In contrast to visible light the local application of ultraviolet light bears a cancerogenic risk. Here, we investigated whether whole body exposure to visible blue light can also decrease blood pressure and increase endothelial function in healthy subjects. Methods In a randomised crossover study, 14 healthy male subjects were exposed on 2 days to monochromatic blue light or blue light with a filter foil (control light) over 30 minutes. We measured blood pressure (primary endpoint), heart rate, forearm vascular resistance, forearm blood flow, endothelial function (flow-mediated dilation), pulse wave velocity and plasma nitric oxide species, nitrite and nitroso compounds (secondary endpoints) during and up to 2 hours after exposure. Results Blue light exposure significantly decreased systolic blood pressure and increased heart rate as compared to control. In parallel, blue light significantly increased forearm blood flow, flow-mediated dilation, circulating nitric oxide species and nitroso compounds while it decreased forearm vascular resistance and pulse wave velocity. Conclusion Whole body irradiation with visible blue light at real world doses improves blood pressure, endothelial function and arterial stiffness by nitric oxide released from photolabile intracutanous nitric oxide metabolites into circulating blood.

Background: Visible light is absorbed by photoacceptors in pigmented and non-pigmented mammalian cells, activating signaling cascades and downstream mechanisms that lead to the modulation of cellular processes. Most studies have investigated the molecular mechanisms and therapeutic applications of UV and the red to near infrared regions of the visible spectrum. Considerably less effort has been dedicated to the blue, UV-free part of the spectrum. Objective: In this review, we discuss the current advances in the understanding of the molecular photoacceptors, signaling mechanisms, and corresponding therapeutic opportunities of blue light photoreception in non-visual mammalian cells in the context of inflammatory skin conditions. Methods: The literature was scanned for peer-reviewed articles focusing on the molecular mechanisms, cellular effects, and therapeutic applications of blue light. Results: At a molecular level, blue light is absorbed by flavins, porphyrins, nitrosated proteins, and opsins; inducing the generation of ROS, nitric oxide release, and the activation of G protein coupled signaling. Limited and contrasting results have been reported on the cellular effects of blue light induced signaling. Some investigations describe a regulation of proliferation and differentiation or a modulation of inflammatory parameters; others show growth inhibition and apoptosis. Regardless of the elusive underlying mechanism, clinical studies show that blue light is beneficial in the treatment of inflammatory skin conditions. Conclusion: To strengthen the use of blue light for therapeutic purposes, further in depth studies are clearly needed with regard to its underlying molecular and cellular mechanisms, and their translation into clinical applications.

Clinical investigations prove that blue light irradiation reduces the severity of psoriasis vulgaris. Nevertheless, the mechanisms involved in the management of this condition remain poorly defined. Despite the encouraging results of the clinical studies, no clear guidelines are specified in the literature for the irradiation scheme regime of blue light-based therapy for psoriasis. We investigated the underlying mechanism of blue light irradiation of psoriatic skin, and tested the hypothesis that regulation of proliferation is a key process. We implemented a mechanistic model of cellular epidermal dynamics to analyze whether a temporary decrease of keratinocytes hyper-proliferation can explain the outcome of phototherapy with blue light. Our results suggest that the main effect of blue light on keratinocytes impacts the proliferative cells. They show that the decrease in the keratinocytes proliferative capacity is sufficient to induce a transient decrease in the severity of psoriasis. To study the impact of the therapeutic regime on the efficacy of psoriasis treatment, we performed simulations for different combinations of the treatment parameters, i.e., length of treatment, fluence (also referred to as dose), and intensity. These simulations indicate that high efficacy is achieved by regimes with long duration and high fluence levels, regardless of the chosen intensity. Our modeling approach constitutes a framework for testing diverse hypotheses on the underlying mechanism of blue light-based phototherapy, and for designing effective strategies for the treatment of psoriasis.

