Chemodiversity of Volatile Oils in Thapsia garganica L. (Apiaceae)

The chemical composition of the volatile oils obtained from the roots, leaves, flowers, and stems of Thapsia garganica of Tunisian origin was investigated by GC‐FID and GC/MS analyses. Sesquiterpene hydrocarbons and oxygenated monoterpenes were predominant in the oils of all plant parts. Bicyclogermacrene (21.59–35.09%) was the main component in the former compound class, whereas geranial (3.31–14.84%) and linalool (0.81–10.9%) were the most prominent ones in the latter compound class. Principal‐component (PCA) and hierarchical‐cluster (HCA) analyses revealed some common constituents, but also significant variability amongst the oils of the different plant parts. This organ‐specific oil composition was discussed in relation to their biological and ecological functions. For the evaluation of the intraspecific chemical variability in T. garganica, the composition of the flower volatile oils from four wild populations was investigated. Bicyclogermacrene, linalool, and geranial were predominant in the oils of three populations, whereas epicubenol, β‐sesquiphellandrene, and cadina‐1,4‐diene were the most prominent components of the oil of one population. PCA and HCA allowed the separation of the flower oils into three distinct groups, however, no relationship was found between the volatile‐oil composition and the geographical distribution and pedoclimatic conditions of the studied populations.     

Serotype Distribution,Antibiotic Resistance and Clonality of Streptococcus pneumoniae Isolated from Immunocompromised Patients in Tunisia

BackgroundPneumococcal disease, a major cause of morbidity and mortality globally, has higher incidence among young children, the elderly and the immunocompromised of all ages. In Tunisia, pneumococcal conjugate vaccines (PCVs) are not included in the national immunization program. Also, few studies have described the epidemiology of S. pneumoniae in this country and, in particular, no molecular typing studies have been performed. The aim of this study was to evaluate serotype distribution, antimicrobial resistance and clonality of Streptococcus pneumoniae isolated from neutropenic patients in Tunisia.MethodsFifty-nine S. pneumoniae were isolated from infection (n = 31) and colonization (n = 28) sites of patients (children and adults) attending the National Centre of Bone Marrow Transplantation in Tunis between 2005–2011. All isolates were characterized by serotype, antimicrobial resistance pattern and multilocus sequence typing (MLST).ResultsThe majority (66.1%) of the isolates belonged to five serotypes all included in PCVs: 6B, 9V, 14, 19F and 23F. The potential coverage of the 10-valent and 13-valent PCV was of 71.2% and 76.3% respectively. Resistance rates were very high and 69.5% of the isolates were multidrug resistant: non-susceptibility rates to penicillin, amoxicillin and cefotaxime were 66.1%, 40.7% and 27.1%, respectively; resistance rates to erythromycin, clindamycin, tetracycline, chloramphenicol and trimethoprim-sulfamethoxazole, were 69.5%, 61.0%, 37.3%, 22.0% and 67.8%, respectively. The most frequent serotypes had STs characteristic of multidrug resistant international clones known to be highly successful and important causes of pneumococcal infection: Spain 23F-ST81, France 9V/14-ST156, Spain 6B-ST90, 19F-ST320, and Portugal 19F-ST177.ConclusionsThe majority of S. pneumoniae strains recovered from immunocompromised patients in Tunisia are representatives of multidrug resistant pandemic clones that express serotypes targeted by PCVs. To contain the burden of pneumococcal disease and improve treatment choices among Tunisian immunocompromised patients PCVs should be offered to all of them.     

Evaluation of cultivar susceptibility and storage periods towards aflatoxin B1 contamination on pistachio nuts

Aflatoxins (AFs) are potent sources of health risks to both humans and animals. Among them, AFB1 is the most hazardously toxic and the most frequent in various food commodities, including pistachio nuts. In this survey, the effect of the storage period on AFB1 accumulation on pistachio nuts was investigated. A total of 49 samples collected during the crop year of 2005 from the most cultivated pistachio cultivars in Tunisia were rapidly screened by enzyme-linked immunosorbent assay (ELISA) combined with an immunoaffinity step. The obtained results showed that the contamination of pistachio nuts has occurred clearly after two years of storage for all the tested cultivars except the case of Mateur variety and Thyna ecotypes. In this study, the cultivar Mateur was found to be the most susceptible cultivar to contamination by AFB1. After 4 years of storage, the average contamination levels in nut samples ranged from 2.7 ± 0.3 to 12.7 ± 2.2 μg/kg for AFB1, according to the cultivar. These levels exceeded the maximum permitted limit of 2 μg/kg set by the European Commission in nuts.     

Changes in cellular levels of inositol polyphosphates during apoptosis

Accumulations of higher inositol polyphosphates, diphosphoinositol polyphosphates or pyrophosphates, have been implicated to mediate cellular apoptosis. Whether cellular levels of lower inositol phosphates (lower than inositol hexakisphosphates) change during apoptosis is not known, although these inositol phosphates are known to play crucial roles in a number of cellular signaling processes including calcium mobilization. Therefore, in this study, we have examined changes in cellular levels of inositol phosphates following metabolic labeling of these compounds by [³H]myo-inositol and induction of apoptosis. The levels of inositol mono- and bis-phosphates were increased, whereas the levels of inositol tris- and tetrakis-phosphates decreased significantly with an increasing rate of apoptosis induced by etoposide in a dose-dependent manner. NaF treatment, which increased the rate of apoptosis in a time- and dose-dependent manner, also increased the levels of inositol mono- and bis-phosphates and drastically reduced the levels of inositol tris- and tetrakis-phosphates. Prior treatment with antimycin A, a strategy used to reverse the NaF-induced accumulations of higher InsPs, partially reduced the effects of NaF on apoptosis as well as the levels of lower InsPs. Taken together, our results suggest that cellular levels of lower InsPs are altered during apoptosis.     

