Protection against H5N1 highly pathogenic avian and pandemic (H1N1 2009 influenza virus infection in cynomolgus monkeys by an inactivated H5N1 whole particle vaccine.

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Misako Nakayama

Full Text Available H5N1 highly pathogenic avian influenza virus (HPAIV infection has been reported in poultry and humans with expanding clade designations. Therefore, a vaccine that induces immunity against a broad spectrum of H5N1 viruses is preferable for pandemic preparedness. We established a second H5N1 vaccine candidate, A/duck/Hokkaido/Vac-3/2007 (Vac-3, in our virus library and examined the efficacy of inactivated whole particles of this strain against two clades of H5N1 HPAIV strains that caused severe morbidity in cynomolgus macaques. Virus propagation in vaccinated macaques infected with either of the H5N1 HPAIV strains was prevented compared with that in unvaccinated macaques. This vaccine also prevented propagation of a pandemic (H1N1 2009 virus in macaques. In the vaccinated macaques, neutralization activity, which was mainly shown by anti-hemagglutinin antibody, against H5N1 HPAIVs in plasma was detected, but that against H1N1 virus was not detected. However, neuraminidase inhibition activity in plasma and T-lymphocyte responses in lymph nodes against H1N1 virus were detected. Therefore, cross-clade and heterosubtypic protective immunity in macaques consisted of humoral and cellular immunity induced by vaccination with Vac-3.

Effects of Transportation on Antioxidant Status in Cynomolgus Macaques (Macaca fascicularis).

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Pan, Xueying; Lu, Liang; Zeng, Xiancheng; Chang, Yan; Hua, Xiuguo

2016-01-01

To evaluate the effects of transportation on oxidative stress in cynomolgus monkeys, we measured serum levels of reduced glutathione (GSH), malondialdehyde, and protein carbonyl (PC) and the activities of total antioxidant capacity (TAOC), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase in cynomolgus macaques before transportation (day 0), on the day of arrival (day 1), and on days 7, 14, and 21 after transportation. Compared with that on day 0, TAOC and catalase activities on days 1, 7, and 14 after transportation were significantly decreased, reached their nadirs on day 7, and increased thereafter to reach their pretransportation levels by day 21 after transportation. Compared with day 0 levels, mean SOD activity and GSH concentration were decreased significantly on day 1; they thereafter increased to reach their pretransportation measures by day 7 after transportation. In contrast, PC and malondialdehyde concentrations in serum and the activity of GSH-Px were increased on day 1 compared with day 0 and thereafter decreased to reach their pretransportation levels by day 14 after transportation. In summary, GSH, TAOC, catalase, and SOD levels decreased and malondialdehyde, PC, and GSH-Px concentrations increased in cynomolgus macaques after transportation. These results suggest that transportation might imbalance oxidant and antioxidant levels to create excess oxidative stress in cynomolgus macaques. Therefore, cynomolgus macaques should have at least 21 d to recover after transportation and regain their healthy status.

Memory immune responses against pandemic (H1N1 2009 influenza virus induced by a whole particle vaccine in cynomolgus monkeys carrying Mafa-A1*052:02.

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Masahiko Arikata

Full Text Available We made an H1N1 vaccine candidate from a virus library consisting of 144 ( = 16 HA×9 NA non-pathogenic influenza A viruses and examined its protective effects against a pandemic (2009 H1N1 strain using immunologically naïve cynomolgus macaques to exclude preexisting immunity and to employ a preclinical study since preexisting immunity in humans previously vaccinated or infected with influenza virus might make comparison of vaccine efficacy difficult. Furthermore, macaques carrying a major histocompatibility complex class I molecule, Mafa-A1*052:02, were used to analyze peptide-specific CD8(+ T cell responses. Sera of macaques immunized with an inactivated whole particle formulation without addition of an adjuvant showed higher neutralization titers against the vaccine strain A/Hokkaido/2/1981 (H1N1 than did sera of macaques immunized with a split formulation. Neutralization activities against the pandemic strain A/Narita/1/2009 (H1N1 in sera of macaques immunized twice with the split vaccine reached levels similar to those in sera of macaques immunized once with the whole particle vaccine. After inoculation with the pandemic virus, the virus was detected in nasal samples of unvaccinated macaques for 6 days after infection and for 2.67 days and 5.33 days on average in macaques vaccinated with the whole particle vaccine and the split vaccine, respectively. After the challenge infection, recall neutralizing antibody responses against the pandemic virus and CD8(+ T cell responses specific for nucleoprotein peptide NP262-270 bound to Mafa-A1*052:02 in macaques vaccinated with the whole particle vaccine were observed more promptly or more vigorously than those in macaques vaccinated with the split vaccine. These findings demonstrated that the vaccine derived from our virus library was effective for pandemic virus infection in macaques and that the whole particle vaccine conferred more effective memory and broader cross-reactive immune responses

Newly Identified CYP2C93 Is a Functional Enzyme in Rhesus Monkey, but Not in Cynomolgus Monkey

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Uno, Yasuhiro; Uehara, Shotaro; Kohara, Sakae; Iwasaki, Kazuhide; Nagata, Ryoichi; Fukuzaki, Koichiro; Utoh, Masahiro; Murayama, Norie; Yamazaki, Hiroshi

2011-01-01

Cynomolgus monkey and rhesus monkey are used in drug metabolism studies due to their evolutionary closeness and physiological resemblance to human. In cynomolgus monkey, we previously identified cytochrome P450 (P450 or CYP) 2C76 that does not have a human ortholog and is partly responsible for species differences in drug metabolism between cynomolgus monkey and human. In this study, we report characterization of CYP2C93 cDNA newly identified in cynomolgus monkey and rhesus monkey. The CYP2C9...

Limited Susceptibility of Cynomolgus Monkeys (Macaca fascicularis) to Leprosy after Experimental Administration of Mycobacterium leprae

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Walsh, Gerald P.; Dela Cruz, Eduardo C.; Abalos, Rodolfo M.; Tan, Esterlina V.; Fajardo, Tranquilino T.; Villahermosa, Laarni G.; Cellona, Roland V.; Balagon, Maria V.; White, Valerie A.; Saunderson, Paul R.; Walsh, Douglas S.

2012-01-01

Cynomolgus monkeys are a useful model for human tuberculosis, but susceptibility to M. leprae is unknown. A cynomolgus model of leprosy could increase understanding of pathogenesis—importantly, neuritis and nerve-damaging reactions. We administered viable Mycobacterium leprae to 24 cynomolgus monkeys by three routes, with a median follow-up period of 6 years (range = 1–19 years) involving biopsies, nasal smears, antiphenolic glycolipid-1 (PGL-1) antibody serology, and lepromin skin testing. Most developed evanescent papules at intradermal M. leprae inoculation sites that, on biopsy, showed a robust cellular immune response akin to a lepromin skin test reaction; many produced PGL-1 antibodies. At necropsy, four monkeys, without cutaneous or gross neurological signs of leprosy but with elevated PGL-1 antibodies, including three with nasal smears (+) for acid fast bacilli (AFB), showed histological features, including AFB, suggestive of leprosy at several sites. Overall, however, cynomolgus monkeys seem minimally susceptible to leprosy after experimental M. leprae administration. PMID:22855766

Expression of cytochrome P450 regulators in cynomolgus macaque.

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Uno, Yasuhiro; Yamazaki, Hiroshi

2017-09-11

1. Cytochrome P450 (P450) regulators including nuclear receptors and transcription factors have not been fully investigated in cynomolgus macaques, an important species used in drug metabolism studies. In this study, we analyzed 17 P450 regulators by sequence and phylogenetic analysis, and tissue expression. 2. Gene and genome structures of 17 P450 regulators were similar to the human orthologs, and the deduced amino acid sequences showed high sequence identities (92-95%) and more closely clustered in a phylogenetic tree, with the human orthologs. 3. Many of the P450 regulator mRNAs were preferentially expressed in the liver, kidney, and/or jejunum. Among the P450 regulator mRNAs, PXR was most abundant in the liver and jejunum, and HNF4α in the kidney. In the liver, the expression of most P450 regulator mRNAs did not show significant differential expression (>2.5-fold) between cynomolgus macaques bred in Cambodia, China, and Indonesia, or rhesus macaques. 4. By correlation analysis, most of the P450 regulators were significantly (p < 0.05) correlated to other P450 regulators, and many of them were also significantly (p < 0.05) correlated with P450s. 5. These results suggest that 17 P450 regulators of cynomolgus macaques had similar molecular characteristics to the human orthologs.

