Ultramafic vegetation and soils in the circumboreal region of the Northern Hemisphere

The paper summarizes literature on climate, soil chemistry, vegetation and metal accumulation by plants found on ultramafic substrata in the circumboreal zone (sensu Takhtajan, Floristic regions of the world, 1986) of the Northern Hemisphere. We present a list of 50 endemic species and 18 ecotypes obligate to ultramafic soils from the circumboreal region of Holarctic, as well as 30 and 2 species of Ni and Zn hyperaccumulators, respectively. The number of both endemics and hyperaccumulators are markedly lower compared to that of the Mediterranean and tropical regions. The diversity of plant communities on ultramafics soils of the circumboral region is also described. The underlying causes for the differences of ultramafic flora between arctic, cold, cool temperate and Mediterranean and tropical regions are also discussed. © 2018, The Ecological Society of Japan

Histopathological and immunohistochemical features of thyroid carcinoma

Thyroid-specific malignant tumors are derived from follicle cells (papillary and follicular carcinoma), and from parafollicular, calcitonin-producing C-cells (medullary carcinoma). The main criterion for diagnosis of papillary carcinoma is the occurrence of ground glass, hypochromic nuclei, often associated with papillae as the prominent pattern of the tumor, and psammoma bodies. The diagnosis of follicular carcinoma is based on the true infiltration of the venous vessels outside the tumor capsule and the fungus-like infiltration through the tumor capsule into the surrounding parenchyma. Anaplastic carcinoma is mostly detected by the pathologist by fine-needle aspiration biopsy, or tumor reduction specimen. Medullary thyroid carcinoma is typically composed of solid nests and infiltrating formations of polygonal or spindle-shaped cells and amyloid deposits within the stroma of the tumor. Two main discriminatory immunohistochemical markers for tumors with follicular and parafollicular origin are thyroglobulin and calcitonin, respectively. Thyroglobulin is present in more than 95% of papillary and follicular carcinomas, whereas anaplastic thyroid carcinomas are mostly immunonegative for thyroglobulin. Medullary carcinoma is characteristically positive for calcitonin, pan-neuroendocrine markers, and often numerous peptides

Galectin-3: A promising marker of thyroid malignancy

Background: Galectin-3 is an endogenous beta-galactoside binding lectin implicated in neoplastic transformation and tumor progression. High levels of this lectin have recently been found in malignant thyroid tumors, but not in normal or benign thyroid tissue, suggesting galectin-3 as a promising presurgical marker of thyroid malignancy. Methods: We analyzed immunohistochemically galectin-3 expression in thyroid tissue using a monoclonal antibody. The total of 108 tissue specimens included 55 cases of thyroid carcinoma (30 papillary, 15 follicular, and 10 anaplastic type), 15 samples of follicular adenoma, 15 samples of normal thyroid tissue, and 23 thyroid tissue specimens from human fetuses (16 to 37 weeks of intrauterine life). Results: The results showed galectin-3 expression in 20/30 papillary carcinomas, 11/15 follicular carcinomas, 10/10 anaplastic carcinomas, and 4/15 follicular adenomas. Thyroid follicular cells in normal adult and fetal tissue were negative. Conclusions: These results further confirm that galectin-3 expression is a feature of malignant thyroid cells, and that immunohistochemical detection of galectin-3 could be useful in thyroid carcinoma diagnostics. The absence of galectin-3 in thyroid cells during fetal development suggests that galectin-3 is expressed de novo during malignant transformation of thyroid epithelium, thus it should not be considered an oncofetal antigen

