Imagerie moléculaire nucléaire des paragangliomes

Paragangliomas (PGL) are relatively rare neural crest tumors originating in the adrenal medulla (usually called pheochromocytoma), chemoreceptors (i.e., carotid and aortic bodies) or autonomic ganglia. These tumors are highly vascular, usually benign and slow-growing. PGL may occur as sporadic or familial entities, the latter mostly in association with germline mutations of the succinate dehydrogenase (SDH) B, SDHC, SDHD, SDH5, von Hippel-Lindau (VHL), ret proto-oncogene (RET), neurofibromatosis 1 (NF1) (von Recklinghausen's disease), prolyl hydroxylase domain protein 2 (PHD2) genes and TMEM127. Molecular nuclear imaging has a central role in characterization of PGL and include: somatostatine receptor imaging (¹¹¹In, ⁶⁸Ga), MIBG scintigraphy (¹³¹I, ¹²³I), ¹⁸F-dihydroxyphenylalanine (¹⁸F-DOPA) positron emission tomography (PET), and ¹⁸F-deoxyglucose (¹⁸F-FDG) PET. The choice of the tracer is not yet fully established but the work-up of familial forms often require the combination of multiple approaches.     

Berberine increases the expression of cytokines and proteins linked to apoptosis in human melanoma cells

Molecular Biology Reports - Melanoma is the most lethal form of skin cancer, and its incidence has increased considerably in the last decades. Melanoma presents difficult treatment with strong...     

Changes in maize-stalk proteins during ear development

Although the stalk of maize ( Zea mays L.) functions as a reservoir for N, little is known of qualitative changes which accompany the remobilization of N to the developing ear. SDS-PAGE analysis revealed that certain stalk proteins were lost, whereas others were not. The removal of ears and the prevention of pollination eliminated the selective protein loss. The use of ¹⁵N labelling showed that some stalk-protein fractions turned over faster with ear development, whereas the turnover of others was unchanged or slowed. The data indicate that at least 7 proteins function as temporary storage forms of N in the stalk, and that they are degraded during the first 3 weeks after silking to provide organic N for ear development.     

The ACE gene D/I polymorphism as a modulator of severity of cystic fibrosis

ABSTRACT: BACKGROUND: Cystic Fibrosis (CF) is a monogenic disease with complex expression because of the action of genetic and environmental factors. We investigated whether the ACE gene D/I polymorphism is associated with severity of CF. METHODS: A cross-sectional study was performed, from 2009 to 2011, at University of Campinas - UNICAMP. We analyzed 180 patients for the most frequent mutations in the CFTR gene, presence of the ACE gene D/I polymorphism and clinical characteristics of CF. RESULTS: There was an association of the D/D genotype with early initiation of clinical manifestations (OR: 1.519, CI: 1.074 to 2.146), bacterium Burkholderia cepacia colonization (OR: 3.309, CI: 1.476 to 6.256) and Bhalla score (BS) (p = 0.015). The association was observed in subgroups of patients which were defined by their CFTR mutation genotype (all patients; subgroup I: no mutation detected; subgroup II: one CFTR allele identified to mutation class I, II or III; subgroup III: both CFTR alleles identified to mutation class I, II and/or III). CONCLUSION: An association between the D allele in the ACE gene and the severity of CF was found in our study.     

Thermoluminescence properties of the rock naturally annealed for thousands of years by flames from the earth's inner layers

The gas leak in Chimaera near Çıralı, Antalya, has been active for thousands of years. It is also known to be the source of the first Olympic flame in the Hellenistic period. The sample taken from the Chimaere seepage annealed for thousands of years was determined to be calcite-magnesian (Ca, Mg)O₃. In this study, thermoluminescence (TL) properties of calcite-magnesian annealed for thousands of years in the fire caused by methane gas were investigated for particle size, dose–response, heating rate, and fading experiments. It exhibits a clear TL glow curve with two distinct peaks positioned at 160 and 330°C, and its shape is not affected by variation in applied dose and reproduciility of experiment. There is a wide linear relationship between TL output and applied dose up to 614 Gy. Although the positions of the TL peaks are stable with the cycle of measurement, a poor reusability was observed in terms of the area under the TL glow curve and peak intensity.     