Fatores de risco para infecção pelo HIV em pacientes com o vírus da hepatite C Risk factors for HIV infection among patients infected with hepatitis C virus

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Anita Campos Mendonça Silva

2006-06-01

Full Text Available OBJETIVO: Os vírus da imunodeficiência humana e o vírus da hepatite C apresentam fatores de transmissão em comum. Atualmente, há alta freqüência da co-infecção, principalmente em indivíduos usuários de drogas injetáveis e com história de transfusões. O objetivo do estudo foi avaliar os fatores de risco para infecção pelo HIV em pacientes infectados pelo vírus da hepatite C. MÉTODOS: Trata-se de estudo epidemiológico do tipo caso-controle, realizado com 118 pacientes (casos infectados pelos vírus HIV e vírus da hepatite C e 233 pacientes (controles infectados somente pelo vírus da hepatite C. Entre janeiro de 1999 a novembro de 2001, os pacientes foram submetidos a questionário sobre características sociodemográficas, profissionais, e principais fatores de risco para infecção pelos vírus. Após descritas e comparadas, as variáveis foram submetidas à análise univariada, e em seguida à análise de regressão logística para variáveis selecionadas pelo teste da razão da máxima verossimilhança. RESULTADOS: A co-infecção está associada ao sexo feminino (OR=2,89; IC 95%: 1,16-7,08, aos estados civis separado/viúvo (OR=3,91; IC 95%: 1,34-11,35, ao uso pregresso ou atual de drogas ilícitas (OR=3,96; IC 95%: 1,55-0,13 e ao hábito de compartilhar canudos ou seringas (OR=10,28; IC 95%: 4,00-6,42. CONCLUSÕES: Em pacientes infectados pelo vírus da hepatite C, o sexo feminino é fator de risco para a infecção pelo HIV quando ajustado à variável compartilhar canudos ou seringas. Os estados civis separado/viúvo, uso de drogas ilícitas e hábito de compartilhar canudos ou seringas são, também, fatores associados ao risco para esta co-infecção.OBJECTIVE: Human immunodeficiency virus and hepatitis C virus share the same routes of transmission. Currently, there is a high frequency of co-infection worldwide, especially among users of injectable drugs and in subjects with history of blood transfusions. The aim of

Spontaneous transformation of adult mesenchymal stem cells from cynomolgus macaques in vitro

International Nuclear Information System (INIS)

Ren, Zhenhua; Wang, Jiayin; Zhu, Wanwan; Guan, Yunqian; Zou, Chunlin; Chen, Zhiguo; Zhang, Y. Alex

2011-01-01

Mesenchymal stem cells (MSCs) have shown potential clinical utility in cell therapy and tissue engineering, due to their ability to proliferate as well as to differentiate into multiple lineages, including osteogenic, adipogenic, and chondrogenic specifications. Therefore, it is crucial to assess the safety of MSCs while extensive expansion ex vivo is a prerequisite to obtain the cell numbers for cell transplantation. Here we show that MSCs derived from adult cynomolgus monkey can undergo spontaneous transformation following in vitro culture. In comparison with MSCs, the spontaneously transformed mesenchymal cells (TMCs) display significantly different growth pattern and morphology, reminiscent of the characteristics of tumor cells. Importantly, TMCs are highly tumorigenic, causing subcutaneous tumors when injected into NOD/SCID mice. Moreover, no multiple differentiation potential of TMCs is observed in vitro or in vivo, suggesting that spontaneously transformed adult stem cells may not necessarily turn into cancer stem cells. These data indicate a direct transformation of cynomolgus monkey MSCs into tumor cells following long-term expansion in vitro. The spontaneous transformation of the cultured cynomolgus monkey MSCs may have important implications for ongoing clinical trials and for models of oncogenesis, thus warranting a more strict assessment of MSCs prior to cell therapy. -- Highlights: ► Spontaneous transformation of cynomolgus monkey MSCs in vitro. ► Transformed mesenchymal cells lack multipotency. ► Transformed mesenchymal cells are highly tumorigenic. ► Transformed mesenchymal cells do not have the characteristics of cancer stem cells.

Ancestry, Plasmodium cynomolgi prevalence and rhesus macaque admixture in cynomolgus macaques (Macaca fascicularis) bred for export in Chinese breeding farms.

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Zhang, Xinjun; Meng, Yuhuan; Houghton, Paul; Liu, Mingyu; Kanthaswamy, Sreetharan; Oldt, Robert; Ng, Jillian; Trask, Jessica Satkoski; Huang, Ren; Singh, Balbir; Du, Hongli; Smith, David Glenn

2017-04-01

Most cynomolgus macaques (Macaca fascicularis) used in the United States as animal models are imported from Chinese breeding farms without documented ancestry. Cynomolgus macaques with varying rhesus macaque ancestry proportions may exhibit differences, such as susceptibility to malaria, that affect their suitability as a research model. DNA of 400 cynomolgus macaques from 10 Chinese breeding farms was genotyped to characterize their regional origin and rhesus ancestry proportion. A nested PCR assay was used to detect Plasmodium cynomolgi infection in sampled individuals. All populations exhibited high levels of genetic heterogeneity and low levels of inbreeding and genetic subdivision. Almost all individuals exhibited an Indochinese origin and a rhesus ancestry proportion of 5%-48%. The incidence of P. cynomolgi infection in cynomolgus macaques is strongly associated with proportion of rhesus ancestry. The varying amount of rhesus ancestry in cynomolgus macaques underscores the importance of monitoring their genetic similarity in malaria research. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Apolipoprotein A-I metabolism in cynomolgus monkey. Identification and characterization of beta-migrating pools

International Nuclear Information System (INIS)

Melchior, G.W.; Castle, C.K.

1989-01-01

Fresh plasma from control (C) and hypercholesterolemic (HC) cynomolgus monkeys was analyzed by agarose electrophoresis-immunoblotting with antibody to cynomolgus monkey apolipoprotein (apo) A-I. Two bands were evident on the autoradiogram: an alpha-migrating band (high density lipoprotein) and a beta-migrating band that comigrated exactly with cynomolgus monkey low density lipoprotein (LDL). The presence of beta-migrating apo A-I in the plasma of these monkeys was confirmed by Geon-Pevikon preparative electrophoresis, crossed immunoelectrophoresis, and isotope dilution studies in which radiolabeled apo A-I was found to equilibrate also with alpha- and beta-migrating pools of apo A-I in the plasma. Subfractionation of C and HC plasma by agarose column chromatography (Bio-Gel A-0.5M and A-15M) followed by agarose electrophoresis-immunoblotting indicated that the beta-migrating apo A-I in C was relatively homogeneous and eluted with proteins of Mr approximately 50 kD [apo A-I(50 kD)], whereas two beta-migrating fractions were identified in HC, one that eluted with the 50-kD proteins, and the other that eluted in the LDL Mr range [apo A-I(LDL)]. The apo A-I(LDL) was precipitated by antibody to cynomolgus monkey apo B. The apo A-I(50 kD) accounted for 5 +/- 1% (mean +/- SD) of the plasma apo A-I in C plasma, and 15 +/- 7% in HC plasma. No apo A-I(LDL) was detected in C plasma, but that fraction accounted for 9 +/- 7% of the apo A-I in HC plasma. These data establish the presence of multiple pools of apo A-I in the cynomolgus monkey, which must be taken into consideration in any comprehensive model of apo A-I metabolism in this species

Natural and cross-inducible anti-SIV antibodies in Mauritian cynomolgus macaques.

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Hongzhao Li

Full Text Available Cynomolgus macaques are an increasingly important nonhuman primate model for HIV vaccine research. SIV-free animals without pre-existing anti-SIV immune responses are generally needed to evaluate the effect of vaccine-induced immune responses against the vaccine epitopes. Here, in order to select such animals for vaccine studies, we screened 108 naïve female Mauritian cynomolgus macaques for natural (baseline antibodies to SIV antigens using a Bio-Plex multiplex system. The antigens included twelve 20mer peptides overlapping the twelve SIV protease cleavage sites (-10/+10, respectively (PCS peptides, and three non-PCS Gag or Env peptides. Natural antibodies to SIV antigens were detected in subsets of monkeys. The antibody reactivity to SIV was further confirmed by Western blot using purified recombinant SIV Gag and Env proteins. As expected, the immunization of monkeys with PCS antigens elicited anti-PCS antibodies. However, unexpectedly, antibodies to non-PCS peptides were also induced, as shown by both Bio-Plex and Western blot analyses, while the non-PCS peptides do not share sequence homology with PCS peptides. The presence of natural and vaccine cross-inducible SIV antibodies in Mauritian cynomolgus macaques should be considered in animal selection, experimental design and result interpretation, for their best use in HIV vaccine research.

Predicting Human Clearance of OATP substrates using Cynomolgus monkey: In vitro-in vivo scaling of hepatic uptake clearance.

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de Bruyn, Tom; Ufuk, Ayse; Cantrill, Carina; Kosa, Rachel E; Bi, Yi-An; Niosi, Mark; Modi, Sweta; Rodrigues, A David; Tremaine, Larry M; Varma, Manthena Vs; Galetin, Aleksandra; Houston, J Brian

2018-05-02

This work explores the utility of the cynomolgus monkey as a preclinical model to predict hepatic uptake clearance mediated by organic anion transporting polypeptide (OATP) transporters. Nine OATP substrates (rosuvastatin, pravastatin, repaglinide, fexofenadine, cerivastatin, telmisartan, pitavastatin, bosentan and valsartan) were investigated in plated cynomolgus monkey and human hepatocytes. Total uptake clearance and passive diffusion were measured in vitro from initial rates in the absence and presence of the OATP inhibitor rifamycin SV, respectively. Total uptake clearance values in plated hepatocytes ranged over three orders of magnitude in both species with a similar rank order and good agreement in the relative contribution of active transport to total uptake between cynomolgus monkey and human. In vivo hepatic clearance for these nine drugs was determined in cynomolgus monkey after intravenous dosing. Hepatic clearances showed a similar range to human parameters and good predictions from respective hepatocyte parameters (with 2.7 and 3.8-fold bias on average, respectively). The use of cross species empirical scaling factors (based on either dataset average or individual drug scaling factor from cynomolgus monkey data) improved prediction (less bias, better concordance) of human hepatic clearance from human hepatocyte data alone. In vitro intracellular binding in hepatocytes also correlated well between species. It is concluded that the minimal species differences observed for the current dataset between cynomolgus monkey and human hepatocyte uptake, both in vitro and in vivo, support future use of this preclinical model to delineate drug hepatic uptake and enable prediction of human in vivo intrinsic hepatic clearance. The American Society for Pharmacology and Experimental Therapeutics.

