Combination Therapy for the Cardiovascular Effects of Perinatal Lead Exposure in Young and Adult Rats

Background: Combination therapy can play a significant role in the amelioration of several toxic effects of lead (Pb) and recovery from associated cardiovascular changes. Objective: To investigate the effects of combination therapy on the cardiovascular effects of perinatal lead exposure in young and adult rats Methods: Female Wistar rats received drinking water with or without 500 ppm of Pb during pregnancy and lactation. Twenty-two- and 70-day-old rat offspring who were or were not exposed to Pb in the perinatal period received meso-dimercaptosuccinic acid (DMSA), L-arginine, or enalapril and a combination of these compounds for 30 additional days. Noradrenaline response curves were plotted for intact and denuded aortas from 23-, 52-, 70-, and 100-day-old rats stratified by perinatal Pb exposure (exposed/unexposed) and treatment received (treated/untreated). Results: Systolic blood pressure was evaluated and shown to be higher in the 23-, 52-, 70-, and 100-day age groups with Pb exposure than in the corresponding control age groups: 117.8 ± 3.9*, 135.2 ± 1.3*, 139.6 ± 1.6*, and 131.7 ± 2.8*, respectively and 107.1 ± 1.8, 118.8 ± 2.1, 126.1 ± 1.1, and 120.5 ± 2.2, respectively (p < 0.05). Increased reactivity to noradrenaline was observed in intact, but not denuded, aortas from 52-, 70-, and 100-day-old exposed rats, and the maximum responses (g of tension) in the respective Pb-exposed and control age groups were as follows: 3.43 ± 0.16*, 4.32 ± 0.18*, and 4.21 ± 0.23*, respectively and 2.38 ± 0.33, 3.37 ± 0.13, and 3.22 ± 0.21, respectively (p < 0.05). Conclusions: All treatments reversed the changes in vascular reactivity to noradrenaline in rats perinatally exposed to Pb. The combination therapy resulted in an earlier restoration of blood pressure in Pb-exposed rats compared with the monotherapies, except for enalapril therapy in young rats. These findings represent a new approach to the development of therapeutic protocols for the treatment of Pb-induced hypertension.

Efeitos do arsênico sôbre a cultura do algodoeiro em terra arenosa

The authors studied the action of arsenic, in the form of lead arsenate and sodium arsenite, on cotton in white sandy soil of Piracicaba, State of S. Paulo, Brazil. The experiment was carried out in Mitscherlich pots, applying increasing quantities of the above mentioned compounds. The following conclusions were reached: sodium arsenite is more toxic than lead arsenate. 48 pounds per acre of lead arsenate and 16 pounds per acre of sodium arsenite reduced the vegetative development and the production of cotton. The roots were more seriously affected than the aerial parts. Sandy soils were sensitive to arsenic toxicity. The arsenic mobilization in the soil seems to depend upon factors such as, the a- cidity, the concentration of Fe2O3, CaO, P2O5 and soil colloids, both clay and humus components. The authors suggest, based on their own experiment and after a detailed study of the literature, the use of organic insecticids which may not leave toxic residues, rotation of crops, application of lime and reduction of arsenical sprays to a mini mum. Arsenic compounds should not be used in soils destined to the cultivation of food plants. Rice should not be planted in soils contaminated by arsenic compounds during several years of cotton cultivation. Future experiments are planed, using other soils such as "terra roxa", in Mitscherlich pots and in field plots.

Influência do cloro, sôbre a composição do caldo da cana de açúcar Co 290, aplicado no solo, na forma de cloreto de sódio

Considering the economic importance of the sugar industry among ourselves, the authors carried out a field experiment (Latin square) with Co 290 sugar cane, on a white sandy soil of Piracicaba, State of São Paulo, Brazil, applying NaCl in increasing rates (from 6.8 to 54.5 grams per plant), in order to study the effects of chlorides, on productivity and on the composition of juice. No toxic or stimulating effect was found, and there was no change in yield, in degree of purity of the juice, in general aspect of plants or in colour of leaves and culms. No difference was observed between potassium sulphate or chloride, as source of potash for sugar cane culture. Data collected and the literature cited suggest: (a) that the use of the variety Co 290 is indicated for soils rich in chlorine, such as the saline soils of the North-east and Atlantic Coast of Brazil; (b) that it is necessary to extend studies in Research Institutes and Agricultural Experiment Stations of the country to verify the behaviour of other varieties of sugar cane in the types of soils mentioned, especially with respect their yielding capacity. The authors are already planning such investigations.

