Oxidative Stress and Modification of Renal Vascular Permeability Are Associated with Acute Kidney Injury during P. berghei ANKA Infection

Malaria associated-acute kidney injury (AKI) is associated with 45% of mortality in adult patients hospitalized with severe form of the disease. However, the causes that lead to a framework of malaria-associated AKI are still poorly characterized. Some clinical studies speculate that oxidative stress products, a characteristic of Plasmodium infection, as well as proinflammatory response induced by the parasite are involved in its pathophysiology. Therefore, we aimed to investigate the development of malaria-associated AKI during infection by P. berghei ANKA, with special attention to the role played by the inflammatory response and the involvement of oxidative stress. For that, we took advantage of an experimental model of severe malaria that showed significant changes in the renal pathophysiology to investigate the role of malaria infection in the renal microvascular permeability and tissue injury. Therefore, BALB/c mice were infected with P. berghei ANKA. To assess renal function, creatinine, blood urea nitrogen, and ratio of proteinuria and creatininuria were evaluated. The products of oxidative stress, as well as cytokine profile were quantified in plasma and renal tissue. The change of renal microvascular permeability, tissue hypoxia and cellular apoptosis were also evaluated. Parasite infection resulted in renal dysfunction. Furthermore, we observed increased expression of adhesion molecule, proinflammatory cytokines and products of oxidative stress, associated with a decrease mRNA expression of HO-1 in kidney tissue of infected mice. The measurement of lipoprotein oxidizability also showed a significant increase in plasma of infected animals. Together, our findings support the idea that products of oxidative stress, as well as the immune response against the parasite are crucial to changes in kidney architecture and microvascular endothelial permeability of BALB/c mice infected with P. berghei ANKA.     

L-NAME co-treatment prevent oxidative damage in the lung of adult Wistar rats treated with vitamin A supplementation

Based on the fact that vitamin A in clinical doses is a potent pro-oxidant agent to the lungs, we investigated here the role of nitric oxide (NO?) in the disturbances affecting the lung redox environment in vitamin A-treated rats (retinol palmitate, doses of 1000-9000 IU?kg(-1)?day(-1)) for 28 days. Lung mitochondrial function and redox parameters, such as lipid peroxidation, protein carbonylation and the level of 3-nytrotyrosine, were quantified. We observed, for the first time, that vitamin A supplementation increases the levels of 3-nytrotyrosine in rat lung mitochondria. To determine whether nitric oxide (NO ?) or its derivatives such as peroxynitrite (ONOO-) was involved in this damage, animals were co-treated with the nitric oxide synthase inhibitor L-NAME (30 mg?kg(-1), four times a week), and we analysed if this treatment prevented (or minimized) the biochemical disturbances resulting from vitamin A supplementation. We observed that L-NAME inhibited some effects caused by vitamin A supplementation. Nonetheless, L-NAME was not able to reverse completely the negative effects triggered by vitamin A supplementation, indicating that other factors rather than only NO? or ONOO- exert a prominent role in mediating the redox effects in the lung of rats that received vitamin A supplementation.     

New systematic assignments in Gonyleptoidea (Arachnida, Opiliones, Laniatores)