The genetic composition of populations of cynomolgus macaques (Macaca fascicularis) used in biomedical research.

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Kanthaswamy, S; Ng, J; Satkoski Trask, J; George, D A; Kou, A J; Hoffman, L N; Doherty, T B; Houghton, P; Smith, D G

2013-06-01

The genetic composition of cynomolgus macaques used in biomedical research is not as well-characterized as that of rhesus macaques. Populations of cynomolgus macaques from Sumatra, Corregidor, Mauritius, Singapore, Cambodia, and Zamboanga were analyzed using 24 STRs. The Sumatran and Cambodian populations exhibited the highest allelic diversity, while the Mauritian population exhibited the lowest. Sumatran cynomolgus macaques were the most genetically similar to all others, consistent with an Indonesian origin of the species. The high diversity among Cambodian animals may result from interbreeding with rhesus macaques. The Philippine and Mauritian samples were the most divergent from other populations, the former due to separation from the Sunda Shelf by deepwater and the latter due to anthropogenic translocation and extreme founder effects. Investigators should verify their research subjects' origin, ancestry, and pedigree to minimize risks to biomedical experimentation from genetic variance stemming from close kinship and mixed ancestry as these can obscure treatment effects. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Newly identified CYP2C93 is a functional enzyme in rhesus monkey, but not in cynomolgus monkey.

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Yasuhiro Uno

Full Text Available Cynomolgus monkey and rhesus monkey are used in drug metabolism studies due to their evolutionary closeness and physiological resemblance to human. In cynomolgus monkey, we previously identified cytochrome P450 (P450 or CYP 2C76 that does not have a human ortholog and is partly responsible for species differences in drug metabolism between cynomolgus monkey and human. In this study, we report characterization of CYP2C93 cDNA newly identified in cynomolgus monkey and rhesus monkey. The CYP2C93 cDNA contained an open reading frame of 490 amino acids approximately 84-86% identical to human CYP2Cs. CYP2C93 was located in the genomic region, which corresponded to the intergenic region in the human genome, indicating that CYP2C93 does not correspond to any human genes. CYP2C93 mRNA was expressed predominantly in the liver among 10 tissues analyzed. The CYP2C93 proteins heterologously expressed in Escherichia coli metabolized human CYP2C substrates, diclofenac, flurbiprofen, paclitaxel, S-mephenytoin, and tolbutamide. In addition to a normal transcript (SV1, an aberrantly spliced transcript (SV2 lacking exon 2 was identified, which did not give rise to a functional protein due to frameshift and a premature termination codon. Mini gene assay revealed that the genetic variant IVS2-1G>T at the splice site of intron 1, at least partly, accounted for the exon-2 skipping; therefore, this genotype would influence CYP2C93-mediated drug metabolism. SV1 was expressed in 6 of 11 rhesus monkeys and 1 of 8 cynomolgus monkeys, but the SV1 in the cynomolgus monkey was nonfunctional due to a rare null genotype (c.102T>del. These results suggest that CYP2C93 can play roles as a drug-metabolizing enzyme in rhesus monkeys (not in cynomolgus monkeys, although its relative contribution to drug metabolism has yet to be validated.

Dose Response of MARV/Angola Infection in Cynomolgus Macaques following IM or Aerosol Exposure

Science.gov (United States)

Johnston, Sara C.; Lin, Kenny L.; Twenhafel, Nancy A.; Raymond, Jo Lynne W.; Shamblin, Joshua D.; Wollen, Suzanne E.; Wlazlowski, Carly B.; Wilkinson, Eric R.; Botto, Miriam A.; Goff, Arthur J.

2015-01-01

Marburg virus infection in humans causes a hemorrhagic disease with a high case fatality rate. Countermeasure development requires the use of well-characterized animal models that mimic human disease. To further characterize the cynomolgus macaque model of MARV/Angola, two independent dose response studies were performed using the intramuscular or aerosol routes of exposure. All animals succumbed at the lowest target dose; therefore, a dose effect could not be determined. For intramuscular-exposed animals, 100 PFU was the first target dose that was not significantly different than higher target doses in terms of time to disposition, clinical pathology, and histopathology. Although a significant difference was not observed between aerosol-exposed animals in the 10 PFU and 100 PFU target dose groups, 100 PFU was determined to be the lowest target dose that could be consistently obtained and accurately titrated in aerosol studies. PMID:26413900

Dose Response of MARV/Angola Infection in Cynomolgus Macaques following IM or Aerosol Exposure.

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Sara C Johnston

Full Text Available Marburg virus infection in humans causes a hemorrhagic disease with a high case fatality rate. Countermeasure development requires the use of well-characterized animal models that mimic human disease. To further characterize the cynomolgus macaque model of MARV/Angola, two independent dose response studies were performed using the intramuscular or aerosol routes of exposure. All animals succumbed at the lowest target dose; therefore, a dose effect could not be determined. For intramuscular-exposed animals, 100 PFU was the first target dose that was not significantly different than higher target doses in terms of time to disposition, clinical pathology, and histopathology. Although a significant difference was not observed between aerosol-exposed animals in the 10 PFU and 100 PFU target dose groups, 100 PFU was determined to be the lowest target dose that could be consistently obtained and accurately titrated in aerosol studies.

Survey of prevalence of overweight body condition in laboratory-housed cynomolgus macaques (Macaca fascicularis).

Science.gov (United States)

Bauer, Sharon A; Leslie, Ken E; Pearl, David L; Fournier, Jocelyn; Turner, Patricia V

2010-07-01

Excessive weight gain has been reported to occur in captive cynomolgus macaques with little to no change in diet. Overweight body condition can result in development of hyperglycemia and type 2 diabetes and should be avoided. The purpose of this survey was to assess the prevalence of overweight cynomolgus macaques in North American research facilities, including breeding colonies and short-term and long-term facilities, and to describe current methods used to assess body condition. The survey consisted of 51 questions covering animal population demographics, body weight and body condition scoring, feeding, and behavior. Voluntary participants included veterinarians and animal care managers. Respondents from 13 facilities completed the survey, and information was collected on 17,500 cynomolgus macaques. The majority of surveyed facilities housed juvenile and young adult macaques. The reported prevalence of overweight (greater than 10% of ideal body weight) animals ranged between 0% and 20% and reportedly was more frequent in animals younger than 10 y. Most facilities had weight reduction strategies in place. Despite these programs, a significant proportion of animals were reported as being overweight. The results of this survey demonstrate that most North American facilities housing cynomolgus macaques recognize the importance of tracking body condition regularly. However, implementing effective weight reduction programs may be difficult in captive housing environments. Because of the potential for adverse health effects, facilities should have a means of regularly tracking body weight as well as an action plan for managing overweight animals.

ABO blood group phenotype frequency estimation using molecular phenotyping in rhesus and cynomolgus macaques.

Science.gov (United States)

Kanthaswamy, S; Ng, J; Oldt, R F; Valdivia, L; Houghton, P; Smith, D G

2017-11-01

A much larger sample (N = 2369) was used to evaluate a previously reported distribution of the A, AB and B blood group phenotypes in rhesus and cynomolgus macaques from six different regional populations. These samples, acquired from 15 different breeding and research facilities in the United States, were analyzed using a real-time quantitative polymerase chain reaction (qPCR) assay that targets single nucleotide polymorphisms (SNPs) responsible for the macaque A, B and AB phenotypes. The frequency distributions of blood group phenotypes of the two species differ significantly from each other and significant regional differentiation within the geographic ranges of each species was also observed. The B blood group phenotype was prevalent in rhesus macaques, especially those from India, while the frequencies of the A, B and AB phenotypes varied significantly among cynomolgus macaques from different geographic regions. The Mauritian cynomolgus macaques, despite having originated in Indonesia, showed significant (P ≪ .01) divergence from the Indonesian animals at the ABO blood group locus. Most Mauritian animals belonged to the B blood group while the Indonesian animals were mostly A. The close similarity in blood group frequency distributions between the Chinese rhesus and Indochinese cynomolgus macaques demonstrates that the introgression between these two species extends beyond the zone of intergradation in Indochina. This study underscores the importance of ABO blood group phenotyping of the domestic supply of macaques and their biospecimens. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Telemetric assessment of social and single housing: Evaluation of electrocardiographic intervals in jacketed cynomolgus monkeys.

