The Duffy antigen receptor for chemokines (DARC or Fy glycoprotein) carries antigens that are important in blood transfusion and is the main receptor used by Plasmodium vivax to invade reticulocytes. Southeast Asian ovalocytosis (SAO) results from an alteration in RBC membrane protein band 3 and is thought to mitigate susceptibility to falciparum malaria. Expression of some RBC antigens is suppressed by SAO, and we hypothesized that SAO may also reduce Fy expression, potentiallyleading to reduced susceptibility to vivax malaria. Blood samples were collected from individuals living in the Madang Province of Papua New Guinea. Samples were assayed using a flow cytometry assay for expression of Fy on the surface of RBC and reticulocytes by measuring the attachment of a phycoerythrin-labeled Fy6 antibody. Reticulocytes were detected using thiazole orange. The presence of the SAO mutation was confirmed by PCR. There was a small (approximately 10%) but statistically significant (p=0.049, Mann-Whitney U test) increase in Fy expression on SAO RBC compared with RBC from individuals without this polymorphism: mean Fy expression (mean fluorescence intensity [MFI]) was 10.12 +/- 1.22 for SAO heterozygotes versus an MFI of 8.95 +/- 1.1 for individuals without SAO. For reticulocytes the MFI values were 27.61 +/- 19.12 for SAO heterozygotes and 16.47 +/- 3.81 for controls. SAO is associated with increased and not decreased Fy6 expression so that susceptibility to P. vivax infection is unlikely to be affected.

1. A study was conducted to evaluate the possible protective effect of a feed additive containing aluminosilicate and phytogenic substances against the adverse effects of aflatoxins in turkey poults. 2. Dietary treatments (6) were given to turkey poults from d 1 to d 42 of age. From d 1 to 21 the dietary treatments were as follows: 1, negative control, no aflatoxins or feed additive added; 2, feed additive control, 1 kg/t feed additive, no aflatoxins; 3, 250 ppb (microg/kg) aflatoxins, no feed additive; 4, 250 ppb aflatoxins + 1 kg/t feed additive; 5, 500 ppb aflatoxins, no feed additive; and 6, 500 ppb aflatoxins + 1 kg/t feed additive. From d 22 to 42, the dietary concentration of the feed additive was increased from 1 to 2 kg/t in all treatment groups receiving the feed additive (2, 4 and 6), while keeping constant the dietary concentrations of aflatoxins. 3. Aflatoxins at 250 ppb did not cause adverse effects on performance but affected certain toxicopathological parameters. At 500 ppb, adverse effects on performance and several toxicological parameters were observed. 4. Some of the adverse affects were partially or completely overcome by supplementation with the feed additive, including amelioration of the performance parameters, suppression of mortality and correction of the immunological alterations induced by the exposure to the aflatoxins.

To determine whether molecular parameters could be partly responsible for resistance or sensitivity to oxaliplatin (OX)-based chemotherapy used as first-line treatment in advanced colorectal cancer (CRC). We studied the usefulness of the excision repair cross-complementing 1 (ERCC1), xeroderma pigmentosum group D (XPD), XRCC1 and GSTP1 polymorphisms as predictors of clinical outcome in these patients. We treated 126 CRC patients with a first-line OX/5-fluorouracil chemotherapeutic regimen. Genetic polymorphisms were determined by real-time PCR on an ABI PRISM 7000, using DNA from peripheral blood. Clinical response (CR), progression-free survival (PFS) and overall survival (OS) were evaluated according to each genotype. In the univariate analysis for CR, ERCC1-118 and XPD 751 polymorphisms were significant (P=0.02 and P=0.05, respectively). After adjustment for the most relevant clinical variables, only ERCC1-118 retained significance (P=0.008). In the univariate analysis for PFS, ERCC1-118 and XPD 751 were significant (P=0.003 and P=0.009, respectively). In the multivariant analysis, only the XPD 751 was significant for PFS (P=0.02). Finally, ERCC1-118 and XPD 751 polymorphisms were significant in the univariate analysis for OS (P=0.006 and P=0.015, respectively). Both genetic variables remained significant in the multivariate Cox survival analysis (P=0.022 and P=0.03). Our data support the hypothesis that enhanced DNA repair diminishes the benefit of platinum-based treatments.British Journal of Cancer advance online publication, 16 September 2008; doi:10.1038/sj.bjc.6604671 www.bjcancer.com.

