Association hyperthyroïdie et cancer thyroïdien différencié (médullaire exclu). À propos de sept observations

The aim of this study was to draw attention to the fact that hyperthyroidism does not exclude the possibility of concurrent thyroid carcinoma. We analyzed the frequency and consequences of this association through seven cases of thyrotoxic patients with differentiated thyroid carcinoma followed by a review of literature.

Patients and methods

The nuclear medicine department of the CHU Ibn Sina has more than 3000 cases of differentiated thyroid carcinoma where 10 patients with association of hyperthyroidism could be retrieved. Our study focused on seven cases well documented and regularly followed. The main parameters collected were the following: age, sex, personal and family history of thyroid disease, clinical presentation, etiology of hyperthyroidism, preoperative paraclinical explorations, surgery performed, histopahological findings, complementary therapy and follow-up.

Results

Group included six females and one male, average age was 41.4 years. There were four cases of Graves’ disease, two cases of single toxic nodule and one case of functional multinodular goiter. All patients underwent total thyroidectomy. Final pathologic examination disclosed five papillary carcinomas and two follicular carcinomas. During 2 to 8 years follow-up, there was neither local recurrence nor metastasis.

Conclusion

The diagnosis of hyperthyroidism does not preclude concurrent thyroid carcinoma. Careful assessment of such patients is mandatory to exclude an associated thyroid malignancy particularly in the presence of a nodule in a hyperfunctioning thyroid.     

Characterization of two cysteine proteases secreted by Blastocystis ST7, a human intestinal parasite

Blastocystis spp. are unicellular anaerobic intestinal parasites of both humans and animals and the most prevalent ones found in human stool samples. Their association with various gastrointestinal disorders raises the questions of its pathogenicity and of the molecular mechanisms involved. Since secreted proteases are well-known to be implicated in intestinal parasite virulence, we intended to determine whether Blastocystis spp. possess such pathogenic factors. In silico analysis of the Blastocystis subtype 7 (ST7) genome sequence highlighted 22 genes coding proteases which were predicted to be secreted. We characterized the proteolytic activities in the secretory products of Blastocystis ST7 using specific protease inhibitors. Two cysteine proteases, a cathepsin B and a legumain, were identified in the parasite culture supernatant by gelatin zymographic SDS-PAGE gel and MS/MS analysis. These proteases might act on intestinal cells and disturb gut function. This work provides serious molecular candidates to link Blastocystis spp. and intestinal disorders.     

Mixed human intra- and inter-subtype infections with the parasite Blastocystis sp

Because of their limitations, current subtyping methods likely underestimate mixed human intra- and inter-subtype infections with Blastocystis sp. leading to erroneous data in the context of epidemiological studies. We confirmed this hypothesis by the identification of several isolates belonging to three subtypes in a patient considered at high risk of mixed infection through her lifestyle in rural area and long history of travelling.     

Acute and chronic toxicity of Nigella sativa fixed oil

We investigated the toxicity of the fixed oil of Nigella sativa L seeds in mice and rats through determination of LD50 values and examination of possible biochemical, hematological and histopathological changes. The acute toxicity of Nigella sativa fixed oil was investigated in mice. LD50 values, obtained by single doses, orally and intraperitoneally administered in mice, were 28.8 ml/kg body wt. p.o. [26.2-31.6] and 2.06 ml/kg body wt. i.p. [1.86-2.26], respectively. Chronic toxicity was studied in rats treated daily with an oral dose of 2 ml/kg body wt. for 12 weeks. Changes in key hepatic enzymes levels, including aspartate-aminotransferase, alanine-aminotranferase, and gamma-glutamyltransferase and histopathological modifications (heart, liver, kidneys and pancreas) were not observed in rats treated with Nigella sativa after 12 weeks of treatment. The serum cholesterol, triglyceride and glucose levels and the count of leukocytes and platelets decreased significantly, compared to control values, while hematocrit and hemoglobin levels increased significantly. A slowing of body weight gain was also observed in Nigella sativa treated rats, as compared to control animals. The low toxicity of Nigella sativa fixed oil, evidenced by high LD50 values, key hepatic enzyme stability and organ integrity, suggests a wide margin of safety for therapeutic doses of Nigella sativa fixed oil, but the changes in hemoglobin metabolism and the fall in leukocyte and platelet count must be taken into consideration.     

Proteolytic activity in Encephalitozoon cuniculi sporogonial stages: predominance of metallopeptidases including an aminopeptidase-P-like enzyme

A fraction enriched in spore precursor cells (sporoblasts) of the microsporidian Encephalitozoon cuniculi, an intracellular parasite of mammals, was obtained by Percoll gradient centrifugation. Soluble extracts of these cells exhibited proteolytic activity towards azocasein, with an alkaline optimum pH range (9-10). Prevalence of some metallopeptidases was supported by the stimulating effect of Ca2+, Mg2+, Mn2+ and Zn2+ ions, and inhibition by two chelating agents (EDTA and 1,10-phenanthroline), a thiol reductant (dithiothreitol) and two aminopeptidase inhibitors (bestatin and apstatin). Zymographic analysis revealed four caseinolytic bands at about 76, 70, 55 and 50 kDa. Mass spectrometry of tryptic peptides from one-dimensional gel slices identified a cytosol (leucine) aminopeptidase homologue (M17 family) in 50-kDa band and an enzyme similar to aminopeptidase P (AP-P) of cytosolic type (M24B subfamily) in 70-kDa band. Multiple sequence alignments showed conservation of critical residues for catalysis and metal binding. A long insertion in a common position was found in AP-P sequences from E. cuniculi and Nosema locustae, an insect-infecting microsporidian. The expression of cytosolic AP-P in sporogonial stages of microsporidia may suggest a key role in the attack of proline-containing peptides as a prerequisite to long-duration biosynthesis of structural proteins destined to the sporal polar tube.     

