Collembola are Unlikely to Cause Human Dermatitis

There have been several unconfirmed case reports of dermatitis caused by Collembola (springtails). We recently investigated two nurses with dermatitis suspected to be caused by Drepanura Schött (Collembola: Entomobryidae). IgE antibodies to Collembola proteins were not detected in sera from the nurses and skin tests with the Collembola extract and crushed whole Collembola were negative in both the nurses and volunteers. This study suggests that the springtail Drepanura may not cause human dermatitis and that other organisms and organic matter that are also found in the moist environment inhabited by Collembola might instead be responsible

Collembola are Unlikely to Cause Human Dermatitis

There have been several unconfirmed case reports of dermatitis caused by Collembola (springtails). We recently investigated two nurses with dermatitis suspected to be caused by Drepanura Schött (Collembola: Entomobryidae). IgE antibodies to Collembola proteins were not detected in sera from the nurses and skin tests with the Collembola extract and crushed whole Collembola were negative in both the nurses and volunteers. This study suggests that the springtail Drepanura may not cause human dermatitis and that other organisms and organic matter that are also found in the moist environment inhabited by Collembola might instead be responsible

Photo-antagonism of the GABAA receptor

Neurotransmitter receptor trafficking is fundamentally important for synaptic transmission and neural network activity. GABAA receptors and inhibitory synapses are vital components of brain function, yet much of our knowledge regarding receptor mobility and function at inhibitory synapses is derived indirectly from using recombinant receptors, antibody-tagged native receptors and pharmacological treatments. Here we describe the use of a set of research tools that can irreversibly bind to and affect the function of recombinant and neuronal GABAA receptors following ultraviolet photoactivation. These compounds are based on the competitive antagonist gabazine and incorporate a variety of photoactive groups. By using site-directed mutagenesis and ligand-docking studies, they reveal new areas of the GABA binding site at the interface between receptor β and α subunits. These compounds enable the selected inactivation of native GABAA receptor populations providing new insight into the function of inhibitory synapses and extrasynaptic receptors in controlling neuronal excitation

The cost of uncomplicated childhood fevers to Kenyan households: implications for reaching international access targets

BACKGROUND: Fever is the clinical hallmark of malaria disease. The Roll Back Malaria (RBM) movement promotes prompt, effective treatment of childhood fevers as a key component to achieving its optimistic mortality reduction goals by 2010. A neglected concern is how communities will access these new medicines promptly and the costs to poor households when they are located in rural areas distant to health services. METHODS: We assemble data developed between 2001 and 2002 in Kenya to describe treatment choices made by rural households to treat a child's fever and the related costs to households. Using a cost-of-illness approach, we estimate the expected cost of a childhood fever to Kenyan households in 2002. We develop two scenarios to explore how expected costs to households would change if more children were treated at a health care facility with an effective antimalarial within 48 hours of fever onset. RESULTS: 30% of uncomplicated fevers were managed at home with modern medicines, 38% were taken to a health care facility (HCF), and 32% were managed at home without the use of modern medicines. Direct household cash expenditures were estimated at $0.44 per fever, while the total expected cost to households (cash and time) of an uncomplicated childhood fever is estimated to be$1.91. An estimated mean of 1.42 days of caretaker time devoted to each fever accounts for the majority of household costs of managing fevers. The aggregate cost to Kenyan households of managing uncomplicated childhood fevers was at least $96 million in 2002, equivalent to 1.00$1.86 because caretakers also save time with prompt treatment if the child has malaria. CONCLUSION: The management of uncomplicated childhood fevers imposes substantial costs on Kenyan households. Achieving substantial improvements in the numbers of fevers treated within 48 hours at a HCF with an effective antimalarial drug (Scenario 1) will not impose additional costs on households. Achieving additional improvements in fevers treated promptly at a HCF (Scenario 2) will impose additional costs on some households roughly equal to average cash expenses for transportation to a HCF. Additional financing mechanisms that further reduce the costs of accessing care at a HCF and/or that make artemisinin-based combination therapies (ACTs) accessible for home management need to be developed and evaluated as a top priority

