Potentially toxic elements in commonly consumed fish species from the western Mediterranean Sea (Almería Bay): Bioaccumulation in liver and muscle tissues in relation to biometric parameters.

Marine pollution is one of today's most relevant problems. Public awareness has been raised about the harmful potential of heavy metals (HMs) accumulating in edible fish and possibly ending up in human diet through the food chain. This study aimed to characterize and evaluate As, Cd, Cr, Cu, Ni and Pb contents in four edible fish species from the western Mediterranean Sea. Liver and muscle toxic elements were determined by GF-AAS in Mullus surmuletus, Merluccius merluccius, Auxis rochei and Scomber japonicus from Almería Bay (Spain). Muscular composition, biometrics and trophic levels were also determined. The mean PTE concentration levels (mg kg-1, DW) in fish muscle tissue were: As (2.90-53.74), Cd (0.01-0.18), Cr (0.53-2.01), Cu (0.78-6.93), Ni (0.06-0.24), Pb (0.0-0.32). These concentrations did not exceed the maximum limits set by European legislation (Commission Regulation (EC) No. 1881/2006) for the intake of these marine species. Accumulation of toxic elements tends to be seen in the liver (As (7.31-26.77), Cd (0.11-8.59), Cr (0.21-2.94), Cu (2.64-16.90), Ni (0.16-1.03), Pb (0.0-0.99)). As was the element at highest risk in this Mediterranean region, especially due to red mullet values in muscle. The high As contents with living habits as benthic species that feed near the coast. HMs, especially muscle Cd contents, were associated with higher contents of lipids and organic matter, and bigger specimen size (length and weight), while As was linked to higher fish protein content. However, these relationships between potentially toxic elements (PTE) and biometric indices and body composition parameters depend on species. Finally, the THQ indices indicated that eating fish from Almería Bay poses no human health risk despite pollution from the Almería coastline.

Radioiodine treatment of differentiated thyroid cancer related to guidelines and scientific literature. / Tratamiento del cáncer diferenciado de tiroides con radioyodo a la luz de las guías y de la literatura científica.

In differentiated thyroid cancer (DTC), radioiodine is administered to eliminate residual normal thyroid tissue after thyroidectomy (ablative treatment), to treat residual microscopic disease (adjuvant treatment), and to treat macroscopic or metastatic disease. Currently, treatment of DTC with 131I is still a matter of controversy due to the absence of prospective clinical trials assessing its benefit in terms of overall survival and recurrence-free interval. The current recommendations of the experts are based on observational retrospective data and on their interpretation of the literature. Pending the results of the prospective trials that are currently underway, the use of 131I seems to be justified not only in high-risk patients, but also in intermediate-risk and low-risk patients. The guidelines of The American and British Thyroid Association, European and American Societies of Nuclear Medicine, The European Consensus Group and the latest edition of National Comprehensive Cancer Network (NCCN) were considered in drawing up this continuing education document, we also undertook a review of the related scientific literature.

Mercury contents in relation to biometrics and proximal composition and nutritional levels of fish eaten from the Western Mediterranean Sea (Almería bay).

Total liver and muscle mercury, and muscular composition, biometrics and trophic levels, were determined in four species (Mullus surmuletus, Merluccius merluccius, Auxis rochei and Scomber japonicus) of the Mediterranean Sea (Almería Bay, Spain). Mercury levels did not exceed the maximum residue limit, and M. merluccius obtained the highest level in muscle. Considerable variations in Hg content among individuals were observed in non-gregarious species. A positive correlation between Hg and trophic level or length was found in muscle, but not in liver. Organs (liver or muscle) with major Hg accumulation depend on species; muscle in M. merluccius and liver in S. japonicus. The results indicate that Hg levels in fish depend on intra- and interspecies factors that should be taken into account in systems to monitor Hg levels.

Cost-effectiveness of using recombinant human thyroid-stimulating hormone before radioiodine ablation for thyroid cancer treatment in Spanish hospitals. / Coste-efectividad de la utilización de la tirotropina recombinante humana previa a la ablación con radioyodo en el tratamiento del cáncer de tiroides en hospitales españoles.

