Acute rejection is associated with antibodies to non-Gal antigens in baboons using Gal-knockout pig kidneys

We transplanted kidneys from α1,3-galactosyltransferase knockout (GalT-KO) pigs into six baboons using two different immunosuppressive regimens, but most of the baboons died from severe acute humoral xenograft rejection. Circulating induced antibodies to non-Gal antigens were markedly elevated at rejection, which mediated strong complement-dependent cytotoxicity against GalT-KO porcine target cells. These data suggest that antibodies to non-Gal antigens will present an additional barrier to transplantation of organs from GalT-KO pigs to humans. © 2005 Nature Publishing Group

Supplementation of a western diet with golden kiwifruits (Actinidia chinensis var.'Hort 16A':) effects on biomarkers of oxidation damage and antioxidant protection

<p>Abstract</p> <p>Background</p> <p>The health positive effects of diets high in fruits and vegetables are generally not replicated in supplementation trials with isolated antioxidants and vitamins, and as a consequence the emphasis of chronic disease prevention has shifted to whole foods and whole food products.</p> <p>Methods</p> <p>We carried out a human intervention trial with the golden kiwifruit, Actinidia chinensis, measuring markers of antioxidant status, DNA stability, plasma lipids, and platelet aggregation. Our hypothesis was that supplementation of a normal diet with kiwifruits would have an effect on biomarkers of oxidative status. Healthy volunteers supplemented a normal diet with either one or two golden kiwifruits per day in a cross-over study lasting 2 × 4 weeks. Plasma levels of vitamin C, and carotenoids, and the ferric reducing activity of plasma (FRAP) were measured. Malondialdehyde was assessed as a biomarker of lipid oxidation. Effects on DNA damage in circulating lymphocytes were estimated using the comet assay with enzyme modification to measure specific lesions; another modification allowed estimation of DNA repair.</p> <p>Results</p> <p>Plasma vitamin C increased after supplementation as did resistance towards H₂O₂-induced DNA damage. Purine oxidation in lymphocyte DNA decreased significantly after one kiwifruit per day, pyrimidine oxidation decreased after two fruits per day. Neither DNA base excision nor nucleotide excision repair was influenced by kiwifruit consumption. Malondialdehyde was not affected, but plasma triglycerides decreased. Whole blood platelet aggregation was decreased by kiwifruit supplementation.</p> <p>Conclusion</p> <p>Golden kiwifruit consumption strengthens resistance towards endogenous oxidative damage.</p

Neuroinflammation and structural injury of the fetal ovine brain following intra-amniotic Candida albicans exposure.

BackgroundIntra-amniotic Candida albicans (C. Albicans) infection is associated with preterm birth and high morbidity and mortality rates. Survivors are prone to adverse neurodevelopmental outcomes. The mechanisms leading to these adverse neonatal brain outcomes remain largely unknown. To better understand the mechanisms underlying C. albicans-induced fetal brain injury, we studied immunological responses and structural changes of the fetal brain in a well-established translational ovine model of intra-amniotic C. albicans infection. In addition, we tested whether these potential adverse outcomes of the fetal brain were improved in utero by antifungal treatment with fluconazole.MethodsPregnant ewes received an intra-amniotic injection of 10(7) colony-forming units C. albicans or saline (controls) at 3 or 5 days before preterm delivery at 0.8 of gestation (term ~ 150 days). Fetal intra-amniotic/intra-peritoneal injections of fluconazole or saline (controls) were administered 2 days after C. albicans exposure. Post mortem analyses for fungal burden, peripheral immune activation, neuroinflammation, and white matter/neuronal injury were performed to determine the effects of intra-amniotic C. albicans and fluconazole treatment.ResultsIntra-amniotic exposure to C. albicans caused a severe systemic inflammatory response, illustrated by a robust increase of plasma interleukin-6 concentrations. Cerebrospinal fluid cultures were positive for C. albicans in the majority of the 3-day C. albicans-exposed animals whereas no positive cultures were present in the 5-day C. albicans-exposed and fluconazole-treated animals. Although C. albicans was not detected in the brain parenchyma, a neuroinflammatory response in the hippocampus and white matter was seen which was characterized by increased microglial and astrocyte activation. These neuroinflammatory changes were accompanied by structural white matter injury. Intra-amniotic fluconazole reduced fetal mortality but did not attenuate neuroinflammation and white matter injury.ConclusionsIntra-amniotic C. albicans exposure provoked acute systemic and neuroinflammatory responses with concomitant white matter injury. Fluconazole treatment prevented systemic inflammation without attenuating cerebral inflammation and injury

