Late-onset and long-lasting neutropenias in the young: A new entity anticipating immune-dysregulation disorders.

This study identifies a new chronic form of immune neutropenia in the young with or without detectable indirect anti-neutrophil antibodies, characterized by mild/moderate neutropenia low risk of severe infection (14%), tendency to develop autoimmune phenomena over the course of the disease (cumulative incidence of 58.6% after 20 years of disease duration), leukopenia, progressive reduction of absolute lymphocyte count and a T- and B-cell profile similar to autoimmune disorders like Sjogren syndrome, rheumatoid arthritis, and systemic lupus erythematosus (increased HLADR+ and CD3 + TCRγδ cells, reduced T regulatory cells, increased double-negative B and a tendency to reduced B memory cells). In a minority of patients, P/LP variants related to primary immuno-regulatory disorders were found. This new form may fit the group of "Likely acquired neutropenia," a provisional category included in the recent International Guidelines on Diagnosis and Management of Neutropenia of EHA and EUNET INNOCHRON ACTION 18233. The early recognition of this form of neutropenia would help clinicians to delineate better specific monitoring plans, genetic counseling, and potentially targeted therapies.

Co-benefits of changing diet. A modelling assessment at the regional scale integrating social acceptability, environmental and health impacts.

Several commentaries have suggested that the overconsumption of animal foods exerts several detrimental effects on human and environmental health. However, no studies have accurately estimated the impact of a reduction in animal food consumption on mortality due to the direct effects on metabolic health (i.e. animal protein and saturated fat intake as modulators of pathways leading to cardiovascular disease, cancer and accelerated ageing), and indirect effects on health due to excessive exposure to pollutants (i.e. PM10 concentrations originated by livestock ammonia emissions). The proposed modelling approach is innovative since it integrates social acceptability, environmental and health impacts. It is adopted to investigate different scenarios at a regional scale presenting the Lombardy region case study. The work focuses on the impact on the human and environmental health of diets characterized by three different animal protein intake levels. Our integrated assessment modelling approach faces the issue from two points of view. On one side, it estimates the mortality due to the population exposure to PM10 concentrations including the inorganic fraction originated by livestock ammonia emissions, on the other, it evaluates the mortality (i.e. total, cardiovascular and cancer) due to high dietary animal protein and/or saturated fat intake. The impacts of the mentioned animal protein intake levels of diets are also estimated through the people willingness to change their eating behaviour. The importance of putting in place end-of-pipe and energy measures in order to reduce ammonia and methane emissions from the breeding activities, going further the current EU legislation on air quality and climate, is emphasized.

Impact of reduced mass of light commercial vehicles on fuel consumption, CO2 emissions, air quality, and socio-economic costs.

This study presents a modelling system to evaluate the impact of weight reduction in light commercial vehicles with diesel engines on air quality and greenhouse gas emissions. The PROPS model assesses the emissions of one vehicle in the aforementioned category and its corresponding reduced-weight version. The results serve as an input to the RIAT+ tool, an air quality integrated assessment modelling system. This paper applies the tools in a case study in the Lombardy region (Italy) and discusses the input data pre-processing, the PROPS-RIAT+ modelling system runs, and the results.

In vitro anti-angiogenic effects of Hemidesmus indicus in hypoxic and normoxic conditions.