Ectopic corticotroph syndrome

INTRODUCTION Endogenous Cushing's syndrome is a clinical state resulting from prolonged, inappropriate exposure to excessive endogenous secretion of Cortisol and hence excess circulating free cortisol, characterized by loss of the normal feedback mechanisms of the hypothalamo-pituitary-adrenal axis and the normal circadian rhythm of cortisol secretion [2]. The etiology of Cushing's syndrome may be excessive ACTH secretion from the pituitary gland, ectopic ACTH secretion by nonpituitary tumor, or excessive autonomous secretion of cortisol from a hyperfunctioning adrenal adenoma or carcinoma. Other than this broad ACTH-dependent and ACTH-independent categories, the syndrome may be caused by ectopic CRH secretion, PPNAD, MAH, ectopic action of GIP or catecholamines, and other adrenel-dependent processes associated with adrenocortical hyperfunction. CASE REPORT A 31 year-old men with b-month history of hyperpigmentation, weight gain and proximal myopathy was refereed to Institute of Endocrinology for evaluation of hypercortisolism. At admission, patient had classic cushingoid habit with plethoric face, dermal and muscle atrophy, abdominal strie rubrae and centripetal obesity. The standard laboratory data showed hyperglycaemia and hypokaliemia with high potassium excretion level. The circadian rhythm of cortisol secretion was blunted, with moderately elevated ACTH level, and without cortisol suppression after low-dose and high-dose dexamethason suppression test. Urinary 5HIAA was elevated. Abdominal and sellar region magnetic resonance imaging was negative. CRH stimulation resulted in ACTH increase of 87% of basal, but without significant increase of cortisol level, only 7%. Thoracal CT scan revealed 14 mm mass in right apical pulmonary segment. A wedge resection of anterior segment of right upper lobe was performed. Microscopic evaluation showed tumor tissue consisting of solid areas of uniform, oval cells with eosinophilic cytoplasm and centrally located nuclei. Stromal tissue was scanty, and mitotic figures were infrequent. Tumor cells were immunoreactive for synaptophysin, neuron-specific enolase, and ACTH. The postoperative course was uneventful and the patient was discharged on glucocorticoid supplementation. Signs of Cushing's syndrome were in regression, and patient remained normotensive and normoglycaemic without therapy. DISCUSSION A multitude of normal nonpituitary cells from different organs and tissues have been shown to express the POMC gene from which ACTH is derived. The tumors most commonly associated the ectopic ACTH syndrome arise from neuroendocrine tissues, APUD cells. POMC gene expression in non-pituitary cells differs from that in pituitary cells both qualitatively and quantitatively [8], Aggressive tumors, like small cell cancer of the lung (SCCL) preferentially release intact POMC, whereas carcinoids rather overprocess the precursor, releasing ACTH and smaller peptides like CLIP. Some tumors associated with ectopic ACTH syndrome express other markers of neuroendocrine differentiation like two specific prohormone convertases (PCs). Assessment of vasopressin (V3) receptor gene expression in ACTH-producing nonpituitary tumors revealed bronchial carcinoid as a particular subset of tumors where both V3 receptor and POMC gene may be expressed in pattern indistinguishable from that in corticotroph adenoma [9]. In most, but not all, patients with ectopic ACTH syndrome, cortisol is unresponsive to high-dose dexamethason suppression test, what is used as diagnostic tool. It is not clear if the primary resistance resulted from structural abnormality of the native glucocorticoid receptor (GR), a low level of expression, or some intrinsic property of the cell line [9]. It appears that ectopic ACTH syndrome is made of two different entities. When it is because of highly differentiated tumors, with highest level of pituitary-like POMC mRNA, expressing PCs, high level of V3 receptors and GR, like bronchial carcinoids, it might be called ectopic corticotroph syndrome. In contrast, when it is caused by aggressive, poorly differentiated tumors, with much lower expression of V3 receptor, like SCCL, it might be called aberrant ACTH secretion syndrome. Carcinoid tumors have been reported in a wide range of organs but most commonly involve the lungs, bronchi, and gastrointestinal tract. They arise from neuroendocrine cells and are characterized by positive reactions to markers of neuroendocrine tissue, including neuron specific enolase, synaptophysin, and chromogranina [11]. Carcinoid tumors are typically found to contain numerous membrane-bound neurosecretory granules composed of variety of hormones and biogenic amines. One of the best characterized is serotonin, subsequently metabolized to 5-hydrohy-indolacetic acid (5-HIAA), which is excreted in the urine. In addition to serotonin, carcinoid tumors have been found to secrete ACTH, histamine, dopamine, substance P, neurotensin, prostaglandins and kallikrein. The release of serotonin and other vasoactive substances is thought to cause carcinoid syndrome, which manifestations are episodic flushing, weezing, diarrhea, and eventual right-sided valvular heart disease. These tumors have been classified as either well-differentiated or poorly differentiated neuroendocrine carcinomas. The term „pulmonary tumorlets" describes multiple microscopic nests of neuroendocrine cells in the lungs [12]. Pulmonary carcinoids make up approximately 2 percents of primary lung tumors. The majority of these tumors are perihilar in location, and patients often presents with recurrent pneumonia, cough, hemoptisis, or chest pain. The carcinoid syndrome occurs in less than 5 percent of cases. Ectopic secretion of ACTH from pulmonary carcinoid accounts for 1 percent of all cases of Cushing's syndrome. They are distinct clinical and pathologic entity, generally peripheral in location. Although they are usually typical by standard histologie criteria, they have mush greater metastatic potential than hormonally quiescent typical carcinoids [13]. Surgical treatment therefore should be one proposed for more aggressive malignant tumors. In all cases of ACTH-dependent Cushing's syndrome with regular pituitary MRI and bilateral inferior petrosal sinus sampling, thin-section and spiral CT scanning of the chest should be routine diagnostic procedure [14], We present thirty-one year old patient with typical pulmonary carcinod with ACTH ectopic secretion consequently confirmed by histology

