Induction of oral tolerance in a case of severe allergy to coconut

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High circulating sclerostin is present in patients with thalassemia-associated osteoporosis and correlates with bone mineral density.

Osteoporosis is a severe complication of thalassemia. Sclerostin is a Wnt signaling inhibitor, which is produced by osteocytes and inhibits osteoblast function. Sclerostin is implicated in the pathogenesis of osteoporosis of different etiology. The aim of the study was to evaluate circulating sclerostin in 66 patients (median age 42 years) with thalassemia and osteoporosis who participated in a phase 2, randomized study (zoledronic acid vs. placebo) and the results were compared with those of 30 healthy controls (median age 44 years) without osteopenia/osteoporosis and 62 women with postmenopausal osteoporosis (median age 63 years). At baseline, thalassemic patients with osteoporosis had elevated circulating levels of sclerostin (median: 605 pg/ml, range: 22-1,227 pg/ml) compared to healthy controls without osteopenia/osteoporosis (250 pg/ml, 0-720 pg/ml, p<0.001) and reduced levels of sclerostin compared with postmenopausal women with osteoporosis (840 pg/ml, 181-1,704 pg/ml, p<0.001). Thalassemia patients had also increased serum dickkopf-1 (Dkk-1) and high bone turnover. Circulating sclerostin levels correlated with bone mineral density in lumbar spine (r=0.619, p<0.001), distal radius (r=0.401, p=0.001) and femoral neck (r=0.301, p=0.021). Zoledronic acid did not alter sclerostin levels after 12 months of therapy, although it reduced circulating Dkk-1. We conclude that circulating sclerostin is elevated in thalassemia patients with osteoporosis and correlated with their BMD, but it was not reduced post zoledronic acid administration. These findings suggest that high sclerostin may serve as a marker of increased osteocyte activity in thalassemia patients. Drugs targeting sclerostin may also be used in this difficult to treat disorder associated with bone loss.

Differences in AMPK expression between subcutaneous and visceral adipose tissue in morbid obesity.

Adenine monophosphate (AMP) activated protein kinase (AMPK) is an important regulator of obesity. The objective of the present work was to study and compare AMPK protein expression in visceral vs. subcutaneous adipose tissue of morbid obese subjects and to correlate it with adipose tissue characteristics. We selected a total population of 17 extreme obese (BMI>or=40 kg/m2) aged 42.8+/-10.2 years were included in this study. We measured anthropometric and body composition parameters. Adiponectin expression by qRT-PCR, isoproterenol-stimulated lipolytic rates, and AMPK alpha subunits expression by Western blot in adipose tissue explants were determined. Finally plasma concentrations of glucose, triacylglycerols, total cholesterol, HDL-c, LDL-c and insulin were also measured. Our results showed that AMPK alpha expression was higher in subcutaneous than in visceral tissue. A positive correlation between AMPK expression and adiponectin expression in human subcutaneous adipose tissue was observed. Furthermore, a positive correlation between AMPK expression and isoproterenol evoked upregulation of lipolysis rate was also observed. In conclusion, AMPK alpha expression differed according to adipose tissue location. The positive correlation between subcutaneous adipose tissue AMPK and adiponectin or the evoked lipolysis rate could indicate a protective role of AMPK in this tissue, counteracting insulin resistance in morbid obese patients.

A class-wide phylogenetic assessment of Dothideomycetes.

We present a comprehensive phylogeny derived from 5 genes, nucSSU, nucLSU rDNA, TEF1, RPB1 and RPB2, for 356 isolates and 41 families (six newly described in this volume) in Dothideomycetes. All currently accepted orders in the class are represented for the first time in addition to numerous previously unplaced lineages. Subclass Pleosporomycetidae is expanded to include the aquatic order Jahnulales. An ancestral reconstruction of basic nutritional modes supports numerous transitions from saprobic life histories to plant associated and lichenised modes and a transition from terrestrial to aquatic habitats are confirmed. Finally, a genomic comparison of 6 dothideomycete genomes with other fungi finds a high level of unique protein associated with the class, supporting its delineation as a separate taxon.

Unravelling the phylogenetic relationships of lichenised fungi in Dothideomyceta.

