VITAMIN D LEVEL AND ITS RELATIONSHIP WITH CANCER STAGE IN PATIENTS WITH DIFFERENTIATED THYROID CARCINOMA.

Background: Differentiated thyroid carcinoma (DTC) has witnessed an increase in incidence and although it is considered to have a slow grow potential and a 90% 10-year survival rate, local or distant metastases can be observed in 20%. It is essential to recognize other factors associated with malignancy and poor prognosis. Vitamin D and its deficiency has proven useful as a prognostic biomarker for many types of cancer, including thyroid cancer. Aim: Evaluate the relationship between vitamin D status in DTC and benign thyroid disorders patients and correlation between vitamin D and histopathological findings in DTC group. Methods: Study included 170 patients with confirmed DTC and 200 with benign thyroid pathology. Evaluation included 25-hydroxy vitamin D [25(OH)D], ultrasound and histopathologic features. Results: In DTC patients, mean value of vitamin D was significantly lower (17.86 ng/mL ± 9.31 DS versus 20.26 ng/mL ± 9.31 DS, p=0.029). Statistical analysis confirmed a negative correlation between vitamin D levels and tumor size (T) according to TNM classification (r=-0.176, p=0.02). Conclusions: Vitamin D level was significantly lower in the DTC group and 25(OH)D levels may be correlated with histopathology features like tumor size and aggressiveness according to TNM classification.

THE MULTIFARIOUS CUSHING'S - LESSONS FROM A CASE SERIES.

Endogenous Cushing's syndrome is rare, with an incidence of 0.7-2.4 per a million people a year. Clinical presentation of Cushing syndrome can be pleomorphic, and establishing diagnosis can be difficult. Early recognition and rapid control of hypercortisolaemia are necessary to decrease morbidity and mortality in these patients. We report a series of 6 endogenous Cushing's syndromes of different etiologies (4 Cushing's disease and 2 adrenal Cushing's syndrome) assessed in our endocrine department over a decade (2009-2019). In order to highlight the diversity of clinical forms, diagnostic tools and specific management of this condition we labelled each case suggestively: the typical Cushing's disease, the Pseudo Cushing's, the elusive Cushing's disease, the mild autonomous cortisol hypersecretion, Cushing's syndrome in pregnancy and Cushing's disease with thromboembolism. We discussed their particularities which were revelatory for the diagnosis, such as dermatologic, cardiovascular, musculoskeletal, neuropsychiatric, or reproductive signs, reviewing literature for each manifestation. We also discuss the commonalities and differences in laboratory and imagistic findings. Therapeutic approach can also differ with respect to the particular condition of each patient and the multiple choices of therapy will be reviewed.

CRANIOPHARYNGIOMA - CLINICAL AND THERAPEUTIC OUTCOME DATA IN A MIXED COHORT OF ADULT AND PAEDIATRIC CASES.

BACKGROUND: Craniopharyngiomas are benign but locally invasive tumours of the sellar region that arise from ectopic embryonic remnants of Rathke's pouch, affecting both children (adamantinomatous type -aCP) and adults (papillary type -pCP) and associated with significant morbidity. OBJECTIVE: To study the clinical presentation of CRF as well as the posttreatment evolution of craniopharyngioma in children versus adults in a large mixed cohort. MATERIAL AND METHODS: We performed a retrospective review of CRF patients evaluated in the National Institute of Endocrinology in Bucharest between 1990 and 2016. RESULTS: A total of 107 patients (72 adults, 35 children) with a mean follow-up of 6.2 years were included. The presenting symptoms were mostly headache, visual impairment, symptoms of hypopituitarism, diabetes insipidus. Some symptoms or hormonal abnormalities were significantly more prevalent in the children group (p<0.05): nausea/ vomiting (47.8% vs 16.7%), photophobia (21.7% vs 5.6%), diabetes insipidus(28.5% vs 8.3%), GH deficiency (68.8% vs 17.1%). Impaired visual acuity (67.6%of cases) or visual fields (71.4%) were more frequent in adults compared to children (44.1%; 51.6%). The tumor dimensions were similar in both groups (3.05± 1.05 cm in children; 2.7± 1.07 cm in adults). Massive suprasellar extension reaching the third ventricle was frequently present in all cases. All cases underwent surgery but only a minority of those not cured received postoperative adjuvant radiotherapy. Frequent postoperative complications were: aggravation of the endocrine deficit (>80% of cases in both groups needed chronic replacement therapy), central diabetes insipidus (68.2% children, 34.3% of adults). CONCLUSIONS: Despite similar tumor dimensions and extension compared to adults, craniopharyngioma in children is more frequently associated with signs of intracranial pressure. The results and complications of treatment are similar in adults and children.

