Protease-activated receptor-2 mediates the expression of inflammatory cytokines, antimicrobial peptides, and matrix metalloproteinases in keratinocytes in response to Propionibacterium acnes

Propionibacterium acnes (P. acnes) has been known to produce various exogenous proteases, however, their role in acne pathogenesis remains largely unknown. Proteases elicit cellular responses, at least in part, via proteinase-activated receptor-2 (PAR-2), which is known to mediate inflammation and immune response. In this study, we investigated whether proteases from P. acnes could activate PAR-2 on keratinocytes and induce pro-inflammatory cytokines, antimicrobial peptides (AMPs), and matrix metalloproteinases (MMPs) via PAR-2 signaling. We examined PAR-2 expression and protease activity in acne lesions using immunofluorescence staining and in situ zymography. The effect of the culture supernatant of P. acnes on Ca2+ signaling in immortalized keratinocytes (HaCaT) was measured using a fluorescence method. HaCaT cells were treated with P. acnes strain ATCC 6919 culture supernatant, with or without pretreatment with serine protease inhibitor or selective PAR-2 antagonist and the gene expression of pro-inflammatory cytokines, AMPs, and MMPs was detected using real-time reverse transcription-polymerase chain reaction. We found that the protease activity and PAR-2 expression were increased in acne lesions. The P. acnes culture supernatant induced calcium signaling in keratinocytes via PAR-2 and stimulated the mRNA expression of interleukin (IL)-1α, -8, tumor necrosis factor (TNF)-α, human beta defensin (hBD)-2, LL-37, MMP-1, -2, -3, -9, and -13 in keratinocytes, which was significantly inhibited by serine protease inhibitor as well as selective PAR-2 specific antagonist. These results indicate that PAR-2 plays an important role in the pathogenesis of acne by inducing inflammatory mediators in response to proteases secreted from P. acnes

Modelling the effects of standard prognostic factors in node-positive breast cancer

Prognostic models that predict the clinical course of a breast cancer patient are important in oncology. We propose an approach to constructing such models based on fractional polynomials in which useful transformations of the continuous factors are determined. The idea may be applied with all types of regression model, including Cox regression, the method of choice for survival-time data. We analyse a prospective study of node-positive breast cancer. Seven standard prognostic factors – age, menopausal status, tumour size, tumour grade, number of positive lymph nodes, progesterone and oestrogen receptor concentrations – were investigated in 686 patients, of whom 299 had an event for recurrence-free survival and 171 died. We determine a final model with transformations of prognostic factors and compare it with the more traditional approaches using categorized variables or assuming a straight line relationship. We conclude that analysis using fractional polynomials can extract important prognostic information which the traditional approaches may miss. © 1999 Cancer Research Campaig

Differential Attraction of Malaria Mosquitoes to Volatile Blends Produced by Human Skin Bacteria

The malaria mosquito Anopheles gambiae sensu stricto is mainly guided by human odour components to find its blood host. Skin bacteria play an important role in the production of human body odour and when grown in vitro, skin bacteria produce volatiles that are attractive to A. gambiae. The role of single skin bacterial species in the production of volatiles that mediate the host-seeking behaviour of mosquitoes has remained largely unknown and is the subject of the present study. Headspace samples were taken to identify volatiles that mediate this behaviour. These volatiles could be used as mosquito attractants or repellents. Five commonly occurring species of skin bacteria were tested in an olfactometer for the production of volatiles that attract A. gambiae. Odour blends produced by some bacterial species were more attractive than blends produced by other species. In contrast to odours from the other bacterial species tested, odours produced by Pseudomonas aeruginosa were not attractive to A. gambiae. Headspace analysis of bacterial volatiles in combination with behavioural assays led to the identification of six compounds that elicited a behavioural effect in A. gambiae. Our results provide, to our knowledge, the first evidence for a role of selected bacterial species, common on the human skin, in determining the attractiveness of humans to malaria mosquitoes. This information will be used in the further development of a blend of semiochemicals for the manipulation of mosquito behaviour