Transactional paths between children and parents in pediatric asthma: Associations between family relationships and adaptation

Introduction. The particular challenges posed by pediatric asthma may have a negative impact on the adaptation of children and their parents. From a transactional approach it is important to examine how reciprocal links between children and parents contribute to explain their adaptation and under which conditions these associations occur. This cross-sectional study aimed at examining the direct and indirect links between children’s and parents’ perceptions of family relationships and adaptation, separately (within-subjects) and across participants (cross-lagged effects), and the role of asthma severity in moderating these associations. Method. The sample comprised 257 children with asthma, aged between 8 and 18 years-old, and one of their parents. Both family members completed self-reported questionnaires on family relationships (cohesion and expressiveness) and adaptation indicators (quality of life and psychological functioning). Physicians assessed asthma severity. Structural Equation Modeling was used to test within-subjects and cross-lagged paths between children’s and parents’ family relationships and adaptation. Results. The model explained 47% of children’s and 30% of parents’ adaptation: family relationships were positively associated with adaptation, directly for children and parents, and indirectly across family members. Asthma severity moderated the association between family relationships and health-related quality of life for children: stronger associations were observed in the presence of persistent asthma. Conclusion. These results highlight the need of including psychological interventions in pediatric healthcare focused on family relationships as potential targets for improving children’s and parents’ quality of life and psychological functioning, and identified the children with persistent asthma as a group that would most benefit from family-based interventions.This study was supported by the R&D Unit Institute of Cognitive Psychology, Vocational and Social Development of the University of Coimbra (PEst-OE/PSI/UI0192/2011) and by the Portuguese Foundation for Science and Technology (PhD Grant SFRH/BD/69885/2010)

The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) family

The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) enzymes are secreted, multi-domain matrix-associated zinc metalloendopeptidases that have diverse roles in tissue morphogenesis and patho-physiological remodeling, in inflammation and in vascular biology. The human family includes 19 members that can be sub-grouped on the basis of their known substrates, namely the aggrecanases or proteoglycanases (ADAMTS1, 4, 5, 8, 9, 15 and 20), the procollagen N-propeptidases (ADAMTS2, 3 and 14), the cartilage oligomeric matrix protein-cleaving enzymes (ADAMTS7 and 12), the von-Willebrand Factor proteinase (ADAMTS13) and a group of orphan enzymes (ADAMTS6, 10, 16, 17, 18 and 19). Control of the structure and function of the extracellular matrix (ECM) is a central theme of the biology of the ADAMTS, as exemplified by the actions of the procollagen-N-propeptidases in collagen fibril assembly and of the aggrecanases in the cleavage or modification of ECM proteoglycans. Defects in certain family members give rise to inherited genetic disorders, while the aberrant expression or function of others is associated with arthritis, cancer and cardiovascular disease. In particular, ADAMTS4 and 5 have emerged as therapeutic targets in arthritis. Multiple ADAMTSs from different sub-groupings exert either positive or negative effects on tumorigenesis and metastasis, with both metalloproteinase-dependent and -independent actions known to occur. The basic ADAMTS structure comprises a metalloproteinase catalytic domain and a carboxy-terminal ancillary domain, the latter determining substrate specificity and the localization of the protease and its interaction partners; ancillary domains probably also have independent biological functions. Focusing primarily on the aggrecanases and proteoglycanases, this review provides a perspective on the evolution of the ADAMTS family, their links with developmental and disease mechanisms, and key questions for the future