We present a revised phylogeny of lichenised Dothideomyceta (Arthoniomycetes and Dothideomycetes) based on a combined data set of nuclear large subunit (nuLSU) and mitochondrial small subunit (mtSSU) rDNA data. Dothideomyceta is supported as monophyletic with monophyletic classes Arthoniomycetes and Dothideomycetes; the latter, however, lacking support in this study. The phylogeny of lichenised Arthoniomycetes supports the current division into three families: Chrysothrichaceae (Chrysothrix), Arthoniaceae (Arthonia s. l., Cryptothecia, Herpothallon), and Roccellaceae (Chiodecton, Combea, Dendrographa, Dichosporidium, Enterographa, Erythrodecton, Lecanactis, Opegrapha, Roccella, Roccellographa, Schismatomma, Simonyella). The widespread and common Arthonia caesia is strongly supported as a (non-pigmented) member of Chrysothrix. Monoblastiaceae, Strigulaceae, and Trypetheliaceae are recovered as unrelated, monophyletic clades within Dothideomycetes. Also, the genera Arthopyrenia (Arthopyreniaceae) and Cystocoleus and Racodium (Capnodiales) are confirmed as Dothideomycetes but unrelated to each other. Mycomicrothelia is shown to be unrelated to Arthopyrenia s.str., but is supported as a monophyletic clade sister to Trypetheliaceae, which is supported by hamathecium characters. The generic concept in several groups is in need of revision, as indicated by non-monophyly of genera, such as Arthonia, Astrothelium, Cryptothecia, Cryptothelium, Enterographa, Opegrapha, and Trypethelium in our analyses.

New primers for promising single-copy genes in fungal phylogenetics and systematics.

Developing powerful phylogenetic markers is a key concern in fungal phylogenetics. Here we report degenerate primers that amplify the single-copy genes Mcm7 (MS456) and Tsr1 (MS277) across a wide range of Pezizomycotina (Ascomycota). Phylogenetic analyses of 59 taxa belonging to the Eurotiomycetes, Lecanoromycetes, Leotiomycetes, Lichinomycetes and Sordariomycetes, indicate the utility of these loci for fungal phylogenetics at taxonomic levels ranging from genus to class. We also tested the new primers in silico using sequences of Saccharomycotina, Taphrinomycotina and Basidiomycota to predict their potential of amplifying widely across the Fungi. The analyses suggest that the new primers will need no, or only minor sequence modifications to amplify Saccharomycotina, Taphrinomycotina and Basidiomycota.

Bovine glycomacropeptide ameliorates experimental rat ileitis by mechanisms involving downregulation of interleukin 17.

BACKGROUND AND PURPOSE: Bovine glycomacropeptide (BGMP) is an inexpensive, non-toxic milk peptide with anti-inflammatory effects in rat experimental colitis but its mechanism of action is unclear. It is also unknown whether BGMP can ameliorate inflammation in proximal regions of the intestine. Our aim was therefore two-fold: first, to determine the anti-inflammatory activity of BGMP in the ileum; second, to characterise its mechanism of action. EXPERIMENTAL APPROACH: We used a model of ileitis induced by trinitrobenzenesulphonic acid in rats. Rats were treated orally with BGMP and its efficacy compared with that of oral 5-aminosalicylic acid or vehicle, starting 2 days before ileitis induction. KEY RESULTS: BGMP pretreatment (500 mg kg(-1) day(-1)) resulted in marked reduction of inflammatory injury, as assessed by lower extension of necrosis and damage score, myeloperoxidase, alkaline phosphatase, inducible nitric oxide synthase, interleukin 1beta, tumour necrosis factor and interleukin 17. These effects were generally comparable to those of 5-aminosalicylic acid (200 mg kg(-1) day(-1)). Neither compound affected the production of interferon gamma, tumour necrosis factor and interleukin 2 by mesenteric lymph node cells isolated from animals with ileitis. The expression of Foxp3 was increased in ileitis and not reduced significantly by BGMP or aminosalicylate treatment. CONCLUSIONS AND IMPLICATIONS: These results demonstrate that BGMP has anti-inflammatory activity in the ileum with similar efficacy to 5-aminosalicylic acid. The mechanism of action may involve Th17 and regulatory T cells and perhaps macrophages but probably not Th1 lymphocytes. Patients with Crohn's ileitis may benefit from treatment with BGMP.

Rituximab monotherapy is highly effective in splenic marginal zone lymphoma.