Background Psoriasis and atopic dermatitis are two inflammatory skin diseases with a high prevalence and a significant burden on the patients. Underlying molecular mechanisms include chronic inflammation and abnormal proliferation. However, the cell types contributing to these molecular mechanisms are much less understood. Recently, deconvolution methodologies have allowed the digital quantification of cell types in bulk tissue based on mRNA expression data from biopsies. Using these methods to study the cellular composition of the skin enables the rapid enumeration of multiple cell types, providing insight into the numerical changes of cell types associated with chronic inflammatory skin conditions. Here, we use deconvolution to enumerate the cellular composition of the skin and estimate changes related to onset, progress, and treatment of these skin diseases. Methods A novel signature matrix, i.e. DerM22, containing expression data from 22 reference cell types, is used, in combination with the CIBERSORT algorithm, to identify and quantify the cellular subsets within whole skin biopsy samples. We apply the approach to public microarray mRNA expression data from the skin layers and 648 samples from healthy subjects and patients with psoriasis or atopic dermatitis. The methodology is validated by comparison to experimental results from flow cytometry and immunohistochemistry studies, and the deconvolution of independent data from isolated cell types. Results We derived the relative abundance of cell types from healthy, lesional, and non-lesional skin and observed a marked increase in the abundance of keratinocytes and leukocytes in the lesions of both inflammatory dermatological conditions. The relative fraction of these cells varied from healthy to diseased skin and from non-lesional to lesional skin. We show that changes in the relative abundance of skin-related cell types can be used to distinguish between mild and severe cases of psoriasis and atopic dermatitis, and trace the effect of treatment. Conclusions Our analysis demonstrates the value of this new resource in interpreting skin-derived transcriptomics data by enabling the direct quantification of cell types in a skin sample and the characterization of pathological changes in tissue composition. Electronic supplementary material The online version of this article (10.1186/s12920-019-0567-7) contains supplementary material, which is available to authorized users.

Loss of anti-human immunodeficiency virus type 1 (HIV-1) memory cytotoxic T-lymphocyte (CTLm) responses is associated with disease progression in HIV-1 infection. In this study, nonspecific stimulation of peripheral blood mononuclear cells (PBMC) from HIV-1-infected homosexual men with anti-CD3 monoclonal antibody (MAb) was compared with antigen-specific stimulation with inactivated, autologous B lymphoblastoid cells (B-LCL) infected with a vaccinia virus vector encoding HIV-1 IIIb Gag, Pol, and Env (VV-GPE) for activation of HIV-1-specific CTLm responses in a bulk lysis assay and by precursor frequency analysis. The results show that VV-GPE-infected B-LCL stimulated on average 10-fold greater anti-HIV-1 CTLm activity, as detected in the bulk lysis assay, and 55-fold-greater CTLm precursor frequencies specific for the three HIV-1 structural proteins than did stimulation with anti-CD3 MAb. This effect was noted with both freshly donated and frozen-thawed PBMC. The lysis was mediated by CD8+ T cells and was restricted by the major histocompatibility class I complex. These data indicate that antigen-specific stimulation with VV-GPE-infected B-LCL is a highly efficient method for detection of anti-HIV-1 CTLm responses that is applicable to noncurrent prospective studies with frozen PBMC.

Background: In a collaborative study, patients with untreated normal-tension glaucoma were randomly assigned to a marked intraocular pressure reduction group or to a no therapy group. It was anticipated that medical therapy and laser trabeculoplasty would generally not achieve adequate pressure lowering and that fistulizing surgery would be required. This hypothesis was examined using current observations in the study. Methods: Patients randomized to the therapy group had a pressure reduction of at least 30% from their last prerandomization level. This was achieved within 6 months by means of fistulizing surgery or with pilocarpine and/or laser trabeculoplasty. Betablockers and adrenergic agonists were excluded from both eyes. Results: Of 30 patients with documented stable 30% pressure reduction, 17 (57%) achieved this with topical medication and/or laser trabeculoplasty: 8 with pilocarpine alone, 2 with laser trabeculoplasty alone, and 7 with laser trabeculoplasty after initial topical medication. The remaining 13 (43%) patients required a single fistulizing procedure. There was no statistically significant difference between the mean follow-up time for the nonfistulized group (533.8 ± 437.6 days) and for the fistulized group (502.7 ± 344.7 days). Both treatment groups had similar baseline profiles. Conclusion: Marked pressure reduction can be achieved and maintained on a longterm basis by means other than fistulizing surgery in a large proportion of patients with untreated normal-tension glaucoma.

Lack of disease in long-term nonprogressors with human immunodeficiency virus type 1 (HIV-1) infection was strongly associated with very low copy numbers of HIV-1 DNA and RNA in peripheral blood mononuclear cells and plasma and the presence of high levels of anti-HIV-1 CD8+ memory cytotoxic T lymphocytes specific for Gag, Pol, and Env, compared with levels present in intermediate and advanced progressors. CD8+ memory cytotoxic T lymphocytes may have an important role in controlling HIV-1 replication and preventing disease in long-term nonprogressors.

