Praziquantel efficacy and long-term appraisal of schistosomiasis control in Pemba Island.

OBJECTIVE: To determine whether praziquantel (PZQ) has retained its efficacy against Schistosoma haematobium on Pemba Island after 20 years of mass administration--albeit discontinuous--and to analyse retrospectively the performance of schistosomiasis control programmes. METHODS: A sample of Pemba schoolchildren was examined before and after PZQ treatment by urine filtration, macro- and micro-haematuria and viability of excreted eggs. RESULTS: Although 5% of treated children continued to pass some eggs in the urine up to the seventh week after PZQ administration, none of these eggs was viable, indicating an effective schistosomicidal activity followed by a slow release of dead eggs from host tissues. CONCLUSION: No signs of PZQ resistance could be detected in the population under study. An overall retrospective analysis of schistosomiasis control activities in Pemba Island revealed that mass drug administration is clearly effective in reducing infection prevalence, but soon after interruption of drug distribution prevalence returns rapidly to pre-intervention levels.

Tricyclic structures in medicinal chemistry: an overview of their recent uses in non-CNS pathologies.

Tricyclic compounds are sometimes considered as synonima of drugs healing central nervous system pathologies, although there are some well known examples of tricyclic derivatives marketed for different indications, such as antihistamines, antivirals and antiulceratives. Following the insertion of tricyclic structures in the "privileged structures" pool, several compounds bearing a central 7-membered ring and two aryl rings at its sides have been reported, and some of them have been progressed to advanced clinical trials. An overview of tricyclic derivatives reported in the literature since 1995, that are investigated for indications not directly related to central nervous system affections, shows the potential of these structures in a broad range of therapeutical indications, going from antiviral and anticancer compounds to the therapy of cardiovascular diseases. Very recent examples confirm the usefulness of tricyclic structures for the modern medicinal chemists.

Anisakis spp. larvae in different kinds of ready to eat products made of anchovies (Engraulis encrasicolus) sold in Italian supermarkets.

In this study the occurrence of visible anisakid larvae in semi-preserved anchovy products sold on the Italian market was investigated. Totally, 107 ready to eat products (33 salted-ripened, 49 in oil and 25 marinated) were sampled. Each sample was digested, then the digested material was observed under natural and UV light. Parasites were counted, collected and microscopically identified to genus level. A representative subset was molecularly identified using the cox2 gene. At least one visible Anisakis sp. larva was found in 54.2% of the total 107 products analysed and totally 1283 dead larvae were collected. Anisakis sp. larvae were found in all the 33 salted products and 1139 (88.8%) larvae were collected, with a range of 1-105 parasites per product. Larval density per gram was 0.13. Anisakis sp. larvae were found in 49.0% of the products in oil and 143 (11.1%) larvae were isolated, with a range of 0-28 and a density of 0.03. Only 1 larva was found in the 25 marinated products (4.0%, density 0.00). A highly significant difference between all the product categories in respect of number of larvae per product, frequency of products contaminated by at least one larva and larval density per gram was found. Within the subset of larvae molecularly analysed (n=122), 92 (75.4%) were identified as A. pegreffii and 30 (24.6%) as A. simplex. This study showed that semi-preserved anchovy products heavily contaminated with Anisakis spp. larvae reach the market. Beyond the negligible risk for anisakidosis, the presence of dead visible parasites may cause immediate rejection in consumers. In addition, the potential risk related to allergic reactions in sensitized individuals needs to be further assessed. In order to avoid commercialization of obviously contaminated products, fresh anchovies' batches intended for the production of such products should be accurately selected by the processing industry applying inspection methods.

Visceral larvae as a predictive index of the overall level of fish batch infection in European anchovies (Engraulis encrasicolus): A rapid procedure for Food Business Operators to assess marketability.