ETHNOPHARMACOLOGICAL RELEVANCE: The decoction of the roots of Hemidesmus indicus is widely used in the Indian traditional medicine for many purposes and poly-herbal preparations containing Hemidesmus are often used by traditional medical practitioners for the treatment of cancer. In the context of anticancer pharmacology, anti-angiogenic therapy has become an effective strategy for inhibiting new vessel formation and contrast tumor growth. These considerations are supported by the evidence that most tumors originate in hypoxic conditions and limitation of oxygen diffusion stimulates the formation of tumor abnormal microvasculature. Aim of this study was to evaluate the in vitro anti-angiogenic potential of Hemidesmus indicus (0.31-0.93 mg/mL) on human umbilical vein endothelial cells and delineate the main molecular mechanisms involved in its anti-angiogenic activity both in normoxia and hypoxia. MATERIALS AND METHODS: The decoction of Hemidesmus indicus was subjected to an extensive HPLC phytochemical characterization. Its in vitro anti-angiogenic potential was investigated in normoxia and hypoxia. Cell proliferation, apoptosis induction, and inhibition of endothelial cell migration and invasion were analyzed by flow cytometry. The endothelial tube formation assay was evaluated in matrix gel. The capillary tube branch points formed were counted using a Motic AE21 microscope and a VisiCam videocamera. The regulation of key factors of the neovascularization process such as VEGF, HIF-1α and VEGFR-2 was explored at mRNA and protein level by real time PCR and flow cytometry, respectively. RESULTS: Treatment with Hemidesmus resulted in a significant inhibition of cell proliferation and tube formation in both normoxia and hypoxia. Hemidesmus differently regulated multiple molecular targets related to angiogenesis according to oxygen availability. In normoxia, the inhibition of VEGF was the main responsible for its anti-angiogenic effect; the angiogenesis inhibition induced in hypoxia was regulated by a more complex mechanism involving firstly HIF-1α inhibition, and then VEGF and VEGFR-2 down-regulation. Additionally, the inhibition of endothelial cell migration and invasion by Hemidesmus was more pronounced in normoxia than in hypoxia, possibly due to the physiological enhanced induction of invasion characteristic of hypoxia. CONCLUSIONS: Our results indicate that Hemidesmus might represent a promising therapeutic strategy for diseases in which the inhibition of angiogenesis could be beneficial, such as cancer. The antiangiogenic activity of Hemidesmus is based on multiple interactions with critical steps in the angiogenic cascade. VEGF expression stimulated by HIF-1α as well as endothelial cell migration and differentiation represent important targets of Hemidesmus action and might contribute to its cancer therapeutic efficacy that is presently emerging and offer a scientific basis for its use in traditional medicine.

Hemidesmus indicus induces apoptosis as well as differentiation in a human promyelocytic leukemic cell line.

ETHNOPHARMACOLOGICAL RELEVANCE: The decoction of the roots of Hemidesmus indicus is widely used in the Indian traditional medicine for the treatment of blood diseases, dyspepsia, loss of taste, dyspnea, cough, poison, menorrhagia, fever, and diarrhea. Poly-herbal preparations containing Hemidesmus are often used by traditional medical practitioners for the treatment of cancer. The aim of this study was to investigate the cytodifferentiative, cytostatic and cytotoxic potential of a decoction of Hemidesmus indicus's roots (0.31-3 mg/mL) on a human promyelocytic leukemia cell line (HL-60). MATERIALS AND METHODS: The decoction of Hemidesmus indicus was characterized by HPLC to quantify its main phytomarkers. Induction of apoptosis, cell-cycle analysis, levels of specific membrane differentiation markers were evaluated by flow cytometry. The analysis of cell differentiation by nitroblue tetrazolium (NBT) reducing activity, adherence to the plastic substrate, α-napthyl acetate esterase activity and morphological analysis was performed through light microscopy (LM) and transmission electron microscopy (TEM). RESULTS: Starting from the concentration of 0.31 mg/ml, Hemidesmus indicus induced cytotoxicity and altered cell-cycle progression, through a block in the G0/G1 phase. The decoction caused differentiation of HL-60 cells as shown by NBT reducing activity, adherence to the plastic substrate, α-naphtyl acetate esterase activity, and increasing expression of CD14 and CD15. The morphological analysis by LM and TEM clearly showed the presence of granulocytes and macrophages after Hemidesmus indicus treatment. CONCLUSIONS: The cytodifferentiating, cytotoxic and cytostatic activities of Hemidesmus indicus offers a scientific basis for its use in traditional medicine. Its potent antileukemic activity provides a pre-clinical evidence for its traditional use in anticancer pharmacology. Further experiments are worthwhile to determine the in vivo anticancer potential of this plant decoction and its components.

Impact of ABCC2 haplotypes on transcriptional and posttranscriptional gene regulation and function.

