Uso de drogas: a alter-ação como evento

Este artigo problematiza o elenco de questões e de respostas que costumamos formular a respeito dos usos de drogas e propõe outro modo de pensar essas práticas. Sugere-se que já não é mais suficiente indagar "por que as pessoas usam drogas?" e "qual o significado do uso de drogas?", nem se contentar com as respostas que são apresentadas quando essas questões são colocadas, pois elas costumam concluir pelo "erro", pela "falta" ou pela "fraqueza". Propõem-se, então, outras questões: "o que ocorre em práticas como essas?", "que experiência usuários e substâncias realizam?". Conseqüentemente, propõem-se também outras respostas. Estas novas respostas apontam para a existência de eventos - as 'ondas' das drogas - que envolvem agenciamentos paradoxais de auto-abandono. Propõe-se que o evento 'onda' não resulta de fantasias subjetivas dos usuários, nem de determinações objetivas da substância, mas exige modalidades de (in)ação como aquelas presentes no paradoxo da paixão e nos jogos profundos. Sustenta-se que o evento 'onda' envolve modos singulares de engajamento no mundo, nos quais as substâncias são mediadores indispensáveis. Por fim, sugere-se que, em vez de se indagar quem controla a 'onda', cabe perguntar se ela ocorre ou não, ou, baseado em Gabriel Tarde, se há ou não alter-ação.

Contaminação provocada por um depósito de lixo no aqüífero Alter do Chão em Manaus - AM

Este trabalho discute a composição química da água do aqüífero Alter do Chão na área do entorno de um lixão na cidade de Manaus. Foram analisados pH, Eh, turbidez, nitrato, nitrito, amônia e os elementos Cl, F, Si, K, Na, Ca, Mg, Al, As, Mn, P, Sb, Ba, Cr, Fe, Se, Sn, Cd, Cu, Pb e Zn, em dois períodos, no final do período chuvoso e na estiagem, em 18 poços e cacimbas. De acordo com os resultados obtidos, a água está comprometida para consumo humano na quase totalidade dos poços amostrados, em conseqüência dos elevados teores de Al, Fe, As, Cd, Pb, Sb e Se, dos compostos nitrogenados e também por contaminações pontuais de Mn e Zn. A pluma de contaminação, que se expande no final do período chuvoso, estende-se para leste e sudeste do lixão, em função das direções naturais de fluxo do aqüífero e do baixo potenciométrico gerado pelo igarapé que corta a área.