In Vivo Methods for the Assessment of Topical Drug Bioavailability

This paper reviews some current methods for the in vivo assessment of local cutaneous bioavailability in humans after topical drug application. After an introduction discussing the importance of local drug bioavailability assessment and the limitations of model-based predictions, the focus turns to the relevance of experimental studies. The available techniques are then reviewed in detail, with particular emphasis on the tape stripping and microdialysis methodologies. Other less developed techniques, including the skin biopsy, suction blister, follicle removal and confocal Raman spectroscopy techniques are also described

First Evidence of Reproductive Adaptation to “Island Effect” of a Dwarf Cretaceous Romanian Titanosaur, with Embryonic Integument In Ovo

<div><h3>Background</h3><p>The Cretaceous vertebrate assemblages of Romania are famous for geographically endemic dwarfed dinosaur taxa. We report the first complete egg clutches of a dwarf lithostrotian titanosaur, from Toteşti, Romania, and its reproductive adaptation to the “island effect”.</p> <h3>Methodology/Findings</h3><p>The egg clutches were discovered in sequential sedimentary layers of the Maastrichtian Sânpetru Formation, Toteşti. The occurrence of 11 homogenous clutches in successive strata suggests philopatry by the same dinosaur species, which laid clutches averaging four ∼12 cm diameters eggs. The eggs and eggshells display numerous characters shared with the positively identified material from egg-bearing level 4 of the Auca Mahuevo (Patagonia, Argentina) nemegtosaurid lithostrotian nesting site. Microscopic embryonic integument with bacterial evidences was recovered in one egg. The millimeter-size embryonic integument displays micron size dermal papillae implying an early embryological stage at the time of death, likely corresponding to early organogenesis before the skeleton formation.</p> <h3>Conclusions/Significance</h3><p>The shared oological characters between the Haţeg specimens and their mainland relatives suggest a highly conservative reproductive template, while the nest decrease in egg numbers per clutch may reflect an adaptive trait to a smaller body size due to the “island effect”. The combined presence of the lithostrotian egg and its embryo in the Early Cretaceous Gobi coupled with the oological similarities between the Haţeg and Auca Mahuevo oological material evidence that several titanosaur species migrated from Gondwana through the Haţeg Island before or during the Aptian/Albian. It also suggests that this island might have had episodic land bridges with the rest of the European archipelago and Asia deep into the Cretaceous.</p> </div

Environmental biological hazards for pregnant women – occurrence and prophylaxis

Toxoplasma gondii, Listeria monocytogenes i Borrelia burgdorferi należą do istotnych środowiskowych zagrożeń biologicznych dla kobiet ciężarnych i ich dzieci. Toksoplazmoza jest jednym z najbardziej rozpowszechnionych zakażeń pasożytniczych człowieka. Dane Światowej Organizacji Zdrowia wskazują, iż zakażenie T. gondii obejmuje około 1/3 ludności świata. Zakażenie T. gondii jest rozpowszechnione na całym świecie wśród ludzi i zwierząt (szczury, psy, koty, bydło, owce, kury, świnie). W populacji ludzkiej częstość zakażenia waha się zależnie od klimatu, sposobu odżywiania oraz warunków sanitarno-epidemiologicznych od 5 do 90%. Listerioza jest chorobą wywołaną zakażeniem przez wszechobecną Gram-dodatnią pałeczkę Listeria monocytogenes (wywołującą hemolizę), chorobotwórczą dla wielu gatunków zwierząt. Najczęściej objawowa listerioza występuje u płodów (rozsiana niemowlęca postać listeriozy), u noworodków i u pacjentów z obniżoną odpornością. Borelioza występuje na całym świecie. Do infekcji dochodzi w wyniku ukąszenia przez kleszcza z rodzaju Ixodes, zakażonego patogennymi krętkami. W artykule przedstawiono epidemiologię powyższych zakażeń w tym przede wszystkim źródła infekcji oraz potencjalne negatywne skutki infekcji dla kobiet ciężarnych, płodów i dzieci. Omówiono również właściwe zachowania sanitarno-higieniczne umożliwiające zapobieganie tym zakażeniom. We wszystkich przedstawionych infekcjach najbardziej skuteczna jest bowiem profi laktyka, polegająca na niedopuszczeniu do wystąpienia zakażenia