Bioacumulation of cyanotoxins in Hypophthalmichthys molitrix (silver carp) in Paranoá Lake, Brasilia-DF, Brazil.

Three individuals of silver carp (Hypophthalmichthys molitrix) were collected biweekly from Paranoá Lake (DF, Brazil) for analysis of microcystin (MC) concentrations in their muscle and liver tissue. Analysis by high performance liquid chromatography and mass spectrometry revealed MC masses and fragmentation patterns that were identified as MC-LR (995.04 m/z), MC-LA (909.01 m/z) and an unknown MC (987.07 m/z). Concentrations were calculated as MC-LR equivalents using a calibration curve prepared with a standard of MC-LR. May/06 was the month with the highest MC-LR equivalent concentrations in muscle and liver (3.83 ± 2.78, and 12.94 ± 10.51 µg g(-1), respectively). Our results show that during the drought months (April-September), consumption of fish with these MC concentrations would result in exposure to MCs that greatly exceed the World Health Organization's recommended tolerable daily intake limit of 0.04 µg MC kg(-1) body weight.

A missense mutation, p.V132G, in the X-linked spermine synthase gene (SMS) causes Snyder-Robinson syndrome.

Snyder-Robinson syndrome (SRS, OMIM 309583) is a rare X-linked syndrome characterized by mental retardation, marfanoid habitus, skeletal defects, osteoporosis, and facial asymmetry. Linkage analysis localized the related gene to Xp21.3-p22.12, and a G-to-A transition at point +5 of intron 4 of the spermine synthase gene, which caused truncation of the SMS protein and loss of enzyme activity, was identified in the original family. Here we describe another family with Snyder-Robinson syndrome in two Mexican brothers and a novel mutation (c.496T>G) in the exon 5 of the SMS gene confirming its involvement in this rare X-linked mental retardation syndrome.

Cassava diversity in Brazil: the case of carotenoid-rich landraces.

In Brazil, the center of cassava origin, cassava landraces have acquired through their domestication a large diversity in relation to many economic traits such as high content of carotenoids and excellent palatability among other characters. One of these clones, which has been grown by indigenous Brazilian farmers and is now being maintained in the University of Brasília gene bank, showed a high level of lycopene content (5 mg/kg viz. a viz. zero in common cultivars, and 12-20 mg/kg in tomato, a lycopene-rich vegetable). A second landrace called UnB 400 had a high content of beta-carotene, which reached 4 mg/kg.

Cassava diversity in Brazil: the case of carotenoid-rich landraces

In Brazil, the center of cassava origin, cassava landraces have acquired through their domestication a large diversity in relation to many economic traits such as high content of carotenoids and excellent palatability among other characters. One of these clones, which has been grown by indigenous Brazilian farmers and is now being maintained in the University of Brasília gene bank, showed a high level of lycopene content (5 mg/kg viz. a viz. zero in common cultivars, and 12-20 mg/kg in tomato, a lycopene-rich vegetable). A second landrace called UnB 400 had a high content of b-carotene, which reached 4 mg/kg.

Terapia sistémica neoadyuvante en cáncer de mama / Neoadjuvant systemic therapy in breast cancer

La terapia sistémica neoadyuvante, de inducción o inicial en cáncer de mama, es aquella que se realiza previamente al tratamiento quirúrgico o radioterapia, y cuyo objetivo principal es mejorar las tasas de supervivencia, aumentar la posibilidad de efectuar cirugía conservadora y/o evaluar la respuesta al tratamiento específicamente en los casos de cáncer de mama localmente avanzado no inflamatorio y cáncer de mama operable. Lo más habitual es en base a quimioterapia, aunque últimamente se ha introducido la terapia hormonal neoadyuvante, estando también en fases preliminares estudios con terapias moleculares neoadyuvantes. En los casos localmente avanzados e inflamatorios se han cumplido los objetivos planteados, no así en los inicialmente operable, aunque su uso, al menos, no es perjudicial.

Attenuated response to purified protein derivative in patients with rheumatoid arthritis: study in a population with a high prevalence of tuberculosis.

