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Copper(II) complexes have been intensely investigated in a variety of diseases and pathological conditions due to their therapeutic potential. The development of these complexes requires a good knowledge of metal coordination chemistry and ligand design to control species distribution in solution and tailor the copper(II) centers in the right environment for the desired biological activity. Herein we present the synthesis and characterization of two ligands HL1 and H2L2 containing a phenanthroline unit (phen) attached to the amino group of histidine (His). Their copper(II) coordination properties were studied using potentiometry, spectroscopy techniques (UV–vis and EPR), mass spectrometry (ESI-MS) and DFT calculations. The data showed the formation of single copper complexes, [CuL1]+and [CuL2], with high stability within a large pH range (from 3.0 to 9.0 for [CuL1]+and from 4.5 to 10.0 for [CuL2]). In both complexes the Cu2+ion is bound to the phen unit, the imidazole ring and the deprotonated amide group, and displays a distorted square pyramidal geometry as confirmed by single crystal X-ray crystallography. Interestingly, despite having similar structures, these copper complexes show different redox potentials, DNA cleavage properties and cytotoxic activity against different cancer cell lines (human ovarian (A2780), its cisplatin-resistant variant (A2780cisR) and human breast (MCF7) cancer cell lines). The [CuL2] complex has lower reduction potential (Epc= −0.722 V vs −0.452 V for [CuL1]+) but higher biological activity. These results highlight the effect of different pendant functional groups (carboxylate vs amide), placed out of the coordination sphere, in the properties of these copper complexes.

Background Bovine herpesvirus type 5 is an important agent of meningoencephalitis in cattle and has been identified in outbreaks of bovine neurological disease in several Brazilian states. In recent years, oxoquinoline derivatives have become an important focus in antiviral drug research.Methods The cytotoxicity and anti BoHV-5RJ42/01 activity of a set of synthetic 4-oxoquinoline derivatives 4a-k were assayed on Madin–Darby Bovine Kidney cell and antiviral activity by plaque reduction assay. Results: The most promising substance (4h) exhibited CC50and EC50values of 1,239 μM ±5.5 and 6.0 μM ±1.5, respectively, with an SI =206. Two other compounds 4j (CC50= 35 μM ±2 and EC50= 24 μM ±7.0) and 4k (CC50= 55 μM ±2 and EC50= 24 μM ±5.1) presented similar inhibitory profile and selectivity indexes of 1.4 and 2.9, respectively. The results of the time-of-addition studies revealed expressive reduction of virus production (≥80%) in different stages of virus replication cycle except for compound 4h that slightly inhibited virus yield in the first 2 h post infection, but it showed expressive virus inhibition after this time.Conclusions All three compounds slightly interact with the virus on the virucidal assay and they are not able to block virus attachment and penetration. Antiviral effect of oxoquinoline 4h was more prominent than acyclovir which leads us to suggest compound 4h as a promising molecule for further anti-BoHV-5 drug design.

Ethanol (EtOH) exposure during different phases of life may increase the risk of infections and cause alterations in the central nervous system. The present study investigated the effects of binge‐like EtOH exposure in adolescent rats on the febrile response that was induced by lipopolysaccharide (LPS) and interleukin‐1β(IL‐1β). Male rats were exposed to EtOH from postnatal days 25 to 38 in a binge‐like pattern. Fever was induced by LPS(5 and 50 μg/kg, intraperitoneally) and evaluated on postnatal days 51 and 63, or by IL‐β(3 ng) and evaluated on postnatal day 51. Hematological parameters, the status of peritoneal macrophages, and plasma and cerebrospinal IL‐1βlevels were also evaluated on postnatal day 51. EtOH exposure during adolescence did not alter normal body temperature. However, a significant reduction in the febrile response that was induced by LPSat both doses was observed on postnatal day 51. However, no changes in the febrile response were observed on postnatal day 63 in EtOH‐exposed animals. The febrile response that was induced by intracerebroventricular IL‐1βalso significantly decreased in animals that received binge‐like EtOH exposure during adolescence. Acute oral treatment with EtOH 24 h prior to LPSadministration did not alter the febrile response that was induced by LPS. Binge‐like EtOH exposure during adolescence did not alter hematological parameters or the number or viability of peritoneal macrophages. Binge‐like EtOH exposure did not alter plasma IL‐1βlevels but reduced the cerebrospinal fluid levels of this cytokine. These results suggest that binge‐like EtOH exposure during adolescence causes changes in the central nervous system that can impair the febrile response that can be observed after the cessation of EtOH exposure. These changes were reversible and appeared to involve the LPS/IL‐1βsystem. Adolescence is a critical period for the development of several brain areas and the consumption of ethanol during this period of life is increasing. In this study, we investigated the consumption of ethanol in a binge pattern affects the febrile response of rats. The study shows that binge‐like ethanol consumption during adolescence impairs the febrile response for a period of time which may increase the susceptibility of the animals to infectious diseases even after the cessation of ethanol ingestion.