Arsenicais e inseticidas orgânicos sôbre o algodoeiro em terras roxa e arenosa

The authors carried out a series of pots and plots experiments applying arsenical and organic insecticides to cotton plants cultivated in "terra roxa" and in a sandy soil. The first results were presented in 1947, to the la. Reunião Brasileira de Ciência do Solo (First Brazilian Congress of Soil Science); they pointed out the danger resulting from the accumulation of arsenic in soils due to the constant applications of arsenicais to control cotton pests; in the course of the time, the amount of residual arsenic in the soil would determine a decrease in cotton yield caused by its toxic effect on the crop. The following conclusions were drawn from the last three experiments: 1) the field experiment conducted in a sandy soil to which lead arseniate was applied in increasing rates produced a reduction of 50 per cent in the yield (the three highest doses were responsible for this result); by this way, the pot experiment published in 1947 was confirmed); 2) in the pot experiment with "terra roxa" toxic effects appeared only in the plants receiving the last dosis of lead arsenate; this result is explained quite naturally by a considerable absorption of the AsO4 --- ion by "terra roxa" colloidal material; furthermore the CaO, P2O5 and Fe2O3 content and the pH value (higher) would decrease the arsenate solubilization in the soil considered; 3) the pot experiment with organic insecticides applied in the rates usually employed in the control of cotton pests, showed that 10% D.D.TD. and 2.5% Rotenone did not affect cotton plants cultivated in a sandy soil; however we agree with FOSTER (1951), in the point that both mineral and organic insecticides must be applied in the minimum amount as possible; we also think that experiments like those should be carried out with the known insecticides, in several soil conditions and with many crops in order to determine the maximum limits of tolerancy.

Toxicidade de algumas crotolárias

This paper deals with some testes of Crotalaria as forage, using rabbits as laboratory animals to detect toxicity, at Piracicaba, São Paulo, Brazil. 1. C. intermedia and C. juncea were palatable, non toxic, the last more productive. Tests on cattle are recommended and selection to improve characteristics as forage too. 2. C. incana and C. verrucosa were little palatable, probably non toxic, poor productive. 3. C. paulina, C. lanceolata (four strains), C. mysorensis, C. gratiana, C. spectabilis, C. breviflora and C. campista were toxic. This results are not according those of others AA. Others species are beeing tested since Crotalaria is a drought resistent legume on this area.

A raspa de mandioca como sucedâneo dos farelos de trigo na alimentação de pintos

In a feeding trial cassava root meal was used as a substitute for wheat bran and wheat middling (mixed) in several ranges: 10, 15, 20 and 30% of a ration. Five groups of 32 seven day old Rhode I. Red chicks were used during 6 weeks of the trial. The results are shown in the Tables (Quadros) I, II and III. Table I shows an high mortality in R4, receiving 30% of cassava root meal and no wheat by product. It was observed a depression of the development of the chicks that was so much high as the proportion of the cassava meal increased in the ration consumed. The A. suggests cassava root meal might have an antagonistic factor acting as a "toxic", that he imagine could be corrected by a higher vitaminic and mineral proportion. This hipothesis must be investigated.

mRNA metabolism: nonsense mediated mRNA decay as a tool for gene therapy and the role of human DIS3L2 in transcript degradation

Tese de mestrado em Biologia Humana e Ambiente, apresentada à Universidade de Lisboa, através da Faculdade de Ciências, 2015

Efectos del herbicida Paraquat sobre el zooplancton

The effects of 0.1; 0.2; 0.4 and 0.8 mlPQ/L were analized on a zooplankton community, to determine the most sensitive species and to analize the occurence of physical abnormalities. A total of 40 taxa were determined. Paraquat affected significantly the zooplankton density but not the species richness. A progressive state of deformation of these organisms was also observed. Paraquat showed to be highly toxic for the zooplankton, so this herbicide should be strictly regulated in aquatic and terrestrial ecosystems.

Cytochemical characterization of gill and hepatopancreatic cells of the crab Ucides cordatus (Crustacea, Brachyura) validated by cell metal transport