OBJECTIVES: In thyroid cancer treatment, the thyroid-stimulating hormone (TSH) must be elevated before radioiodine ablation, either by exogenous (with recombinant human thyrotropin [rhTSH]) or endogenous stimulation by thyroid hormone withdrawal (THW). The use of rhTSH avoids hypothyroidism and favours the subsequent elimination of radioiodine, but involves the cost of the product. For this reason, a cost-effectiveness analysis was performed, taking into account all costs involved and the benefits associated with the use of this therapy. MATERIAL AND METHODS: Using a Markov modelling with two analysis arms (rhTSH and THW), stratified into high (100mCi/3700 MBq) and low (30mCi/1110 MBq) radioiodine doses, and using 17 weekly cycles, the incremental cost per quality-adjusted life-year (QALY) related to the use of rhTSH was determined. The clinical inputs included in the model were based on published studies and in a treatment survey conducted in Spain. RESULTS: Radioablation preparation with rhTSH is superior to THW, showing additional benefits (0.048 AVAC), as well as cost savings (-€614.16), with an incremental cost-effectiveness rate (ICER) of -€12,795/QALY. The univariate and multivariate sensitivity analyses showed the result to be robust. CONCLUSIONS: The use of rhTSH previous to radioablation in Spain has cost savings, as well as a series of health benefits for the patient, making it highly cost-effective.

The role of early 18F-FDG PET/CT in therapeutic management and ongoing risk stratification of high/intermediate-risk thyroid carcinoma.

Little is known about the role in ongoing risk stratification of fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) performed early after radioactive iodine (RAI) ablation in differentiated thyroid carcinoma (DTC). The aim of the study is to investigate whether 18F-FDG PET/CT performed early after RAI ablation is useful to detect disease and to influence therapy and ongoing risk stratification. Patients with high/intermediate risk of recurrent DTC were included. 18F-FDG PET/CT scan was performed within 6 months after RAI ablation. We confirmed results with other imaging techniques, pathology reports, or follow-up. We classified the patient response as excellent, acceptable, or incomplete. Modified Hicks criteria were used to evaluate clinical impact. We included 81 patients with high/intermediate risk of recurrent DTC. Forty-one (50.6%) had positive uptake in 18F-FDG PET/CT, with negative (131)I whole-body scan ((131)I WBS). Sensitivity, specificity, and diagnostic accuracy of 18F-FDG PET/CT were 92.5, 90.2, and 91.4%, respectively. 18F-FDG PET/CT results had an impact on therapy in 38.3% of patients. One year after initial therapy, 45.7% showed excellent response, 8.6% acceptable response, and 45.7% incomplete response. A statistically significant relationship was found between negative 18F-FDG PET/CT and excellent response (80 vs. 12.2%, p < 0.001; OR 52.8). 18F-FDG PET/CT scan performed early in surveillance of patients with high/intermediate-risk thyroid carcinoma provides important additional information not available with conventional follow-up methods and had a high impact on therapy. A negative 18F-FDG PET/CT predicts an excellent response to therapy in the new ongoing risk stratification.

Relationship between inflammation and microalbuminuria in prehypertension.

Inflammation is a pathogenic factor for target-organ damage (TOD) in hypertension. This study examined the relationship between inflammatory parameters and urinary albumin excretion (UAE) in prehypertension. A total of 65 prehypertensive subjects (blood pressure (BP) 120-139/80-89 mm Hg) and 26 healthy volunteers with BP <120/80 mm Hg were included. High-sensitivity C-reactive protein (hs-CRP), and serum and urinary tumor necrosis factor-α (TNF-α) were measured as inflammatory markers. Prehypertensive individuals had higher levels of inflammatory parameters and UAE than healthy subjects. Analyses carried out in prehypertensive participants showed that BP was similar between individuals with normoalbuminuria or microalbuminuria (MAB) (UAE between 30 and 299 mg per day). However, serum hs-CRP and urinary TNF-α excretion were higher in prehypertensives with MAB. Multiple regression analysis showed that systolic blood pressure (r=0.29, P<0.01), hs-CRP (r=0.20, P<0.001), and urinary TNF-α (r=0.69, P<0.001) were independently correlated with UAE (adjusted R(2)=0.73, P<0.001). Finally, logistic regression analysis performed in the prehypertensive group with the absence or presence of MAB as the dependent variable demonstrated that hs-CRP (3.92 (1.45-10.58), P=0.007) and urinary TNF-α (1.69 (1.20-2.37), P=0.002) were independent risk factors for the presence of MAB. Inflammatory parameters are significantly and independently associated with UAE in prehypertensive subjects, suggesting that inflammation may be a pathogenic factor for the early vascular or TOD in these individuals.