CORTISOL LEVELS AND SUICIDE IN BIPOLAR I DISORDER.

CONTEXT: Hypothalamic-pituitary-adrenal (HPA) axis irregularities have been described both in bipolar disorder and suicidal behaviour, but few studies have examined the relationship between suicidal behaviours and cortisol levels in bipolar disorder. OBJECTIVE: We compared HPA axis activity in bipolar I (BPD I) individuals with and without suicidal ideation and behaviour through multiple measurement of serum and salivary cortisol. DESIGN: Cross-sectional, observational study. SUBJECTS AND METHODS: 75 BPD I patients were assigned into 3 groups (no history of suicidal behaviour, history of suicidal ideation, history of suicide attempt), according to the C-SSRS. Socio-demographical and clinical data was obtained by using MINI 6.0 and a semi-structured questionnaire. Salivary samples were collected using Sarstedt Cortisol Salivette synthetic swab system for two consecutive days at 08:00, 16:00, 23:00 and salivary cortisol concentrations were determined by ELISA technique. A unique 1mg dose of dexamethasone was administered on the first day, at 23:00, after the collection of the saliva sample. Blood was collected on the first day at 8:00 AM and basal morning serum cortisol levels were determined by immunoassay with fluorescence detection. RESULTS: Cortisol parameters in our BPD I sample did not vary significantly in respect to suicidal history. However, patients with a history of suicidal ideation have significantly higher total cortisol outputs than patients with no history of suicidal behaviour in the 18 to 40 age category compared with the above 40 age category. CONCLUSIONS: Total cortisol daily output varies significantly in an age-dependent manner in respect to suicidal thoughts in BPD I individuals.

Increased copeptin levels in metabolic syndrome from a Romanian population.

Rationale: Arginine vasopressin (AVP) is secreted under conditions of water deprivation. Since AVP has a low half-life in the plasma, the C-terminal fragment of AVP-precursor (copeptin) was used to estimate the AVP levels. High copeptin levels increase the risk for the development of diabetes mellitus. Aim: This study was aimed to measure copeptin levels in the metabolic syndrome (MetS) in Romanians using a competitive enzyme immunoassay. Methods and results: Patients prone to present MetS (n = 63) were compared to controls (n = 42). In the MetS group, the syndrome was confirmed in 93.6%. Affected patients displayed 85.7% obesity and insulin resistance (HOMAIR of 4.9 ± 0.4 versus 1.1 ± 0.8 in controls). Low HDL-cholesterol was less represented (47.5%). Copeptin levels were 0.6 ± 0.0 in MetS versus 0.42 ± 0.0 ng/ mL in controls (P < 0.004). Higher copeptin (0.79 to 1.83 ng/ mL) was associated with MetS, P < 0.0018, OR 20, 95%CI [3.03 - 131.7]. In ANOVA, high copeptin was equally explained by MetS or obesity (P < 0.05,α = 3.8). The best correlation was found with high triglyceride levels (P < 0.013,α = 6.3) while the correlation with HOMAIR remained not significant. Discussion: These data indicated a concordant correlation between increased copeptin and MetS or its components. In the light of epidemiological data, indicating that more than 50% of the European population has a lower daily water intake and a fraction of 25% displaying high copeptin, our data further sustained that copeptin may be a good biomarker for MetS and/ or obesity, which should be further investigated with other members of the osmoregulation pathway at both pathogenesis and genetic levels.