The basidiomycetous yeast Trichosporon may cause severe lung exacerbation in cystic fibrosis patients - clinical analysis of Trichosporon positive patients in a Munich cohort

Background: The relevance of Trichosporon species for cystic fibrosis (CF) patients has not yet been extensively investigated. Methods: The clinical course of CF patients with Trichosporon spp. in their respiratory secretions was analysed between 2003 and 2010 in the Munich CF center. All respiratory samples of 360 CF patients (0 - 52.4 years; mean FEV1 2010 81.4% pred) were investigated. Results: In 8 patients (2.2%, 3 male, mean age 21.8 years) Trichosporon was detected at least once. One patient carried T. asahii. One patient carried T. mycotoxinivorans and one patient T. inkin as determined by DNA sequencing. As potential risk factors for Trichosporon colonization steroid treatment, allergic bronchopulmonary aspergillosis (ABPA) and CF associated diabetes were identified in 6, 5, and 2 patients respectively. For one patient, the observation period was not long enough to determine the clinical course. One patient had only a single positive specimen and exhibited a stable clinical course determined by change in forced expiratory volume in one second (FEV1), body-mass-index (BMI), C-reactive protein (CRP) and immunoglobulin G (IgG). Of 6 patients with repeatedly positive specimen (mean detection period 4.5 years), 4 patients had a greater decline in FEV1 than expected, 2 of these a decline in BMI and 1 an increase in IgG above the reference range. 2 patients received antimycotic treatment: one patient with a tormenting dry cough subjectively improved under Amphotericin B inhalation; one patient with a severe exacerbation due to T. inkin was treated with i.v. Amphotericin B, oral Voriconazole and Posaconazole which stabilized the clinical condition. Conclusions: This study demonstrates the potential association of Trichosporon spp. with severe exacerbations in CF patients

Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.

The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition

The Orexigenic Effect of Ghrelin Is Mediated through Central Activation of the Endogenous Cannabinoid System

INTRODUCTION Ghrelin and cannabinoids stimulate appetite, this effect possibly being mediated by the activation of hypothalamic AMP-activated protein kinase (AMPK), a key enzyme in appetite and metabolism regulation. The cannabinoid receptor type 1 (CB1) antagonist rimonabant can block the orexigenic effect of ghrelin. In this study, we have elucidated the mechanism of the putative ghrelin-cannabinoid interaction. METHODS The effects of ghrelin and CB1 antagonist rimonabant in wild-type mice, and the effect of ghrelin in CB1-knockout animals, were studied on food intake, hypothalamic AMPK activity and endogenous cannabinoid content. In patch-clamp electrophysiology experiments the effect of ghrelin was assessed on the synaptic inputs in parvocellular neurons of the hypothalamic paraventricular nucleus, with or without the pre-administration of a CB1 antagonist or of cannabinoid synthesis inhibitors. RESULTS AND CONCLUSIONS Ghrelin did not induce an orexigenic effect in CB1-knockout mice. Correspondingly, both the genetic lack of CB1 and the pharmacological blockade of CB1 inhibited the effect of ghrelin on AMPK activity. Ghrelin increased the endocannabinoid content of the hypothalamus in wild-type mice and this effect was abolished by rimonabant pre-treatment, while no effect was observed in CB1-KO animals. Electrophysiology studies showed that ghrelin can inhibit the excitatory inputs on the parvocellular neurons of the paraventricular nucleus, and that this effect is abolished by administration of a CB1 antagonist or an inhibitor of the DAG lipase, the enzyme responsible for 2-AG synthesis. The effect is also lost in the presence of BAPTA, an intracellular calcium chelator, which inhibits endocannabinoid synthesis in the recorded parvocellular neuron and therefore blocks the retrograde signaling exerted by endocannabinoids. In summary, an intact cannabinoid signaling pathway is necessary for the stimulatory effects of ghrelin on AMPK activity and food intake, and for the inhibitory effect of ghrelin on paraventricular neurons

Lipoic acid plays a role in scleroderma: insights obtained from scleroderma dermal fibroblasts