Almost all existing models for G-protein-coupled receptors (GPCRs) are based on the occurrence of monomers. Recent studies show that many GPCRs are dimers. Therefore for some receptors dimers and not monomers are the main species interacting with hormones/neurotransmitters/drugs. There are reasons for equivocal interpretations of the data fitting to receptor dimers assuming they are monomers. Fitting data using a dimer-based model gives not only the equilibrium dissociation constants for high and low affinity binding to receptor dimers but also a 'cooperativity index' that reflects the molecular communication between monomers within the dimer. The dimer cooperativity index (D(C)) is a valuable tool that enables to interpret and quantify, for instance, the effect of allosteric regulators. For different receptors heteromerization confers a specific functional property for the receptor heteromer that can be considered as a 'dimer fingerprint'. The occurrence of heteromers with different pharmacological and signalling properties opens a complete new field to search for novel drug targets useful to combat a variety of diseases and potentially with fewer side effects. Antagonists, which are quite common marketed drugs targeting GPCRs, display variable affinities when a given receptor is expressed with different heteromeric partners. This fact should be taken into account in the development of new drugs.British Journal of Pharmacology advance online publication, 26 November 2007; doi:10.1038/sj.bjp.0707571.

Introduction. The serotoninergic system seems to be implicated in characteristic symptoms of borderline personality disorder (BPD) such as affective instability, impulsivity or suicide. Some studies suggest an association between serotonin transporter gene (5-HTT) polymorphisms and some BPD symptoms. Short allele (S) of the 5-HTTLPR polymorphism in the promoter region has been shown to be associated with impulsivity, aggressive behavior, anxiety and neuroticism. Of the variable number of tandem repeat (VNTR) polymorphism in intron 2, BPD patients showed higher frequencies of the allele with the 10 repeats. The aim of this study was to determine the association between 5- HTTLPR and VNTR polymorphism of 5-HTT and personality traits in borderline personality disorder. Method. A total of 65 BPD patients diagnosed by means of semi-structured interviews SCID-II and DIB-R were included. Two common polymorphisms of 5-HTT were genotyped: the 5-HTTLPR in the promoter region and VNTR in intron 2. Personality traits were assessed by the Zuckerman-Kuhlman Personality Questionnaire (ZKPQ). Results. Patients with L allele (L/S or L/L) in the 5-HTTLPR polymorphism showed lower scores on the subscale of liking parties and friends. Patients with the allele with 10 repeat of the VNTR polymorphism, showed lower scores in impulsivity, sensation seeking and in the subscale liking of parties and friends. Conclusions. The results suggest a significant association between the 5-HTT gene and some personality traits in BPD. This gene may play a role in the etiology of borderline personality disorder. Key words: Borderline personality disorder. Genetics. Serotonin transporter gene. Zuckerman-Kuhlman Personality Questionnaire (ZKPQ). Actas Esp Psiquiatr 2007;35(6):382-386.

Introduction. The serotoninergic system seems to be implicated in characteristic symptoms of borderline personality disorder (BPD) such as affective instability, impulsivity or suicide. Some studies suggest an association between serotonin transporter gene (5-HTT) polymorphisms and some BPD symptoms. Short allele (S) of the 5-HTTLPR polymorphism in the promoter region has been shown to be associated with impulsivity, aggressive behavior, anxiety and neuroticism. Of the variable number of tandem repeat (VNTR) polymorphism in intron 2, BPD patients showed higher frequencies of the allele with the 10 repeats. The aim of this study was to determine the association between 5-HTTLPR and VNTR polymorphism of 5-HTT and personality traits in borderline personality disorder. Method. A total of 65 BPD patients diagnosed by means of semi-structured interviews SCID-II and DIB-R were included. Two common polymorphisms of 5-HTT were genotyped: the 5-HTTLPR in the promoter region and VNTR in intron 2. Personality traits were assessed by the Zuckerman-Kuhlman Personality Questionnaire (ZKPQ). Results. Patients with L allele (L/S or L/L) in the 5-HTTLPR polymorphism showed lower scores on the subscale of liking parties and friends. Patients with the allele with 10 repeat of the VNTR polymorphism, showed lower scores in impulsivity, sensation seeking and in the subscale liking of parties and friends. Conclusions. The results suggest a significant association between the 5-HTT gene and some personality traits in BPD. This gene may play a role in the etiology of borderline personality disorder. Key words: Borderline personality disorder. Genetics. Serotonin transporter gene. Zuckerman-Kuhlman Personality Questionnaire (ZKPQ). Actas Esp Psiquiatr 2005;33(0):00-00.