Short-term Administration of Alphacalcidol is Associated with More Significant Improvement of Muscular Performance in Women with Vitamin D Deficiency Compared to Native Vitamin D.

Introduction: Positive relationships between muscle function and vitamin D (VD) status, defined by serum 25-hydroxy VD (25OHD) levels have been reported and muscle strength is generally improved with VD supplementation in deficient individuals. The effects of active VD analogs have been less studied. Aim: We aim to investigate the effect of short-term treatment with native VD (cholecalciferol) or alphacalcidol on the muscular function and physical performance in women with vitamin D deficiency. Material and methods: We analysed 178 women with VD deficiency, defined as serum 25-hydroxyVD-25OHD concentration below 30 ng/ml. We recorded the grip-strength and the results of the chair-rise test (CRT) and timed-up-and-go test (TUG). We randomised the patients to receive cholecalciferol 1 000 IU daily or alphacalcidol 1 µg daily, for 6 months. Results: The mean baseline 25OHD concentration was 14.47±6.57 ng/ml. After treatment the serum 25OHD level rose to 20.85±8.88 ng/ml, significantly higher in cases supplemented with cholecalciferol (22.7±8.32 ng/ml) compared to those treated with alphacalcidol (13.5±7.29 ng/ml, p=0.000). After treatment, significant improvements of TUG and CRT test results (- 6.48 and-5.05% compared to baseline, respectively, p=0.000) and gripstrength (7.85% compared to baseline, p=0.000) occurred. The benefit was more significant in cases treated with alphacalcidol for gripstrength (p=0.001), TUG (p=0.002), CRT (p=0.033). After treatment, the gripstrength increased significantly more in patients with severe baseline VD deficiency. Conclusions: VD status improvement is associated with an increase in muscular performance in women with VD deficiency. Alphacalcidol exerts significantly better effects compared to cholecalciferol, and this can not be explained by a larger increase in serum 25OHD concentration.

PLATELET SEROTONIN AS BIOMARKER FOR ASSESSING SUICIDAL BEHAVIOUR IN PATIENTS WITH BIPOLAR I DISORDER.

CONTEXT: Suicide is a global public health issue. Bipolar disorder (BPD) has the highest suicide risk among individuals suffering from mental disorders. Serotoninergic dysfunctions have been linked to suicidal behaviour and platelet serotonin is recognised as a reliable index for the presynaptic serotonin activity. OBJECTIVE: Our aim was to assess whether alterations occur in platelet serotonin concentrations in BPD type I in respect to suicide attempters compared with non-attempters. DESIGN: This was a cross-sectional, observational study. SUBJECTS AND METHODS: Plasma platelet serotonin concentrations were measured using ELISA technique in 71 BPD I patients. The participants were assigned into 3 groups (non-attempters, low lethality and high lethality suicide attempters), according to the Columbia-Suicide Severity Rating Scale. Socio-demographical and clinical data was obtained by using MINI 6.0 and a semi-structured questionnaire designed specifically for this research. RESULTS: Our study showed significant lower levels of platelet serotonin in suicide attempters compared with non-attempters (p = 0.030) and in high-lethality attempters compared with low-lethality attempters (p = 0.015). The study recorded a higher number of total lifetime and lifetime depressive episodes for suicide attempters with BPD I. CONCLUSIONS: Our results subscribe to the importance of platelet serotonin as a reliable biomarker in suicide risk assessment.

Mechanistic aspects of ligand exchange in Au nanoparticles.