[Treatment protocols and follow-up of differentiated thyroid carcinoma: results of a questionnaire sent to the Spanish Metabolic Therapy Units]. / Los protocolos de tratamiento y seguimiento del carcinoma diferenciado de tiroides: resultados de un cuestionario enviado a las Unidades de Terapia Metabólica españolas.

OBJECTIVE: To know the treatment and follow-up protocols of differentiated thyroid carcinoma patients in Spanish Metabolic Therapy Units, the clinical variability between them and the adaptation to the consensus guidelines. MATERIALS AND METHODS: Analysis of the results obtained from the questionnaire submitted by E-mail to the Spanish Society of Nuclear Medicine (SEMNIM) members on the treatment and follow-up of differentiated thyroid carcinoma patients. A descriptive study was made of the qualitative variables (frequency, percentage) and quantitative variables (mean, standard deviation). RESULTS: Twenty Radiometabolic Therapy Units responded to the questionnaire. In spite of the varied origin of the patients, the Units receive sufficient clinical information and have specialized surgeons. There is variability in the surgical protocols and indication for ablation in patients with intermediate and low risk of recurrence. The Units agree on the use of (131)I doses for ablation and therapy, but show great variability regarding the preparation protocols (previous (131)I-whole body scan or other imaging techniques, (131)I-whole body scan dose, diet and radioiodine contrast prohibition, total dose per patient). Nuclear Medicine physicians perceive radioiodine adverse effects and prevention methods are used. The post-ablation follow-up protocol differs between Units. CONCLUSIONS: Treatment and follow-up protocols of differentiated thyroid carcinoma patients in the Spanish Radiometabolic Therapy Units show variability in aspects such as surgery and ablation indications, patient preparation for radioiodine therapy and follow-up. Our clinical practice differs in several aspects from the recent consensus guideline recommendations.

Annual variations of the plasmatic levels of glucose and amino acid and daily changes under different natural conditions of temperature and photoperiod in Gilthead Sea bream (Sparus aurata, L.).

Daily and annual changes in the plasmatic glucose and amino acid concentration have been determined in Sparus aurata L. Fish (average weight 330 g) were kept in cages under natural conditions of temperature and photoperiod and fed with a commercial diet. The months studied were chosen to establish whether there is any influence on the plasmatic glucose and amino acid concentration due to the change in temperature and photoperiod (equal photoperiod and different temperature, March and October; different photoperiod and equal temperature, May and November; and different photoperiod and temperature, June and January). To study the daily profile of glucose and amino acids concentrations, blood was extracted from six fish every 3 h during 24 h. Annual changes were determined as the average of the samples obtained during 1 day. Results show an annual rhythm with acrophase in June with a positive correlation with photoperiod for glucose and amino acids and with temperature only for amino acids. Daily profiles are rhythmical with a period of 24 h except in November with a period of 8 h for amino acids.

Serum and gene expression profile of tumor necrosis factor-alpha and interleukin-6 in hypertensive diabetic patients: effect of amlodipine administration.

Pro-inflammatory cytokines are critical factors in type 2 diabetes-associated atherosclerosis. We aim to analyze in hypertensive type 2 diabetic patients the serum concentrations and the mRNA expression levels in peripheral blood mononuclear cells (PBMC) of the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), as well as to evaluate the effect of amlodipine administration. Twenty-one hypertensive diabetic patients and 10 healthy non-diabetic controls were included in the study. Serum levels of cytokines were measured by chemiluminescent immunometric assay, and mRNA expression levels by RT-PCR. The mean serum concentrations of TNF-alpha and IL-6 in diabetic patients showed a 6.1-fold and 2.9-fold increase with respect to non-diabetic control subjects, respectively (p less than 0.0001). Likewise, there was a 3.3- and a 4-fold increase in the PBMC mRNA expression level of TNF-alpha and IL-6 (p less than 0.0001) in diabetic subjects. After amlodipine administration, a significant decrease (p less than 0.01) was observed in the serum TNF-alpha and IL-6 levels. In addition, pre-treatment mRNA expression of TNF-alpha and IL-6 also decreased, with a mean percent reduction of 26 percent (p less than0.01) and 25 percent (p less than 0.001), respectively. In conclusion, serum concentrations and PBMC mRNA expression levels of TNF-alpha and IL-6 are significantly elevated in hypertensive type 2 diabetic patients. Administration of amlodipine is associated with a significant reduction of the increased levels of these inflammatory parameters, both at the protein as well as at the transcriptional level. These modulatory effects of amlodipine on proinflammatory cytokine level and expression may be related to its suggested anti-atherosclerotic actions.