Since 1990 it has been known that dimers are the basic functional form of nearly all G-protein-coupled receptors (GPCRs) and that homo- and heterodimerization may play a key role in correct receptor maturation and trafficking to the plasma membrane. Nevertheless, homo- and heterodimerization of GPCR has become a matter of debate especially in the search for the precise physiological meaning of this phenomenon. This article focuses on how heterodimerization of adenosine A(1) and A(2A) receptors, which are coupled to apparently opposite signalling pathways, allows adenosine to exert a fine-tuning modulation of striatal glutamatergic neurotransmission, providing a switch mechanism by which low and high concentrations of adenosine inhibit and stimulate, respectively, glutamate release.

OBJECTIVES: Hyperhomocysteinaemia is a well-known risk factor for venous thromboembolic disease (VTD). However, it is not clear whether homocysteine (Hc) itself or a related metabolite or a cofactor is primarily responsible for VTD. We carried out a case-control study to investigate whether vitamin concentrations that are involved in the Hc metabolism are associated or not with an elevated risk of VTD. DESIGN: Case-control study. METHODS: We measured serum vitamin B12, folate, creatinine and albumin concentrations and plasma Hc concentrations in 101 consecutive patients with VTD, diagnosed by image tests and 101 control subjects, matched for age and sex. RESULTS: Serum vitamin B12 concentrations were significantly lower in VTD patients than in the control subjects. There were no differences in plasma Hc or serum folate concentrations between the groups. Among the male subgroup aged more than 70 years, serum vitamin B12 concentrations were significantly lower (240.88 +/- 103.07 vs. 421.20 +/- 314.31 pmol L(-1); P = 0.03) and plasma Hc concentrations were significantly higher (13.1 +/- 4.18 vs. 10.56 +/- 3.06 micromol L(-1); P =0.04) in VTD patients than in the control group. On multivariate analysis, in patients aged more than 70 years, serum vitamin B12 concentrations were independently associated with VTD. Compared with the highest quartile of vitamin B12 (>512.6 pmol L(-1)) the odds ratio (OR) for VTD in the lowest quartile (<230.9 pmol L(-1)) was 3.8 (95% CI 1.44-10.18; P = 0.01). In the VTD group, lowest vitamin B12 concentrations (percentile 10 <152.8 pmol L(-1)) were associated with the factor V Leiden mutation (OR = 6.07, 95% CI 0.93-38.55; P = 0.04). CONCLUSIONS: Measuring vitamin B12 concentrations in elderly males may help in identifying people at risk of venous thromboembolism in our population.