Science.gov (United States)

Kaiser, Robert A; Tichenor, Stephen D; Regalia, Douglas E; York, Kristina; Holzgrefe, Henry H

2015-01-01

Proactive efforts to socially house laboratory animals are a contemporary, important focus for enhancing animal welfare. Jacketing cynomolgus monkeys has been traditionally considered an exclusionary criterion for social housing based on unsubstantiated concerns that study conduct or telemetry equipment might be compromised. Our objective was to evaluate the effects of jacketing naïve, adolescent cynomolgus monkeys in different single and social housing types based on parallel comparisons of heart rate. Eight naive cynomolgus monkeys were randomized into pairs and ECG data were collected for 24h from each animal in each housing condition using a crossover design. Caging paradigms consisted of standard individual, standard pair, quaternary pair (4 linked cages), and European-style pair housing in non-sequential order varied by pair to control for possible time bias. Dosing and blood collection procedures were performed to characterize any effects of housing on ECG data during study conduct. There was no increase in the incidence of equipment damage in pair vs. individually housed animals. Further, animals in all 4 housing paradigms showed similar acclimation assessed as heart rate (mean 139-154 beats per minute), and maintained similar diurnal rhythms, with an expected slowing of the heart rate at night (aggregate lights out HR 110±4bpm compared to daytime 146±7bpm). This study demonstrates the effects of different social access and housing types on the study-naïve cynomolgus monkeys during jacketed cardiovascular telemetry data collection in a repeat-dose toxicology study design. There were no discernible effects of social housing on baseline ECG parameters collected via jacketed telemetry, and all animals maintained expected diurnal rhythms in all housing settings tested. These data demonstrate that cynomolgus monkeys can be socially housed during data collection as a standard practice, consistent with global efforts to improve study animal welfare. Copyright

Delayed response task performance as a function of age in cynomolgus monkeys (Macaca fascicularis)

DEFF Research Database (Denmark)

Darusman, H S; Call, J; Sajuthi, D

2014-01-01

We compared delayed response task performance in young, middle-aged, and old cynomolgus monkeys using three memory tests that have been used with non-human primates. Eighteen cynomolgus monkeys-6 young (4-9 years), 6 middle-aged (10-19 years), and 6 old (above 20 years)-were tested. In general......, the old monkeys scored significantly worse than did the animals in the two other age groups. Longer delays between stimulus presentation and response increased the performance differences between the old and younger monkeys. The old monkeys in particular showed signs of impaired visuo-spatial memory...

Impact of menstruation on select hematology and clinical chemistry variables in cynomolgus macaques.

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Perigard, Christopher J; Parrula, M Cecilia M; Larkin, Matthew H; Gleason, Carol R

2016-06-01

In preclinical studies with cynomolgus macaques, it is common to have one or more females presenting with menses. Published literature indicates that the blood lost during menses causes decreases in red blood cell mass variables (RBC, HGB, and HCT), which would be a confounding factor in the interpretation of drug-related effects on clinical pathology data, but no scientific data have been published to support this claim. This investigation was conducted to determine if the amount of blood lost during menses in cynomolgus macaques has an effect on routine hematology and serum chemistry variables. Ten female cynomolgus macaques (Macaca fascicularis), 5 to 6.5 years old, were observed daily during approximately 3 months (97 days) for the presence of menses. Hematology and serum chemistry variables were evaluated twice weekly. The results indicated that menstruation affects the erythrogram including RBC, HGB, HCT, MCHC, MCV, reticulocyte count, RDW, the leukogram including neutrophil, lymphocyte, and monocyte counts, and chemistry variables, including GGT activity, and the concentrations of total proteins, albumin, globulins, and calcium. The magnitude of the effect of menstruation on susceptible variables is dependent on the duration of the menstrual phase. Macaques with menstrual phases lasting ≥ 7 days are more likely to develop changes in variables related to chronic blood loss. In preclinical toxicology studies with cynomolgus macaques, interpretation of changes in several commonly evaluated hematology and serum chemistry variables requires adequate clinical observation and documentation concerning presence and duration of menses. There is a concern that macaques with long menstrual cycles can develop iron deficiency anemia due to chronic menstrual blood loss. © 2016 American Society for Veterinary Clinical Pathology.

Comparative plasma lipidome between human and cynomolgus monkey: are plasma polar lipids good biomarkers for diabetic monkeys?

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Guanghou Shui

Full Text Available BACKGROUND: Non-human primates (NHP are now being considered as models for investigating human metabolic diseases including diabetes. Analyses of cholesterol and triglycerides in plasma derived from NHPs can easily be achieved using methods employed in humans. Information pertaining to other lipid species in monkey plasma, however, is lacking and requires comprehensive experimental analysis. METHODOLOGIES/PRINCIPAL FINDINGS: We examined the plasma lipidome from 16 cynomolgus monkey, Macaca fascicularis, using liquid chromatography coupled with mass spectrometry (LC/MS. We established novel analytical approaches, which are based on a simple gradient elution, to quantify polar lipids in plasma including (i glycerophospholipids (phosphatidylcholine, PC; phosphatidylethanolamine, PE; phosphatidylinositol, PI; phosphatidylglycerol, PG; phosphatidylserine, PS; phosphatidic acid, PA; (ii sphingolipids (sphingomyelin, SM; ceramide, Cer; Glucocyl-ceramide, GluCer; ganglioside mannoside 3, GM3. Lipidomic analysis had revealed that the plasma of human and cynomolgus monkey were of similar compositions, with PC, SM, PE, LPC and PI constituting the major polar lipid species present. Human plasma contained significantly higher levels of plasmalogen PE species (p<0.005 and plasmalogen PC species (p<0.0005, while cynomolgus monkey had higher levels of polyunsaturated fatty acyls (PUFA in PC, PE, PS and PI. Notably, cynomolgus monkey had significantly lower levels of glycosphingolipids, including GluCer (p<0.0005 and GM(3 (p<0.0005, but higher level of Cer (p<0.0005 in plasma than human. We next investigated the biochemical alterations in blood lipids of 8 naturally occurring diabetic cynomolgus monkeys when compared with 8 healthy controls. CONCLUSIONS: For the first time, we demonstrated that the plasma of human and cynomolgus monkey were of similar compositions, but contained different mol distribution of individual molecular species. Diabetic monkeys

Genetic polymorphisms of drug-metabolizing cytochrome P450 enzymes in cynomolgus and rhesus monkeys and common marmosets in preclinical studies for humans.

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Uno, Yasuhiro; Uehara, Shotaro; Yamazaki, Hiroshi

2017-12-23

Cynomolgus monkeys (Macaca fascicularis, Old World Monkeys) and common marmosets (Callithrix jacchus, New World Monkeys) have been widely, and expectedly, used as non-human primate models in drug development studies. Major drug-metabolizing cytochrome P450 (P450) enzymes information is now available that supports these primate species as animal models, and it is established that multiple forms of cynomolgus monkey and common marmoset P450 enzymes have generally similar substrate recognition functionality to human P450 enzymes. This research update provides information on genetic polymorphisms of P450 enzymes in cynomolgus monkey and common marmoset like human P450 enzymes. Information on rhesus monkeys (Macaca mulatta), another macaque species used in drug metabolism studies, is also included for comparison. Among a variety of cynomolgus monkey P450 variants investigated, typical examples include individual pharmacokinetic data for efavirenz and R-warfarin associated with cynomolgus monkey P450 2C9 (formerly 2C43) and 2C19 (2C75) variants, respectively, and for R-omeprazole and S-warfarin associated with marmoset P450 2C19 variants. These findings provide a foundation for understanding the individual pharmacokinetic and toxicological results in non-human primates as preclinical models and will help to further support understanding of molecular mechanisms of human P450 function. In addition to these polymorphic P450 enzymes, effects of aging on some drug clearances mediated by cynomolgus monkey and common marmoset P450 enzymes were found in elder animals or animals pretreated with rifampicin. This review describes genetic and acquired individual differences in cynomolgus monkey and common marmoset P450 enzymes involved in drug oxidation associated with pharmacological and/or toxicological effects. Copyright © 2017 Elsevier Inc. All rights reserved.

Spontaneous extracutaneous systemic mastocytosis in a cynomolgus macaque ()

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Martina , Z. Zöller; Joachim , Kaspareit

2010-01-01

Abstract A uniform cell population of proliferating mast cells with poor cytoplasmic granularity and few eosinophilic infiltrates was observed in hepatic portal tracts and the cecal submucosa of an adult male cynomolgus macaque (Macaca fascicularis) that was part of a drug safety assessment toxicity study. The proliferating mast cells were positive for Giemsa and toluidine blue staining and had strong immunoreactivity for mast cell tryptase and CD68. Considering size, morphology, i...

Comparison of the vaginal environment in rhesus and cynomolgus macaques pre- and post-lactobacillus colonization.

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Daggett, Gregory J; Zhao, Chunxia; Connor-Stroud, Fawn; Oviedo-Moreno, Patricia; Moon, Hojin; Cho, Michael W; Moench, Thomas; Anderson, Deborah J; Villinger, Francois

2017-10-01

Rhesus and cynomologus macaques are valuable animal models for the study of human immunodeficiency virus (HIV) prevention strategies. However, for such studies focused on the vaginal route of infection, differences in vaginal environment may have deterministic impact on the outcome of such prevention, providing the rationale for this study. We tested the vaginal environment of rhesus and cynomolgus macaques longitudinally to characterize the normal microflora based on Nugent scores and pH. This evaluation was extended after colonization of the vaginal space with Lactobacilli in an effort to recreate NHP models representing the healthy human vaginal environment. Nugent scores and pH differed significantly between species, although data from both species were suggestive of stable bacterial vaginosis. Colonization with Lactobacilli was successful in both species leading to lower Nugent score and pH, although rhesus macaques appeared better able to sustain Lactobacillus spp over time. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Similar substrate specificity of cynomolgus monkey cytochrome P450 2C19 to reported human P450 2C counterpart enzymes by evaluation of 89 drug clearances.

