Dimeric bisindole alkaloids from the stem bark of Strychnos nux-vomica L.

in Phytochemistry (2013), 87

Strychnos nux-vomica L. (Loganiaceae) is famous for its monomeric alkaloid content, such as strychnine, a convulsant poison. The stem bark of the tree is traditionally used to treat intermittent fever in ... [more ▼]

Strychnos nux-vomica L. (Loganiaceae) is famous for its monomeric alkaloid content, such as strychnine, a convulsant poison. The stem bark of the tree is traditionally used to treat intermittent fever in South East Asia. In various studies, it appeared that dimeric indolo-monoterpenic alkaloids possess a promising activity on Plasmodium falciparum. Three bisindolomonoterpenic alkaloids together with strychnochrysine, previously identified in the root bark of S. nux-vomica, were isolated from the stem bark. The structures of these compounds were established using NMR spectroscopy and mass spectrometry. Stereochemistry of the compounds was confirmed by molecular modelling. This then allowed the structural determination of strychnoflavine, a coloured bisindole alkaloid previously isolated from the root bark of the tree. Moreover, the conformational inversion in alkaloids possessing an ether bond in the strychnane moiety could be easily predicted by specific δ 13C NMR values. These longicaudatine-type alkaloids were found to display in vitro antiplasmodial activity against a chloroquine resistant strain and a chloroquine sensitive strain. The most interesting was strychnochrysine showing an IC 50 value at around 10 μM. © 2012 Elsevier Ltd. All rights reserved. [less ▲]

Use of Raman spectrometry in the pharmaceutical field

in STP Pharma Pratiques (2013), 23(2), 97-117

This document sets out the theoretical and practical fundamentals to guide users in the imple- mentation of Raman spectroscopy in industry or the university-hospital sector. It describes the principle of ... [more ▼]

This document sets out the theoretical and practical fundamentals to guide users in the imple- mentation of Raman spectroscopy in industry or the university-hospital sector. It describes the principle of this technique and currently available instruments. Since Raman spectrometers are used in a regulated context, the methodology of instru- ment qualification is discussed. Different types of applications encountered in the pharmaceutical field are presented: process monitoring, searching for and detecting counterfeits, and identifying raw materials on receipt. [less ▲]

Oceanic forcing of Antarctic climate change: A study using a stretched-grid atmospheric general circulation model

E-print/Working paper (2013)

A variable-resolution atmospheric general circulation model is used for climate change projections over the Antarctic. The present-day simulation uses prescribed observed sea-surface conditions, while a ... [more ▼]

A variable-resolution atmospheric general circulation model is used for climate change projections over the Antarctic. The present-day simulation uses prescribed observed sea-surface conditions, while a set of five simulations for the end of the 21st century (2070-2099) under the SRES-A1B scenario uses sea-surface condition anomalies from selected CMIP3 coupled models. Analysis of the results shows that the prescribed sea- surface condition anomalies have a very strong influence on the simulated climate change on the Antarctic continent, up to twice the direct effect of the prescribed greenhouse gas concentration changes in the AGCM simulations. An analysis of circulation changes using self-organizing maps shows that the simulated climate change on regional scales is not principally caused by shifts of the frequencies of the dominant circulation patterns, except for precipitation changes in some coastal regions. We suggest that in some respects the use of bias-corrected sea-surface boundary conditions in climate projections with a variable-resolution atmospheric general circulation model has some distinct advantages over the use of limited-area atmospheric circulation models directly forced by generally biased AOGCM output. [less ▲]

Comparison of Immune Reconstitution after Hematopoietic Stem Cell Transplantation with Flu-TBI versus TLI-ATG Conditioning

in Belgian Journal of Hematology (2013), Abstracts book(Supplement of 28th General Meeting of the Belgian Hematological Society), 38

Genetic analysis in young patients with sporadic pituitary macroadenomas:Beside AIP don't forget MEN1 genetic analysis.

in European Journal of Endocrinology (2013)

CONTEXT: germline mutations in the AIP gene have been identified in young patients (age </= 30 years old) with sporadic pituitary macroadenomas. Otherwise, there are few data concerning the prevalence of ... [more ▼]