Hereditariedade da homeose

A preliminary account on the normal development of the imaginai discs in holometabolic Insects is made to serve as an introduction to the study of the hereditary homoeosis. Several facts and experimental data furnished specially by the students of Drosophila are brought here in searching for a more adequate explanation of this highly interesting phenomenon. The results obtained from the investigations of different homoeotic mutants are analysed in order to test Goldschmidt's theory of homoeosis. Critical examination of the basis on which this theory was elaborated are equally made. As a result from an extensive theoretical consideration of the matter and a long discussion of the most recent papers on this subject the present writer concludes that the Goldschmidt explanation of the homoeotic phenomena based on the action of diffusing substances produced by the genes, the "evocators", and on the alteration of the normal speed of maturation of the imaginai discs equally due to the activity of the genes, could not be proved and therefore should be abandoned. In the same situation is any other explanation like that of Waddington or Villee considered as fundamentally identical to that of Goldschmidt. In order to clear the problem of homoeosis in terms which seem to put the phenomenon in complete agreement with the known facts the present writer elaborated a theory first published a few years ago (1941) based entirely on the assumption that the imaginai discs are specifically determined by some kind of substances, probably of chemical nature, contained in the cytoplam of the cells entering in the consti- tution of each individual disc. These substances already present in the blastem of the egg in which they are distributed in a definite order, pass to different cells at the time the blastem is transformed into blastoderm. These substances according to their organogenic potentiality may be called antenal-substance, legsubstance, wing-substance, eye-substance, etc. The hipoderm of the embryo resulting from the multiplication of the blastoderm cells would be constituted by a series of cellular areas differing from each other in their particular organoformative capacity. Thus the hypoderm giving rise to the imaginai discs, it follows that each disc must have the same organogenic power of the hypodermal area it came from. Therefore the discs i*re determinated since their origin by substances enclosed in the cytoplasm of their cells and consequently can no longer alter their potentiality. When an antennal disc develops into a leg one can conclude that this disc in spite of its position in the body of the larva is not, properly speaking, an antennal disc but a true leg disc whose cells instead of having in their cytoplasm the antennal substance derived from the egg blastem have in its place the leg-substance. Now, if a disc produces a tarsus or an antenna or even a compound appendage partly tarsus-like, partly antenna-like, it follows tha,t both tarsal and antennal substances are present in it. The ultimate aspect of the compound structure depends upon the reaction of each kind of substance to the different causes influencing development. For instance, temperature may orient the direction of development either lowards arista or tarsus, stimulating, or opposing to the one or the other of these substances. Confering to the genes the faculty of altering the constitution of the substances containing in the cytoplasm forming the egg blastem or causing transposition of these substances from one area to another or promoting the substitution of a given substance by a different one, the hereditary homoeocis may be easily explained. However, in the opinion of the present writer cytoplasm takes the initiative in all developmental process, provoking the chromosomes to react specifically and proportionally. Accordingly, the mutations causing homoeotic phenomena may arise independently at different rime in the cytoplasm and in the chromosomes. To the part taken by the chromosomes in the manifestation of the homoeotic characters is due the mendalian ratio observed in homoeotic X normal crosses. Expression, in itself, is mainly due to the proportion of the different substances in the cells of the affected discs. Homoeotic phenomena not presenting mendelian ratio may appear as consequence of cytoplasmic mutation not accompanied by chromosomal mutation. The great variability in the morphology of the homoeotic characteres, some individual being changed towards an extreme expression of the mutant phenotype while others in spite of their homozigous constitution cannot be distinguished from the normal ones, strongly supports the interpretation based on the relative proportion of the determining substances in the discs. To the same interpretation point also asymetry and other particularities observed in the exteriorization of the phenomenon. In conformity with this new conception homoeosis should not prove homology of Insect appendages (Villee 1942) since a more replacement of substances may cause legs to develop in substitution of the wings, as it was already observed (requiring confirmation in the opinion of Bateson 1894, p. 184) and no one would conclude for the homology of these organs in the usual meaning of the term.

Aluminum hydroxide associated to Schistosoma mansoni 22.6 kDa protein abrogates partial protection against experimental infection but not alter interleukin-10 production

The need to develop a vaccine against schistosomiasis led several researches and our group to investigate proteins from Schistosoma mansoni as vaccine candidates. Sm22.6 is a protein from S. mansoni that shows high identity with Sj22.6 and Sh22.6 (79 and 91%, respectively). These proteins are associated with high levels of IgE and protection to reinfection. Previously, we have shown that Sm22.6 induced a partial protection of 34.5% when used together with Freund's adjuvant and produced a Th0 type of immune response with interferon-g and interleukin-4. In this work, mice were immunized with Sm22.6 alone or with aluminum hydroxide adjuvant and high levels of IgG, IgG1, and IgG2a were measured. Unfortunately, no protection was detected. Since IL-10 is a modulating cytokine in schistosomiasis, we also observed a high level of this molecule in splenocytes of vaccinated mice. In conclusion, we did not observe the adjuvant effect of aluminum hydroxide associated with rSm22.6 in protective immunity.

