Tyrosine availability prevents tyramine-induced tachyphylaxis in the isolated rat heart

Isolated rat hearts perfused with Chenoweth-Koelle solution exhibit tachyphylaxis to tyramine. This tachyphylaxis was prevented if tyrosine was included in the perfusion solution. Other amino acids, including glycine, serine, phenylalanine, valine, tryptophan, glutamate, aspartate, arginine, lysine and -tyrosine, failed to prevent the tyramine-induced tachyphylaxis. Hearts from reserpinized animals showed increased chronotropy after tyramine only when tyrosine was present in the medium. This response could be blocked by , m-hydroxybenzyl-hydrazine and d,l-propanolol, indicating that it was mediated by the synthesis and release of catecholamines. These experiments suggest that sympathetic nerves in the isolated rat heart exhibit a requirement for tyrosine when catecholamine release is enhanced.     

Hydroxylated analogues of the orally active broad spectrum antifungal, Sch 51048 (1), and the discovery of posaconazole [Sch 56592; 2 or (S,S)-5

As part of a detailed study, the syntheses, biological activities, and pharmacokinetic properties of hydroxylated analogues of the previously described broad spectrum antifungal agents, Sch 51048 (1), Sch 50001 (3), and Sch 50002 (4), are described. Based on an overall superior profile, one of the alcohols, Sch 56592 (2), was selected for clinical studies.     

Secretory structures at syconia and flowers of Ficus enormis (Moraceae): A specialization at ostiolar bracts and the first report of inflorescence colleters

The fig (Ficus L.) infructescence, called syconium, is a receptacle with an apical opening, the ostiole, closed by bracts. The ostiolar bracts produce an exudate, which is rather conspicuous in some species. It has not been histochemically analyzed yet, and the structures responsible for its production are still unknown. Some wild growing species of Ficus from Brazil produce high amounts of this ostiolar exudate. Ficus enormis (Mart. ex Miq.) Miq. grows as trees or shrubs in the Atlantic rainforest. Our goal was to identify the secretory structures present in the inflorescence and, to characterize histochemically the ostiolar tissues and exudates. Syconia samples of F. enormis were processed and stained according to the usual techniques in plant anatomy. The morphological analysis revealed different types of bracts, one type specialized in secretion, another showing transitional characteristics between secretory and non-secreting bracts, and a third one being non-secreting. They are designated as secretory ostiolar bracts, transitional bracts and wall bracts. The floral bracteoles, digital-shaped colleters present in the ostiole, at the syconium axis and at the flower receptacle, were also analyzed. All have similar structure, like finger-shaped secretory trichomes. The colleters present among ostiolar bracts may contribute to production and composition of the ostiole exudate.     

Elastic fiber assembly in the adult mouse pubic symphysis during pregnancy and postpartum

Impairment of pelvic organ support has been described in mice with genetic modifications of the proteins involved in elastogenesis, such as lysyl oxidase-like 1 (LOXL1) and fibulin 5. During pregnancy, elastic fiber-enriched pelvic tissues are modified to allow safe delivery. In addition, the mouse pubic symphysis is remodeled in a hormone-controlled process that entails the modification of the fibrocartilage into an interpubic ligament (IpL) and the relaxation of this ligament. After first parturition, recovery occurs to ensure pelvic tissue homeostasis. Because ligaments are the main supports of the pelvic organs, this study aimed to evaluate elastogenesis in the IpL during mouse pregnancy and postpartum. Accordingly, virgin, pregnant, and postpartum C57BL/6 mice were studied using light, confocal, and transmission electron microscopy as well as Western blots and real-time PCR. Female mice exhibited the separation of the pubic bones and the formation, relaxation, and postpartum recovery of the IpL. By the time the IpL was formed, the elastic fibers had increased in profile length and diameter, and they consisted of small conglomerates of amorphous material distributed among the bundles of microfibrils. Our analyses also indicated that elastin/tropoelastin, fibrillin 1, LOXL1/Loxl1, and fibulin 5 were spatially and temporally regulated, suggesting that these molecules may contribute to the synthesis of new elastic fibers during IpL development. Overall, this work revealed that adult elastogenesis may be important to assure the elasticity of the pelvic girdle during preparation for parturition and postpartum recovery. This finding may contribute to our understanding of pathological processes involving elastogenesis in the reproductive tract.     