Galectin-3 expression in medullary thyroid carcinoma in relation to tumor progression

BACKGROUND: Galectin-3, a lectin with specificity for beta galactosides, is believed to be implicated in multiple biological processes through interactions with complementary glycoconjugates. Alterations in galectin-3 expression are observed in a variety of human tumors. In thyroid, this lectin has been found to be highly expressed in malignancies of epithelial origin. We analyzed galectin-3 expression in medullary thyroid carcinoma (MTC). MATERIALS AND METHODS: An immunohistochemical study using monoclonal antibody was performed on paraffin sections of twenty cases of sporadic MTC comprising ten cases without and ten cases with lymph node metastases at the time of surgery. RESULTS: Positive cytoplasmic staining for galectin-3 was found in 16/20 cases, but varied in intensity and distribution from weak/focal (7/16) to moderate (7/16) or strong (2/16). Advanced stage of MTC (with lymph node metastases at the time of surgery) showed moderate to strong galectin-3 expression more frequently (8/10) than cases without lymph node metastases (1/10). CONCLUSION: These findings suggest that galectin-3 expression is associated with the advanced stage of disease and that this lection might play a role in the pathobiology of MTC

Optimal feeding and maintenance technology for dairy cows in intensive production conditions

Over the past 50 years, milk production in our country was only partly based on economic principles, the social aspect being predominant, as for most strategic agricultural products. Only towards the end of 2000, when the key disparities in prices were somewhat corrected, it began to acquire characteristics of economically organized production. Nevertheless, some things remained, like the existence of state premiums for milk which are an effort to bridge the differences between real production costs, on the one hand, and the very low purchasing power of the wider strata of society, on the other. The objective of this work was to review several farm models typical for our country, and to point out the best solutions for developing industrial dairy farming in our very good geographic conditions and other natural resources, and all for the purpose of introducing optimal conditions for feeding and technology with economically justified production

Can thyroidectomy be performed in secondary thyroid cancer?

Background: Secondary thyroid cancer is much less frequent than primary and in the majority of cases represents disseminated disease where operation on thyroid is useless or thyroid tumor is not operable, infiltrating surrounding structures. Methods: Five case reports of patients operated for secondary thyroid cancer. Results: Case 1: In male patient aged 64 years thyroidectomy was done for thyroid solid tumor 5 years after lung lobectomy for bronchogenic planocellular cancer. FNB suspected nonthyroid cancer histological analysis revealed planocellular cancer (Grimelius staining excluded medullar cancer) and multinodular goiter. Case 2: In female patient aged 65 years, thyroidectomy was done 4 years after left mastectomy with the history of long standing multinodular toxic goiter. Infiltrate remained in trachea and esophagus, histology revealed breast cancer metastasis in thyroid, confirmed with special mucin I, and estrogen receptor staining with negative thyroglobulin staining. Case 3: In female patient aged 76 years thyroidectomy was performed for metastatic lucidocellular kidney cancer in recurrent goiter (with Vimentin staining), a year after nephrectomy and 50 years after first goiter operation. Case 4: In female patient aged 58 years thyroidectomy was performed for planocellular infiltration of esophagus into the left thyroid lobe. Case 5: In female patient aged 77 years thyroidectomy was done for hemorrhage into thyrotoxic goiter, histology revealed metastasis of planocellular cancer of unknown origin into thyroid. Case 6: In male patient aged 54 years, thyroidectomy was done for thyroid metastatic lucidocellular cancer of kidney, 2 years after nephrectomy. Conclusion: Although prognosis of secondary thyroid cancer is poor, in rare cases aggressive surgery with adjuvant therapy may be successful