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Hosaka, Shinya; Murayama, Norie; Satsukawa, Masahiro; Uehara, Shotaro; Shimizu, Makiko; Iwasaki, Kazuhide; Iwano, Shunsuke; Uno, Yasuhiro; Yamazaki, Hiroshi

2015-12-01

Cynomolgus monkeys are used widely in preclinical studies as non-human primate species. The amino acid sequence of cynomolgus monkey cytochrome P450 (P450 or CYP) 2C19 is reportedly highly correlated to that of human CYP2C19 (92%) and CYP2C9 (93%). In the present study, 89 commercially available compounds were screened to find potential substrates for cynomolgus monkey CYP2C19. Of 89 drugs, 34 were metabolically depleted by cynomolgus monkey CYP2C19 with relatively high rates. Among them, 30 compounds have been reported as substrates or inhibitors of, either or both, human CYP2C19 and CYP2C9. Several compounds, including loratadine, showed high selectivity to cynomolgus monkey CYP2C19, and all of these have been reported as human CYP2C19 and/or CYP2C9 substrates. In addition, cynomolgus monkey CYP2C19 formed the same loratadine metabolite as human CYP2C19, descarboethoxyloratadine. These results suggest that cynomolgus monkey CYP2C19 is generally similar to human CYP2C19 and CYP2C9 in its substrate recognition functionality. Copyright © 2015 John Wiley & Sons, Ltd.

Establishment of reference values for complete blood count and blood gases in cynomolgus monkeys (Macaca fascicularis)

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NAKAYAMA, Shunya; KOIE, Hiroshi; KANAYAMA, Kiichi; KATAKAI, Yuko; ITO-FUJISHIRO, Yasuyo; SANKAI, Tadashi; YASUTOMI, Yasuhiro; AGEYAMA, Naohide

2017-01-01

Cynomolgus monkeys are closely related to humans phylogenetically, and this has resulted in their widespread use as a preclinical model. Hematological data with regard to these monkeys are thus important. Although reference values for blood components and sex hormones have been established for cynomolgus monkeys, those for arterial blood gases have not. The arterial blood gases quickly reflect respiratory and circulatory dynamics, and are thus useful for animal management and safe general anesthesia and surgical operations. Furthermore, since O2 is transported by RBC, CBC and blood gases are closely related. The present study aimed to establish reference values for arterial blood gases and CBC in cynomolgus monkeys over a wide age range. Blood gases and CBC of arterial blood, collected from 41 female and 21 male anesthetized monkeys, were measured. Age correlated with RBC, HGB and HCT in the CBC. Values differed significantly between males and females in pCO2, CO2 concentration, MCV and MCH. The pH of blood was equivalent to that of humans and pCO2 was more stable, whereas MCV and MCH were lower than those in humans. Erythrocytes were smaller and less pigmented than in other Macaca species. Several relationships between gender and age, and blood gases and CBC were identified in cynomolgus monkeys. In conclusion, these reference values will be useful as markers for veterinary applications and in the care and maintenance of these animals. PMID:28381665

Comparative reactivity of human IgE to cynomolgus monkey and human effector cells and effects on IgE effector cell potency

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Saul, Louise; Saul, Louise; Josephs, Debra H; Josephs, Debra H; Cutler, Keith; Cutler, Keith; Bradwell, Andrew; Bradwell, Andrew; Karagiannis, Panagiotis; Karagiannis, Panagiotis; Selkirk, Chris; Selkirk, Chris; Gould, Hannah J; Gould, Hannah J; Jones, Paul; Jones, Paul; Spicer, James F; Spicer, James F; Karagiannis, Sophia N; Karagiannis, Sophia N

2014-01-01

Background: Due to genetic similarities with humans, primates of the macaque genus such as the cynomolgus monkey are often chosen as models for toxicology studies of antibody therapies. IgE therapeutics in development depend upon engagement with the FcεRI and FcεRII receptors on immune effector cells for their function. Only limited knowledge of the primate IgE immune system is available to inform the choice of models for mechanistic and safety evaluations.   Methods: The recognition of human IgE by peripheral blood lymphocytes from cynomolgus monkey and man was compared. We used effector cells from each species in ex vivo affinity, dose-response, antibody-receptor dissociation and potency assays. Results: We report cross-reactivity of human IgE Fc with cynomolgus monkey cells, and comparable binding kinetics to peripheral blood lymphocytes from both species. In competition and dissociation assays, however, human IgE dissociated faster from cynomolgus monkey compared with human effector cells. Differences in association and dissociation kinetics were reflected in effector cell potency assays of IgE-mediated target cell killing, with higher concentrations of human IgE needed to elicit effector response in the cynomolgus monkey system. Additionally, human IgE binding on immune effector cells yielded significantly different cytokine release profiles in each species. Conclusion: These data suggest that human IgE binds with different characteristics to human and cynomolgus monkey IgE effector cells. This is likely to affect the potency of IgE effector functions in these two species, and so has relevance for the selection of biologically-relevant model systems when designing pre-clinical toxicology and functional studies. PMID:24492303

[Uterine autologous transplantation in cynomolgus monkeys: a preliminary report of 6 case].

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Wang, Yifeng; Zhu, Ying; Yu, Ping; Chen, Gaowen; Cai, Baota; Zhang, Zhengguang; Liu, Na; Lü, Xiaogang; Xiong, Juxiang; Zhong, Lijuan; Rao, Junhua

2014-12-23

To evaluate the surgical feasibility of uterine autologous transplantation in female cynomolgus monkeys and explore the effect of microsurgical technique. From May 2011 to March 2014, 6 female cynomolgus monkeys, aged 7 to 12 years, were randomly divided into 2 surgical groups. In group A, gross surgeries were performed with naked eyes. In group B, uterine re-transplantation was performed under 10-time-magnifying microscopy. Anatomical data and operative durations were recorded and analyzed. Viable uterine tissue and vascular patency were observed on trans-abdominal ultrasonography and second-look laparotomy after 3 months. The average uterus retrieval time, average vascular anastomotic time, average perfusion time and average total operative time of group B were 88.7, 147.3 and 320.0 min versus 123.7, 180.7 and 393.7 min in group A. The average perfusion durations were 35.0 and 27.3 min. And there was no inter-group difference. A total of 12 successful vascular procedures (including 6 internal iliac arteries and 6 uterine-ovary veins) of vascular anastomosis were recorded in group B versus 4 cases (including 1 artery and 3 veins) in group A (vein, P > 0.05; artery, P trans-abdominal ultrasonography and second-look laparotomy. Two survivors resumed cyclicity at days 17 and 50 respectively as a sign of re-established uterine function. This study has demonstrated the feasibility of uterus transplantation by vascular anastomosis in cynomolgus monkeys. And assistance of microsurgical technique can significantly improve the success rate of arterial anastomosis during uterus transplantation.

Vulvovaginites em mulheres infectadas pelo vírus da imunodeficiência humana Vaginal infections in human immunodeficiency virus-infected women

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Paula Matos Oliveira

2008-03-01

Full Text Available OBJETIVO: comparar a freqüência de vulvovaginites em mulheres infectadas pelo vírus da imunodeficiência humana (HIV com mulheres não infectadas. MÉTODOS: estudo de corte transversal com 64 mulheres infectadas pelo HIV e 76 não infectadas. Foram calculadas as freqüências de vaginose bacteriana, candidíase e tricomoníase, que foram diagnosticadas por critérios de Amsel, cultura e exame a fresco, respectivamente. Para análise dos dados, utilizaram-se o teste do c2, teste exato de Fisher e regressão múltipla para verificar a independência das associações. RESULTADOS: a infecção vaginal foi mais prevalente em pacientes infectadas pelo HIV quando comparadas ao Grupo Controle (59,4 versus 28,9%, pPURPOSE: to compare the frequency of vulvovaginitis in women infected with human imunnodeficiency virus (HIV with the frequency in non-infected women. METHODS: a transversal study including 64 HIV infected women and 76 non-infected ones. The frequencies of bacterial vaginosis, candidiasis and trichomoniasis, diagnosed by Amsel's criteria, culture and fresh exam, respectively, were calculated. Chi-square test, Fisher's exact test and multiple regressions to verify the independence of associations were used to analyze the data. RESULTS: the vaginal infection was more prevalent in HIV infected patients, as compared to the control group (59.4 versus 28.9%, p<0,001; Odds Ratio=2.7, IC95%=1.33-5.83, p=0.007. Bacterial vaginosis occurred in 26.6% of the positive-HIV women; vaginal candidiasis, in 29.7% and trichomoniasis, in 12.5% of them. All the infections were significantly more frequent in the group of HIV infected women (p=0.04, 0.02 e 0.04, respectively. CONCLUSIONS: vulvovaginitis is more frequent in HIV infected women.

Probing around implants and teeth with healthy or inflamed peri-implant mucosa/gingival. A histologic comparison in cynomolgus monkeys. (Macaca fascicularis)

DEFF Research Database (Denmark)

Schou, Søren; Holmstrup, Palle; Stoltze, K.