The European anchovy (Engraulis encrasicolus), one of the most important pelagic fish resources in the Mediterranean Sea, is frequently infected by anisakid larvae. Food Business Operators (FBOs) should use appropriate sampling plans and analytical methods to avoid commercialization of massively infected batches and reduce the risk of transmission of viable zoonotic larvae. In this study, performed at FishLab (Department of Veterinary Sciences of the University of Pisa) during 2016, an official sampling plan was associated with a digestion protocol for the inspection of anchovies. Considering that anisakid larvae are usually located in the fish visceral cavity and in the adjacent muscles (VM), this part was analyzed. In particular, we assessed the reliability of the digestion of a subsample of 150g (±30g) of VM, randomly collected from 29 specimens, in estimating the marketability of the anchovies' batch. Fifty-seven samples of 29 anchovies were collected. Each anchovy was sectioned to separate VM. All the subsamples were digested, and visible larvae counted. A high correlation between the number of larvae in VM regions and in the total batch was observed, indicating a very significant contribution of the VM region on total number of parasites. The Mean Abundance (MA) was used to assess the batch marketability according to a threshold calculated on the basis of the maximum number of nematodes tolerated per sample. Considering that the MA can be calculated only when the number of examined specimens is known, the number of visible Larvae per gram of tissue (LpG) was calculated on 150g (±30g) of VM subsamples. A LpG marketability threshold was calculated dividing the maximum number of tolerated nematodes by the average weight of a sample of 29 anchovies calculated considering data available in literature. To evaluate the diagnostic performance of the LpG threshold, the marketability of 57 batches assessed on the basis of the MA threshold was assumed as the gold standard. The proposed LpG showed very high Specificity and Sensitivity. These findings suggest that the analysis of VM is representative of the overall infestation of the batch, both when considering the absolute number of parasites and the LpG, and may represent a valid alternative to the whole anchovy digestion. In particular, the use of an automated digestive method, coupled with the aforesaid sampling plan, could allow the procedure to be used by FBOs in operational conditions.

Microvessel density and distribution in ductal carcinoma in situ of the breast.

BACKGROUND: Prior studies have suggested that microvessel density is an important prognostic factor in invasive breast cancer. However, the extent and distribution of microvessels in association with ductal carcinoma in situ (DCIS) have not been well defined. PURPOSE: Our goal was to determine the density and distribution of stromal microvessels in DCIS and to investigate the relationships among microvessel density, histopathologic features, HER2/neu oncogene expression, and tumor proliferation rate. METHODS: Of 61 consecutive cases of DCIS identified from hospital pathology reports, 55 cases were evaluated. Breast biopsy specimens had been preserved in paraffin blocks for each DCIS case. Histologic sections of formalin-fixed, paraffin-embedded tissue were stained with hematoxylin-eosin and immunostained for factor VIII-related antigen, the HER2/neu oncoprotein, and the proliferative-associated antigen detected by the Ki-S1 antibody. Factor VIII-stained sections from each case were independently examined by two pathologists and overall tumor-associated stromal microvessel density was scored semiquantitatively on a 1+ to 3+ scale by each observer. Quantitative microvessel counts of DCIS-associated stromal microvessel density were performed. The presence or absence of a cuff of microvessels in immediate apposition to the basement membrane of involved spaces was also evaluated. RESULTS: A variable number of microvessels were found to be present in a diffuse pattern surrounding spaces involved with DCIS. Semiquantitative microvessel scores were 2+ in the majority of cases (53%); 22% of cases were 1+, and 25% were 3+. Quantitative microvessel counts ranged from 17 to 80 vessels per 100x field (0.45 mm2), with a mean +/- SD of 42.9 +/- 16.6. Comedo-type lesions were significantly (P = .004) more often associated with 3+ microvessel density than non-comedo-type lesions by semiquantitative assessment. As determined by both semiquantitative and quantitative analysis, respectively, the presence of prominent microvessel density was significantly associated with marked stromal desmoplasia (P = .05 and P = .04), HER2/neu expression (P = .03 and P = .0002), and high Ki-S1 proliferation index (P = .05 and P = .01). Vascular cuffing around involved spaces was identified in 21 of the 55 cases (38%) and was not significantly associated with histologic features, HER2/neu expression, or Ki-S1 proliferation index. CONCLUSIONS: DCIS of the breast is characterized by two patterns of stromal microvessels. The first pattern is a diffuse increase in stromal microvessels surrounding involved spaces. This pattern is particularly prominent in comedo-type lesions with marked stromal desmoplasia. The second pattern is microvessel cuffing of involved spaces that is present in only a minority of cases and appears unrelated to histologic features evaluated, including DCIS subtype.