Relationship between Trace Elements and Matrix Metalloproteinases 2 and 9 and their Tissue Inhibitors in Medullary Thyroid Carcinoma

Medullary Thyroid Carcinoma (MTC) constitutes around 5% of all thyroid cancers. Trace elements assessment has emerged as a useful strategy in the diagnostics of MTC combined with Matrix Metalloproteinases (MMPs) and Tissue Inhibitors of Matrix Metalloproteinases (TIMPs) analysis. The aim of this study was to compare the presence and content of trace elements (i.e., Copper (Cu), Zinc (Zn), Iron (Fe), and Manganese (Mn)) in MTC with respect to control samples and their potential relationship with markers of MTC in tissues. The study included 26 patients who had undergone thyroidectomy, due to the diagnosis of MTC and 17 patients as control. We combined tumour pathology and staging, immunohistochemical analysis of calcitonin, MMPs, and TIMPs, with analytical biochemistry using Inductively Coupled Plasma – Mass Spectrometry (ICP-MS) to determine the levels of trace elements. No differences by MTC type for MMPs and their TIPMs, although strong TIMP-1 and TIMP-2 immunohistochemical expression of MTC were unveiled. Additionally, Zn, Fe, and Mn tended to be decreased, and Cu to be increased in samples presenting MTC with respect to controls. Moreover, Zn was the unique trace element which seemed to be correlated with MMPs and TIMPs. Trace elements such as Zn, Fe, and Mn are decreased in tissues affected by MTC. In addition, Zn may be the trace element which saves more relationship with the proportion and intensity of MMPs, being considered altogether useful biomarkers of MTC. We therefore suggest the analysis of novel and traditional markers of MTC as a novel approach in this pathology.Funding for open access charge: Universidad de Granada / CBUA. This study was supported by Zinc-Net “The Biology of Zinc”—COST action TD 1304 and the bilateral scientific cooperation between the Republic of Serbia and the Republic of Portugal -451–03-01765/2014–09/20. Héctor Vázquez-Lorente is under a FPU fellowship from the Spanish Ministry of Education with grant reference FPU18/03655

Glucocorticoid Receptor and Molecular Chaperones in the Pathogenesis of Adrenal Incidentalomas: Potential Role of Reduced Sensitivity to Glucocorticoids

Glucocorticoid (GC) sensitivity depends on glucocorticoid receptor (GR) and heat shock proteins (Hsps). We investigated whether common GR genes (ER22/23EK N363S, BclI, and 9 beta) and adrenocorticotropin receptor promoter polymorphisms influence susceptibility for unilateral adrenal incidentaloma (AI), plus GR and Hsp expression in tumorous (n = 19), peritumorous (n = 13) and normal adrenocortical (n = 11) tissues. Patients (n = 112), population-matched controls (n = 100) and tumor tissues (n = 32) were genotyped for these polymorphisms. Postdexamethasone serum cortisol was higher in patients (p<0.001). GR gene variants, larger allele of BclI (odds ratio (OR) 2.9; 95% confidence interval (CI) 1.7-5.1; p < 0.001) and minor allele of 9 beta (OR 3.0; 95% CI 1.6-5.7; p < 0.001) were independent predictors of Al. In patients, the first allele is linked with larger tumors (p = 0.002) and the latter with higher postdexamethasone cortisol levels (p = 0.025). Both allele carriers had lesser waist circumference (p = 0.02), similar adrenocorticotropin and higher basal (p = 0.024) and postdexamethasone cortisol concentrations (p < 0.001). Tumorous and constitutional genotypes were similar. GR-D is the major receptor isoform in normal adrenal cortex by Western blotting. Loss of other receptor isoforms, decrease in immunostaining for GR (p < 0.0001), underexpression of chaperones (p <= 0.01) and the presence of inducible Hsp70 were found in adenomas. In conclusion, GR gene variants, C allele of BclI and minor allele of 9 beta, are associated with Als. Their concurrent presence in patients reduces GC sensitivity Normal adrenal cortex preferentially expresses GR-D. In adenomas, the lack of other GR isoforms and underexpression of heat shock proteins perhaps permanently impair GC signaling, which could promote dysregulated cortisol production and tumor growth. The innate GC sensitivity probably modifies these effects. Online address: http://www.molmed.org doi: 10.2119/molmed.2012.00261Ministry of Science and Technological Development of Serbia [III41009