Maternal separation and maternal care act independently on the development of HPA responses in male rats

Postnatal manipulations such as brief (early handling, EH) and long, daily mother-offspring separations (maternal separation, MS) in rats are used to study the mechanisms underlying developmental plasticity of stress and fear responses, and to model stress-related disorders in humans and in non-human animals. Current evidence suggests that, compared to non-handled rats, EH reduces hypothalamic-pituitary-adrenal (HPA) reactivity in the adult offspring through stimulating increased levels of active maternal care. In contrast, despite a similar increase in active maternal care, MS does not reduce HPA reactivity, thus suggesting that long mother-offspring separations may counteract the effects of increased active maternal care. We therefore attempted to selectively manipulate levels of active maternal care and durations of mother-offspring separations in neonate rats. Rat pups were exposed to different combinations of EH and MS from postnatal day (PND) 2 to 10 using a split-litter design. Maternal behaviour was recorded from PND 2 to 8 and behavioural and endocrine responses to stress were studied in adult male offspring. Low levels of maternal care combined with long mother-offspring separations increased HPA-reactivity compared to both high maternal care combined with long mother-offspring separations and low maternal care combined with brief separations. These findings further support the hypothesis that active maternal care and long mother-offspring separation act independently, and exert opposing effects, on adult offspring's HPA responses, but that increased maternal care may buffer the adverse consequences of long separations.     

Recent trends in the management of dentoalveolar traumatic injuries to primary and young permanent teeth

Abstract – One of the commonly encountered dental emergencies is dentoalveolar traumatic injuries (DTIs). Unfortunately, DTIs result in fractured, displaced, or lost anterior teeth and this could have significant negative functional, esthetic, speech, and psychological effects on children thus affecting their quality of life. Although it is impossible to guarantee permanent retention of a traumatized tooth, patient age, severity of injury, and timely treatment and follow up of the tooth using recommended procedures can maximize the chances for success. This review examines the recent trends in the management of DTI to primary and young permanent teeth. Electronic search of scientific papers written in English from 1990s to 2009 was accomplished using Pub Med search engine. Dental practitioners should follow current literature and consider carefully evidenced‐based recommendations that may enhance periodontal healing and revascularization of avulsed permanent teeth.     

Shifting carbon flow from roots into associated microbial communities in response to elevated atmospheric CO2

Rising atmospheric CO₂ levels are predicted to have major consequences on carbon cycling and the functioning of terrestrial ecosystems. Increased photosynthetic activity is expected, especially for C-3 plants, thereby influencing vegetation dynamics; however, little is known about the path of fixed carbon into soil-borne communities and resulting feedbacks on ecosystem function. Here, we examine how arbuscular mycorrhizal fungi (AMF) act as a major conduit in the transfer of carbon between plants and soil and how elevated atmospheric CO₂ modulates the belowground translocation pathway of plant-fixed carbon. Shifts in active AMF species under elevated atmospheric CO₂ conditions are coupled to changes within active rhizosphere bacterial and fungal communities. Thus, as opposed to simply increasing the activity of soil-borne microbes through enhanced rhizodeposition, elevated atmospheric CO₂ clearly evokes the emergence of distinct opportunistic plant-associated microbial communities. Analyses involving RNA-based stable isotope probing, neutral/phosphate lipid fatty acids stable isotope probing, community fingerprinting, and real-time PCR allowed us to trace plant-fixed carbon to the affected soil-borne microorganisms. Based on our data, we present a conceptual model in which plant-assimilated carbon is rapidly transferred to AMF, followed by a slower release from AMF to the bacterial and fungal populations well-adapted to the prevailing (myco-)rhizosphere conditions. This model provides a general framework for reappraising carbon-flow paths in soils, facilitating predictions of future interactions between rising atmospheric CO₂ concentrations and terrestrial ecosystems.     

High-dose imatinib improves cytogenetic and molecular remissions in patients with pretreated Philadelphia-positive, BCR-ABL-positive chronic phase chronic myeloid leukemia: first results from the randomized CELSG phase III CML 11 ��ISTAHIT�� study

Background

Imatinib 400 mg/day is the standard treatment for patients with chronic phase chronic myeloid leukemia. Recent reports suggested higher and more rapid cytogenetic and molecular responses with higher doses of imatinib.

Design and Methods

In this prospective international, multicenter phase III study, 227 patients with pre-treated Philadelphia chromosome-positive, BCR-ABL-positive chronic myeloid leukemia were randomized to a standard-dose imatinib arm (400 mg/day) or a high-dose imatinib arm (800 mg/day for 6 months followed by 400 mg/day as maintenance therapy). In this planned interim analysis hematologic, cytogenetic and molecular responses as well as toxicity were evaluated.

Results

Compared to the standard-dose, high-dose imatinib led to higher rates of major and complete cytogenetic responses at both 3 months (major: 21% versus 37%, P=0.01; complete: 6% versus 25%, P<0.001) and 6 months (major: 34% versus 54%, P=0.009; complete: 20% versus 44%, P<0.001). This was paralleled by a significantly higher major molecular response rate at 6 months in the high-dose imatinib arm (11.8% versus 30.4%; P=0.003). At 12 months, the rates of major cytogenetic response (the primary end-point) were comparable between the two arms (57% versus 59%). In contrast to non-hematologic toxicities, grade 3/4 hematologic toxicities were more common in the high-dose arm. Cumulative complete cytogenetic response rates were higher in patients without dose reduction in the high-dose arm (61%) than in the patients with no dose reduction in the standard-dose arm (36%) (P=0.014).

Conclusions

This is the first randomized phase III trial in patients with pre-treated chronic phase chronic myeloid leukemia demonstrating improvements in major cytogenetic response, complete cytogentic response and major molecular response rates with high-dose imatinib therapy (ClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT00327262","term_id":"NCT00327262"}}NCT00327262).     

Mucosal but not peripheral FOXP3+ regulatory T cells are highly increased in untreated HIV infection and normalize after suppressive HAART

Recent evidence indicates that regulatory T cells (T(regs)) play an important role in HIV infection. However, although the gastrointestinal mucosa is a key compartment in HIV disease, no data on mucosal T(regs) in HIV infection are available. In this study, we compared the frequency of T(regs) in duodenal mucosa and peripheral blood (PB) of 13 treatment-naive and 13 suppressively treated HIV-infected patients with that of 6 patients with norovirus infection and 12 healthy controls. T(regs) were quantified by immunohistochemistry (CD3/FOXP3) and further characterized (CD25, CTLA-4, GITR) by immunohistochemistry, immunofluorescence, and fluorescence-activated cell sorting (FACS). Both the frequency and the absolute count of mucosal T(regs) were highly increased in untreated HIV patients but were normal in treated HIV patients. In contrast, in peripheral blood of HIV patients, the absolute number of T(regs) was not increased, and their frequency was only slightly elevated. In norovirus infection, frequency of mucosal T(regs) in the CD4+ T-cell subset was not elevated. The high increase in count and frequency of mucosal T(regs) seems to be a characteristic feature of untreated HIV infection, suggesting a significant contribution of T(regs) to the pathogenesis of HIV disease. Their role may be 2-edged: attenuating HIV-induced immune hyperactivation while suppressing the immune response to HIV and mucosal pathogens.