Schistosoma mansoni antigens alter the cytokine response in vitro during cutaneous leishmaniasis

Schistosoma mansoni infection or associated products are able to down-modulate the type 1 CD4+ T cell inflammatory response characteristic of autoimmune diseases. In this study, we evaluated how S. mansoni antigens altered the immune response that was induced by the soluble Leishmania antigen (SLA) from cutaneous leishmaniasis (CL) patients. Cytokines were measured from the supernatants of peripheral blood mononuclear cell cultures stimulated with SLA. This was performed using the sandwich enzyme linked immunosorbent assay technique in the presence or absence of S. mansoni recombinant antigens Sm29, SmTSP-2 and PIII. The addition of S. mansoni antigens to the cultures resulted in the reduction of interferon gamma (IFN-γ) levels in 37-50% of patients. Although to a lesser extent, the antigens were also able to decrease the production of tumour necrosis factor-alpha (TNF-α). We compared patients that either had or did not have reduction in IFN-γ and TNF-α production in cultures stimulated with SLA in the presence of S. mansoni antigens. We found that there was no significant difference in the levels of interleukin (IL)-10 and IL-5 in response to S. mansoni antigens between the groups. The antigens used in this study down-modulated the in vitro proinflammatory response induced by SLA in a group of CL patients through a currently undefined mechanism.

WHEAT HERBAGE AMENDMENTS ALTER EMERGENCE DYNAMICS, SEEDLING GROWTH OF LAMBSQUARTER AND SOIL PROPERTIES

ABSTRACT Crop allelopathy is a potential tool for weed management but allelopathic potential often varies among cultivars and developmental stages of crop. Bioassays were conducted to appraise the allelopathic potential of herbage (incorporated at 8 g kg-1 soil) of different hexaploid wheat (Triticum aestivum) cultivars (Millat-2011, AARI-2011, Lasani-2008 and Faisalabad-2008) collected at different crop growth stages [tillering (Z-30), anthesis (Z-60) and maturity (Z-90)] against lambsquarter (Chenopodium album). Mean emergence time taken by lambsquarter was prolonged over control by anthesis and maturity stage herbage of all wheat cultivars. Final emergence percentage was dropped by 3-17% in response to different growth stages of herbage collection. Maximum suppression in shoot (45 and 78%) and root (60 and 90%) length, and seedling dry biomass (65 and 96%) of lambsquarter over control was recorded under the amendment of anthesis and maturity stages herbage of wheat cultivars. Total chlorophyll contents declined in response to herbage collected at anthesis and maturity stage of all wheat cultivars over control. Phenolic contents on the other hand were increased. Activities of enzymatic antioxidants also varied among all wheat cultivars, and declined by the incorporation of tillering, anthesis and maturity stage herbage. Wheat herbage induced lipid peroxidation in lambsquarter seedling and higher malondialdehyde content (0.56 and 0.77 nmol g-1 FW) was observed by the incorporation of wheat cultivars herbage collected at anthesis and maturity stage, respectively. Anthesis and maturity stage herbage of wheat cultivars Millat-2011, AARI-2011 and Lasani-2008 was more phytotoxic than Faisalabad-2008. Moreover, tillering stage herbage of all wheat cultivars had less inhibitory potential against emergence, seedling growth and biochemical attributes of lambsquarter. Wheat herbage amendment increased the soil pH, phenolic, organic carbon and nitrogen contents as compared to control.

Composição florística e cobertura vegetal das savanas na região de Alter do Chão, Santarém - PA

Neste estudo foi determinado a cobertura vegetal e a composição florística em 38 parcelas de 3,75 ha (250 m x 150 m), distribuídas por 30.000 ha na savana de Alter do Chão, Município de Santarém, Pará. Nas 38 parcelas foram registradas 130 espécies em 45 famílias. As únicas espécies de dicotiledôneas que cobriram 1% ou mais da área no estrato herbáceo-arbustivo foram Dioclea bicolor Benth. e Lafoensia pacari A. St.-Hil. A maior parte da área foi coberta pelas gramíneas Paspalum carinatum Humb. & Bonpl. ex Flügge (16%) e Trachypogon plumosus (Humb. & Bonpl. ex Willd.) Nees (22%). A gramínea Axonopus canescens (Nees ex Trin.) Pilg. e a ciperácea Rhyncospora hirsuta Vahl também cobriram mais que 1% da área. Apenas oito espécies, Anacardium occidentale L., Himatanthus fallax (Müll. Arg.) M. M. Plumel, Lafoensia pacari A. St.-Hil., Byrsonima coccolobifolia Kunth, Byrsonima crassifolia (L.) Kunth, Pouteria ramiflora (Mart.) Radlk., Qualea grandiflora Mart. e Salvertia convallariodora A. St.-Hil. tinham copas no estrato arbóreo que projetaram sobre mais que 1% da área. Destas, somente B. crassifolia (5,7%), S. convallariodora (6,0%) e P. ramiflora (2,1%) projetaram sobre mais que 2% da área. Cinqüenta e três por cento da área não tinha cobertura de arbustos, gramíneas ou ciperáceas, e 45% também não tinha cobertura de copas de árvores. Gramíneas e ciperáceas cobriram em média 39,2% das parcelas, e arbustos 11,0%. As correlações entre matrizes de similaridade para as espécies em diferentes estratos e grupos taxonômicos da vegetação foram geralmente baixas e houve pouca correlação entre matrizes baseadas em dados quantitativos e matrizes baseadas em dados de presença/ausência. Portanto, deve-se ter cautela em comparações entre áreas de savana baseadas somente em um estrato vegetativo ou em um grupo taxonômico.