2002-01-01

Osseointegrated oral implants; teeth; phathology; peri-implant mucositis; gingivitis; peri-implantitis; periodontitis; diagnosis; probing depth; non-human primates; cynomolgus monkeys: Macaca fascicularis......Osseointegrated oral implants; teeth; phathology; peri-implant mucositis; gingivitis; peri-implantitis; periodontitis; diagnosis; probing depth; non-human primates; cynomolgus monkeys: Macaca fascicularis...

Effects of long-term estrogen replacement therapy on bone turnover in periarticular tibial osteophytes in surgically postmenopausal cynomolgus monkeys

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Olson, Erik J.; Lindgren, Bruce R.; Carlson, Cathy S.

2007-01-01

The aims of the present study were to assess the effects of long-term estrogen replacement therapy (ERT) on size and indices of bone turnover in periarticular osteophytes in ovariectomized cynomolgus monkeys and to compare dynamic indices of bone turnover in osteophyte bone with those of subchondral bone (SCB) and epiphyseal/metaphyseal cancellous (EMC) bone. One hundred sixty-five adult female cynomolgus macaques were bilaterally ovariectomized and randomly divided into three age- and weight...

High Infection Rates for Adult Macaques after Intravaginal or Intrarectal Inoculation with Zika Virus

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Nalca, Aysegul; Rossi, Franco D.; Miller, Lynn J.; Wiley, Michael R.; Perez-Sautu, Unai; Washington, Samuel C.; Norris, Sarah L.; Wollen-Roberts, Suzanne E.; Shamblin, Joshua D.; Kimmel, Adrienne E.; Bloomfield, Holly A.; Valdez, Stephanie M.; Sprague, Thomas R.; Principe, Lucia M.; Bellanca, Stephanie A.; Cinkovich, Stephanie S.; Lugo-Roman, Luis; Cazares, Lisa H.; Pratt, William D.; Palacios, Gustavo F.; Bavari, Sina; Pitt, M. Louise; Nasar, Farooq

2017-01-01

Unprotected sexual intercourse between persons residing in or traveling from regions with Zika virus transmission is a risk factor for infection. To model risk for infection after sexual intercourse, we inoculated rhesus and cynomolgus macaques with Zika virus by intravaginal or intrarectal routes. In macaques inoculated intravaginally, we detected viremia and virus RNA in 50% of macaques, followed by seroconversion. In macaques inoculated intrarectally, we detected viremia, virus RNA, or both, in 100% of both species, followed by seroconversion. The magnitude and duration of infectious virus in the blood of macaques suggest humans infected with Zika virus through sexual transmission will likely generate viremias sufficient to infect competent mosquito vectors. Our results indicate that transmission of Zika virus by sexual intercourse might serve as a virus maintenance mechanism in the absence of mosquito-to-human transmission and could increase the probability of establishment and spread of Zika virus in regions where this virus is not present. PMID:28548637

High Infection Rates for Adult Macaques after Intravaginal or Intrarectal Inoculation with Zika Virus.

Science.gov (United States)

Haddow, Andrew D; Nalca, Aysegul; Rossi, Franco D; Miller, Lynn J; Wiley, Michael R; Perez-Sautu, Unai; Washington, Samuel C; Norris, Sarah L; Wollen-Roberts, Suzanne E; Shamblin, Joshua D; Kimmel, Adrienne E; Bloomfield, Holly A; Valdez, Stephanie M; Sprague, Thomas R; Principe, Lucia M; Bellanca, Stephanie A; Cinkovich, Stephanie S; Lugo-Roman, Luis; Cazares, Lisa H; Pratt, William D; Palacios, Gustavo F; Bavari, Sina; Pitt, M Louise; Nasar, Farooq

2017-08-01

Unprotected sexual intercourse between persons residing in or traveling from regions with Zika virus transmission is a risk factor for infection. To model risk for infection after sexual intercourse, we inoculated rhesus and cynomolgus macaques with Zika virus by intravaginal or intrarectal routes. In macaques inoculated intravaginally, we detected viremia and virus RNA in 50% of macaques, followed by seroconversion. In macaques inoculated intrarectally, we detected viremia, virus RNA, or both, in 100% of both species, followed by seroconversion. The magnitude and duration of infectious virus in the blood of macaques suggest humans infected with Zika virus through sexual transmission will likely generate viremias sufficient to infect competent mosquito vectors. Our results indicate that transmission of Zika virus by sexual intercourse might serve as a virus maintenance mechanism in the absence of mosquito-to-human transmission and could increase the probability of establishment and spread of Zika virus in regions where this virus is not present.

Occurrence of feline immunodeficiency virus infection in cats Ocorrência da infecção pelo vírus da imunodeficiência felina em gatos

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Valéria Maria Lara

2008-11-01

Full Text Available The occurrence of feline immunodeficiency virus (FIV in Brazil has been previously described. This study aimed to investigate the frequency of FIV infection in 454 blood samples from healthy and sick domestic cats from 13 cities of São Paulo State, Brazil as well as to evaluate the risk factors associated with the infection. The results showed that 14.7% (67/454 of the cats were infected with FIV. The clinical evaluation showed that 29.2% of the FIV-positive animals were sick, while 7.3% did not show any type of clinical manifestation. In addition, the vast majority (23.1% of positive cases corresponded to free-roaming owned cats. The incidence of FIV infection was higher in males (20.3% than in females (9.7%. The results suggest that certain characteristics such as gender, health status and lifestyle may be associated with the risk of being infected with FIV in the population of cats studied.No Brasil, a ocorrência da infecção pelo vírus da imunodeficiência felina (FIV já foi descrita. Neste estudo, objetivou-se investigar a freqüência da infecção pelo FIV em 454 amostras de sangue de gatos domésticos doentes e sadios, oriundos de 13 cidades do Estado de São Paulo, assim como avaliar os fatores de risco associados à infecção pelo FIV. Os resultados demonstraram que 14,7% (67/454 dos gatos estavam infectados pelo FIV. A avaliação clínica dos animais investigados mostrou que 29,2% dos animais soropositivos para FIV estavam doentes, enquanto 7,3% não apresentavam nenhuma manifestação clínica. Além disso, a vasta maioria dos animais positivos (23,1% vivia em residências e tinha livre acesso à rua. A incidência da infecção pelo FIV foi maior nos gatos machos (20,3% do que nas fêmeas (9,7%. Os resultados sugerem que certas características como sexo, estilo de vida e estado de saúde podem estar associadas ao risco de contrair a infecção pelo FIV na população de gatos estudada.

Pharmacodynamic model of interleukin-21 effects on red blood cells in cynomolgus monkeys

DEFF Research Database (Denmark)

Overgaard, Rune Viig; Karlsson, M.; Ingwersen, S.H.

2007-01-01

of treatment. The present analysis investigates the observed pharmacodynamics effects on red blood cells following various treatment schedules of human IL-21 administrated to cynomolgus monkeys. These effects are described by a novel non-linear mixed-effects model that enabled separation of drug effects......Interleukin-21 (IL-21) is a novel cytokine that is currently under clinical investigations as a potential anti-cancer agent. Like many other anti-cancer agents, including other interleukins, IL-21 is seen to produce a broad range of biological effects that may be related to both efficacy and safety...... and sampling effects, the latter believed to be due partly to blood loss and partly to stress induced haemolysis in connection with blood sampling. Two different studies with a total of 9 different treatment groups of cynomolgus monkeys were used for model development. In conclusion, the model describes the IL...

Infecção mista pelo Sugarcane mosaic virus e Maize rayado fino virus provoca danos na cultura do milho no estado de São Paulo Mixed infection by Sugarcane mosaic virus and Maize rayado fino virus causing breaking yields in maize in São Paulo state

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Marcos César Gonçalves

2007-12-01

Full Text Available Os dois principais vírus que infectam o milho no Brasil são o Sugarcane mosaic virus (SCMV e o Maize rayado fino virus (MRFV, cujos principais vetores são o afídeo Rhopalosiphum maidis e a cigarrinha Dalbulus maidis, respectivamente. O MRFV é freqüentemente encontrado em infecções mistas com fitoplasmas e espiroplasmas, causando as doenças denominadas enfezamentos do milho. Em uma lavoura de milho próxima a Santo Antonio da Posse, SP, cercada por campos de cana-de-açúcar, foi encontrada alta incidência de plantas apresentando mosaico, riscas, nanismo e espigas com falhas no enchimento de grãos. Análises serológicas com anti-soros específicos detectaram a presença do SCMV e MRFV nessas plantas. A infecção pelo SCMV também foi confirmada por RT-PCR com primers específicos e análise de seqüências. Em observações de preparações contrastadas negativamente em TEM, partículas flexuosas (ca.770 nm e isométricas (ca.30 nm foram detectadas. Em cortes ultrafinos, inclusões citoplasmáticas, típicas de Potyviridae, foram observadas; não foi encontrada a presença de espiroplasmas nem de fitoplasmas. Esses resultados mostram que a infecção conjunta por SCMV e MRFV pode ser responsável pelos danos encontrados nessa lavoura.The two main viruses infecting maize in Brazil are Sugarcane mosaic virus (SCMV and Maize rayado fino virus (MRFV, whose main vectors are the aphid Rhopalosiphum maidis and the leafhopper Dalbulus maidis, respectively. MRFV is frequently found in mixed infections with phytoplasms and spiroplasms causing the so-called corn stunting diseases. In a maize commercial field close to Santo Antonio da Posse, São Paulo state, surrounded by sugarcane fields, it was found a high incidence of plants showing mosaic, striping, stunting and cobs with decreased number of grains. Serological analysis with specific antisera detected the presence of SCMV and MRFV in these plants. SCMV infection was also confirmed by RT