Ucides cordatus (Linnaeus, 1763) is a hypo-hyper-regulating mangrove crab possessing gills for respiratory and osmoregulatory processes, separated in anterior and posterior sections. They also have hepatopancreas, which is responsible for digestion and absorption of nutrients and detoxification of toxic metals. Each of these organs has specific cells that are important for in vitro studies in cell biology, ion and toxic metals transport. In order to study and characterize cells from gills and hepatopancreas, both were separated using a Sucrose Gradient (SG) from 10 to 40% and cells in each gradient were characterized using the vital mitochondrial dye DASPEI (2-(4-dimethylaminostyryl)-N- ethylpyridinium iodide) and Trichrome Mallory's stain. Both in 20 and 40% SG for gill cells and 30% SG for hepatopancreatic cells, a greater number of cells were colored with DASPEI, indicating a larger number of mitochondria in these cells. It is concluded that the gill cells present in 20% and 40% SG are Thin cells, responsible for respiratory processes and Ionocytes responsible for ion transport, respectively. For hepatopancreatic cells, the 30% SG is composed of Fibrillar cells that possess larger number of membrane ion and nutrient transporters. Moreover, the transport of toxic metal cadmium (Cd) by isolated hepatopancreatic cells was performed as a way of following cell physiological integrity after cell separation and to study differences in transport among the cells. All hepatopancreatic cells were able to transport Cd. These findings are the first step for further work on isolated cells of these important exchange epithelia of crabs, using a simple separation method and to further develop successful in vitro cell culture in crabs.

Efficacy of ivermectin against the bloodsucking insect, Rhodnius prolixus (Hemiptera, Triatominae)

Ivermectin (0.2 mg/kg body weight) caused a high mortality in nymphs and adults of Rhodnius prolixus following a single meal in mice sub-cutaneously injected with the drug. This effect was more evident in nymphs of 1st-and 2nd-instar than in older nymphs and adults. Third-instar nymphs presented a high mortality when fed on mice treated with ivermectin 24 and 48 hours previously, while mortality was significantly reduced in nymphs fed on mice treated 72 hours before. Surviving 3rd-instar nymphs did not molt. When adult females were fed once on mice treated for 24 hours with ivermectin there was a considerable reduction in egg production. This inhibition was not reversed by a second feeding on normal mice. We concluded that sub-lethal doses of ivermectin caused toxic effects interfering in the neuro-endocrine control of development and reproduction of this bloodsucking insect.

La résistance bactérienne aux antibiotiques.

50 years ago, the introduction of penicillin, followed by many other antibacterial agents, represented an often underestimated medical revolution. Indeed, until that time, bacterial infections were the prime cause of mortality, especially in children and elderly patients. The discovery of numerous new substances and their development on an industrial scale gave us the illusion that bacterial infections were all but vanquished. However, the widespread and sometimes uncontrolled use of these agents has led to the selection of bacteria resistant to practically all available antibiotics. Bacteria utilize three main resistance strategies: (1) modification of their permeability, (2) modification of target, and (3) modification of the antibiotic. Bacteria modify their permeability either by becoming impermeable to antibiotics, or by actively excreting the drug accumulated in the cell. As an alternative, they can modify the structure of the antibiotic's molecular target--usually an essential metabolic enzyme of the bacterium--and thus escape the drug's toxic effect. Lastly, they can produce enzymes capable of modifying and directly inactivating antibiotics. In addition, bacteria have evolved extremely efficient genetic transfer systems capable of exchanging and accumulating resistance genes. Some pathogens, such as methicillin-resistant Staphylococcus aureus and multiresistant Mycobacterium tuberculosis, have become resistant to almost all available antibiotics and there are only one or two substances still active against such organisms. Antibiotics are very precious drugs which must be administered to patients who need them. On the other hand, the development of resistance must be kept under control by a better comprehension of its mechanisms and modes of transmission and by abiding by the fundamental rules of anti-infectious chemotherapy, i.e.: (1) choose the most efficient antibiotic according to clinical and local epidemiological data, (2) target the bacteria according to the microbiological data at hand, and (3) administer the antibiotic in an adequate dose which will leave the pathogen no chance to develop resistance.