Selective destruction of nigrostriatal dopaminergic neurons does not alter [3H]-ryanodine binding in rat striatum

Dopamine nigrostriatal neurons are important for motor control and may contain a particularly dense population of ryanodine receptors involved in the control of dopamine release. To test this hypothesis, we used a classical model of unilateral selective lesion of these neurons in rats based on 6-hydroxydopamine (6-OHDA) injection into the substantia nigra. Binding of [3H]-GBR 12935, used as a presynaptic marker since it labels specifically the dopamine uptake complex, was dramatically decreased by 83-100% in striatum homogenates after 6-OHDA lesion. On the contrary, no reduction of [3H]-ryanodine binding was observed. The present data indicate that [3H]-ryanodine binding sites present in rat striatum are not preferentially localized in dopaminergic terminals.

The secondary alcohol and aglycone metabolites of doxorubicin alter metabolism of human erythrocytes

Anthracyclines, a class of antitumor drugs widely used for the treatment of solid and hematological malignancies, cause a cumulative dose-dependent cardiac toxicity whose biochemical basis is unclear. Recent studies of the role of the metabolites of anthracyclines, i.e., the alcohol metabolite doxorubicinol and aglycone metabolites, have suggested new hypotheses about the mechanisms of anthracycline cardiotoxicity. In the present study, human red blood cells were used as a cell model. Exposure (1 h at 37ºC) of intact human red blood cells to doxorubicinol (40 µM) and to aglycone derivatives of doxorubicin (40 µM) induced, compared with untreated red cells: i) a ~2-fold stimulation of the pentose phosphate pathway (PPP) and ii) a marked inhibition of the red cell antioxidant enzymes, glutathione peroxidase (~20%) and superoxide dismutase (~60%). In contrast to doxorubicin-derived metabolites, doxorubicin itself induced a slighter PPP stimulation (~35%) and this metabolic event was not associated with any alteration in glutathione reductase, glutathione peroxidase, catalase or superoxide dismutase activity. Furthermore, the interaction of hemoglobin with doxorubicin and its metabolites induced a significant increase (~22%) in oxygen affinity compared with hemoglobin incubated without drugs. On the basis of the results obtained in the present study, a new hypothesis, involving doxorubicinol and aglycone metabolites, has been proposed to clarify the mechanisms responsible for the doxorubicin-induced red blood cell toxicity.

Does acute hyperglycemia alter rat aortic depressor nerve function?