Estudo ao microscópio electrônico de tecidos de plantas infetadas pelo vírus do mosaico comum e mosaico amarelo do feijoeiro Electron microscopy of common and yellow bean mosaic viruses in infected tissues

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I. J. B. de Camargo

1968-01-01

Full Text Available Exames ao microscópio electrônico de tecidos foliares e radiculares de plantas infetadas pelo vírus do mosaico comum ou do mosaico amarelo do feijoeiro, mostraram a presença de dois tipos de inclusões no cito-plasma: filamentosas, consideradas como partículas de vírus, e lamelares, típicas dos vírus do grupo Y. Essas inclusões não foram encontradas no pólen ou no óvulo de feijoeiros infetados. Como o vírus do mosaico comum do feijoeiro é transmitido pelo pólen, sugere-se que êle ocorre nestas células em concentração muito baixa, ou mesmo na forma de ácido nucléico.Two types of cytoplasmic inclusions were observed in leaf and root tissues of host plants infected with the common and yellow bean mosaic viruses: (1 filamentous inclusions considered as an aggregate of virus particles and (2 lamellar inclusions which appeared with varied configurations that represent sections at different angles of the same cylindrical structure. No type of inclusion or virus particle was seen in pollen and ovule from bean plants infected with each of the two viruses. Since, however, the common bean mosaic virus is transmitted through the pollen it is suggested that it occurs in very low concentration in this structure or else as viral nucleic acid.

The influence of rearing conditions on maternal behavior in cynomolgus macaques (Macaca fascicularis)

NARCIS (Netherlands)

Timmermans, P.J.A.; Vossen, J.M.H.

1996-01-01

We studied the influence of rearing on the adequacy of maternal behavior by comparing 20 harem-reared and 15 peer-reared primiparous cynomolgus monkeys. We used them plus 11 wild-caught females to extend this comparison to multiparous subjects and also to compare primiparae with multiparae. We

Evaluation of novel biomarkers of nephrotoxicity in Cynomolgus monkeys treated with gentamicin

International Nuclear Information System (INIS)

Gautier, Jean-Charles; Zhou, Xiaobing; Yang, Yi; Gury, Thierry; Qu, Zhe; Palazzi, Xavier; Léonard, Jean-François; Slaoui, Mohamed; Veeranagouda, Yaligara; Guizon, Isabelle; Boitier, Eric; Filali-Ansary, Aziz; Berg, Bart H.J. van den; Poetz, Oliver; Joos, Thomas; Zhang, Tianyi; Wang, Jufeng; Detilleux, Philippe; Li, Bo

2016-01-01

Most studies to evaluate kidney safety biomarkers have been performed in rats. This study was conducted in Cynomolgus monkeys in order to evaluate the potential usefulness of novel biomarkers of nephrotoxicity in this species. Groups of 3 males were given daily intramuscular injections of gentamicin, a nephrotoxic agent known to produce lesions in proximal tubules, at dose-levels of 10, 25, or 50 mg/kg/day for 10 days. Blood and 16-h urine samples were collected on Days − 7, − 3, 2, 4, 7, and at the end of the dosing period. Several novel kidney safety biomarkers were evaluated, with single- and multiplex immunoassays and in immunoprecipitation-LC/MS assays, in parallel to histopathology and conventional clinical pathology parameters. Treatment with gentamicin induced a dose-dependent increase in kidney tubular cell degeneration/necrosis, ranging from minimal to mild severity at 10 mg/kg/day, moderate at 25 mg/kg/day, and to severe at 50 mg/kg/day. The results showed that the novel urinary biomarkers, microalbumin, α1-microglobulin, clusterin, and osteopontin, together with the more traditional clinical pathology parameters, urinary total protein and N-acetyl-β-D-glucosaminidase (NAG), were more sensitive than blood urea nitrogen (BUN) and serum creatinine (sCr) to detect kidney injury in the monkeys given 10 mg/kg/day gentamicin for 10 days, a dose leading to an exposure which is slightly higher than the desired therapeutic exposure in clinics. Therefore, these urinary biomarkers represent non-invasive biomarkers of proximal tubule injury in Cynomolgus monkeys which may be potentially useful in humans. - Highlights: • Gentamicin induced kidney tubular cell degeneration/necrosis in Cynomolgus monkey • Urinary clusterin and osteopontin were sensitive biomarkers of kidney injury. • Microalbumin and α1-microglobulin in urine were also more sensitive than serum creatinine.

Evaluation of novel biomarkers of nephrotoxicity in Cynomolgus monkeys treated with gentamicin

Energy Technology Data Exchange (ETDEWEB)

Gautier, Jean-Charles, E-mail: jean-charles.gautier@sanofi.com [Sanofi R& D, Vitry-sur-Seine (France); Zhou, Xiaobing [National Center for Safety Evaluation of Drugs (NCSED), National Institutes for Food and Drug Control, Beijing (China); Yang, Yi [Sanofi R& D, Bridgewater (United States); Gury, Thierry [Sanofi R& D, Vitry-sur-Seine (France); Qu, Zhe [National Center for Safety Evaluation of Drugs (NCSED), National Institutes for Food and Drug Control, Beijing (China); Palazzi, Xavier; Léonard, Jean-François; Slaoui, Mohamed; Veeranagouda, Yaligara; Guizon, Isabelle; Boitier, Eric; Filali-Ansary, Aziz [Sanofi R& D, Vitry-sur-Seine (France); Berg, Bart H.J. van den; Poetz, Oliver; Joos, Thomas [Natural and Medical Sciences Institute at the University Tübingen (Germany); Zhang, Tianyi [Frontage Laboratories, Shanghai (China); Wang, Jufeng [National Center for Safety Evaluation of Drugs (NCSED), National Institutes for Food and Drug Control, Beijing (China); Detilleux, Philippe [Sanofi R& D, Vitry-sur-Seine (France); Li, Bo, E-mail: libo@nifdc.org.cn [National Center for Safety Evaluation of Drugs (NCSED), National Institutes for Food and Drug Control, Beijing (China)

2016-07-15

Most studies to evaluate kidney safety biomarkers have been performed in rats. This study was conducted in Cynomolgus monkeys in order to evaluate the potential usefulness of novel biomarkers of nephrotoxicity in this species. Groups of 3 males were given daily intramuscular injections of gentamicin, a nephrotoxic agent known to produce lesions in proximal tubules, at dose-levels of 10, 25, or 50 mg/kg/day for 10 days. Blood and 16-h urine samples were collected on Days − 7, − 3, 2, 4, 7, and at the end of the dosing period. Several novel kidney safety biomarkers were evaluated, with single- and multiplex immunoassays and in immunoprecipitation-LC/MS assays, in parallel to histopathology and conventional clinical pathology parameters. Treatment with gentamicin induced a dose-dependent increase in kidney tubular cell degeneration/necrosis, ranging from minimal to mild severity at 10 mg/kg/day, moderate at 25 mg/kg/day, and to severe at 50 mg/kg/day. The results showed that the novel urinary biomarkers, microalbumin, α1-microglobulin, clusterin, and osteopontin, together with the more traditional clinical pathology parameters, urinary total protein and N-acetyl-β-D-glucosaminidase (NAG), were more sensitive than blood urea nitrogen (BUN) and serum creatinine (sCr) to detect kidney injury in the monkeys given 10 mg/kg/day gentamicin for 10 days, a dose leading to an exposure which is slightly higher than the desired therapeutic exposure in clinics. Therefore, these urinary biomarkers represent non-invasive biomarkers of proximal tubule injury in Cynomolgus monkeys which may be potentially useful in humans. - Highlights: • Gentamicin induced kidney tubular cell degeneration/necrosis in Cynomolgus monkey • Urinary clusterin and osteopontin were sensitive biomarkers of kidney injury. • Microalbumin and α1-microglobulin in urine were also more sensitive than serum creatinine.

R-warfarin clearances from plasma associated with polymorphic cytochrome P450 2C19 and simulated by individual physiologically based pharmacokinetic models for 11 cynomolgus monkeys.

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Utoh, Masahiro; Kusama, Takashi; Miura, Tomonori; Mitsui, Marina; Kawano, Mirai; Hirano, Takahiro; Shimizu, Makiko; Uno, Yasuhiro; Yamazaki, Hiroshi

2018-02-01

1. Cynomolgus monkey cytochrome P450 2C19 (formerly known as P450 2C75), homologous to human P450 2C19, has been identified as R-warfarin 7-hydroxylase. In this study, simulations of R-warfarin clearance in individual cynomolgus monkeys genotyped for P450 2C19 p.[(Phe100Asn; Ala103Val; Ile112Leu)] were performed using individual simplified physiologically based pharmacokinetic (PBPK) modeling. 2. Pharmacokinetic parameters and absorption rate constants, volumes of the systemic circulation, and hepatic intrinsic clearances for individual PBPK models were estimated for eleven cynomolgus monkeys. 3. One-way ANOVA revealed significant effects of the genotype (p warfarin among the homozygous mutant, heterozygous mutant, and wild-type groups. R-Warfarin clearances in individual cynomolgus monkeys genotyped for P450 2C19 were simulated by simplified PBPK modeling. The modeled hepatic intrinsic clearances were significantly associated with the P450 2C19 genotypes. The liver microsomal elimination rates of R-warfarin for individual animals after in vivo administration showed significant reductions associated with the genotype (p warfarin and related medicines associated with polymorphic P450 2C19 in individual cynomolgus monkeys, thereby facilitating calculation of the fraction of hepatic clearance.