To evaluate the prevalence and circulation of rotavirus genotypes before and after the introduction of oral vaccine against human rotavirus, and to check for a possible change in the age of occurence of the infection by RV-A.

This investigation describes the molecular characterization of P[6]G2 rotavirus strains from hospitalized neonates with community‐acquired diarrhea (CAD), nosocomial diarrhea (ND), and asymptomatic nosocomial infection (ANI) in Belém, Brazil. Twenty‐six rotavirus strains with P[6]G2 genotype were sequenced to genes coding for VP4, VP7, and NSP4 proteins. Phylogenetic analysis of the VP4gene, including prototype strains RV3, ST3, M37, and U1205, showed that local P[6]G2 strains clustered forming a distinct lineage (bootstrap of 99%). Brazilian P[6]G2 strains had the highest homology (ranging from 96.0%–98.3%) with the African strain GR1107, G4P[6]. Phylogenetic tree for VP7gene was constructed including old and new G2 African strains SA3958GR/97, SA356PT/96, SA514GR/87, SA4476PT/97, BF3676/99, GH1803/99, and representative strains of G1, G3, G4, G5, G8, and G9 genotypes. The Brazilian P[6]G2 samples fell into a distinct group (bootstrap value of 97%) and showed homology rates ranging from 92.1% to 93.5% with P[6]G2 African strains BF3676/99, GH1803/99, and SA3958GR/97. Nucleotide sequence analysis of the NSP4gene, including human prototype strains S2, KUN, DS‐1, RV5, RV3 and ST3, and animal prototype OSU, showed that all neonatal isolates fell into genotype A and clustered with a bootstrap value of 100%, with in‐group similarities ranging from 99.3% to 100%. In this study no significant differences in nucleotide sequences of the VP4, VP7, and NSP4genes could be observed when comparing diarrheic (CAD and ND) and non‐diarrheic (ANI) babies. Monitoring of rotavirus strains in hospital environments is of particular importance, since it is claimed currently that an efficacious rotavirus vaccine, when available for routine use, will determine an impact on hospital‐acquired rotavirus disease. J. Med. Virol.78:281–289, 2006. © 2005 Wiley‐Liss, Inc.

Rotavirus strains from 91 patients treated at a children's hospital from 1996 to 1998 in Rio de Janeiro, Brazil, were characterized by electropherotyping, reverse transcription-PCR amplification for P and G genotypes, and Southern hybridization. Results obtained showed that following predominant [P],G type combination: P[4], G2 (21 per cent), P[8], G1 (17 per cent), P[8], G3 (13 per cent), which are prevalent throughout the world. However, an unexpected number of cases were associated with uncommon genotypes: P[8], G2 (13 per cent), P[8], G5 (11 per cent), P[8], G9 (7 per cent), P[8], G10 (4 per cent), P[6], G4 (3 per cent), P[6], G3 (1 per cent), P[4], G9 (1 per cent), and P[6], G9 (1 per cent). Mixed infections with more than one type were identified in only two cases and 16 per cent of the samples were not G and/or P typeable. A subset of G types was confirmed by Southern hybridization and chemiluminescent detection. Rotavirus seasonal distribution was observed between April and July. The contribution of the results obtained in the present investigation corroborates the required epidemiological surveillance for rotavirus infection in Brazil.