Characterization of three functional high-affinity ammonium transporters in Lotus japonicus with differential transcriptional regulation and spatial expression

Ammonium is a primary source of nitrogen for plants. In legume plants ammonium can also be obtained by symbiotic nitrogen fixation, and NH(4)(+) is also a regulator of early and late symbiotic interaction steps. Ammonium transporters are likely to play important roles in the control of nodule formation as well as in nitrogen assimilation. Two new genes, LjAMT1;2 and LjAMT1;3, were cloned from Lotus japonicus. Both were able to complement the growth defect of a yeast (Saccharomyces cerevisiae) ammonium transport mutant. Measurement of [(14)C]methylammonium uptake rates and competition experiments revealed that each transporter had a high affinity for NH(4)(+). The K(i) for ammonium was 1.7, 3, and 15 microm for LjAMT1;1, 1;2, and 1;3, respectively. Real-time PCR revealed higher expression of LjAMT1;1, 1;2, and 1;3 genes in leaves than in roots and nodule, with expression levels decreasing in the order LjAMT1;1 > 1;2 > 1;3 except in flowers, in which LjAMT1;3 was expressed at higher level than in leaves, and LjAMT1;1 showed the lowest level of expression. Expression of LjAMT1;1 and 1;2 in roots was induced by nitrogen deprivation. Expression of LjAMT1;1 was repressed in leaves exposed to elevated CO(2) concentrations, which also suppress photorespiration. Tissue and cellular localization of LjAMT1 genes expression, using promoter-beta-glucuronidase and in situ RNA hybridization approaches, revealed distinct cellular spatial localization in different organs, including nodules, suggesting differential roles in the nitrogen metabolism of these organs.     

Determination of antioxidant activity,total phenolics and fatty acids in essential oils and other extracts from callus culture,seeds and leaves of Argania spinosa (L.) Skeels

Plant Cell, Tissue and Organ Culture (PCTOC) - Argan (Argania spinosa (L.) Skeels) is an endangered and endemic agroforestry species of Morocco highly appreciated for its nutraceutical properties....     

Affinity comparison of different THCA synthase to CBGA using modeling computational approaches

The Δ^9-Tetrahydrocannabinol (THCA) is the primary psychoactive compound of Cannabis Sativa. It is produced by Δ^1- Tetrahydrocannabinolic acid synthase (THCA) which catalyzes the oxidative cyclization of cannabigerolic acid (CBGA) the precursor of the THCA. In this study, we were interested by the three dimensional structure of THCA synthase protein. Generation of models were done by MODELLER v9.11 and homology modeling with Δ1-tetrahydrocannabinolic acid (THCA) synthase X ray structure (PDB code 3VTE) on the basis of sequences retrieved from GenBank. Procheck, Errat, and Verify 3D tools were used to verify the reliability of the six 3D models obtained, the overall quality factor and the Prosa Z-score were also used to check the quality of the six modeled proteins. The RMSDs for C-alpha atoms, main-chain atoms, side-chain atoms and all atoms between the modeled structures and the corresponding template ranged between 0.290 Å-1.252 Å, reflecting the good quality of the obtained models. Our study of the CBGA-THCA synthase docking demonstrated that the active site pocket was successfully recognized using computational approach. The interaction energy of CBGA computed in ‘fiber types’ proteins ranged between -4.1 95 kcal/mol and -5.95 kcal/mol whereas in the ‘drug type’ was about -7.02 kcal/mol to -7.16 kcal/mol, which maybe indicate the important role played by the interaction energy of CBGA in the determination of the THCA level in Cannabis Sativa L. varieties. Finally, we have proposed an experimental design in order to explore the binding energy source of ligand-enzyme in Cannabis Sativa and the production level of the THCA in the absence of any information regarding the correlation between the enzyme affinity and THCA level production. This report opens the doors to more studies predicting the binding site pocket with accuracy from the perspective of the protein affinity and THCA level produced in Cannabis Sativa.     

Crystallization of the Photosystem II core complex and its chlorophyll binding subunit CP43 from transplastomic plants of <Emphasis Type="Italic">Nicotiana</Emphasis><Emphasis Type="Italic">tabacum</Emphasis>

Photosystem II from transplastomic plants of Nicotiana tabacum with a hexahistidine tag at the N-terminal end of the PsbE subunit (α-chain of the cytochrome b₅₅₉) was purified according to the protocol of Fey et al. (BBA 12:1501–1509, 2008). The protein sample was then subjected to two additional gel filtration runs in order to increase its homogeneity and to standardize the amount of detergent. Large three dimensional crystals of the core complex were obtained. Crystals of one of its chlorophyll binding subunits (CP43) in isolation grew in very similar conditions that differed only in the concentration of the detergent. Diffraction of Photosystem II and CP43 crystals at various synchrotron beamlines was limited to a resolution of 7 and 14 Å, respectively. In both cases the diffraction quality was insufficient for an unambiguous assignment of the crystallographic lattice or space group.