ABCC2 (MRP2) is an important export pump, expressed at tissue barriers. The genetic variants -24C>T, 1249G>A and 3972C>T are leading to inter-individual differences of bioavailability of various endogenous and exogenous compounds. Considering ABCC2 haplotypes, we investigated DNA-protein binding properties, mRNA secondary structure, mRNA stability, protein expression and transport activity in various cell lines and analyzed the bioavailability of talinolol in 24 healthy Caucasian volunteers; -24C>T had no clear influence on DNA-protein binding and the mRNA stability did not differ significantly. In transfected HEK293T/17 cells, haplotypes H9 (CGT), H10 (TGC) and H12 (TGT) had significantly lower protein expression, whereas H2 (CAC) exhibited significantly increased protein expression compared to the wild type (H1, CGC): 32.7 ± 8.8, 73.1 ± 6.3; 44.0 ± 15.5 and 115.2 ± 8.2%, respectively. This corresponded with efflux rates of the fluorescent dye glutathione-methylfluorescein in vitro and by trend with talinolol bioavailability in vivo. In conclusion our results show a haplotype-dependent influence on transport capacity of ABCC2, which seems to be mainly based on posttranscriptional modification of protein expression rather than transport rates.

Fungus colonisation of pulmonary rheumatoid nodule.

This report describes a 69 year old woman, suffering from active rheumatoid arthritis since the age of 60 and presenting with severe dyspnoea and cough. A computed tomography scan of the chest showed multiple bilateral pulmonary nodules, sometimes cavitated, associated with reticular opacities and pleural effusion. A videothoracoscopic excision of a cavitated nodule was performed. Seven days after surgery, a right pneumothorax developed, and the patient died of septicaemia one month later. Microscopically, the excised nodule was composed of necrotic fibrinoid material with a peripheral rim of palisaded histiocytes, extending to the pleural surface and containing several fungal hyphae morphologically consistent with aspergillus. A diagnosis of pulmonary rheumatoid nodule with fungus colonisation was made. In the lung, fungus colonisation is a rare complication of rheumatoid nodules. The most important differential diagnostic considerations are briefly discussed.

[Value of magnetic resonance in the staging of non-small-cell lung carcinoma]. / Valore della risonanza magnetica nella stadiazione del tumore polmonare non-microcitoma.

In the last six years, 544 consecutive patients with nonsmall-cell bronchogenic carcinoma were studied with MRI. MR results were compared with surgical specimens and pathologic findings. Both TNM classification and ATS nodal mapping were considered. Local tumor extent (T parameter) was correctly identified in 67.2% of cases, understaged in 19.4% and overstaged in 13.4%. Lymph node metastases (N parameter) were adequately assessed in 55.5% of cases, understaged in 20.3% and overstaged in 24.2%. Considering two groups of patients, the first one with early stage disease (T1-T2, N0-N1) and the second one with advanced stages (T3-T4, N2-N3), MRI exhibited 84.6% overall accuracy, 57.3% sensitivity and 93.7% specificity for the T parameter and 72.3% accuracy, 65.2% sensitivity and 75.1% specificity for the N parameter. In conclusion, MRI did not provide the expected results in the staging of nonsmall-cell bronchogenic carcinoma, but improvement will probably be achieved with technological evolution.

[Muscular tumors: MR patterns, integrated diagnostic imaging, staging, and follow-up]. / Tumori muscolari: quadri RM, cenni di diagnostica integrata, staging e follow-up.

The goals of radiologic imaging in the study of tumors can be summarized as follows: 1) Definition of the exact volume and site of the lesion; 2) Tumor differentiation from surrounding structures; 3) Possible definition of tumor nature; 4) Follow-up. The radiologic imaging modalities to be considered are: a) conventional radiography; b) angiography; c) US; d) CT; e) MR. Of the above techniques, MR imaging can be considered as adequate to differentiate benign from malignant masses. Moreover, MR provides detailed information on both lesion and surrounding structure and allows histopathologic diagnosis. Finally, it is superior to CT with i.v. contrast medium in recognizing small lesions. Thus, dynamic MR imaging with paramagnetic contrast medium is currently considered the method of choice in evaluating recurrences and differentiating the latter from recent fibroses. MR limitations include the small number of units, their complexity and cost and exam duration.

Adrenal gland metastasis in osteogenic osteosarcoma. A radiological case report.

Adrenal gland metastases from osteogenic sarcoma are rare and an unusual pattern of relapse. The recognition of solitary metastases, particularly when located in uncommon sites is very important for subsequent treatment. The authors describe the radiological features of an adrenal metastases from osteogenic sarcoma.