CONTEXT: germline mutations in the AIP gene have been identified in young patients (age </= 30 years old) with sporadic pituitary macroadenomas. Otherwise, there are few data concerning the prevalence of MEN1 mutations in such population. OBJECTIVE: We assessed the prevalence of both AIP and MEN1 genetic abnormalities (mutations and large gene deletions) in young patients (age </= 30 years old) diagnosed with sporadic and isolated macroadenoma, without hypercalcemia and/or MEN1-associated lesions. DESIGN: The entire coding sequences of AIP and MEN1 were screened for mutations. In cases of negative sequencing screening, multiplex ligation-dependent probe amplification was performed for the detection of large genetic deletions. PATIENTS AND SETTINGS: 174 patients from Endocrinology Departments of 15 French University Hospital Centers were eligible for this study. RESULTS: 21/174(12%) patients had AIP (n=15, 8.6%) or MEN1 (n=6, 3.4%) mutations. In pediatric patients (age </= 18 years old), AIP/MEN1 mutation frequency reached nearly 22% (n=10/46). AIPmut and MEN1mut were respectively identified in 8/79 (10.1%) and 1/79 (1.2%) somatotropinoma patients; they each accounted for 4/74 (5.4%) prolactinoma patients with mutations. Half of patients (n=3/6) with gigantism displayed mutations in AIP. Interestingly, 4/12 (33%) patients with non-secreting adenomas bore either AIP or MEN1 mutations, whereas none of the 8 corticotroph-adenomas and a single thyrotropinoma case had mutations. No large gene deletions were observed in sequencing-negative patients. CONCLUSION: mutations in MEN1 can be of significance in young patients with sporadic isolated pituitary macroadenomas, particularly prolactinomas, and together with AIP, we suggest genetic analysis of MEN1 in such population. [less ▲]

Chromatography in the detection and characterisation of illegal pharmaceutical preparations

in Journal of Chromatographic Science (2013)

Counterfeit and illegal pharmaceutical products are an increasing worldwide problem and constitute a major challenge for analytical laboratories to detect and characterize them. Spectroscopic techniques ... [more ▼]

Counterfeit and illegal pharmaceutical products are an increasing worldwide problem and constitute a major challenge for analytical laboratories to detect and characterize them. Spectroscopic techniques as infrared spectroscopy and Raman spectroscopy were always the first methods of choice to detect counterfeits and illegal preparations, but due to the evolution in the products seized and the necessity of risk assessment, chromatographic methods are becoming more important in this domain. This review intends to give a general overview of the techniques described in literature to characterize counterfeit and illegal pharmaceutical preparations, focussing on the role of chromatographic techniques, with different detection tools. [less ▲]

Familial Isolated Pituitary Adenomas (FIPA) and the Pituitary Adenoma Predisposition due to Mutations in the Aryl Hydrocarbon Receptor Interacting Protein (AIP) Gene.

in Endocrine Reviews (2013)

Pituitary adenomas are one of the most frequent intracranial tumors and occur with a prevalence of approximately 1:1000 in the developed world. Pituitary adenomas have a serious disease burden, and their ... [more ▼]

Pituitary adenomas are one of the most frequent intracranial tumors and occur with a prevalence of approximately 1:1000 in the developed world. Pituitary adenomas have a serious disease burden, and their management involves neurosurgery, biological therapies, and radiotherapy. Early diagnosis of pituitary tumors while they are smaller may help increase cure rates. Few genetic predictors of pituitary adenoma development exist. Recent years have seen two separate, complimentary advances in inherited pituitary tumor research. The clinical condition of familial isolated pituitary adenomas (FIPA) has been described, which encompasses the familial occurrence of isolated pituitary adenomas outside of the setting of syndromic conditions like multiple endocrine neoplasia type 1 and Carney complex. FIPA families comprise approximately 2% of pituitary adenomas and represent a clinical entity with homogeneous or heterogeneous pituitary adenoma types occurring within the same kindred. The aryl hydrocarbon receptor interacting protein (AIP) gene has been identified as causing a pituitary adenoma predisposition of variable penetrance that accounts for 20% of FIPA families. Germline AIP mutations have been shown to associate with the occurrence of large pituitary adenomas that occur at a young age, predominantly in children/adolescents and young adults. AIP mutations are usually associated with somatotropinomas, but prolactinomas, nonfunctioning pituitary adenomas, Cushing disease, and other infrequent clinical adenoma types can also occur. Gigantism is a particular feature of AIP mutations and occurs in more than one third of affected somatotropinoma patients. Study of pituitary adenoma patients with AIP mutations has demonstrated that these cases raise clinical challenges to successful treatment. Extensive research on the biology of AIP and new advances in mouse Aip knockout models demonstrate multiple pathways by which AIP may contribute to tumorigenesis. This review assesses the current clinical and therapeutic characteristics of more than 200 FIPA families and addresses research findings among AIP mutation-bearing patients in different populations with pituitary adenomas. [less ▲]