Association of angiogenesis in lymph node metastases with outcome of breast cancer.

BACKGROUND: Microvessel density (MVD) is a measure of the extent of new blood vessel growth or angiogenesis, which is required for tumor progression. Increased MVD in primary breast cancers appears to adversely affect disease-free survival and overall survival in patients with breast cancer. However, the clinical implications of angiogenesis in breast cancer metastases have not been well studied. The purpose of this study was to compare intratumoral MVD in primary breast cancer tissues with MVD in axillary lymph node metastases and to evaluate the relationships among primary- and metastatic-tumor MVD, disease-free survival, and overall survival in patients with lymph node-positive, stage II breast cancer who were treated with adjuvant chemotherapy in Cancer and Leukemia Group B Protocol 8082. METHODS: Immunostaining for factor VIII-related antigen was performed on tissue sections from 47 primary tumors and 91 axillary lymph nodes containing metastases from 110 patients with lymph node-positive breast cancer. Sections were examined for the presence or absence of focal areas of relatively intense neovascularization (vascular hot spots), and a quantitative assessment of intratumoral MVD was performed. RESULTS: The presence of vascular hot spots in axillary lymph node metastases, but not primary breast cancers, was associated with statistically significantly decreased disease-free survival (P =.006) and overall survival (P =.004) by univariate analysis. Similarly, increased MVD in metastases, but not in primary tumors, was statistically significantly associated with diminished overall survival in these patients (P =.02). In multivariate analysis, the number of positive axillary lymph nodes and the presence of vascular hot spots in axillary lymph node metastases predicted decreased disease-free survival (P =.0001 and.02, respectively) and overall survival (P =.0001 and.007, respectively). All P values were two-sided. CONCLUSION: This pilot study suggests that assessing neovascularization in axillary lymph node metastases may provide clinically useful information regarding survival in patients with primary breast cancer.

Vascular permeability factor (vascular endothelial growth factor) expression and angiogenesis in cervical neoplasia.

BACKGROUND: Angiogenesis is a critical factor in the progression of solid tumors, including cervical cancers. The mechanisms responsible for angiogenesis in cervical neoplasia, however, are not well defined. PURPOSE: Our goal was to determine the relationship between angiogenesis and the expression of the angiogenic cytokine vascular permeability factor (VPF), also known as vascular endothelial growth factor, and its receptors in cervical neoplasia. METHODS: Sixty-six cervical biopsy specimens were evaluated; among these, 16 samples were designated as benign, 17 as low-grade squamous intraepithelial lesions, 18 as high-grade squamous intraepithelial lesions, and 15 as invasive squamous cell carcinomas. Histologic sections immunostained for factor VIII-related antigen were evaluated quantitatively for microvessel density and for the presence of epithelial-stromal vascular cuffing. Sections were also evaluated for VPF messenger RNA (mRNA) expression by in situ hybridization. RESULTS: VPF mRNA expression, epithelial-stromal vascular cuffing, and microvessel density counts were significantly increased in invasive carcinoma and in high-grade intraepithelial lesions as compared with low-grade intraepithelial lesions and benign squamous epithelium. Vascular cuffing and increased microvessel density counts were also significantly associated with increased VPF mRNA expression. CONCLUSIONS: These observations suggest that VPF is an important angiogenic factor in cervical neoplasia.

