Optimization of 131I ablation in patients with differentiated thyroid carcinoma: comparison of early outcomes of treatment with 100 mCi versus 60 mCi

INTRODUCTION: The aim of this study was to compare the early outcomes between two groups of patients with differentiated thyroid carcinoma (DTC) who received 60 or 100 mCi of (131)I for remnant ablation. MATERIAL AND METHODS: 224 DTC patients with primary tumor > 1 cm of diameter or multifocal were randomised into prospective clinical trial. Patients with extrathyroideal extension of primary tumor and nodal metastases or M1 were not enrolled. 99 patients received 60 mCi, and 125--100 mCi of radioiodine as the first ablative dose. RESULTS: The effectiveness of thyroid ablation was evaluated after one year, during endogenous TSH (thyroid stimulating hormone) stimulation, and after two years during Lthyroxine therapy. Whole body scintigraphy (WBS) was performed under thyroxine withdrawal and thyroglobulin serum level was assessed. Distant micrometastases were detected in 9.8% of patients by post-therapy WBS, 11 patients in group A treated with 60 mCi and 11 in group B treated with 100 mCi. In other patients no symptoms of persistent disease were detected. At one year follow up full remission was diagnosed in 176 patients: 76 in group A and 100 in group B. The remaining ones, 13.3% and 11.2% respectively, received the second course of (131)I for remnant ablation. There were no statistically significant differences in Tg (thyroglobulin) serum level either 12 or 24 months after 131I treatment. CONCLUSIONS: Our evaluation of early efficacy of adjuvant radioiodine treatment in low risk DTC patients shows no differences between two radioiodine activities - 60 and 100 mCi in relation to thyroid ablation. Thus, the activity of 60 mCi is recommended.     

Completion total thyroidectomy in children with differentiated thyroid cancer

INTRODUCTION: The optimal surgical treatment of children with differentiated thyroid cancer remains an important point of discussion. Especially the need for completion operation is questioned in young patients. Our objective was to examine the rate of residual neoplastic disease after non radical initial operation. MATERIAL AND METHODS: From the 235 children diagnosed with differentiated thyroid cancer, 131 (56%) needed completion operation due to incomplete primary surgery. Completion operation involved thyroid bed, lymph nodes or both respectively in 91 (39%), 13 (6%) and 27 (11%) cases. Risk factors responsible for residual disease were evaluated by means of logistic regression analysis. RESULTS: Residual disease was detected in 46 (35%) of reoperated children (25% in thyroid bed and 85% in lymph node of lateral neck compartment). Sex and age did not influence the risk of residual disease in thyroid bed or lymph nodes. Papillary type of cancer and multifocality increased risk of residual disease in thyroid bed respectively by the factor of 15 (95% CI: 2-125) and 2.3 (95% CI: 1.2-4.4). Infiltration of thyroid capsule did not correlate with the risk of residual disease. Lymph node metastases in primary operation increased risk of residual disease by the factor of 16 (95% CI: 1.2-245). Histopathology, multifocality of primary tumour or infiltration of lymph node capsule did not influence the risk of residual disease in lymph nodes of lateral neck compartment. CONCLUSIONS: In children with differentiated thyroid cancer residual disease is diagnosed in about 1/3 of non radically operated cases. This high incidence justifies completion operations. The risk of residual disease is significantly increased in papillary thyroid cancer, multifocal tumours and cases with lymph node metastases.     

The secretion antigen SA5K has a role in the adaptation of Mycobacterium bovis bacillus Calmette-Guérin to intracellular stress and hypoxia

The Mycobacterium tuberculosis TB8.4 (Rv1174c) gene encodes a secreted protein of 8.4 kDa (TB8.4) which has been suggested to be involved in reactivation of dormant mycobacteria. We have previously reported that inactivation of an identical gene (sa5k) in Mycobacterium bovis BCG causes impaired ability of the mutant strain (BCGsa5k::aph) to grow inside human macrophages. This study aimed to investigate the role of TB8.4 in the reactivation of aged cultures of BCG as well as the role of the sa5k gene in the resistance of BCG to intracellular stress conditions and adaptation to hypoxia. Although when added to aged cultures of BCG, TB8.4 caused a statistically significant increase in the number of colony-forming units, a similar effect was obtained in cultures incubated with BSA, suggesting a non-specific growth stimulation by TB8.4. Compared to parental BCG, the BCGsa5k::aph strain showed an increased susceptibility to reactive oxygen and nitrogen intermediates and to acid stress and an impaired ability to adapt to reduced O2 concentrations, when tested in the oxygen-limited Wayne culture system. These results suggest that the product of the sa5k gene (SA5K protein) has a role in both resistance of BCG to intracellular stress and in its adaptation to hypoxia.     

