Phentolamine relaxes human corpus cavernosum by a nonadrenergic mechanism activating ATP-sensitive K+ channel

To investigate the pharmacodynamics of phentolamine in human corpus cavernosum (HCC) with special attention to the role of the K+ channels. Strips of HCC precontracted with nonadrenergic stimuli and kept in isometric organ bath immersed in a modified Krebs-Henseleit solution enriched with guanethidine and indomethacine were used in order to study the mechanism of the phentolamine-induced relaxation. Phentolamine caused relaxation (approximately 50%) in HCC strips precontracted with K+ 40 mM. This effect was not blocked by tetrodotoxin (1 microM) (54.6+/-4.6 vs 48.9+/-6.4%) or (atropine (10 microM) (52.7+/-6.5 vs 58.6+/-5.6%). However, this relaxation was significantly attenuated by L-NAME (100 microM) (59.7+/-5.8 vs 27.8+/-7.1%; P<0.05; n = 8) and ODQ (100 microM) (62.7+/-5.1 vs 26.8+/-3.9%; P<0.05; n = 8). Charybdotoxin and apamin (K(Ca)-channel blockers) did not affect the phentolamine relaxations (54.6+/-4.6 vs 59.3+/-5.2%). Glibenclamide (100 microM), an inhibitor of K(ATP)-channel, caused a significant inhibition (56.7+/-6.3 vs 11.3+/-2.3%; P<0.05; n = 8) of the phentolamine-induced relaxation. In addition, the association of glibenclamide and L-NAME almost abolished the phentolamine-mediated relaxation (54.6+/-5.6 vs 5.7+/-1.4%; P<0.05; n = 8). The results suggest that phentolamine relaxes HCC by a nonadrenergic-noncholinergic mechanism dependent on nitric oxide synthase activity and activation of K(ATP)-channel.     

Growth and production of laccases by the ligninolytic fungi, Pleurotus ostreatus and Botryosphaeria rhodina , cultured on basal medium containing the herbicide, Scepter (imazaquin)

The herbicide, Scepter, whose active principle is imazaquin, is commonly used in soybean farming to combat wide-leaf weeds. The basidiomycete, Pleurotus ostreatus , and the ascomycete, Botryosphaeria rhodina , were evaluated for their growth and laccase production when cultured on basal media containing Scepter. Both fungi could grow on the herbicide when cultivated in solid and submerged liquid culture in the presence of Scepter at concentrations of 0-6% (v/v) for P. ostreatus , and up to 0-50% (v/v) for B. rhodina , and in each case produced laccases when assayed against ABTS [2,2(1)-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid)] and 2,6-dimethoxyphenol. P . ostreatus could tolerate up to 6% of Scepter before it became toxic to the fungus, while in the case of B. rhodina , 50% (v/v) Scepter was the highest amount that supported grow, and laccase activity was detectable up to 25% (v/v). An inverse relationship existed between the level of Scepter in the culture medium that supported fungal growth and laccase production. Analysis of the results showed that the fungi studied presented different behaviour towards Scepter in the culture environment.     

Neuro-apoptogenic and blood platelet targeting toxins in benthic marine cyanobacteria from the Portuguese coast

Six strains of marine cyanobacteria, of which five benthic, were isolated from an area of the Portuguese coast with no known apparent toxic microbial bloom. Five strains were lethal for mice. Four of them produced lethargy and four lead to bleeding. One of the toxic strains was from a genus (Aphanothece) not previously associated with toxin production. Extracts from four isolates induced SH-SY5Y-neuroblastoma cell apoptosis without affecting the viability of hepatocytes, NRK kidney cells, or fibroblasts. Aqueous extract from four isolates inhibited thrombin-induced blood platelet activation, with decreased P-selectin expression, platelet aggregation and shedding of platelet-derived micro-vesicles. Curiously, platelets treated with organic extracts from two of the cyanobacterial strains formed platelet micro-vesicles, expressed P-selectin on the surface and showed a distinct phosphotyrosine protein pattern, but failed to aggregate. We conclude that low-abundance marine cyanobacteria growing at low rates may be an important source for novel toxins that may be useful to dissect mammalian signalling pathways of apoptosis and platelet function.     

Dermatomyositis-like syndrome and HMG-CoA reductase inhibitor (statin) intake

A patient developed an adult-onset dermatomyositis-like syndrome characterized by skin rash and progressive proximal muscle weakness concurrent with the intake of simvastatin. Despite discontinuation of the statin, symptoms progressed and required conventional steroid therapy for remission. The association between statins and the development of a musculocutaneous syndrome closely resembling dermatomyositis in susceptible subjects is poorly understood and has been reported rarely. The purpose of this report is to provide additional support for this pathological association. Since the population receiving statins is large and rapidly growing, caregivers are urged to be alert regarding the early recognition and proper care of the spectrum of neuromuscular complications linked to statin intake.     