Biochemical survey on episodic localized darkening in turkey deboned thigh meat packaged in modified atmosphere.

The color of food, especially meat and meat products, is a parameter that strongly influences consumer choice. In Italy, repeated cases of darkening in deboned thigh meat of male turkeys packaged in modified atmosphere (MAP; 80% 02, 20% CO2) have been reported. The pH, lipid oxidation (TBARS), heme proteins, and iron content were investigated in MAP samples of turkey males, females, and in oxygen-permeable film-packaged males. Furthermore, the absorbance spectrum (400 to 700 nm) of the meat extracts was analyzed to better delineate the evolution and characteristics of the darkening process. Results showed that darkening occurred only in males with higher content of total iron, independently of the content of heme proteins, which differs only between males and females. Furthermore, pH was higher in muscles taken as controls, with respect to muscles involved in the darkening, as well as in females. Finally, TBARS values were found to be higher in darkened regions than in not darkened ones, as well as in MAP samples with respect to oxygen-permeable film-packaged samples. These findings suggest that darkening occurrence might depend on kind of muscle, sex, and individual characteristics of the animals raised under the same breeding conditions.

Vasculopatía Livedoide, la punta del témpano: a propósito de un caso / Livedoid vasculopathy, the tip of the iceberg: a case report

Resumen La vasculopatía livedoide (VL), es una enfermedad vascular oclusiva que afecta la microvasculatura, se caracteriza por ser recurrente y no inflamatoria. Su incidencia es de 1/100.000 casos por habitantes, afectando en su mayoría a mujeres de edad media. Su patogenia se desconoce, pero se destaca el componente trombótico de la misma, causado por un estado de hipercoagulabilidad, que conduce a la oclusión vascular, debiendo distinguirse una forma primaria y una secundaria.Clínicamente se observan úlceras dolorosas a nivel maleolar que evolucionan progresivamente a una cicatrización atrófica, blanquecina nacarada y estrellada característica.Presentamos un caso clínico en un varón con múltiples comorbilidades y difícil tratamiento, el cual requirió un trabajo multidisciplinario.

Abstract Livedoid vascular disease (VL), is an occlusive vascular disease that affects the microvasculature, is characterized by being recurrent and non-inflammatory. Its incidence is 1 / 100,000 cases per inhabitant, affecting mostly middle-aged women. Its pathogenesis is unknown, but its thrombotic component stands out, caused by a state of hypercoagulability, which leads to vascular occlusion, and a primary and secondary form must be distinguished. Clinically, painful ulcers are observed at the malleolar level, progressing progressively to characteristic atrophic, pearly whitish and starry healing. We present a clinical case in a male with multiple comorbidities and difficult management, which required multidisciplinary work.

Vascular stroma formation in carcinoma in situ, invasive carcinoma, and metastatic carcinoma of the breast.

The generation of vascular stroma is essential for solid tumor growth and involves stimulatory and inhibiting factors as well as stromal components that regulate functions such as cellular adhesion, migration, and gene expression. In an effort to obtain a more integrated understanding of vascular stroma formation in breast carcinoma, we examined expression of the angiogenic factor vascular permeability factor (VPF)/vascular endothelial growth factor (VEGF); the VPF/VEGF receptors flt-1 and KDR; thrombospondin-1, which has been reported to inhibit angiogenesis; and the stromal components collagen type I, total fibronectin, ED-A+ fibronectin, versican, and decorin by mRNA in situ hybridization on frozen sections of 113 blocks of breast tissue from 68 patients including 28 sections of breast tissue without malignancy, 18 with in situ carcinomas, 56 with invasive carcinomas, and 8 with metastatic carcinomas. A characteristic expression profile emerged that was remarkably similar in invasive carcinoma, carcinoma in situ, and metastatic carcinoma, with the following characteristics: strong tumor cell expression of VPF/VEGF; strong endothelial cell expression of VPF/VEGF receptors; strong expression of thrombospondin-1 by stromal cells and occasionally by tumor cells; and strong stromal cell expression of collagen type I, total fibronectin, ED-A+ fibronectin, versican, and decorin. The formation of vascular stroma preceded invasion, raising the possibility that tumor cells invade not into normal breast stroma but rather into a richly vascular stroma that they have induced. Similarly, tumor cells at sites of metastasis appear to induce the vascular stroma in which they grow. We conclude that a distinct pattern of mRNA expression characterizes the generation of vascular stroma in breast cancer and that the formation of vascular stroma may play a role not only in growth of the primary tumor but also in invasion and metastasis.

