Response to GH Treatment After Radiation Therapy Depends on Location of Irradiation

OBJECTIVES: Cancer survivors with GH deficiency (GHD) receive GH therapy (GHT) after 1+ year observation to ensure stable tumor status/resolution. HYPOTHESIS: Radiation therapy (RT) to brain, spine, or extremities alters growth response to GHT. AIM: Identify differences in growth response to GHT according to type/location of RT. METHODS: The Pfizer International Growth Database was searched for cancer survivors on GHT for ≥5 years. Patient data, grouped by tumor type, were analyzed for therapy (surgery, chemotherapy, RT of the focal central nervous system, cranial, craniospinal, or total body irradiation [TBI] as part of bone marrow transplantation), sex, peak stimulated GH, age at GHT start, and duration from RT to GHT start. Kruskal-Wallis test and quantile regression modeling were performed. RESULTS: Of 1149 GHD survivors on GHT for ≥5 years (male 733; median age 8.4 years; GH peak 2.8 ng/mL), 431 had craniopharyngioma (251, cranial RT), 224 medulloblastoma (craniospinal RT), 134 leukemia (72 TBI), and 360 other tumors. Median age differed by tumor group (P < 0.001). Five-year delta height SD score (SDS) (5-year ∆HtSDS; median [10th-90th percentile]) was greatest for craniopharyngioma, 1.6 (0.3-3.0); for medulloblastoma, 5-year ∆HtSDS 0.9 (0.0-1.9); for leukemia 5-year ∆HtSDS, after TBI (0.3, 0-0.7) versus without RT (0.5, 0-0.9), direct comparison P < 0.001. Adverse events included 40 treatment-related, but none unexpected. CONCLUSIONS: TBI for leukemia had significant impact on growth response to GHT. Medulloblastoma survivors had intermediate GHT response, whereas craniopharyngioma cranial RT did not alter GHT response. Both craniospinal and epiphyseal irradiation negatively affect growth response to GH therapy compared with only cranial RT or no RT

Depth-dependent fractionation of light solar wind noble gases in a Genesis target

We analyzed light noble gases in a bulk metallic glass (BMG) that was exposed to solar wind (SW) irradiation on Genesis for its total exposure time and all SW regimes [1]. The BMG was especially designed to look for a putative solar energetic particle (SEP) component, reported to be present in lunar soils [2], by using the closed system stepwise etching (CSSE) technique. Here we present the depth distribution of He and Ne isotopes and discuss different processes leading to the observed fractionation patterns. Moreover, this will be compared with measurements of Ar isotopes that are actually in progress

Evaluation of three instrumentation techniques at the precision of apical stop and apical sealing of obturation

OBJECTIVE: The aim of this study was to investigate the ability of two NiTi rotary apical preparation techniques used with an electronic apex locator-integrated endodontic motor and a manual technique to create an apical stop at a predetermined level (0.5 mm short of the apical foramen) in teeth with disrupted apical constriction, and to evaluate microleakage following obturation in such prepared teeth. MATERIAL AND METHODS: 85 intact human mandibular permanent incisors with single root canal were accessed and the apical constriction was disrupted using a #25 K-file. The teeth were embedded in alginate and instrumented to #40 using rotary Lightspeed or S-Apex techniques or stainless-steel K-files. Distance between the apical foramen and the created apical stop was measured to an accuracy of 0.01 mm. In another set of instrumented teeth, root canals were obturated using gutta-percha and sealer, and leakage was tested at 1 week and 3 months using a fluid filtration device. RESULTS: All techniques performed slightly short of the predetermined level. Closest preparation to the predetermined level was with the manual technique and the farthest was with S-Apex. A significant difference was found between the performances of these two techniques (