Abstract Introduction Systemic sclerosis (SSc) is a connective tissue disease characterized by fibrosis of the skin and organs. Increase in oxidative stress and platelet-derived growth factor receptor (PDGFR) activation promote type I collagen (Col I) production, leading to fibrosis in SSc. Lipoic acid (LA) and its active metabolite dihydrolipoic acid (DHLA) are naturally occurring thiols that act as cofactors and antioxidants and are produced by lipoic acid synthetase (LIAS). Our goals in this study were to examine whether LA and LIAS were deficient in SSc patients and to determine the effect of DHLA on the phenotype of SSc dermal fibroblasts. N-acetylcysteine (NAC), a commonly used thiol antioxidant, was included as a comparison. Methods Dermal fibroblasts were isolated from healthy subjects and patients with diffuse cutaneous SSc. Matrix metalloproteinase (MMPs), tissue inhibitors of MMPs (TIMP), plasminogen activator inhibitor 1 (PAI-1) and LIAS were measured by enzyme-linked immunosorbent assay. The expression of Col I was measured by immunofluorescence, hydroxyproline assay and quantitative PCR. PDGFR phosphorylation and α-smooth muscle actin (αSMA) were measured by Western blotting. Student’s t-tests were performed for statistical analysis, and P-values less than 0.05 with two-tailed analysis were considered statistically significant. Results The expression of LA and LIAS in SSc dermal fibroblasts was lower than normal fibroblasts; however, LIAS was significantly higher in SSc plasma and appeared to be released from monocytes. DHLA lowered cellular oxidative stress and decreased PDGFR phosphorylation, Col I, PAI-1 and αSMA expression in SSc dermal fibroblasts. It also restored the activities of phosphatases that inactivated the PDGFR. SSc fibroblasts produced lower levels of MMP-1 and MMP-3, and DHLA increased them. In contrast, TIMP-1 levels were higher in SSc, but DHLA had a minimal effect. Both DHLA and NAC increased MMP-1 activity when SSc cells were stimulated with PDGF. In general, DHLA showed better efficacy than NAC in most cases. Conclusions DHLA acts not only as an antioxidant but also as an antifibrotic because it has the ability to reverse the profibrotic phenotype of SSc dermal fibroblasts. Our study suggests that thiol antioxidants, including NAC, LA, or DHLA, could be beneficial for patients with SSc.http://deepblue.lib.umich.edu/bitstream/2027.42/112060/1/13075_2014_Article_411.pd

The distinctive gastric fluid proteome in gastric cancer reveals a multi-biomarker diagnostic profile

<p>Abstract</p> <p>Background</p> <p>Overall gastric cancer survival remains poor mainly because there are no reliable methods for identifying highly curable early stage disease. Multi-protein profiling of gastric fluids, obtained from the anatomic site of pathology, could reveal diagnostic proteomic fingerprints.</p> <p>Methods</p> <p>Protein profiles were generated from gastric fluid samples of 19 gastric cancer and 36 benign gastritides patients undergoing elective, clinically-indicated gastroscopy using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry on multiple ProteinChip arrays. Proteomic features were compared by significance analysis of microarray algorithm and two-way hierarchical clustering. A second blinded sample set (24 gastric cancers and 29 clinically benign gastritides) was used for validation.</p> <p>Results</p> <p>By significance analysyis of microarray, 60 proteomic features were up-regulated and 46 were down-regulated in gastric cancer samples (<it>p </it>< 0.01). Multimarker clustering showed two distinctive proteomic profiles independent of age and ethnicity. Eighteen of 19 cancer samples clustered together (sensitivity 95%) while 27/36 of non-cancer samples clustered in a second group. Nine non-cancer samples that clustered with cancer samples included 5 pre-malignant lesions (1 adenomatous polyp and 4 intestinal metaplasia). Validation using a second sample set showed the sensitivity and specificity to be 88% and 93%, respectively. Positive predictive value of the combined data was 0.80. Selected peptide sequencing identified pepsinogen C and pepsin A activation peptide as significantly down-regulated and alpha-defensin as significantly up-regulated.</p> <p>Conclusion</p> <p>This simple and reproducible multimarker proteomic assay could supplement clinical gastroscopic evaluation of symptomatic patients to enhance diagnostic accuracy for gastric cancer and pre-malignant lesions.</p