PROCEDURAL LEARNING ACROSS MODALITIES IN FRENCH SPEAKING CHILDREN WITH SPECIFIC LANGUAGE IMPAIRMENT.

in Applied Psycholinguistics (2013)

It has been suggested that the language problems encountered in specific language impairment (SLI) arise from basal ganglia abnormalities that lead to impaired procedural memory. However, recent serial ... [more ▼]

It has been suggested that the language problems encountered in specific language impairment (SLI) arise from basal ganglia abnormalities that lead to impaired procedural memory. However, recent serial reaction time (SRT) studies did not reveal any differences between the SLI and typically developing (TD) groups on the measures of procedural memory, linked to visual sequence learning. In this paper, sixteen children with and without SLI were compared on two versions of SRT tasks: a visual task and an auditory one. Results showed that children with SLI were as fast as their TD peers in both modalities. All the children obtained similar specific sequence learning indices, indicating that they were able to detect regularities in both modalities. While children with SLI were as accurate as their TD peers for the visual SRT task, they made more errors than their TD peers in auditory SRT conditions. The results indicate that, in relation to procedural memory, the core of the impairment in SLI is not linked to difficulties in the detection of regularities. We argue that when children with SLI present some difficulties, the children’s weaknesses might depend on the type of processing involved (e.g. tasks involving auditory sequences). [less ▲]

Numerical modeling and digital image correlation strain measurements of coated metal sheets submitted to large bending deformation

in Proceedings of the 16th ESAFORM conference on Material Forming (2013)

The recently developed SSH3D solid-shell element, which is based on the Enhanced Assumed Strain (EAS) and the Assumed Natural Strain (ANS) techniques, is utilized for the modeling of a severe bending ... [more ▼]

The recently developed SSH3D solid-shell element, which is based on the Enhanced Assumed Strain (EAS) and the Assumed Natural Strain (ANS) techniques, is utilized for the modeling of a severe bending sheet forming process. To improve the element's ability to capture the through thickness gradients, a specific integration scheme was developed. In this paper, the performances of this element for the modeling of the T-bent process were assessed thanks to comparison between experimental and numerical results in terms of the strain field at the outer surface of the sheet. The experimental results were obtained by Digital Image Correlation. It is shown that a qualitative agreement between experimental and numerical results is obtained but some numerical parameters should be optimized to improve the accuracy of the simulation predictions. In this respect, the influence of the penalty coefficient of the contact modeling was analyzed. [less ▲]

Targeting the tumor microenvironment for cancer therapy.

in Clinical Chemistry (2013), 59(1), 85-93

BACKGROUND: With the emergence of the tumor microenvironment as an essential ingredient of cancer malignancy, therapies targeting the host compartment of tumors have begun to be designed and applied in ... [more ▼]

BACKGROUND: With the emergence of the tumor microenvironment as an essential ingredient of cancer malignancy, therapies targeting the host compartment of tumors have begun to be designed and applied in the clinic. CONTENT: The malignant features of cancer cells cannot be manifested without an important interplay between cancer cells and their local environment. The tumor infiltrate composed of immune cells, angiogenic vascular cells, lymphatic endothelial cells, and cancer-associated fibroblastic cells contributes actively to cancer progression. The ability to change these surroundings is an important property by which tumor cells are able to acquire some of the hallmark functions necessary for tumor growth and metastatic dissemination. Thus in the clinical setting the targeting of the tumor microenvironment to encapsulate or destroy cancer cells in their local environment has become mandatory. The variety of stromal cells, the complexity of the molecular components of the tumor stroma, and the similarity with normal tissue present huge challenges for therapies targeting the tumor microenvironment. These issues and their interplay are addressed in this review. After a decade of intensive clinical trials targeting cellular components of the tumor microenvironment, more recent investigations have shed light on the important role in cancer progression played by the noncellular stromal compartment composed of the extracellular matrix. SUMMARY: A better understanding of how the tumor environment affects cancer progression should provide new targets for the isolation and destruction of cancer cells via interference with the complex crosstalk established between cancer cells, host cells, and their surrounding extracellular matrix. [less ▲]