A total of 614 fecal specimens were obtained during a survey for rotavirus infection conducted between May 1996 and May 1998 among 437 newborns admitted to special care nurseries at a public hospital in the urban area of Belém, Brazil. Routine stool samples were taken weekly from all babies up to the age of 28 days. Overall, 51 (11.7%) of the neonates excreted rotaviruses while in hospital, of whom 42 (82.3%) developed asymptomatic nosocomial infection; nosocomial infection was also proved in five of the nine patients with diarrhea. Three distinct RNA profiles were detected, of which one short electropherotyping pattern was far more frequent (≃90% of the strains). Using monoclonal antibody‐based enzyme immunoassays, 32 (62.7%) of the rotavirus‐positive strains were classified as G2, and 1 (1.9%) as mixed G1 and G2. A G serotype could not be assigned to 18 (35.3%) of the isolates. A reverse transcription‐polymerase chain reaction was used for determining the VP4 type‐specificity of a subset of 28 rotavirus‐positive samples. Characterization of the VP7‐genotype specificity was also sought for 18 of these latter strains. Overall, P[6] and G2 genotypes were identified in 93% and 94% of tested samples respectively, with results being further confirmed by Southern hybridization. Although surveillance was conducted during a 25‐month period, 50 (98%) of 51 rotavirus isolates clustered between January and December 1997. The earliest [P6]G2 rotavirus infections were detected by late January 1997, involving two (13‐ and 14‐day‐old) babies admitted with acute diarrhea. Thereafter, strains bearing these genotype specificities were identified among five infants with hospital‐acquired gastroenteritis, followed by 16 others who were infected asymptomatically. This is the first report from Brazil describing nosocomial transmission of P[6]G2 rotavirus strains among neonates. J. Med. Virol. 67:418–426, 2002. © 2002 Wiley‐Liss, Inc.

Group A rotaviruses are the most important agents of severe diarrhea in children and infants worldwide. The aim of present study was to identify rotavirus G serotypes and P[],G genotypes in cases of reinfection among children who participated in a vaccine trial with the tetravalent rhesus-human reassortant rotavirus vaccine (RRV-TV 4 x 10(4) pfu/dose) in Belém, Brazil. From July 1990 to June 1992, 540 children received, at their first, third and fifth months of life, oral doses of either vaccine or placebo. A total of 90 rotavirus diarrheal episodes among children who completed the three-dose vaccination schedule were recorded. We studied 11 reinfection rotavirus cases among five children (three female and two male). Fecal specimens were tested by using a enzyme immunoassay (IDEIA Rotavirus), followed by EIA with monoclonal antibodies to determine infecting serotypes Gl, G2, G3 and G4 and subgroups I and II. The viral dsRNA was extracted and electrophoresed through polyacrylamide gel and then subjected to reverse-transcription-polymerase chain reaction and nested-PCR for the determination of Gl, G2, G3, G4, G5 and G9 and P[4], P[6], P[8] and P[9] rotavirus genotypes. A total of 11 cases of reinfection (12 per cent) occurred among five children, three from the placebo group and two from the vaccine group. In four of the cases of reinfection G serotypes and P[],G genotypes were as follows: for the first and second infections, respectively: (1) G2/P[4],G2 and Gl/P[4],G1; (2) G2/P[4],G2 and G2/P[6],G5; (3) G2/P[4],G2 and G1/P[8],G1; and (4) G2/P[8],G1 and G1/P[8],G1. A fifth child had three successive infections caused by serotypes/genotypes G1/P[8],G1, in the first and second infections, and G2/P[4],G2 in the third infection. The common genotypes and unusual genotypes were detected in 8 (73 per cent) and 3 (27 per cent) of the isolates, respectively. With regards to the clinical severity, in two children a score indicated moderate/severe disease in both first and second infections. One child had three successive infections; the first episode was moderate/severe, the second very severe and the third was not available. In contrast, in two other children, the first episode was very severe, and the second episode was moderate/severe in one child and data was not available for the other child. The results obtained in the present investigation underscore the need to broaden our knowledge of the immunity in rotavirus reinfection. This should be useful regarding future rotavirus vaccination strategies in Brazil.