The human leukocyte antigen class I genes in nasopharyngeal carcinoma risk

Nasopharyngeal carcinoma (NPC) is a virally associated cancer which is highly prevalent in Southeast Asia and North Africa. Several linkage analysis studies suggested the association of susceptibility HLA (Human Leukocyte Antigen) alleles and haplotypes with NPC development. The HLA system is very polymorphic and according to the ethnic group studied, it has been found to have the capacity to confer susceptibility or resistance to NPC. Our aim was to review the most important described genetic associations of HLA class I in NPC and to comment on the inconsistent associations found in the different NPC incidence areas. We believe that the mechanisms of these associations may involve HLA genes through the differential capacity of each allele to present antigens. However, because HLA genes contain various linked candidate genes, HLA-NPC associations should be carefully interpreted.     

Cytotoxicity and genotoxicity induced by aflatoxin B1, ochratoxin A,and their combination in cultured Vero cells

Aflatoxin B1 (AFB1) and ochratoxin A (OTA) are important food‐borne mycotoxins that have been implicated in human health. In this study, independent and combinative toxicities of AFB1 and OTA were tested in cultured monkey kidney Vero cells. The experiments reported here were conducted to evaluate the effect of these toxins on cell viability followed by the determination of cell death pathways, using the quantification of DNA fragmentation and the expression of p53 and bcl‐2 protein levels. Our results showed that AFB1 and OTA caused a marked decrease of cell viability in a dose‐dependent manner. Under the same conditions, these mycotoxins increased fragmented DNA levels. In addition, p53 was activated in response to DNA damage and the expression of the antiapoptotic factor bcl‐2 decreased significantly. According to these data, AFB1 and OTA seemed to be involved in an apoptotic process. Moreover, combined AFB1 and OTA induced all the toxicities observed with the mycotoxins separately. Therefore, this combination was classified as an additive response of the two mycotoxins. © 2010 Wiley Periodicals, Inc. J Biochem Mol Toxicol 24:42–50, 2010; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/jbt.20310     

Crocin Prevents Patulin‐Induced Acute Toxicity in Cardiac Tissues via the Regulation of Oxidative Damage and Apoptosis

Patulin (PAT) is a mycotoxin produced by several species of the genera of Penicillium, Aspergillus, and Byssochlamys principally by Penicillium expansum. This mycotoxin is suspected to affect several organs including kidney and liver. However, its toxic effect on heart remains unknown. The present study investigated for the first time the cardiotoxic effect of PAT in mice. We demonstrated that PAT increased creatinin phosphokinase (CPK) level, induced lipoperoxydation and protein oxidation, and triggered the antioxidant enzymes such as superoxide dismutase and catalase activities. We also demonstrated that acute administration of PAT triggers apoptosis via P53 overexpression and caspase 3 activation. We further investigated the antioxidant efficiency of crocin (CRO), a carotenoid pigment, against PAT‐induced cardiotoxicity. We found that pretreatment with CRO prevents cardiac impairment by reducing CPK levels, restoring the redox statute and suppressing apoptosis. Collectively, our data provide new preventive effect of CRO toward PAT‐induced cardiotoxicity in mice.     

EpiBrainRad: an epidemiologic study of the neurotoxicity induced by radiotherapy in high grade glioma patients

Background

Radiotherapy is one of the most important treatments of primary and metastatic brain tumors. Unfortunately, it can involve moderate to severe complications among which leukoencephalopathy is very frequent and implies cognitive deficits such as memory, attention and executive dysfunctions. However, the incidence of this complication is not well established and the risk factors and process are poorly understood. The main objective of the study is to improve knowledge on radio-induced leukoencephalopathy based on pluridisciplinar approaches combining cognitive, biologic, imagery and dosimetric investigations.

Method/Design

The EpiBrainRad study is a prospective cohort study including newly diagnosed high grade gliomas patients treated by radiotherapy and concomitant-adjuvant temozolomide chemotherapy. Patients are included between their surgery and first day of radio-chemotherapy, and the follow-up lasts for 3 years after treatment. Cognitive functioning assessments, specific blood biomarkers measures and magnetic resonance imagery are performed at different moment during the follow-up, and a specific dosimetric assessment of organs involved in the beam fields is performed. Firstly, leukoencephalopathy incidence rate will be estimated in this population. Secondly, correlations between cognitive impairments and dosimetry, biomarkers ranges and anomalies on imagery will be analyzed in order to better understand the onset and evolution of cognitive decrement associated with radiotherapy. Furthermore, a new cognitive test, quickly and easily performed, will be studied to determine its sensibility to detect leukoencephalopathy decrement.

Discussion

With an original multidisciplinary approach, the EpiBrainRad study aims to improve knowledge on radio-induced leukoencephalopathy in order to improve its early diagnosis and prevention. The main challenge is to preserve quality-of-life after cancer treatments which imply to study the incidence of radiation-induced complications and their associated risk factors.

Trial Registration

NCT02544178