Clinical and pathological factors related to 18F-FDG-PET positivity in the diagnosis of recurrence and/or metastasis in patients with differentiated thyroid cancer.

BACKGROUND: Objectives were to analyze the relationship between a positive (18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) result and clinical and tumor factors in patients treated for differentiated thyroid cancer (DTC) and under suspicion of recurrence or metastasis, and to determine the diagnostic validity of PET in DTC patients with elevated serum thyroglobulin (Tg) and negative (131)I whole-body scan ((131)I-WBS). METHODS: We studied 50 DTC patients with elevated serum Tg and negative WBS treated with total thyroidectomy and (131)I ablation. Thyroxin treatment was withdrawn and patients were on iodine-free diet before WBS. Tg, anti-Tg antibodies, and thyroid-stimulating hormone (TSH) were determined. Patients with negative WBS and elevated Tg underwent PET study 1 week later. PET findings were verified by pathology findings or other imaging techniques [computed tomography (CT), magnetic resonance imaging (MRI), ultrasound (US)] and/or 12-month follow-up. The relationship between PET findings and tumor (histological type, size, multifocality, thyroid capsular invasion, lymph-node and/or metastatic involvement) and clinical (age at diagnosis, sex, Tg, accumulated iodine dose, and recurrence time) variables was analyzed. RESULTS: PET was positive in 32/39 patients with confirmed disease (82% sensitivity) and negative in 7/11 of disease-free cases (64% specificity), a positive predictive value (PPV) of 89%. Tumor size (P < 0.05) and thyroid capsular invasion (P < 0.05) were significantly associated with positive PET study. The relationship of PET findings with Tg levels and age at diagnosis was close to significance. CONCLUSION: (18)F-FDG-PET study offers a high sensitivity and positive predictive value (PPV) in patients with negative WBS and Tg positive. The use of FDG-PET is strongly recommended in DTC patients with large tumors, thyroid capsule invasion or poor-prognosis variants.

Outcome of treating advanced neuroendocrine tumours with radiolabelled somatostatin analogues.

OBJECTIVES: To evaluate the initial response and outcomes (quality of life and presence of side effects) in patients with advanced neuroendocrine tumours (NET) after treatment with radiolabelled somatostatin analogues: (90)Y-DOTATyr3- octreotide ((90)Y-DOTATOC) and (177)Lu-DOTA-Tyr3- octreotate ((177)Lu-DOTATATE). MATERIAL AND METHODS: The study included 5 patients with advanced NET referred to European centres for treatment with (90)Y-DOTATOC and (177)Lu-DOTATATE after lack of response to conventional treatment. The mean age was 45.6 years (29-68 years). Response to therapy was assessed according to: (1) RECIST criteria, as complete response, partial response, stable disease or disease progression, (2) post-treatment survival time and (3) quality of life, using the Karnofsky performance index. RESULTS: All patients survived for >20 months after treatment; mean survival time was 28 months. At the time of writing, three of the patients are alive after 20, 26 and 37 months. Partial response was observed in one patient, stable disease in three and disease progression in the fifth patient. A good-to-excellent post-treatment quality of life was observed in all patients. CONCLUSION: Therapy with radiolabelled somatostatin analogues showed promising results in patients with advanced NET, with a partial response or disease stabilisation in four of the five patients, who have enjoyed an extended survival period and an improved quality of life.

[Characteristics of the diabetic patients referred for the first time to the nephrologist]. / Características de los pacientes diabéticos referidos por primera vez a las consultas de atención especializada de Nefrología.