A survey was conducted to evaluate nursing home referrals to consultant dietitians of residents with nutrition-related concerns, the frequency of such referrals, and the timeliness of dietitians' responses. The results showed that, although residents with significant weight loss and pressure ulcers constituted a higher proportion of nutrition concerns referred to the dietitian, most referrals were made from a week to a month after the nutrition concern was identified. Residents with tube feedings or dysphagia concerns were more likely to be referred in a more timely manner, within 1 to 2 days.

7602 Background: Numerous reports have demonstrated that the clinical use of thalidomide (THAL) carries a risk for deep venous thrombosis. Only limited investigations into the causative mechanisms for this complication have been conducted. Thrombin generation is a global measurement of hyper or hypocoagulability that has not been used to examine the hypercoagulable state caused by THAL. The aim of this study was to determine if THAL affects thrombin generation in patients with multiple myeloma (MM). Methods: MM patients on and off THAL were recruited. Patients were considered to be “on THAL” if they had been taking the medication for at least three months and “off THAL” if they had not been taking the medication for at least three months. Coagulation tubes of blood containing 3.2% sodium citrate were drawn from each patient. Platelet poor plasma was prepared from these specimens using standard technique. The samples were snap frozen at -70 C and stored until analysis. Thrombin generation was measured using the Calibrated Automated Thrombogram as described by Hemker(Pathophysiol Haemo Thromb 2003;33:4–15) using a microplate fluorometer, the Fluoroskan Ascent from Thermo Electron and the Thrombinoscope software package. The endogenous thrombin potential or ETP (area under the thrombin generation curve) and peak thrombin generation (the maximum release of thrombin per unit of time) were the variables of interest for this study. Results: Twenty seven patients were recruited. Five were excluded from analysis because they were on warfarin or enoxaparin. The normal ETP in females is 1803 ± 241 nM*min and in males is 1745 ± 259 nM *min. Normal peak thrombin generation in females is 318.5 ± 52.9 nM and in males is 293.4 ± 48.5 nM. The t-test was used to compare subjects to normal values.Peak thrombin generation was significantly increased in the 9 subjects taking THAL, 374 ± 10.6 nM (p [Table: see text]

6623 Introduction: R-CHOP is considered standard treatment (tx) for IHGNHL. Administering full doses of R-CHOP is crucial to maximize response. Older patients (pts) may experience a higher incidenc...

A 60-year-old woman was treated postoperatively for carcinoma of the gall bladder with a split course of radiotherapy. The tumour dose (TD) was 61.2 Gy in 34 fractions delivered by an anterior and two lateral wedge fields with 60 Co; the D max was 70% of TD for the anterior field and 150% of the TD at the thin edge of the wedges. She also underwent 5-FU and leucovorin chemotherapy. No skin reaction was seen during radiotherapy or in 1 year of follow-up. A year after radiotherapy she was treated for hypercholesterolaemia by simvastatin. Within 2–3 days a severe skin and subcutaneous reaction developed in the lateral radiation fields but not in the anterior field. To our knowledge, recall of skin radiation reaction after simvastatin therapy has not been previously reported.

(1) Standardization of penicillinase has been made possible by the method for its assay. (2) A purified, dried and sterile penicillinase has been found to be a penicillin-inactivator superior to Clarase for the penicillin sterility test. (3) Preliminary studies show this penicillinase preparation may be used for inactivating penicillin in exudates of body fluids.

(1) A combination of penicillin and immune plasma protein has been obtained which possesses bacteriostatic activity. (2) The presence of the penicillinase immune plasma protein in this mixture protects penicillin in vitro from destruction by penicillinase.

Penicillin ointment mixtures have been observed to be effective in the treatment of certain local cutaneous infections. 1 However, topical therapy with penicillin is not so simple as it first would appear, since many factors affect such forms of penicillin therapy. In previous reports 2 the excellent sensitizing qualities of the penicillin per se or the penicillin mixture, the stability of the mixture and the diffusion of penicillin through the mixture were considered as some of the factors affecting treatment. In this report we should like to mention our initial experiences with the effect of the addition of an active therapeutic agent to the penicillin ointment mixture. Certain obvious qualifications are necessary for the consideration of additional therapeutic, as opposed to vehicular, agents to penicillin ointment mixtures. First, the substance should not inactivate penicillin. Second, the substance should increase the therapeutic quality of the ointment by extending the range of

Oral administration of penicillin suspended in equal parts of corn oil and lanolin extends the maintenance of the penicillin level in the system (as determined by urine bio-assay). Measurable quantities were found 24 to 42 hours after ingestion. Recovery of the penicillin is about five times higher than under administration in saline solution. We wish to express our sincere appreciation to the various members of our staff who volunteered as subjects for these experiments.