BACKGROUND: The purified protein derivative (PPD) skin test is the only widely used method which detects latent tuberculosis infection (LTBI) and is dependent on a normal T cell function. In rheumatoid arthritis (RA) the T cell function is altered, which may result in an inability to develop an adequate PPD reaction. OBJECTIVES: To evaluate the response to PPD in patients with RA and to compare it with that of control subjects. METHODS: 112 patients with RA and 96 healthy controls were studied. PPD 5 U was applied using the Mantoux method, and skin reaction was measured at 72 hours. The reaction was considered negative for PPD <5 mm. RESULTS: There were no significant differences in age, sex, history of bacille Calmette-Guerin vaccination, or tuberculosis contact between the two groups. The median size of the PPD induration in the patients with RA was significantly less than that in the control group (4.5 v 11.5 mm, p<0.01). 79 (70.6%) patients with RA compared with 25 (26%) of the control group had a negative reaction to PPD (p<0.01), a response not influenced by disease activity or duration of disease in the patients with RA. CONCLUSION: A PPD skin test is not an appropriate test for recognising LTBI in patients with RA in our population.

Epidemiología de las vasculitis sistémicas primarias en una población latinoamerica / Epidemiology of primary systemic vasculitis in a latin america population

Objetivos: Evaluar la epidemiología de las Vasculitis Sistémicas Primarias (VSP), Poliangeítis Microscópica (MPA). Granulomatosis de Wegener (GW), Poliarteritis Nodosa (PAN) y Síndrome de Churg-Strauss (SCS) en una población latinoamericana bien definida. Métodos: Entre enero de 1990 y diciembre de 2004 se registraron todos los casos de estas VSP identificados en una población de 930.306 personas mayores de 15 años asignadas a la Red Asistencial del Hospital Almenara (nueve hospitales en 20 distritos de la ciudad de Lima). Los pacientes fueron clasificados de acuerdo a las definiciones de la Conferencia de Consenso de Chapel Hill. Resultados: Se identificaron 72 pacientes con VSP (56 MPA, 7 GW, 7 PAN y 2 SCS), 49 mujeres y 23 varones, con promedio de edad 56,42 ± 13,77 años. La incidencia anual de VSP entre 1990-2004 fue 5,16/millón (95 por ciento IC 5,12-5,20). Fue mayor en mujeres 6,98/millón (95 por ciento IC 6,91-7,05) que en varones 3,32/millón (95 por ciento IC 5,12-5,20) y en pacientes ≥ 50 años que < 50 años (13,96/millón vs 1,96/millón). La incidencia de MPA fue 4,01/millon (95 por ciento IC 3,97-4,05), de GW 0,50/millón (95 por ciento IC 0,49-0,51), de PAN 0,5/millón (95 por ciento IC 0,49-0,51) y de SCS 0,14/millón (95 por ciento IC 0,13-0,15). Por quinquenios la incidencia de VSP fue 3,44/millón (95 por ciento IC 3,40-3,48) entre 1990-1994; 4,73/millón (95 por ciento IC 4,69-4,77) entre 1995-1999 y 7,31/millón (95 por ciento IC 7,26-7,36) entre 2000-2004.

Skin secretion of Siphonops paulensis (Gymnophiona, Amphibia) forms voltage-dependent ionic channels in lipid membranes

The effect of the skin secretion of the amphibian Siphonops paulensis was investigated by monitoring the changes in conductance of an artificial planar lipid bilayer. Skin secretion was obtained by exposure of the animals to ether-saturated air, and then rinsing the animals with distilled water. Artificial lipid bilayers were obtained by spreading a solution of azolectin over an aperture of a Delrin cup inserted into a cut-away polyvinyl chloride block. In 9 of 12 experiments, the addition of the skin secretion to lipid bilayers displayed voltage-dependent channels with average unitary conductance of 258 ± 41.67 pS, rather than nonspecific changes in bilayer conductance. These channels were not sensitive to 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid or tetraethylammonium ion, but the experimental protocol used does not permit us to specify their characteristics

Skin secretion of Siphonops paulensis (Gymnophiona, Amphibia) forms voltage-dependent ionic channels in lipid membranes.

The effect of the skin secretion of the amphibian Siphonops paulensis was investigated by monitoring the changes in conductance of an artificial planar lipid bilayer. Skin secretion was obtained by exposure of the animals to ether-saturated air, and then rinsing the animals with distilled water. Artificial lipid bilayers were obtained by spreading a solution of azolectin over an aperture of a Delrin cup inserted into a cut-away polyvinyl chloride block. In 9 of 12 experiments, the addition of the skin secretion to lipid bilayers displayed voltage-dependent channels with average unitary conductance of 258 +/- 41.67 pS, rather than nonspecific changes in bilayer conductance. These channels were not sensitive to 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid or tetraethylammonium ion, but the experimental protocol used does not permit us to specify their characteristics.