[Perceptive and semantic selection difficulties and cognitive aging]. / Difficulté de sélection perceptive et sémantique liée au vieillissement cognitif.

This work took place within tipper's negative priming paradigm. In a study with two age groups (young and older adults), Connelly and Hasher have measured the identity negative priming, the location negative priming and the "identity and location" negative priming. They used a simple material (letters). For these authors, the young people showed the negative priming effect in all the conditions, but the older people showed this effect only in location and in "identity and location" conditions, but there was no effect in identity condition. Hence, there is a dissociation between identity and location in the older adults group. Our work replicated the procedure of Connelly and Hasher using material presenting semantic (words) and perceptive selection difficulties. Our results were not consistent with the results of the authors. For the two age groups, the "location" and "identity and location" conditions were computed statistically faster than the "identity" condition, and there was no difference in the reaction times between the "location" and "identity and location" conditions. In the young adults group, even if an identity negative priming was obtained, there was no effect in the "location" and "identity and location" conditions (in comparison with a control condition). This led us to conclude is the existence of a dissociation between identity and location for the young adults. In the older adults group, we obtained positive priming in the "identity and location" condition, and no effect in the other conditions. Moreover, the reaction times in the "location" and "identity and location" conditions were faster than in the identity condition. We think about a dissociation between identity and location in the older group. Our data led us to conclude in the existence of a dissociation between identity and location, not only for the older adults, but also for the young adults. Our conclusion agrees with the explanations given by the authors regarding the neurological system; with the existence of two neuronal pathways, one for the identity and the other for the location. We explain the negative priming effect obtained in the young adults group through controlled inhibition processes, and we explain the positive priming obtained in the older adults group through automatic recuperation processes.

[Paraneoplastic dermatomyositis related to breast cancer: rare clinical association in two patients]. / Dermatomiositis paraneoplásica relacionada a cáncer de mama: asociación clínica en dos pacientes.

Paraneoplastic dermatomyositis is an inflammatory disease of the connective tissue that is caused by inmmunologic events in the presence of malignant tumors. It is more likely to happen in middle aged women and is related to ovarian, pancreatic, stomach and colon cancer and non Hogdkin lymphoma. We present two cases of dermatomyositis, with amyopathic origin associated to breast cancer. The first case occurs as the neoplasia evolves and the second one as an initial manifestation that leads to the search and subsequent diagnosis of cancer.

[Subacute diseminated histoplasmosis in HIV patients]. / Histoplasmosis diseminada subaguda en pacientes VIH.

Histoplasmosis is a cosmopolitan mycosis caused by Histoplasma capsulatum. It is endemic of Río de la Plata's riverbed and in immunocompromised patients may be deadly. We present two patients with Human Immunodeficiency Virus diagnosed with subacute disseminated histoplasmosis, which is a marker of Acquired Human Immunodeficiency Syndrome. This situation increases the morbimortality, thus forcing clinicians to diagnose and treat rapidly in order to avoid fatal outcomes.