The ultrastructure of the thyroid medullary carcinoma

The ultrastructure and the morphometrical pattern of secretory granules were studied in six cases of thyroid medullary carcinoma. The tumor cells were fusiform or polyhedral with irregular, mostly elongated nuclei. Phagolysosomes containing a crystalloid material, probably degraded lipoprotein complexes, degeneratively changed mitochondria, moderately developed rough endoplasmic reticulum and Golgi complexes were commonly found. Amyloid occurred as small fibrils in intercellular spaces. Marked dystrophic lesions of tumor cells surrounding amyloid fibrils were found. Numerous roundshaped electron-dense secretory granules were noticed in tumor cell cytoplasms. The morphometrical analysis showed that the size of granules oscillated between 60 and 450 nm with mean values ranging from 171.4 +/- 31.8 to 227.7 +/- 28.1 nm. Frequency distribution curves showed at least two peaks varying with the investigated case at different intervals. In two cases two distinct groups of granules were found within the same cells: one group of electron-dense, compact, smaller sized granules and another group of larger, finely granulated, less dense granules. In the other four cases the granule sizes were more homogeneous. These results might indicate that the granule size depends on the maturation degree and functional activity or that there are several kinds of granules specialized in the secretion of various substances.     

Early effects of the influence of ionizing radiation in relatively small doses on the neuromediator systems responding to the central regulation of the hypothalamo-pituitary-adrenal cortex system

In experiments with mature Wistar male rats changes of mediator interrelations in different brain parts, responsible for the central regulation of the hypothalamo-pituitary-adrenocortical system, were detected at early times after whole-body X-irradiation with a dose of 12.9 mC/kg. These changes represent one of the major mechanisms leading, at later times after irradiation, to the development of syndromes related to diencephalic disturbances.     

Ultrastructural pathology of the adrenal gland in Cushing's syndrome

The ultrastructural pathology of the adrenal glands was studied in fifteen cases of Cushing's syndrome. Some specific features correlated with the pathological aspects of adrenals were found. In the hyperplastic adrenal cortex the cytoplasms contained a rich smooth endoplasmic reticulum and many mitochondria. Increased lipid-pigment complexes were found especially in the compact cells. In adenomas, the clear cells showed large lipid vacuoles; the compact cells presented anisomorphous mitochondria, a well developed smooth endoplasmic reticulum and many pigment bodies. The nuclei of adenomatous cells were irregular, with deep invaginations. In adrenal carcinomas, the pleomorphism of nuclei, nucleoli, mitochondria, and smooth endoplasmic reticulum was more obvious. Absolutely reliable characteristics proving malignancy at ultrastructural level do not, however, exist. The steroidogenic activity of both hyperplastic and tumoral adrenal glands can be assessed using the agranular endoplasmic reticulum and the mitochondria as functional parameters.     

The immune system as a chronotoxicity target of the anticancer mTOR inhibitor everolimus

The circadian timing system controls many biological functions in mammals including xenobiotic metabolism, detoxification, cell proliferation, apoptosis and immune functions. Everolimus is a mammalian target of rapamycin inhibitor, whose immunosuppressant properties are both desired in transplant patients and unwanted in cancer patients, where it is indicated for its antiproliferative efficacy. Here we sought whether everolimus circadian timing would predictably modify its immunosuppressive effects so as to optimize this drug through timing. C57BL/6J mice were synchronized with light-dark 12h:12h, with L onset at Zeitgeber Time (ZT) 0. Everolimus was administered orally to male (5 mg/kg/day) and female mice (15 mg/kg/day) at ZT1, during early rest span or at ZT13, during early activity span for 4 weeks. Body weight loss, as well as hematological, immunological and biochemical toxicities, were determined. Spleen and thymus were examined histologically. Everolimus toxicity was less severe following dosing at ZT13, as compared to ZT1, as shown with least body weight inhibition in both genders; least reductions in thymus weight both in males (p < 0.01) and females (p < 0.001), least reduction in female spleen weight (p < 0.05), and less severe thymic medullar atrophy both in males (p < 0.001) and females (p < 0.001). The mean circulating counts in total leukocytes, total lymphocytes, T-helper and B lymphocytes displayed minor and non-significant changes following dosing at ZT13, while they were decreased by 56.9% (p < 0.01), 45.5% (p < 0.01), 43.1% (p < 0.05) and 48.7% (p < 0.01) after everolimus at ZT1, respectively, in only male mice. Chronotherapy of everolimus is an effective way to increase the general tolerability and decrease toxicity on the immune system.