Toxicity of puffer fish - two species(Lagocephalus laevigatus, LINAEUS 1766 and Sphoeroides spengleri, BLOCH 1785) from the southeastern Brazilian coast

In Brazil, where puffer fish are considered poisonous, there are few documented cases on human consumption and consequent poisoning. In this study, toxicity of two puffer fish species from the Brazilian coast was examined. Specimens of Sphoeroides spengleri and Lagocephalus laevigatus were caught in Säo Sebastiäo Channel (North coast of Säo Paulo State, Brazil) between January 1996 and May 1997. Acidic ethanol extracts from muscle and skin plus viscera were tested for mice acute toxicity using the standard method of Kawabata. Polar extracts of S. spengleri showed high toxicity up to 946 MU/g. Extracts from L. laevigatus showed very low levels of toxicity, never exceeding 1.7 MU/g. All extracts from both species blocked amielinic nerve fiber evoked impulses of crustacean legs; this effect reverted on washing similar to the standard tetrodotoxin TTX. The aqueous extract solutions were partially purified using an ionic exchange column (Amberlit GC-50) followed by treatment with activated charcoal (Norit-A). The presence of TTX and their analogs in the semi-purified extracts were confirmed by HPLC and mass spectrometry (MALDI-TOF).

Toxicity of puffer fish: two species (Lagocephalus laevigatus, linaeus 1766 and Sphoeroides spengleri, Bloch 1785) from the Southeastern Brazilian coast

In Brazil, where puffer fish are considered poisonous, there are few documented cases on human consumption and consequent poisoning. In this study, toxicity of two puffer fish species from the Brazilian coast was examined. Specimens of Sphoeroides spengleri and Lagocephalus laevigatus were caught in São Sebastião Channel (North coast of São Paulo State, Brazil) between January 1996 and May 1997. Acidic ethanol extracts from muscle and skin plus viscera were tested for mice acute toxicity using the standard method of Kawabata. Polar extracts of S. spengleri showed high toxicity up to 946 MU/g. Extracts from L. laevigatus showed very low levels of toxicity, never exceeding 1.7 MU/g. All extracts from both species blocked amielinic nerve fiber evoked impulses of crustacean legs; this effect reverted on washing similar to the standard tetrodotoxin TTX. The aqueous extract solutions were partially purified using an ionic exchange column (Amberlit GC-50) followed by treatment with activated charcoal (Norit-A). The presence of TTX and their analogs in the semi-purified extracts were confirmed by HPLC and mass spectrometry (MALDI-TOF).

Indirect cardiotoxic activity of the caecilian Siphonops paulensis (Gymnophiona, Amphibia) skin secretion.

The skin secretion of the caecilian S. paulensis has an indirect cardiotoxic effect. It induces a rapid blockage of electrical activity and subsequent diastolic arrest on in situ toad heart preparations. This action is not blocked by atropine and is therefore not mediated through a cholinergic mechanism. In addition, S. paulensis skin secretion is ineffective in inducing any response in isolated perfused toad heart assay, in the spontaneously beating isolated toad atria or in the electrically driven toad ventricle strip. These results, and the observation that S. paulensis skin secretion exhibits an hemolytic activity ([Schwartz, E. F., Schwartz, C. A., Sebben, A., Mendes E. G. (1997) Cardiotoxic and hemolytic activities on the caecilian Siphonops paulensis skin secretion. J. Venom. Anim. Toxins 3(1), 190]), suggest that the skin secretion cardiotoxicity could be mediated through an endogenous agent. The cardiotoxic action of S. paulensis skin secretion was investigated in isolated toad cardiac tissues in the presence of toad red blood cells (TRBC). In both atria and ventricle it evoked the same responses observed in the in situ heart. The potassium concentrations of the suspending media, as determined by atomic absorption spectroscopy were 9.5 and 11.7 times greater, respectively, in the presence of TRBC than in its absence. Given that increased levels of potassium also showed a negative inotropic effect in the isolated ventricle strip, the action of the skin secretion was attributed to the hemolytic activity, which causesan increase in K+ concentration of the medium.

Occurrence of hemolytic activity in the skin secretion of the caecilian siphonops paulensis.

The skin secretion of the caecilian Siphonops paulensis (SpSS) induces a time-and dose-dependent hemolytic response on red blood cells (RBC). When RBC from various animals species were subjected to the action of SpSS, a range of sensitivities was evident, sheep erythrocytes being the most susceptible, human, mouse and rabbit having moderate susceptibility, cow, snake and toad erythrocytes being more resistant, while S. paulensis RBC were entirely resistant. The hemolytic activity of SpSS was inhibited at temperatures higher than 60 degrees C. Both trypsin- and chymotrypsin-treated SpSS were ineffective in inducing RBC lysis. The treatment of SpSS with sheep RBC ghosts reduced its activity. There is no phospholipase activity in the SpSS.