BACKGROUND: Diabetic nephropathy (DN) has become the main cause of end-stage renal disease. In our country, this problem is specially relevant in Canary Islands, where DN is the cause of renal failure in 39% of patients included in dialysis programs. The importance of this situation and the relevance of an adequate referral to the nephrologist, prompt us to study the characteristics of diabetic patients referrred to our outpatient clinic. SUBJECTS AND METHODS: One-hundred and fifty patients with diabetes consecutively referred to the outpatient nephrology clinic at the Hospital Universitario Nuestra Señora de Candelaria were included in the study. We analysed demographic and epidemiologic characteristics, therapeutic strategies, as well as serum and urine biochemical parameters. RESULTS: Ninety-eight percent of patients suffered from type 2 diabetes, and 90% were referred by the primary physician. Renal insufficiency and proteinuria were the main causes of referral (48% and 30.6%, respectively). Overweight or obesity were present in 82.6% of patients, 97% were hypertensive and 92.6% presented dyslipidemia. Medical history of cardiovascular disease was present 16% of patients. Two-thirds of patients had a creatinine clearance below 60 ml/min. One-third of patients did not receive therapy with blockers of the renin-angiotensin system, and only 37% were treated with statins. CONCLUSIONS: An elevated percentage of diabetic patients referred to nephrologist did not reach the recommended therapeutic goals. These findings prompt us to reflect on the therapeutic approach in these patients and the referral to the nephrologist.

Annual variations in the specific activity of fructose 1,6-bisphosphatase, alanine aminotransferase and pyruvate kinase in the Sparus aurata liver.

We determined the annual change in the intermediary metabolism of glucose through the variations of specific activity of fructose 1,6-bisphosphatase (FBPase), alanine aminotransferase (AAT) and pyruvate kinase (PK). Fish (average mass 330 g) were kept in cages under natural conditions of temperature and photoperiod and fed with a commercial diet. FBPase, AAT and PK increased their activity in June in different ways: AAT and PK increased V(max), and FBPase increased the velocity at subsaturating substrate concentrations, changing K(m). The reproduction period modified the annual tendency of changes in the enzyme activities in both parameters, K(m) and V(max), except for K(m) of PK which shows a circa-annual rhythm. No relation between the changes of enzymes activity and photoperiod or temperature has been found in this study, except for K(m) of AAT which presents a positive correlation with photoperiod and a negative correlation with temperature.

Feeding entrainment of locomotor activity rhythms, digestive enzymes and neuroendocrine factors in goldfish.

The existence of food anticipatory activity (FAA) in animals subjected to daily feeding schedules seems to be mediated by a feeding-entrainable oscillator (FEO). Such an FEO may help in anticipating meal time and so optimizing food acquisition and nutrient utilization. In this study we investigated the existence of FAA and whether digestive enzymes, plasma cortisol, hypothalamic NPY and gastrointestinal tract (GIT) and plasma melatonin were entrained by periodic feeding in goldfish. We observed that periodically fed goldfish showed FAA in locomotor activity as well as in amylase and NPY. Alkaline protease and GIT melatonin were higher after feeding, whereas plasma cortisol levels were reduced. Plasma melatonin remained unmodified before and after meal time. These results suggested that scheduled feeding entrained both behavioral and certain physiological patterns in goldfish, FAA being of adaptive value to anticipate a meal and prepare the digestive physiology of fish.

Study of the accumulation of tributyltin and triphenyltin compounds and their main metabolites in the sea bass, Dicentrachus labrax, under laboratory conditions.

Accumulation of two triorganotins, tributyltin (TBT) and triphenyltin (TPhT), has been studied by exposing the sea bass, Dicentrachus labrax, to different concentrations of both compounds, under controlled laboratory conditions. D. labrax juvenile fish were acclimatized in a laboratory and isolated to four groups. One group was used as control (first group), while the other three were exposed, during 28 days, in tanks with seawater containing simultaneously 2.5 microg/l TBT and 2.5 microg/l (second group), 5 microg/l TBT and 5 microg/l (third group) and 15 microg/l TBT and 15 microg/l (fourth group), respectively. The higher exposure dose caused mortality to all animals after 48 h. In the other two groups, quantitative analysis of TBT and TPhT was carried out, weekly, on the target organs (muscle and liver). Also, the main metabolites of TBT, monobutyltin (MBT) and dibutyltin (DBT), and TPhT, monophenyltin (MPhT) and diphenyltin (DPhT) were monitored. Gas chromatography (GC) coupled to mass spectrometry in tandem (MS/MS) mode was used for their identification. The results of analysis of TBT and TPhT showed that D. labrax accumulated the compounds from the first week, although the levels depended on medium concentration exposure. Liver was found to accumulate higher concentrations of TBT and TPhT than muscle.