As part of an ongoing revision of the family Gonyleptidae, we have identified many species that are synonyms of previously described species or misplaced in this family. This article summarizes these findings, adding previously unavailable information or correcting imprecise observations to justify the presented taxonomic changes. The following new familial or subfamilial assignments are proposed: Nemastygnus Roewer, 1929 and Taulisa Roewer, 1956 are transferred to Agoristenidae, Agoristeninae; Napostygnus Roewer, 1929 to Cranaidae; Ceropachylinus peruvianus Roewer, 1956 and Pirunipygus Roewer, 1936 are transferred to Gonyleptidae, Ampycinae; Gyndesops Roewer, 1943, Haversia Roewer, 1913 and Oxapampeus Roewer, 1963 are transferred to Gonyleptidae, Pachylinae. The following generic synonymies are proposed for the family Gonyleptidae: Acanthogonyleptes Mello-Leitão, 1922 = Centroleptes Roewer, 1943; Acrographinotus Roewer, 1929 = Unduavius Roewer, 1929; Gonyleptes Kirby, 1819 = Collonychium Bertkau, 1880; Mischonyx Bertkau, 1880 = Eugonyleptes Roewer, 1913 and Gonazula Roewer, 1930; Parampheres Roewer, 1913 = Metapachyloides Roewer, 1917; Pseudopucrolia Roewer, 1912 = Meteusarcus Roewer, 1913; Haversia Roewer, 1913 = Hoggellula Roewer, 1930. The following specific synonymies are proposed for the family Gonyleptidae: Acanthogonyleptes singularis (Mello-Leitão, 1935) = Centroleptes flavus Roewer, 1943, syn. n.; Geraeocormobius sylvarum Holmberg, 1887 = Discocyrtus serrifemur Roewer, 1943, syn. n.; Gonyleptellus bimaculatus (Sørensen, 1884) = Gonyleptes cancellatus Roewer,1917, syn. n.; Gonyleptes atrus Mello-Leitão, 1923 = Weyhia brieni Giltay, 1928, syn. n.; Gonyleptes fragilis Mello-Leitão, 1923 = Gonyleptes banana Kury, 2003, syn. n.; Gonyleptes horridus Kirby, 1819 = Collonychium bicuspidatum Bertkau, 1880, syn. n., Gonyleptes borgmeyeri Mello-Leitão, 1932, syn. n., Gonyleptes curvicornis Mello-Leitão, 1932, syn. n., Metagonyleptes hamatus Roewer, 1913, syn. n. and Paragonyleptes simoni Roewer, 1930, syn. n.; Gonyleptes pustulatus Sørensen, 1884 = Gonyleptes guttatus Roewer, 1917, syn. n.; Haversia defensa (Butler, 1876) = Sadocus vallentini Hogg, 1913, syn. n.; Liogonyleptoides minensis (Piza, 1946) = Currala bahiensis Soares, 1972, syn. n.; Megapachylus grandis Roewer, 1913 = Metapachyloides almeidai Soares & Soares, 1946, syn. n.; Mischonyx cuspidatus (Roewer, 1913) = Gonazula gibbosa Roewer, 1930 syn. n.; Mischonyx scaber (Kirby, 1819) = Xundarava holacantha Mello-Leitão, 1927, syn. n.; Parampheres tibialis Roewer, 1917 = Metapachyloides rugosus Roewer, 1917, syn. n.; Parapachyloides uncinatus (Sørensen, 1879) = Goyazella armata Mello-Leitão, 1931, syn. n.; Pseudopucrolia mutica (Perty, 1833) = Meteusarcus armatus Roewer, 1913, syn. n. The following new combinations are proposed: Acrographinotus ornatus (Roewer, 1929), comb. n. (ex Unduavius); Gonyleptellus bimaculatus (Sørensen, 1884),comb. n. (ex Gonyleptes);Gonyleptes perlatus (Mello-Leitão, 1935), comb. n. (exMoojenia);Mischonyx scaber (Kirby, 1819), comb. n. (ex Gonyleptes); and Neopachyloides peruvianus (Roewer, 1956), comb. n. (ex Ceropachylus). The following species of Gonyleptidae, Gonyleptinae are revalidated: Gonyleptes atrus Mello-Leitão, 1923 and Gonyleptes curvicornis (Roewer, 1913).     

Cdon and Boc: Two transmembrane proteins implicated in cell-cell communication

Cdon and Boc, and their Drosophila homologues Ihog and Boi, are evolutionary conserved transmembrane glycoproteins belonging to a subgroup of the Immunoglobulin superfamily of cell adhesion molecules (CAMs). Initially isolated in vertebrates as CAMs that link cadherin function with MAPK signaling in myoblast differentiation, they have thereafter been shown to act as essential receptors for the Hedgehog (Hh) family of secreted proteins. They associate with both ligand and other Hh receptor components, including Ptch and Gas1, thus forming homo- and heteromeric complexes. In Drosophila, they are also involved in ligand processing and release from Hh producing cells. Cdon/Boc and Ihog/Boi can substitute one another and play redundant functions is some contexts. In addition, Boc, but not Cdon, mediates axon guidance information provided by Hh in specific neuronal populations, whereas mutations in the CDON cause holoprosencephaly, a human congenital anomaly defined by forebrain midline defects prominently associated with diminished Hh pathway activity.     