Granular cell tumor presenting as a tongue nodule: two case reports

<p>Abstract</p> <p>Introduction</p> <p>Granular cell tumor is an uncommon neoplasm that can occur in any part of the body, including the orofacial region. The tumor is usually benign, but there are reports of cases in which the tumor shows a locally aggressive behavior, malignancy, and distant metastases. The most widely accepted hypothesis is that granular cell tumor arises from the altered metabolism of Schwann cells. The tumor is typically asymptomatic and appears as a nodule that does not exceed 3 cm.</p> <p>Case presentation</p> <p>In case 1, a 26-year-old Caucasian man was seen at the Oral Medicine out-patient clinic of the São José dos Campos Dental School, Universidade Estadual Paulista, with a 'small blister on the tongue', which he had noted approximately three years ago. The nodule was located on the dorsum of the tongue, measured about 1.5 cm in diameter, and was not tender to palpation. Treatment consisted of an excisional biopsy performed on the basis of the diagnostic hypothesis of granular cell tumor, which was confirmed by microscopic analysis. In case 2, a 31-year-old Caucasian woman attended the out-patient clinic of the São José dos Campos Dental School, Universidade Estadual Paulista, with a five-year history of a 'painful lump on the tongue'. Intra-oral examination revealed the presence of a nodular lesion measuring approximately 0.8 cm in diameter, which was located deep in the submucosa of the right lateral margin of the tongue. Treatment consisted of an excisional biopsy performed on the basis of the differential diagnosis of neurofibroma and granular cell tumor. Microscopic analysis defined the final diagnosis of granular cell tumor.</p> <p>Conclusions</p> <p>Granular cell tumor is an uncommon tumor that must be carefully diagnosed and treated correctly.</p

Assessing the knowledge of bronchial asthma among primary health care physicians in Crete: A pre- and post-test following an educational course

AIM: To assess the level of knowledge for bronchial asthma of the primary healthcare physicians serving a rural population on the island of Crete, both before and immediately after a one-day educational course. METHODS: Twenty-one primary health care physicians, randomly selected from a list of 14 Health Care Centres on the island of Crete were invited to participate in the study and attended an educational course. Nine of the 21 physicians were fully qualified general practitioners, while the remainder were non-specialized (NSs) physicians who had recently graduated from the University of Crete, Medical School. A questionnaire of 20 items based on current bronchial asthma clinical guidelines was used. Three scores, the mean total, knowledge subscore and attitudes subscore, were calculated for each group of physicians, both before and after the course. RESULTS: At baseline mean total score and knowledge and attitudes subscores were higher for non-specialized physicians than for the general practitioners, but the differences were not statistically significant (p > 0.05). The knowledge subscore was improved in both groups, however the difference was statistically significant only for the non-specialized physicians (t = 2.628, d.f. = 11, p < 0.05). The mean total score after the course was significantly higher for the non-specialized physicians in comparison to that of the general practitioners (t=-2.688, d.f. = 19, p < 0.05). CONCLUSIONS: This study adds to the information about the success of continuing medical education, and also demonstrates that the recent graduates in the studied population, could be educated with more positive results than the fully qualified practitioner

Social Networks among Elderly Women: Implications for Health Education Practice

The general aim of the present study was to examine and help clarify the properties of the distinctions between social networks and social support, their relationship to health status, and their impli cations for health education practice. More specifically, a secondary data analysis was conducted with 130 white women, community resi dents, between the ages of 60 and 68, which examined the relationship between psychological well-being and social network characteristics. These characteristics are categorized along three broad dimensions: structure—links in the overall network (size and density); interaction— nature of the linkages themselves (frequency, homogeneity, content, reciprocity, intensity, and dispersion); and functions which networks provide (affective support and instrumental support). A combination was made and relative strength investigated of several network char acteristics representative of the quality of interactions (i. e., reciprocal affective support, intensity, and affective support) and those repre senting the quantity of interactions (i.e., size, density, and frequency).Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/67277/2/10.1177_109019818301000304.pd