Information on the ontogeny of the fish immune system is largely restricted to a few species of teleosts (e.g., rainbow trout, catfish, zebrafish, sea bass) and has previously focused on morphological features. However, basic questions including the identification of the first lympho-hematopoietic sites, the origin of T- and B-lymphocytes and the acquisition of full immunological capacities remain to be resolved. We review these three main topics with special emphasis on recent results obtained from the zebrafish, a new experimental model particularly suitable for study of the ontogeny of the immune system because of its rapid development and easy manipulation. This species also provides an easy way of creating mutations that can be detected by various types of screens. In some teleosts (i.e., angelfish) the first blood cells are formed in the yolk sac. In others, such as zebrafish, the first hematopoietic site is an intraembryonic locus, the intermediate cell mass (ICM), whereas in both killifish and rainbow trout the first blood cells appear for a short time in the yolk sac but later the ICM becomes the main hematopoietic area. Erythrocytes and macrophages are the first blood cells to be identified in zebrafish embryos. They occur in the ICM, the duct of Cuvier and the peripheral circulation. Between 24 and 30 hour post-fertilization (hpf) at a temperature of 28 degrees C a few myeloblasts and myelocytes appear between the yolk sac and the body walls, and the ventral region of the tail of 1-2 day-old zebrafish also contains developing blood cells. The thymus, kidney and spleen are the major lymphoid organs of teleosts. The thymus is the first organ to become lymphoid, although earlier the kidney can contain hematopoietic precursors but not lymphocytes. In freshwater, but not in marine, teleosts the spleen is the last organ to acquire that condition. We and other authors have demonstrated an early expression of Rag-1 in the zebrafish thymus that correlates well with the morphological identification of lymphoid cells. On the other hand, the origins and time of appearance of B lymphocytes in teleosts are a matter of discussion and recent results are summarized here. The functioning rather than the mere morphological evidence of lymphocytes determines when the full immunocompetence in fish is attained. Information on the histogenesis of fish lymphoid organs can also be obtained by analysing zebrafish mutants with defects in the development of immune progenitors and/or in the maturation of non-lymphoid stromal elements of the lymphoid organs. The main characteristics of some of these mutants will also be described.

A plot study was conducted to assess changes in Co phytoavailability for a tomato cultivar grown on an agricultural soil (a Calcic Petrocalcid) amended with sewage sludge, under controlled conditions in South-eastern Spain. The experiment consisted of three main treatment blocks:(A) without organic fertilisation,(B) with addition of 60 tha(-1) and (C) 120 tha(-1) of sewage sludge. For each block (A, B, and C), four levels of Co (0, 50, 100 and 200 mgkg(-1)) were added, as CoCl2. Diethylenetriaminepentaacetic acid, DTPA (0.005 M plus triethanolamine), ammonium acetate (1 N at pH 7), and water extractable fractions of the soils were analysed for all the plots. The time dependent Co accumulation in different parts (roots, stems, leaves, and fruits) of the tomato plants was studied. Soil Co seemed to be mainly in non-available forms, according to the low concentrations found in the water and ammonium acetate extracts, compared to DTPA. The gradient of Co accumulation in tomato plants was root > leaf > stem + branches > fruit, with a concentration in the edible parts ranging between 4 and 25 mg kg(-1). The organic amendment enhanced the plant extraction of Co, this effect being more significant with time. Plant extraction efficiency decreased with increasing Co concentration in the soils. Co in fruit showed the best correlation with all the Co extraction pools in the soil.

To the Editor: The Hellenic Journal of Nuclear Medicine has published a case report about liver hemangioma diagnosed with a mismatch: decreased focal uptake of technetium-99m ((99m)Tc) sulphur colloid while the uptake of (99m)Tc-red blood cells (RBC) on the delayed images at the same liver area was normal or slightly increased. Our case differs from the above in its clinical presentation and the diagnostic means. A 40 years old woman with papillary thyroid carcinoma (PTC) was referred to our clinic for iodine-131 ((131)I) ablation treatment. Focal liver uptake of the whole body (WB) post ablation scan was shown due to cavernous liver hemangioma, mimicking metastases. Whole-body scans obtained 3 and 8 days after administration of 3,700MBq (131)I showed focal increased uptake in the left lobe of the liver and increased uptake in the thyroid bed. A contrast enhanced computerised tomography (CECT) scan performed for morphological evaluation revealed a cavernous hemangioma 6x5cm, in the left lateral lobe of the liver, at the same location as the increased (131)I uptake on the (131)I scan. There was no other lesion in the liver, the lung, the thorax or the abdomen on the CECT scan. Our patient, had no clinical signs related to liver hemangioma. Liver scan false positive findings in these (131)I scans result from both physiological and non-physiological uptake of (131)I in benign and pathological conditions. Single photon emission tomography (SPET) images of the liver using (99m)Tc-RBC revealed increased uptake in the left lateral lobe compatible with haemangioma. The post-ablation (131)I scan is a reliable method to establish the presence of residual functioning thyroid tissue or metastatic disease in patients with PTC. The liver is seen in these scans as diffuse, homogeneous hepatic uptake due to the incorporation of (131)I into thyroid hormones in part, degraded in the liver by deiodination and conjugation. Diffuse liver uptake generally indicates functioning thyroid remnant or metastasis. Focal increased liver uptake is always a pathologic finding. Functioining liver metastases from PTC are uncommon and there are only isolated case reports of liver metastases in the literature. Focal (131)I liver uptake due to benign disorders such as simple hepatic cyst, hepatic hydatid cyst, hepatic abscess or intrahepatic duct dilatation have been reported. Cavernous liver hemangioma is the most common benign tumor of the liver, with an incidence in autopsy series ranging from 0.4% to 7.3%. There is only one case in the literature concerning (131)I uptake by cavernous liver hemangioma and the authors proposed two possible mechanisms for the visualization of the hemangioma with (131)I: intravascular blood pooling and transcapillary escape of iodine with interstitial retention. Nuclear medicine physicians may keep in mind asymptomatic cavernous liver hemangioma when focal increased liver uptake is seen on the(131)I WB post ablation scan in patients with PTC.