Antinociceptive effect of purine nucleotides.

The antinociceptive effect of purine nucleotides administered systematically (sc) was determined using the formalin and writhing tests in adult male albino mice. The mechanisms underlying nucleotide-induced antinociception were investigated by preinjecting the animals (sc) with specific antagonists for opioid (naloxone, 1 mg/kg), purinergic P1 (caffeine, 5, 10, of 30 mg/kg); theophylline, 10 mg/kg) or purinergic P2 receptors (suramin, 100 mg/kg; Coomassie blue, 30-300 mg/kg; quinidine, 10 mg/kg). Adenosine, adenosine monophosphate (AMP), diphosphate (ADP) and triphosphate (ATP) caused a reduction in the number of writhes and in the time of licking the formalin-injected paw. Naloxone had no effect on adenosine- or adenine nucleotide-induced antinociception. Caffeine (30 mg/kg) and theophylline (10 mg/kg) reversed the antinociceptive action of adenosine and adenine nucleotide derivatives in both tests. P2 antagonists did not reverse adenine nucleotide-induced antinociception. These results suggest that antinociceptive effect of adenine nucleotides is mediated by adenosine.

Antinociceptive effect of purine nucleotides

The antinociceptive effect of purine nucleotides administered systemically (sc) was determined using the formalin and writhing tests in adult male albino mice. The mechanisms underlying nucleotide-induced antinociception were investigated by preinjecting the animals (sc) with specific antagonists for opioid (naloxone, 1 mg/kg), purinergic P1 (caffeine, 5, 10 or 30 mg/kg); theophylline, 10 mg/kg) or purinergic P2 receptors (suramin, 100 mg/kg; Coomassie blue, 30-300 mg/kg; quinidine, 10 mg/kg). Adenosine, adenosine monophosphate (AMP), diphosphate (ADP) and triphosphate (ATP) caused a reduction in the number of writhes and in the time of licking the formalin-injected paw. Naloxone had no effect on adenosine- or adenine nucleotide-induced antinociception. Caffeine (30 mg/kg) and theophylline (10 mg/kg) reversed the antinociceptive action of adenosine and adenine nucleotide derivatives in both tests. P2 antagonists did not reverse adenine nucleotide-induced antinociception. These results suggest that the antinociceptive effect of adenine nucleotides is mediated by adenosine.

Utilization of O-phthalaldehyde-sulphuric acid as a spray reagent in thin-layer chromatographic detection of some indolealkylamines and application to cutaneous secretion extracts of toad species.

An expansion of the utilisation of o-phthalaldehyde in sulphuric acid medium as spray reagent was carried out when tryptophan and some tryptophan-derived indole alkylamines such as tryptamine, serotonin, bufotenine, dehydrobufotenine and bufotenidine were examined by thin-layer chromatography. Rf-values and limits of detection ranging from 20 (serotonin) to 100 (dehydrobufotenine) ng per spot were found. Application of this reagent for the detection of some of these compounds was carried out, using either methanolic extracts or column chromatographic fractions of the skin secretion of the toads Bufo ictericus and Odontophrynus cultripes.

A tetrodotoxin-like substance found in the Brazilian frog Brachycephalus ephippium.

A tetrodotoxin-like substance, denoted ephippiotoxin, was obtained from the tissue of Brachycephalus ephippium, a small pumpkin-coloured frog collected in the Atlantic Forest of the southeast region of Brazil. Ephippiotoxin is a dialyzable substance soluble in water, methanol and ethanol, but insoluble in organic solvents such as chloroform and other apolar solvents. After treatment with active charcoal (Norit-A) and purification with ion-exchange Amberlite IRC-50 resin (NH4 + form), a freeze-dried residue was obtained, with a toxicity of c. 117 micrograms/kg (mice, i.p.). Ephippiotoxin showed the same mobility as crystalline tetrodotoxin (Sankyo) when submitted to thin-layer chromatography (silica gel G) using seven different solvent systems. White mice (20 +/- 1 g) injected i.p. with either B. ephippium tissue extracts or semi-purified toxin showed partial paralysis of the hind limbs, lethargy, altered breathing rhythm and clonic convulsions. Death occurred within 1.5-30 min after injection, depending on the dose. Ephippiotoxin induced atrioventricular diastolic blockade in the toad heart. It also inhibited the response of toad striated muscle to direct and indirect electric stimulation and blocked the compound action potential of isolated frog sciatic nerve.