Effect of genetic modifications by selection for immunological tolerance on fungus infection in mice

Two strains of mice genetically selected for extreme phenotypes of immunological tolerance to ovalbumin, susceptible (TS) and resistant (TR), were experimentally infected with Sporothrix schenckii. The objective was to observe whether the genetic modifications produced by the selection might be associated with interstrain differences in adaptive immune and innate responses to infection. Therefore, we evaluated the LD(50), CFU, phagocytic index, fungicidal activity, pro-inflammatory cytokines, specific antibody titres, and the delayed-type hypersensitivity reactivity. TR mice were tenfold more susceptible to infection than TS mice, as shown by LD(50) (5 x 10(6) conidia i.v.). In TS mice, the resistance was a consequence of the tissue fungal load reduction, consistent specific T-cell-mediated immunity, and tumour necrosis factor (TNF)-alpha activity at onset of infection. In TR mice, these responses were not precociously detected. Therefore, the absence of CD4(+) T-cell response in the first week of infection might explain the non-clearance of pathogen in TR mice. However, TR mice did show an increase in TNF level and delayed-type hypersensitivity response after the first week post-infection; there was also expansion and increase in granulomatous foci and CFU in the spleen. The expansion of granulomatous foci and the increase in TNF-alpha and tissue fungal load to damaging levels induced severe tissue destruction, general failure of the organs, cachexy and death in TR mice. The results show that genetic selection for extreme phenotypes of immunological tolerance also modified the responses to S. schenckii infection.     

Domesticity of Lutzomyia whitmani (Diptera: psychodidae) populations: field experiments indicate behavioural differences

The sandfly Lutzomyia whitmani (Antunes & Coutinho) is an important vector for cutaneous leishmaniasis throughout much of Brazil, and has recently been shown to consist of more than one mitochondrial lineage. It has frequently been asserted that the degree of adaptation of L. whitmani to human environments varies across its range. As a standardized test of indoor feeding for three geographically distant populations of L. whitmani, catches inside experimental chicken sheds of varying degrees of wall closure (0%, 33%, 67% and 98%) were compared. Each increment in shed closure reduced catches of females (relative to the most open shed) by a similar degree for each population: geometric mean catches dropped by 11-40% with 33% closure, by 41-62% with 67% closure, and by 69-100% with 98% closure. Geometric mean catches of males from the two more northerly populations also decreased with increasing shed closure, by 18% and 22% for 33% closure, 58% and 69% for 67% closure, 91% and 93% for 98% closure. Males from the most southerly population showed significantly different behaviour, with 33% closure causing a 54% increase in geometric mean catch, 67% closure causing a 6% increase, and 98% closure causing a 32% reduction. For this southerly population, sex ratios became more male biased with increasing density in more closed sheds, suggesting aggregation driven by intra-specific communication. Lutzomyia intermedia (Lutz & Neiva) was relatively more likely than L. whitmani to approach baits in the three more closed sheds, rather than the most open shed, offering a behavioural explanation for observed differences in indoor biting rates between the species.     

Influence of liposomal local anesthetics on platelet aggregation in vitro

We assessed the effect of local anesthetics (LA) from different families such as esters (benzocaine), linear aminoamides (lidocaine) and cyclic aminoamides (bupivacaine) on the platelet aggregation induced by ADP. Liposomal formulations of the three LA, prepared with egg phosphatidylcholine:cholesterol alpha-tocopherol, were also tested. The three LA were able to inhibit platelet aggregation induced by ADP, in the following order: bupivacaine > lidocaine > benzocaine. After encapsulation into liposomes the inhibitory effect increased for all anesthetics studied, showing that aggregation tests could be used to assess the toxicity of new drug formulations.     

Reserve selection and persistence: complementing the existing Atlantic Forest reserve system

This study is an exercise to check the efficiency of the existing reserve system, and to show how systematic conservation planning—using information available and the complementarity concept—can improve the basis for decisions and minimize costs. We verified the performance, in number of cells and primate species representation, of the existing Atlantic Forest (Brazil) reserve network with a quarter-degree resolution grid, with 1,884 cells. We used occurrence data of 20 endemic primate species, and the maps of 237 existing reserves. Reserve networks were selected to represent primate species first considering no pre-existing reserves in Atlantic Forest, and then, considering the existing reserve system, taking into account the minimum area for viable population of the larger species (Northern muriqui Brachyteles hypoxanthus). Reserve selection was carried out using the complementarity concept implemented by a simulated annealing algorithm. Primate species representation (at least one occurrence in the network) could be achieved with 8% of the existing reserve system (nine cells in relation to the 120 in the existing reserve system). We found that today’s reserve system represents 89% of endemic primate species, excluding the species Coimbra Filho’s titi monkey (Callicebus coimbrai) and Marcgraf’s capuchin (Cebus flavius). The networks selected without considering existing reserves contained nine cells. The networks selected considering existing reserves (120 cells), had two new cells necessary to represent all the primates. This does not mean that a viable alternative is to start from zero (i.e., nonexistent reserves). Identifying critical supplementary areas using biodiversity information to fill the gaps and then starting “conservation in practice” in these areas should be priorities.     

Adenosine Inhibition of 45Ca Uptake by Synaptosomes as Function of Time of Electrical Stimulation

Abstract

The effect of adenosine on ⁴⁵Ca uptake by rat brain synaptosomes electrically stimulated was studied as function of time of stimulation (10, 30, 120 s). Inhibition of ⁴⁵Ca uptake was more evident for 120 s.