Feline Histoplasmosis in Brazil: Clinical and Laboratory Aspects and a Comparative Approach of Published Reports

The present study described clinical and epidemiological aspects of three cases of feline histoplasmosis and compared them to previously described cases. A detailed mycological identification and antifungal susceptibility profile of each isolate are presented. Secondarily, a serological survey for anti-Histoplasma antibodies was performed with domestic and wild cats. Diseased animals presented nodular to ulcerated skin lesions and respiratory disorders as main clinical signs. H. capsulatum var. capsulatum was isolated and the strains showed to be susceptible to antifungal drugs. Considering that feline histoplasmosis is uncommonly observed in veterinary clinics, diagnosis, and clinical management in endemic areas should be improved.     

The diversity, antimicrobial and anticancer activity of endophytic fungi associated with the medicinal plant Stryphnodendron adstringens (Mart.) Coville (Fabaceae) from the Brazilian savannah

The diversity and biological activities of the endophytic fungi associated with the Brazilian medicinal plant Stryphnodendron adstringens were studied. A total of 320 fungal isolates were obtained, and 66 phylotypes comprising 25 genera were identified. The fungal community of S. adstringens displayed high richness, diversity and low dominance indices. The most abundant phylotypes were closely related to Diaporthe phaseolorum, Guignardia camelliae, and Preussia pseudominima. Sixteen fungal extracts displayed biological activities when screened against bacteria, fungi, cancer cell lines, and amastigote forms of Leishmania amazonensis. The extract of phylotype Nigrospora cf. oryzae exhibited a selective antifungal activity and inhibited the growth of Candida albicans and Cladosporium sphaerospermum. The extracts of Diaporthe cf. phaseolorum and Xylaria sp. phylotypes displayed anticancer activities. Our results indicate that the endophytes associate with this medicinal plant may be a source for novel drugs.     

Characterization of suramin binding sites on the human group IIA secreted phospholipase A2 by site-directed mutagenesis and molecular dynamics simulation

Suramin is a polysulphonated naphthylurea with inhibitory activity against the human secreted group IIA phospholipase A(2) (hsPLA2GIIA), and we have investigated suramin binding to recombinant hsPLA2GIIA using site-directed mutagenesis and molecular dynamics (MD) simulations. The changes in suramin binding affinity of 13 cationic residue mutants of the hsPLA2GIIA was strongly correlated with alterations in the inhibition of membrane damaging activity of the protein. Suramin binding to hsPLA2GIIA was also studied by MD simulations, which demonstrated that altered intermolecular potential energy of the suramin/mutant complexes was a reliable indicator of affinity change. Although residues in the C-terminal region play a major role in the stabilization of the hsPLA2GIIA/suramin complex, attractive and repulsive hydrophobic and electrostatic interactions with residues throughout the protein together with the adoption of a bent suramin conformation, all contribute to the stability of the complex. Analysis of the hsPLA2GIIA/suramin interactions allows the prediction of the properties of suramin analogues with improved binding and higher affinities which may be candidates for novel phospholipase A(2) inhibitors.     

Birth of normal infants after transfer of embryos that were twice vitrified/warmed at cleavage stages: Report of two cases

The role of cryopreservation in assisted reproductive technology programs has increased within the last years allowing the transfer of a limited number of embryos and the storage of the remaining for future use. The reduction in the number of transferred embryos decreases the frequency of multiple pregnancy rates and of ovarian hyperstimulation syndrome while the cumulative pregnancy rate can be maximized. Moreover, as not all embryos will survive the warming process more cleavage stage embryos are warmed to improve selection for transfer. Therefore, surplus good quality cleavage stage embryos and/or blastocysts must be re-vitrified for further transfer to achieve pregnancy. To our knowledge, there have been no reports demonstrating that human embryos can be successfully vitrified/warmed twice at the cleavage stage. Thus we report two successful pregnancies and deliveries of healthy babies after transfer of embryos that were twice vitrified/warmed at 2–4 cells stage.