La histoplasmosis es una micosis cosmopolita causada por el Histoplasmacapsulatum. Es un hongo endémico de la cuenca del Río de La Plata que si afecta a inmunosuprimidos puede ser mortal. Presentamos dos pacientes con Virus de Inmunodeficiencia Humana con diagnóstico de histoplasmosis diseminada subaguda. Esta situación los cataloga en estadío de Síndrome de Inmunodeficiencia Adquirida y requiere pronta acción médica para evitar complicaciones.

Red wine mitigates the postprandial increase of LDL susceptibility to oxidation.

The aim of the present study was to verify the extent of oxidative stress induced by a meal at plasma and LDL level, and to investigate the capacity of red wine to counteract this action. In two different sessions, six healthy men ate the same test meal consisting of "Milanese" meat and fried potatoes. The meal was taken either with 400 ml red wine or with an isocaloric hydroalcoholic solution. Oxidative stress at plasma level was estimated through the measure of ascorbic acid, alpha-tocopherol, protein SH groups, uric acid, and antioxidant capacity, measured before and 1 and 3 h after the meal. The change in the resistance of LDL to oxidative modification was taken as an index of exposure to pro-oxidants. The susceptibility to Cu(II)-catalyzed oxidation of baseline and postprandial LDL was measured as conjugated dienes formation, tryptophan residues, and relative electrophoretic mobility. The experimental meal taken with wine provoked a significant increase in the total plasma antioxidant capacity and in the plasma concentration of alpha-tocopherol and SH groups. Postprandial LDL was more susceptible to metal-catalyzed oxidation than the homologous baseline LDL after the ethanol meal. On the contrary, postprandial LDL obtained after the wine meal was as resistant or more resistant to lipid peroxidation than fasting LDL.

Vascular permeability factor/vascular endothelial growth factor and vascular stroma formation in neoplasia. Insights from in situ hybridization studies.

The formation of vascular stroma plays an important role in the pathophysiology of malignancy. We describe the use of in situ hybridization in our laboratory as a tool to study the role of vascular permeability factor/vascular endothelial growth factor in the angiogenesis associated with malignancy.

Expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in breast cancer.

Solid tumors must induce a vascular stroma to grow beyond a minimal size, and the intensity of the angiogenic response has been correlated with prognosis in breast cancer patients. Vascular permeability factor (VPF), also known as vascular endothelial growth factor (VEGF), is a secreted protein that has been implicated in tumor-associated angiogenesis. Vascular permeability factor directly stimulates endothelial cell growth and also increases microvascular permeability, leading to the extravasation of plasma proteins, which alter the extracellular matrix in a manner that promotes angiogenesis. To determine whether VPF has a role in breast cancer, we used in situ hybridization to study VPF mRNA expression in normal breast tissue (13 specimens), comedo-type ductal carcinoma in situ (DCIS) (four specimens), infiltrating ductal carcinoma (12 specimens), infiltrating lobular carcinoma (two specimens), metastatic ductal carcinoma (three specimens) and metastatic lobular carcinoma (one specimen). Vascular permeability factor mRNA was expressed at a low level by normal duct epithelium but was expressed at high levels in tumor cells in all cases of comedo-type DCIS, infiltrating ductal carcinoma, and metastatic ductal carcinoma. In contrast, VPF mRNA was not expressed at high levels in infiltrating lobular carcinoma. We also used in situ hybridization to study the expression of two recently described endothelial cell surface VPF receptors, flt-1 and kdr. Vascular permeability factor receptor mRNA was strongly expressed in endothelial cells of small vessels adjacent to malignant tumor cells in DCIS, infiltrating ductal carcinoma, and metastatic ductal carcinoma. In contrast, no definite labeling for receptor mRNA was detected in infiltrating lobular carcinoma or nonmalignant breast tissue. The intense expression of VPF mRNA by breast carcinoma cells and of VPF receptor mRNA by endothelial cells of adjacent small blood vessels provides strong evidence linking VPF expression to the angiogenesis associated with comedo-type DCIS, infiltrating ductal, and metastatic ductal breast carcinoma.