Individual-based modelling of bacterial cultures to study the lag ohase

Els bacteris són la forma dominant de vida del planeta: poden sobreviure en medis molt adversos, i en alguns casos poden generar substàncies que quan les ingerim ens són tòxiques. La seva presència en els aliments fa que la microbiologia predictiva sigui un camp imprescindible en la microbiologia dels aliments per garantir la seguretat alimentària. Un cultiu bacterià pot passar per quatre fases de creixement: latència, exponencial, estacionària i de mort. En aquest treball s’ha avançat en la comprensió dels fenòmens intrínsecs a la fase de latència, que és de gran interès en l’àmbit de la microbiologia predictiva. Aquest estudi, realitzat al llarg de quatre anys, s’ha abordat des de la metodologia Individual-based Modelling (IbM) amb el simulador INDISIM (INDividual DIScrete SIMulation), que ha estat millorat per poder fer-ho. INDISIM ha permès estudiar dues causes de la fase de latència de forma separada, i abordar l’estudi del comportament del cultiu des d’una perspectiva mesoscòpica. S’ha vist que la fase de latència ha de ser estudiada com un procés dinàmic, i no definida per un paràmetre. L’estudi de l’evolució de variables com la distribució de propietats individuals entre la població (per exemple, la distribució de masses) o la velocitat de creixement, han permès distingir dues etapes en la fase de latència, inicial i de transició, i aprofundir en la comprensió del que passa a nivell cel•lular. S’han observat experimentalment amb citometria de flux diversos resultats previstos per les simulacions. La coincidència entre simulacions i experiments no és trivial ni casual: el sistema estudiat és un sistema complex, i per tant la coincidència del comportament al llarg del temps de diversos paràmetres interrelacionats és un aval a la metodologia emprada en les simulacions. Es pot afirmar, doncs, que s’ha verificat experimentalment la bondat de la metodologia INDISIM.

Disaggregating chaperones: an unfolding story.

Stress, molecular crowding and mutations may jeopardize the native folding of proteins. Misfolded and aggregated proteins not only loose their biological activity, but may also disturb protein homeostasis, damage membranes and induce apoptosis. Here, we review the role of molecular chaperones as a network of cellular defenses against the formation of cytotoxic protein aggregates. Chaperones favour the native folding of proteins either as "holdases", sequestering hydrophobic regions in misfolding polypeptides, and/or as "unfoldases", forcibly unfolding and disentangling misfolded polypeptides from aggregates. Whereas in bacteria, plants and fungi Hsp70/40 acts in concert with the Hsp100 (ClpB) unfoldase, Hsp70/40 is the only known chaperone in the cytoplasm of mammalian cells that can forcibly unfold and neutralize cytotoxic protein conformers. Owing to its particular spatial configuration, the bulky 70 kDa Hsp70 molecule, when distally bound through a very tight molecular clamp onto a 50-fold smaller hydrophobic peptide loop extruding from an aggregate, can locally exert on the misfolded segment an unfolding force of entropic origin, thus destroying the misfolded structures that stabilize aggregates. ADP/ATP exchange triggers Hsp70 dissociation from the ensuing enlarged unfolded peptide loop, which is then allowed to spontaneously refold into a closer-to-native conformation devoid of affinity for the chaperone. Driven by ATP, the cooperative action of Hsp70 and its co-chaperone Hsp40 may thus gradually convert toxic misfolded protein substrates with high affinity for the chaperone, into non-toxic, natively refolded, low-affinity products. Stress- and mutation-induced protein damages in the cell, causing degenerative diseases and aging, may thus be effectively counteracted by a powerful network of molecular chaperones and of chaperone-related proteases.

Array de DNA per identificar espècies de Fusarium: ampliació d'un array existent per incloure espècies del Sud d'Europa

Projecte de recerca elaborat a partir d’una estada al Department for Feed and Food Hygiene del National Veterinary Institute, Noruega, entre novembre i desembre del 2006. Els grans de cereal poden estar contaminats amb diferents espècies de Fusarium capaces de produir metabolits secundaris altament tòxics com trichotecenes, fumonisines o moniliformines. La correcta identificació d’aquestes espècies és de gran importància per l’assegurament del risc en l’àmbit de la salut humana i animal. La identificació de Fusarium en base a la seva morfologia requereix coneixements taxonòmics i temps; la majoria dels mètodes moleculars permeten la identificació d’una única espècie diana. Per contra, la tecnologia de microarray ofereix l’anàlisi paral•lel d’un alt nombre de DNA dianes. En aquest treball, s’ha desenvolupat un array per a la identificació de les principals espècies de Fusarium toxigèniques del Nord i Sud d’Europa. S’ha ampliat un array ja existent, per a la detecció de les espècies de Fusarium productores de trichothecene i moniliformina (predominants al Nord d’Europa), amb l’addició de 18 sondes de DNA que permeten identificar les espècies toxigèniques més abundants al Sud d’Europa, les qual produeixen majoritàriament fumonisines. Les sondes de captura han estat dissenyades en base al factor d’elongació translació- 1 alpha (TEF-1alpha). L’anàlisi de les mostres es realitza mitjançant una única PCR que permet amplificar part del TEF-1alpha seguida de la hibridació al xip de Fusarium. Els resultats es visualitzen mitjançant un mètode de detecció colorimètric. El xip de Fusarium desenvolupat pot esdevenir una eina útil i de gran interès per a l’anàlisi de cereals presents en la cadena alimentària.