Urocortin in the central nervous system of a primate (Cebus apella): sequencing,immunohistochemical, and hybridization histochemical characterization

The urocortin (UCN)-like immunoreactivity and UCN mRNA distribution in various regions of the nonprimate mammalian brain have been reported. However, the Edinger-Westphal nucleus (EW) appears to be the only brain site where UCN expression is conserved across species. Although UCN peptides are present throughout vertebrate phylogeny, the functional roles of both UCN and EW remain poorly understood. Therefore, a study focused on UCN system organization in the primate brain is warranted. By using immunohistochemistry (single and double labeling) and in situ hybridization, we have characterized the organization of UCN-expressing cells and fibers in the central nervous system and pituitary of the capuchin monkey (Cebus apella). In addition, the sequence of the prepro-UCN was determined to establish the level of structural conservation relative to the human sequence. To understand the relationship of acetylcholine cells in the EW, a colocalization study comparing choline acetyltransferase (ChAT) and UCN was also performed. The cloned monkey prepro-UCN is 95% identical to the human preprohormone across the matched sequences. By using an antiserum raised against rat UCN and a probe generated from human cDNA, we found that the EW is the dominant site for UCN expression, although UCN mRNA is also expressed in spinal cord lamina IX. Labeled axons and terminals were distributed diffusely throughout many brain regions and along the length of the spinal cord. Of particular interest were UCN-immunoreactive inputs to the medial preoptic area, the paraventricular nucleus of the hypothalamus, the oral part of the spinal trigeminal nucleus, the flocculus of the cerebellum, and the spinal cord laminae VII and X. We found no UCN hybridization signal in the pituitary. In addition, we observed no colocalization between ChAT and UCN in EW neurons. Our results support the hypothesis that the UCN system might participate in the control of autonomic, endocrine, and sensorimotor functions in primates.     

Comparison of the response of three microalgae species exposed to elutriates of estuarine sediments based on growth and chemical speciation

The elutriate sediment toxicity test (ESTT) provides a measure of the amount of a substance that is exchanged between the sediment and the aqueous phase during resuspension processes such as floods or dredging operations. This study used ESTT with two complementary aims: a comparison of the elutriates of two estuarine sediments (anaerobic muddy [A] and aerobic sandy [B]) in terms of toxicity and a comparison of the response of three different microalgae (Emiliania huxleyi (coccolithophore), Dunaliella minuta (green alga), and Phaeodactylum tricornutum (diatom)) to each elutriate in terms of growth, heavy metals uptake, and organic ligands release or uptake in order to find eventual differences of sensitivity. The interpretation of the results was based on chemical speciation in the culture media. Both elutriates, particularly A, were much richer than seawater (control medium) in some heavy metals and organic ligands able to bind strongly heavy metals. Elutriate A slightly inhibited P. tricornutum growth but stimulated growth of E. huxleyi and D. minuta. Elutriate B stimulated the growth of the three algal species. Therefore, the diatom behaved differently from both the coccolithophore and the green alga. Strong complexation of trace metals by organic ligands could be the cause of absence of the metallic toxicity of the elutriates. Growth inhibition of P. tricornutum in elutriate A could be caused by ammonia-N and/or organic compounds. The concentration of the organic ligands decreased markedly (about 75%) in both elutriates after 10 d of incubation in contrast to the control culture, where their concentration increased about 50% because of exudation. This phenomenon was interpreted to result from ligand uptake by the algae, free or as metal complexes. This work demonstrated that beside the evaluation of toxicity of free heavy metals to alga species, the organic ligands must not be ignored. Depending on the amount of ligand present, the toxicity can be reduced (sequestration) or enhanced (better availability through uptake of metal-ligand complexes). Since the applied ESTT is a standard procedure (U.S. Environmental Protection Agency) for the evaluation of dredged material proposed for ocean disposal, it is necessary to discuss results obtained during toxicity tests with such elutriates in detail.     

Aedes albopictus may not be vector of dengue virus in human epidemics in Brazil

Over 60,500 dengue cases were reported in the state of Espírito Santo (ES), Brazil, between 1995 and 1998. The study's purpose was to identify whether Aedes albopictus was transmitting the dengue virus during an epidemic in the locality of Vila Beth nia (Viana County),Vitória, ES. From April 3 to 9, 1998, blood and serum samples were collected daily for virus isolation and serological testing. Four autochthonous cases were confirmed through DEN 1 virus isolation and two autochthonous cases through MAC ELISA testing. Of 37 Ae. aegypti and 200 Ae. albopictus adult mosquitoes collected and inoculated, DEN1 virus was isolated only from a pool of two Ae. aegypti female mosquitoes. The study results suggest that Ae. albopictus still cannot be considered an inter-human vector in dengue epidemics in Brazil.     

Isolations of yellow fever virus from Haemagogus leucocelaenus in Rio Grande do Sul State,Brazil

Following howling monkey (Alouatta caraya) deaths and yellow fever (YF) antigen detection by immunohistochemistry in the liver sample of a dead monkey in April and May 2001 in the municipalities of Garruchos and Santo Ant?nio das Miss?es, Rio Grande do Sul State, Brazil, epidemiological field investigations were initiated. Two strains of YF virus were isolated in suckling mice from 23 Haemagogus (Conopostegus) leucocelaenus Dyar & Shannon mosquitoes collected from the study sites. The YF virus was isolated from this species in the 1930s in Brazil and in the 1940s in Colombia. No human cases were reported during the current epizootic outbreak. The YF virus isolation and the absence of Hg. (Haemagogus) janthinomys Dyar from the area suggest that Hg. leucocelaenus may be a secondary YF vector and play an important role in the epidemiology of this disease in the Southern Cone.