Splenectomy has traditionally been considered as a standard first line treatment for splenic marginal zone lymphoma (SMZL) conferring a survival advantage over chemotherapy. However it carries significant complications, especially in elderly patients. The purpose of this retrospective study was to report our experience on the efficacy of Rituximab as first line treatment in 16 consecutive SMZL patients, diagnosed in our department. The diagnosis was established using standard criteria. Patients' median age was 57 years (range, 48-78). Prior to treatment initiation all patients had splenomegaly, nine had anemia, five lymphocytosis, five neutropenia and six thrombocytopenia. Rituximab was administered at a dose of 375 mg/m2/week for 6 consecutive weeks. The overall response rate was 100%. After treatment, all patients had a complete resolution of splenomegaly along with restoration of their blood counts. Eleven patients (69%) achieved a CR, three (19%) unconfirmed CR and two (12%) a PR. Among the complete responders seven patients had also a molecular remission. The median time to clinical response was 3 weeks (range, 2-6). Rituximab maintenance was given to 12 patients. Eleven of them had no evidence of disease progression after a median follow-up time of 28.5 months (range, 14-36), while two out of four patients who did not receive maintenance, relapsed 7 and 24 months after the completion of induction treatment. Median follow-up time for the entire series was 29.5 months (range, 15-81). No deaths were recorded during the follow-up period. Therapy was well tolerated. The present study demonstrates that rituximab is an effective treatment for SMZL and could be considered as a substitute or alternative to splenectomy.

FLT3 overexpression in acute promyelocytic leukemia patients without detectable FLT3-ITD or codon 835-836 mutations: a pilot study.

BACKGROUND: Activating mutations of the FLT3 receptor tyrosine kinase are common in acute promyelocytic leukemia (APL) but have uncertain prognostic significance. Information regarding FLT3 expression levels in APL without FLT3 mutations is lacking. MATERIALS AND METHODS: Using RT-PCR, mutation analysis of the FLT3 gene, regarding internal tandem duplications (ITDs) and codon 835-836 point mutations, was performed and real-time PCR was carried out to determine the level of FLT3 expression in 11 APL patients at diagnosis and 5 in haematological remission with molecularly detectable disease. RESULTS: High levels of FLT3 transcript, at least a 10-fold increase compared to the normal controls, were found at diagnosis in all 3 mutated cases and in 2 patients without detectable FLT3 mutations. CONCLUSION: FLT3 overexpression can be documented in patients without FLT3 mutations. These patients might benefit from treatment using specific FLT3 tyrosine kinase inhibitors. Larger studies are needed to evaluate the clinical and biological significance of FLT3 overexpression in the absence of FLT3 mutations.

Clinal patterns of human Y chromosomal diversity in continental Italy and Greece are dominated by drift and founder effects.

We explored the spatial distribution of human Y chromosomal diversity on a microgeographic scale, by typing 30 population samples from closely spaced locations in Italy and Greece for 9 haplogroups and their internal microsatellite variation. We confirm a significant difference in the composition of the Y chromosomal gene pools of the two countries. However, within each country, heterogeneity is not organized along the lines of clinal variation deduced from studies on larger spatial scales. Microsatellite data indicate that local increases of haplogroup frequencies can be often explained by a limited number of founders. We conclude that local founder or drift effects are the main determinants in shaping the microgeographic Y chromosomal diversity.

Conventional and surgical treatment of a two-rooted maxillary central incisor.

Conventional and surgical endodontic management were performed on a two-rooted maxillary central incisor with a periapical lesion. Anatomical complexity of the tooth lead to perforation in the distal root during conventional treatment, thus a surgical approach was taken. A 4-month postoperative radiograph shows repair.

Clinicopathologic correlations of bone marrow angiogenesis in chronic myeloid leukemia: a morphometric study.

Various morphometric characteristics of microvessels, highlighted by means of anti-CD34 immunohistochemical staining, were evaluated in the bone marrow of 52 patients with chronic myeloid leukemia (CML) in chronic phase, in relation to several clinicopathologic parameters. Twenty control bone marrows and 15 cases of CML in blastic phase were also studied. Microvessel density (MVD), total vascular area (TVA) and several size- and shape-related parameters were quantitated in the region of most intense vascularization using image analysis. Overall, the group of chronic phase CML had higher MVD and size-related parameters and more branching microvessels than controls. Blastic phase was characterized by increased numbers of microvessels with a rounder shape and smaller caliber than chronic phase. A positive correlation emerged between marrow fibrosis and MVD as well as between white blood cell counts and rounder vessel sections. No relationship existed between microvascular parameters and Hasford or Sokal prognostic scores. In univariate analysis, overall and progression-free survival were adversely affected by MVD, size-related parameters, increased platelet count, age and spleen size. Multivariate analysis indicated that microvessel area was related to progression-free survival, whereas both MVD and area were significant prognosticators of overall survival, even when Hasford or Sokal scores are introduced into the model. Our data suggest that changes in angiogenic parameters may participate in the conversion of normal marrow to CML and ultimately to blastic transformation. More importantly, MVD and microvessel caliber are significant predictors of patient survival and progression.