Differentiated thyroid cancer metastasizes predominantly to the lymph nodes, lungs, and bones and rarely to the brain, liver, and skin. We present the case of a 56-year-old woman with papillary thyroid cancer with cutaneous metastases, situated in the left upper abdominal region, precisely above the area of the stomach. The location of the metastasis could lead to misinterpretation of iodine uptake in a metastasis as being physiological iodine excretion in the stomach mucosa. Results of I-131 whole-body scintigraphy could be properly interpreted only with some knowledge of the cutaneous metastasis. This is essential to avoid false-positive or false-negative scans.

The I-131 whole-body scan is a useful test to investigate the presence of metastatic disease of thyroid cancer after thyroidectomy. A 53-year-old woman received I-131 4 months after total thyroidectomy for papillary thyroid carcinoma for postsurgical ablation of the residual tumor cells. Whole-body scan demonstrated focal uptake of I-131 in the right iliac fossa that persisted 2 days later even after administration of laxatives. Computed tomography of this area showed only focal bowel scar presumably resulting from a complicated appendectomy 31 years ago. Intestinal adhesions accumulate I-131 and give false-positive activity on whole-body I-131 scans.

The follow-up of Differentiated Thyroid Cancer conventionally includes serum thyroglobulin and periodic Whole Body Scans. The uptake of 131-I in normal and pathological tissues different from metastatic thyroid cancer sites is a cause of false-positive scans. Among them, mediastinal uptake caused by thymic hyperplasia can be observed. The aim of the present study was to review a series of 573 patients with differentiated thyroid cancer treated with 131-I after surgery between 1992 and 2003 looking above all for those with mediastinal images resembling thymus. This evaluation is presented together with some hypotheses on the relationships between thymus and thyroid. Moreover, some considerations are made on the differential diagnosis between thymus and mediastinal tumour thyroid residues.

Unusual features of iodine-131 uptake during thyroid cancer scintigraphy may lead to a false-positive diagnosis of residual or recurrent malignancy and associated metastasis. Radiographic or cross-sectional imaging correlation should help to differentiate truly functioning thyroid lesions from physiological or artifactual tracer accumulation. The authors present a case of iodine-131 mediastinal uptake from an esophageal epiphrenic diverticulum.

Whole body iodine-131 scan is a well-established imaging method for the detection of metastatic or residual tumor sites in patients with well-differentiated thyroid cancer. Many false-positive iodine-131 scan findings mimicking metastatic thyroid cancer have long been reported. The authors describe a false positive uptake in normal gallbladder on post-ablative iodine-131 scan in a patient with papillary thyroid cancer. This finding should be considered to be another possible false-positive finding on iodine-131 whole body scan.

A woman with papillary thyroid carcinoma treated with surgery and postoperative 131I returned 4 y later for a whole-body survey. The imaging results initially suggested disease recurrence but were later found to be false positive and due to 131I uptake in a necklace that had been contaminated by the patient's saliva. This case stresses the importance of having the patient remove all jewelry before undergoing a radioiodine survey.