Because it is not known where in the reflex arch, i.e., afference, central nervous system or efferences, hyperglycemia affects baroreflex function, the present study examined the effect of short-term (30 min) hyperglycemia on aortic depressor nerve function measured by a mean arterial pressure vs aortic depressor nerve activity curve, fitted by sigmoidal regression, or by cross-spectral analysis between mean arterial pressure and aortic depressor nerve activity. Anesthetized male Wistar rats received an intravenous bolus (0.25 mL) injection, followed by 30 min of infusion (1 mL/h) of 30% glucose (N = 14). Control groups received a bolus injection and infusion of 0.9% saline (N = 14), or 30% mannitol (N = 14). Glucose significantly increased both blood glucose and plasma osmolarity (P < 0.05). Mean arterial pressure did not change after glucose, saline or mannitol infusion. Mean arterial pressure vs nerve activity curves were identical before and 10 and 30 min after the beginning of glucose, saline or mannitol infusion. Slow (0.3 Hz) oscillations of arterial pressure were induced by controlled bleeding, and cross-spectral analysis was applied to arterial pressure and aortic nerve activity. Transfer function magnitude (aortic depressor nerve activity/mean arterial pressure ratio in the frequency domain) was calculated as an index of gain of the aortic depressor nerve. Transfer function magnitude was similar in all groups during induced or spontaneous oscillations of arterial pressure. In conclusion, the present study demonstrates, by means of two different approaches for assessing baroreceptor function, that aortic depressor nerve activity was not altered by short-term (30 min) hyperglycemia.

Brief daily postpartum separations from the litter alter dam response to psychostimulants and to stress

Neonatal handling induces several behavioral and neurochemical alterations in pups, including decreased responses to stress and reduced fear in new environments. However, there are few reports in the literature concerning the behavioral effects of this neonatal intervention on the dams during the postpartum period. Therefore, the aim of the current study was to determine if brief postpartum separation from pups has a persistent impact on the dam's stress response and behavior. Litters were divided into two neonatal groups: 1) non-handled and 2) handled [10 min/day, from postnatal day (PND) 1 to 10]. Weaning occurred at PND 21 when behavioral tasks started to be applied to the dams, including sweet food ingestion (PND 21), forced swimming test (PND 28), and locomotor response to a psychostimulant (PND 28). On postpartum day 40, plasma was collected at baseline for leptin assays and after 1 h of restraint for corticosterone assay. Regarding sweet food consumption, behavior during the forced swimming test or plasma leptin levels did not differ between dams briefly separated and non-separated from their pups during the postpartum period. On the other hand, both increased locomotion in response to diethylpropion and increased corticosterone secretion in response to acute stress were detected in dams briefly separated from their pups during the first 10 postnatal days. Taken together, these findings suggest that brief, repeated separations from the pups during the neonatal period persistently impact the behavior and induce signs of dopaminergic sensitization in the dam.

Neonatal hyper- and hypothyroidism alter the myoglobin gene expression program in adulthood

Myoglobin acts as an oxygen store and a reactive oxygen species acceptor in muscles. We examined myoglobin mRNA in rat cardiac ventricle and skeletal muscles during the first 42 days of life and the impact of transient neonatal hypo- and hyperthyroidism on the myoglobin gene expression pattern. Cardiac ventricle and skeletal muscles of Wistar rats at 7-42 days of life were quickly removed, and myoglobin mRNA was determined by Northern blot analysis. Rats were treated with propylthiouracil (5-10 mg/100 g) and triiodothyronine (0.5-50 µg/100 g) for 5, 15, or 30 days after birth to induce hypo- and hyperthyroidism and euthanized either just after treatment or at 90 days. During postnatal (P) days 7-28, the ventricle myoglobin mRNA remained unchanged, but it gradually increased in skeletal muscle (12-fold). Triiodothyronine treatment, from days P0-P5, increased the skeletal muscle myoglobin mRNA 1.5- to 4.5-fold; a 2.5-fold increase was observed in ventricle muscle, but only when triiodothyronine treatment was extended to day P15. Conversely, hypothyroidism at P5 markedly decreased (60%) ventricular myoglobin mRNA. Moreover, transient hyperthyroidism in the neonatal period increased ventricle myoglobin mRNA (2-fold), and decreased heart rate (5%), fast muscle myoglobin mRNA (30%) and body weight (20%) in adulthood. Transient hypothyroidism in the neonatal period also permanently decreased fast muscle myoglobin mRNA (30%) and body weight (14%). These results indicated that changes in triiodothyronine supply in the neonatal period alter the myoglobin expression program in ventricle and skeletal muscle, leading to specific physiological repercussions and alterations in other parameters in adulthood.