Ligand exchange reaction is a very important and useful tool for preparing functionalised metal nanoparticles. Understanding the mechanism of this process is essential for rational design of nanoparticle-based devices. However the underlying chemistry was found to be very rich. In this article, we summarise the research efforts of several groups to unravel the mechanisms of ligand exchange reaction, and discuss implications for future developments.

Aggregation numbers and microstructure characterization of self-assembled aggregates of poly(ethylene oxide) surfactants and related block-copolymers, studied by spectroscopic methods.

This review presents typical examples of micellar size measurements and structural characterization of self-assembled systems as determined with spectroscopic methods, selected from our representative results accumulated in recent years of systematic studies. The choice of examples has aimed at emphasizing the potentiality of the methods used in the study of poly(ethylene oxide) (PEO) surfactants. By using the time-resolved fluorescence quenching method aggregation numbers have been determined for direct and reverse micelles as well as for micelle-like clusters formed in (bio)polymer-surfactant solutions. By using specific spectral parameters of a variety of properly chosen molecular probes [fluorescence, UV-VIS and electron spin resonance (ESR) spin probes], problems such as hydration degree and profile of the PEO chains, local viscosity, ordering and packing of surfactant chains have been addressed. The intention was to correlate results obtained from different spectroscopic methods and to refer all polarity data to a common scale, such as Kosower's polarity factor.

New amino-nitroxide spin labels.

Stable free mono- and diradicals containing reactive primary or secondary amino groups in the side-chain have been synthesized by transesterification of amino-substituted esters with paramagnetic alcohols or from spin-labeled acid derivatives and amines. In the second approach the new radical 18 (1-oxyl-3-(2-bromoethoxycarbonyl)-2,2,5,5-tetramethylpyrroline) is proposed as an efficient alkylating species. The nitroxides described are pH-sensitive spin probes and spin labels potentially useful for a diversity of ESR applications in chemistry and biology. New spin-labeled tyramine 16 (N-(1-oxyl-3-carbonyl-2,2,5,5-tetramethyl-pyrroline)tyramine) was successfully employed in a novel assay of protein oxidative damage.

The development of a radioimmunoassay system for testosterone (T) and dihydrotestosterone (DHT). Part 2. The preparation of antisera to T.

Testosterone-3-O-carboxymethyl-oxime derivative was synthetized and coupled to bovine serum albumin (BSA). The T-3-CMO-BSA conjugate homogenized with Freund's adjuvant used as immunogen was injected multiple sites in rabbits. The antisera collected were characterized in a radioimmunological system, separation with dextran-charcoal using 125I-Testosterone as tracer. The antibody titres varied from one animal to another. The titre of anti-T serum selected for RIA was 1: 10(4)-1: 2 X 10(4) (initial dilution). All anti-T sera 100 percent crossreacted with 5 alpha-dihydrotestosterone but nonsignificant interference was observed with other C19, C21 and C18 steroids. The affinity constant of the selected anti-T serum was in the range 1.4-1.9 X 10(9) litres/mole. The data so far published on the antisera toward testosterone are reviewed. We conclude that the selected anti-T-3-CMO-BSA serum may provide assays for testosterone with potential for clinical applications.

The development of a radioimmunoassay system for testosterone (T) and dihydrotestosterone (DHT). Part 3. The preparation of radioiodinated testosterone.

A two step-method was applied for the preparation of a tracer adequate for a radioimmunoassay (RIA) system for testosterone. Histamine was radioiodinated by the Chloramine-T method and then coupled to testosterone-3-carboxymethyl-oxime (T-3-CMO) derivative. After purification by TLC, the steroid tracer was stable in ethanol for at least four months. Using an anti-T-3-CMO-BSA serum, a (bridge) homologous RIA system for testosterone was developed. The reagents (antiserum, tracer and standard) were incubated 2 hrs at 37 degrees C and then the free radioactivity was removed by a dextran-charcoal suspension. The testosterone RIA system, with the sensitivity of 30 pg/tube, is suitable for the measurement of the steroid hormone in biological fluids and tissues.