Comparison of a conventional immunoassay (ELISA) with a surface plasmon resonance-based biosensor for IGF-1 detection in cows' milk.

Recombinant bovine somatotropin (rBST) treatment is adopted in dairy cows to augment milk yield. Previous studies showed that insulin-like growth factor-1 (IGF-1) is present in milk from cows treated with rBST. Since IGF-1 is a suspected carcinogen, its presence in milk for human consumption is potentially a health hazard. Therefore rBST use, still authorized in the United States, has been revoked in Canada and is under evaluation in the EU. The rising attention on IGF-1 presence in alimentary milk focused the necessity to develop specific, sensitive and rapid IGF-1 detection systems. We have developed a solid phase enzyme-linked immunoassay (ELISA) and also an automated surface plasmon resonance-based biosensor system (BIA-technology) for evaluating IGF-1 in fresh cow's milk. Hyperimmune polyclonal anti-IGF-1 antibodies were characterized with respect to their specific binding capacity to IGF-1. The results obtained with these two methods have been compared. This study shows the potential usefulness of the biosensor technology for biomolecular interaction analysis. The features of this technology (fully automated, measures in real time, sharpened yes/no response) offer several advantages compared to ELISA in the detection of compounds in fresh cows' milk (MURST 40%; CNR P.F. MADESS 2).

Detection and epitope mapping of immunoreactive human endothelin-1 using ELISA and a surface plasmon resonance-based biosensor.

A surface plasmon resonance-based biosensor (BIA technology) and enzyme-linked immunosorbent assays (ELISA) have been used for detecting and characterizing human endothelin (ET), a potent vasoactive 21 amino acid polypeptide. Antibodies produced against the isoform ET-1 and its C-terminal eptapeptide ET-1(15-21) have been characterized with respect to their binding capacity to the two isoforms ET-1 and ET-3, the non-secreted portion of the precursor molecule Big.ET-1(22-38), the C-terminal of ET-1, six analogues of ET-1(16-21) each containing a substitution with Ala of a single amino acid in positions 16-21, respectively, and three synthetic cyclic peptides mimicking the N-terminal portion of ET-1. Antibodies reacting with ET-1 also bound to ET-1(16-21) and, with less affinity, to ET-3 but did not cross-react with Big.ET-1(22-38). Ala substitution in positions 16, 17 and 19 of ET-1(16-21) hardly affected the antibody binding capacity of ET-1(16-21), whereas Ala substitution of Asp18, Ile20 and, in particular, Trp21, inhibited its immunoreactivity. The C-terminus thus represents an immunodominant epitope in ET-1 and is important for antibody binding. Epitope mapping using as antibody pairs polyclonal anti-ET-1 and monoclonal anti-ET-1(15-21) antibodies indicated the presence of another immunogenic domain in the N-terminal portion of the molecule. There was excellent agreement between the epitopes determined using ELISA and BIA analyses.

A new hypothesis: iodine and gastric cancer.

The authors have hypothesized that iodine-deficiency (I-def) or in some cases iodine-excess (I-excess) is associated with the development of gastric cancer. They report a short review of their own work and general literature on this subject in three fields: (1) epidemiology, where geographical and temporal correlations between territories with I-def (or I-excess) endemic goitre and high GC-death rate are reported; (2) immunology, where the possible correlations between I-def, immune-deficiency and GC are reported; and (3) thyroid gland and stomach correlations, both being embryologically derived from primitive gut and able to concentrate iodine. This ability is impaired by nitrates, thiocyanate, salt and by I-excess, which in fact can cause goitre. In our study I-def goitrous people have shown more atrophic gastritis than normal subjects. These data enable us to hypothesize that I-def or I-excess might constitute a new risk factor for gastric cancer, both by regulating gastric trophism and by antagonizing the action of those I-inhibitors (such as nitrates, thiocyanate and salt) previously studied as risk factors for gastric cancer.