Assessment of liposome disruption to quantify drug delivery in vitro

Efficient liposome disruption inside the cells is a key for success with any type of drug delivery system. The efficacy of drug delivery is currently evaluated by direct visualization of labeled liposomes internalized by cells, not addressing objectively the release and distribution of the drug. Here, we propose a novel method to easily assess liposome disruption and drug release into the cytoplasm. We propose the encapsulation of the cationic dye Hoechst 34,580 to detect an increase in blue fluorescence due to its specific binding to negatively charged DNA. For that, the dye needs to be released inside the cell and translocated to the nucleus. The present approach correlates the intensity of detected fluorescent dye with liposome disruption and consequently assesses drug delivery within the cells.Eugénia Nogueira (SFRH/BD/81269/2011), Célia F. Cruz (SFRH/BD/ 100927/2014) and Ana Loureiro (SFRH/BD/81479/2011) hold scholarships from Fundação para a Ciência e a Tecnologia (FCT). This study was funded by the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement NMP4-LA-2009-228827 NANOFOL. This study was also supported by FEDER through POFC – COMPETE and by national funds from FCT through the project PEst-UID/ BIA/4050/2013 and the strategic funding of ID/BIO/04469/2013 unit.We thank the Immuno-haemotherapy Department of Hospital de São João (Porto, Portugal) for providing buffy coats from healthy volunteers

Cross-species Malaria Immunity Induced By Chemically Attenuated Parasites

Vaccine development for the blood stages of malaria has focused on the induction of antibodies to parasite surface antigens, most of which are highly polymorphic. An alternate strategy has evolved from observations that low-density infections can induce antibody-independent immunity to different strains. To test this strategy, we treated parasitized red blood cells from the rodent parasite Plasmodium chabaudi with secocyclopropyl pyrrolo indole analogs. These drugs irreversibly alkylate parasite DNA, blocking their ability to replicate. After administration in mice, DNA from the vaccine could be detected in the blood for over 110 days and a single vaccination induced profound immunity to different malaria parasite species. Immunity was mediated by CD4(+) T cells and was dependent on the red blood cell membrane remaining intact. The human parasite, Plasmodium falciparum, could also be attenuated by treatment with seco-cyclopropyl pyrrolo indole analogs. These data demonstrate that vaccination with chemically attenuated parasites induces protective immunity and provide a compelling rationale for testing a blood-stage parasite-based vaccine targeting human Plasmodium species

Global gene expression patterns in the post-pneumonectomy lung of adult mice

<p>Abstract</p> <p>Background</p> <p>Adult mice have a remarkable capacity to regenerate functional alveoli following either lung resection or injury that exceeds the regenerative capacity observed in larger adult mammals. The molecular basis for this unique capability in mice is largely unknown. We examined the transcriptomic responses to single lung pneumonectomy in adult mice in order to elucidate prospective molecular signaling mechanisms used in this species during lung regeneration.</p> <p>Methods</p> <p>Unilateral left pneumonectomy or sham thoracotomy was performed under general anesthesia (n = 8 mice per group for each of the four time points). Total RNA was isolated from the remaining lung tissue at four time points post-surgery (6 hours, 1 day, 3 days, 7 days) and analyzed using microarray technology.</p> <p>Results</p> <p>The observed transcriptomic patterns revealed mesenchymal cell signaling, including up-regulation of genes previously associated with activated fibroblasts (Tnfrsf12a, Tnc, Eln, Col3A1), as well as modulation of Igf1-mediated signaling. The data set also revealed early down-regulation of pro-inflammatory cytokine transcripts and up-regulation of genes involved in T cell development/function, but few similarities to transcriptomic patterns observed during embryonic or post-natal lung development. Immunohistochemical analysis suggests that early fibroblast but not myofibroblast proliferation is important during lung regeneration and may explain the preponderance of mesenchymal-associated genes that are over-expressed in this model. This again appears to differ from embryonic alveologenesis.</p> <p>Conclusion</p> <p>These data suggest that modulation of mesenchymal cell transcriptome patterns and proliferation of S100A4 positive mesenchymal cells, as well as modulation of pro-inflammatory transcriptome patterns, are important during post-pneumonectomy lung regeneration in adult mice.</p

Charged domain walls as quantum strings living on a lattice

A generic lattice cut-off model is introduced describing the quantum meandering of a single cuprate stripe. The fixed point dynamics is derived, showing besides free string behavior a variety of partially quantum disordered phases, bearing relationships both with quantum spin-chains and surface statistical physics.Comment: 22 page, 17 figure