Zinc ions stimulate the cooperative RNA binding of hordeiviral gammab protein

A small regulatory gammab protein of the Poa semilatent hordeivirus (PSLV) contains two zinc finger-like motifs separated by a basic motif in the N-terminal part and a C-terminal coiled-coil motif. Interactions of the recombinant PSLV gammab protein and its mutants with various RNAs (ssRNA, dsRNA, ssRNA oligonucleotides) and ssDNA were studied in gel-shift assays. The results demonstrated that zinc ions are essential for effective nucleic-acid-binding activity of the gammab protein, suggesting the important role of zinc finger motifs in these interactions. Deletion of the C-proximal coiled-coil region did not affect highly cooperative RNA-protein binding, indicating that the N-terminal part of the protein contributes to the protein-protein interactions needed for the protein-RNA cooperativity.     

Mononuclear and polymorphonuclear leukocytes show increased fructose-1,6-bisphosphatase activity in patients with type 1 diabetes mellitus

The activity and localization of fructose-1,6-bisphosphatase (FBPase; EC 3.1.3.11) in blood leukocytes of patients with type 1 diabetes mellitus and healthy adults were investigated immunocytochemically. The amount of polymorphonuclear (PMN) and mononuclear (MN) cells with positive FBPase immunocytochemical reaction was 57% and 68%, respectively, in pathological, and 38% and 42%, respectively, in healthy donors. Results of light microscopic investigations were confirmed by measurements of FBPase activity following lysis of PMN and MN cells. The enzyme activity of PMN and MN leukocytes was higher in diabetes mellitus than in healthy adults, by 30% and 127%, respectively. Using immunocytochemistry together with electron microscopy, FBPase was detected not only in the cytoplasm but also in the nucleus of leukocytes of both patients with insulin-dependent diabetes mellitus and healthy donors.     

Exploring the genome sequence of Bifidobacterium bifidum S17 for potential players in host-microbe interactions

Bifidobacterium bifidum S17 is a promising probiotic candidate, which displays potent anti-inflammatory activity both in vitro and in vivo. Furthermore, tight adhesion to intestinal epithelial cells (IECs) has been shown for this strain and is considered to be an important prerequisite for host colonization and consequently the anti-inflammatory properties. By analyzing the recently sequenced genome at least 9 surface proteins and various gene clusters encoding for putative pili were identified. Most of these proteins are expressed in vitro, with higher expression during exponential growth phase. Increased expression of the putative adhesins in exponential growth phase was associated with higher adhesion of B. bifidum S17 to Caco-2 cells.     

Effect of age and sex on digestive tract morphometry of guinea fowl (Numida meleagris L.)

As guinea fowl age, their body weights and length of the esophagus and crop increased significantly, and relative length (cm x 100 g b.w(-1)) of the small intestine, caeca and total intestine decreased significantly (P < or = 0.05) in males and females. In addition, 52-week-old males had a significantly higher percentage length of rectum and heart weight, and females a significantly higher gizzard weight compared to 13-week-old birds. Compared to females, adult males differed significantly (P < or = 0.05) in the length of caeca and also in the proportion of the gizzard, proventriculus, heart and liver in total weight.     

The Role of Energy in the Emergence of Biology from Chemistry

Any scenario of the transition from chemistry to biology should include an ??energy module?? because life can exist only when supported by energy flow(s). We addressed the problem of primordial energetics by combining physico-chemical considerations with phylogenomic analysis. We propose that the first replicators could use abiotically formed, exceptionally photostable activated cyclic nucleotides both as building blocks and as the main energy source. Nucleoside triphosphates could replace cyclic nucleotides as the principal energy-rich compounds at the stage of the first cells, presumably because the metal chelates of nucleoside triphosphates penetrated membranes much better than the respective metal complexes of nucleoside monophosphates. The ability to exploit natural energy flows for biogenic production of energy-rich molecules could evolve only gradually, after the emergence of sophisticated enzymes and ion-tight membranes. We argue that, in the course of evolution, sodium-dependent membrane energetics preceded the proton-based energetics which evolved independently in bacteria and archaea.     

Open Questions on the Origin of Life at Anoxic Geothermal Fields

We have recently reconstructed the ??hatcheries?? of the first cells by combining geochemical analysis with phylogenomic scrutiny of the inorganic ion requirements of universal components of modern cells (Mulkidjanian et al. Proc Natl Acad Sci U S A 109:E821?C830, 2012). These ubiquitous, and by inference primordial, proteins and functional systems show affinity to and functional requirement for K⁺, Zn²⁺, Mn²⁺, and phosphate. Thus, protocells must have evolved in habitats with a high K⁺/Na⁺ ratio and relatively high concentrations of Zn, Mn and phosphorous compounds. Geochemical reconstruction shows that the ionic composition conducive to the origin of cells could not have existed in marine settings but is compatible with emissions of vapor-dominated zones of inland geothermal systems. Under an anoxic, CO₂-dominated atmosphere, the ionic composition of pools of cool, condensed vapor at anoxic geothermal fields would resemble the internal milieu of modern cells. Such pools would be lined with porous silicate minerals mixed with metal sulfides and enriched in K⁺ ions and phosphorous compounds. Here we address some questions that have appeared in print after the publication of our anoxic geothermal field scenario. We argue that anoxic geothermal fields, which were identified as likely cradles of life by using a top-down approach and phylogenomics analysis, could provide geochemical conditions similar to those which were suggested as most conducive for the emergence of life by the chemists who pursuit the complementary bottom-up strategy.