The Cynomolgus Macaque Natural History Model of Pneumonic Tularemia for Predicting Clinical Efficacy Under the Animal Rule

Science.gov (United States)

Guina, Tina; Lanning, Lynda L.; Omland, Kristian S.; Williams, Mark S.; Wolfraim, Larry A.; Heyse, Stephen P.; Houchens, Christopher R.; Sanz, Patrick; Hewitt, Judith A.

2018-01-01

Francisella tularensis is a highly infectious Gram-negative bacterium that is the etiologic agent of tularemia in animals and humans and a Tier 1 select agent. The natural incidence of pneumonic tularemia worldwide is very low; therefore, it is not feasible to conduct clinical efficacy testing of tularemia medical countermeasures (MCM) in human populations. Development and licensure of tularemia therapeutics and vaccines need to occur under the Food and Drug Administration's (FDA's) Animal Rule under which efficacy studies are conducted in well-characterized animal models that reflect the pathophysiology of human disease. The Tularemia Animal Model Qualification (AMQ) Working Group is seeking qualification of the cynomolgus macaque (Macaca fascicularis) model of pneumonic tularemia under Drug Development Tools Qualification Programs with the FDA based upon the results of studies described in this manuscript. Analysis of data on survival, average time to death, average time to fever onset, average interval between fever and death, and bacteremia; together with summaries of clinical signs, necropsy findings, and histopathology from the animals exposed to aerosolized F. tularensis Schu S4 in five natural history studies and one antibiotic efficacy study form the basis for the proposed cynomolgus macaque model. Results support the conclusion that signs of pneumonic tularemia in cynomolgus macaques exposed to 300–3,000 colony forming units (cfu) aerosolized F. tularensis Schu S4, under the conditions described herein, and human pneumonic tularemia cases are highly similar. Animal age, weight, and sex of animals challenged with 300–3,000 cfu Schu S4 did not impact fever onset in studies described herein. This study summarizes critical parameters and endpoints of a well-characterized cynomolgus macaque model of pneumonic tularemia and demonstrates this model is appropriate for qualification, and for testing efficacy of tularemia therapeutics under Animal Rule. PMID

Modificação da virulência do virus do mixoma provocada pelos raios X Changes in virulence of the mixoma virus produced by X-Rays

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F. Rocha Lagôa

1952-03-01

Full Text Available Foi estudada a ação dos raios X sôbre a vírus sêco do mixoma dos coelhos. Ao atingir a incidência dos raios X a concentração de 294.000 r até 378.000, quando desapareceu tôda a atividade patogênica do vírus, nem todos os animais inoculados adquiriam a moléstia, passando a evoluir a mesma em alguns dêsses animais de forma muito mais lenta que a presente nas testemunhas. concordando com esta sintomatologia, o exame histopatológico do material colhido no ponto de lesão mais intensa de animais atacados com mixoma de evolução lenta, revelou a existência de lesões menos extensas e intesas que aquelas presentes nos animais inoculados com o vírus normal, o que mostra terem os raios X determinado uma diminuição da virulência do vírus do mixoma, mas não uma mutação. Os animais inoculados sucessivamente com vírus irradiado acima de 378.000 r, portanto inativados, foram, após 30 dias, inoculados com vírus de virulência íntegra, adquirindo, no entanto, a infecção mixomatosa com todos os caracteres típicos, o que revelou não conservar o vírus do mixoma inativado pelos raios X as suas propriedades antigênicas, não conferindo, portanto, proteção contra inoculações ulteriores de vírus mixomatoso virulento.The action of X Rays on the dried virus of myxoma of the rabbits has been studied. When the incidence of X-Rays reaches the concentration of 294.000 r to 378.000, a dosage which results in the destruction of all the pathogenic activity of the virus, not all the inoculated animals acquired the disease, which, when developing; has in several of these animals, a much slower than in the control animals. In accordance, with this symptomatology, the histopathological study of the material collected on the point of where the lesions are more marked in the animals suffering from a myxomatous infection of slow evolution, shows that the lesions are less extensive and less severe that the ones produced in the animals inoculated

Analysis of prostate-specific antigen transcripts in chimpanzees, cynomolgus monkeys, baboons, and African green monkeys.

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James N Mubiru

Full Text Available The function of prostate-specific antigen (PSA is to liquefy the semen coagulum so that the released sperm can fuse with the ovum. Fifteen spliced variants of the PSA gene have been reported in humans, but little is known about alternative splicing in nonhuman primates. Positive selection has been reported in sex- and reproductive-related genes from sea urchins to Drosophila to humans; however, there are few studies of adaptive evolution of the PSA gene. Here, using polymerase chain reaction (PCR product cloning and sequencing, we study PSA transcript variant heterogeneity in the prostates of chimpanzees (Pan troglodytes, cynomolgus monkeys (Macaca fascicularis, baboons (Papio hamadryas anubis, and African green monkeys (Chlorocebus aethiops. Six PSA variants were identified in the chimpanzee prostate, but only two variants were found in cynomolgus monkeys, baboons, and African green monkeys. In the chimpanzee the full-length transcript is expressed at the same magnitude as the transcripts that retain intron 3. We have found previously unidentified splice variants of the PSA gene, some of which might be linked to disease conditions. Selection on the PSA gene was studied in 11 primate species by computational methods using the sequences reported here for African green monkey, cynomolgus monkey, baboon, and chimpanzee and other sequences available in public databases. A codon-based analysis (dN/dS of the PSA gene identified potential adaptive evolution at five residue sites (Arg45, Lys70, Gln144, Pro189, and Thr203.

Polymorphisms of cytochrome P450 2B6 (CYP2B6) in cynomolgus and rhesus macaques.

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Uno, Yasuhiro; Uehara, Shotaro; Yamazaki, Hiroshi

2018-02-22

Cytochrome P450 2B6 (CYP2B6) is an important drug-metabolizing enzyme and is expressed in liver. Although human CYP2B6 variants account for variable enzyme properties among individuals and populations, CYP2B6 genetic variants have not been investigated in cynomolgus macaques, widely used in drug metabolism studies. CYP2B6 was resequenced in 120 cynomolgus macaques and 23 rhesus macaques by direct sequencing. Twenty-three non-synonymous variants were found, of which 12 and 3 were unique to cynomolgus macaques and rhesus macaques, respectively. By functional characterization using the 14 variant proteins, 8 variants (V114I, R253C, M435I, V459M, L465P, C475S, R487C, and R487H) showed different rate (>1.5-fold) of testosterone 16β-hydroxylation to wild type. However, the four variants (M435I, L465P, C475S, and R487H) were analyzed in liver microsomes, and the catalytic rates were not substantially different from wild type. Macaque CYP2B6 was polymorphic, and the genotype could partly account for variable enzyme activities of macaque CYP2B6. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Acute traumatic spinal cord injury induces glial activation in the cynomolgus macaque (Macaca fascicularis).

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Miller, A D; Westmoreland, S V; Evangelous, N R; Graham, A; Sledge, J; Nesathurai, S

2012-06-01

Traumatic spinal cord injury leads to direct myelin and axonal damage and leads to the recruitment of inflammatory cells to site of injury. Although rodent models have provided the greatest insight into the genesis of traumatic spinal cord injury (TSCI), recent studies have attempted to develop an appropriate non-human primate model. We explored TSCI in a cynomolgus macaque model using a balloon catheter to mimic external trauma to further evaluate the underlying mechanisms of acute TSCI. Following 1hour of spinal cord trauma, there were focal areas of hemorrhage and necrosis at the site of trauma. Additionally, there was a marked increased expression of macrophage-related protein 8, MMP9, IBA-1, and inducible nitric oxide synthase in macrophages and microglia at the site of injury. This data indicate that acute TSCI in the cynomolgus macaque is an appropriate model and that the earliest immunohistochemical changes noted are within macrophage and microglia populations. © 2012 John Wiley & Sons A/S.

Myotoxicity of Gemfibrozil in Cynomolgus Monkey Model and Its Relationship to Pharmacokinetic Properties

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Liu, Aiming; Xie, Shuilin; Sun, He; Gonzalez, Frank J.; Wei, Xiaoxiong; Dai, Renke

2008-01-01

Fibrate drugs are PPARα agonists prescribed for the treatment of dyslipidemia. Severe myotoxicity has been reported associated with their use albeit at a low frequency, especially for gemfibrozil. Few studies have investigated the mechanism of fibrate-induced myotoxicity in vivo. Considering the apparent species-related differences in PPARα agonist-induced hepatotoxicity, we studied the myotoxicity of gemfibrozil in a Cynomolgus monkey model and explored the relationship between myotoxicity and pharmacokinetics. Six Cynomolgus monkeys were dosed with gemfibrozil twice daily at 600 mg/kg/day for the first two periods (P1 and P2, 8 days and 9 days respectively) and 300 mg/kg/day for the third period (P3, 14 days). Creatine kinase and myoglobin were measured, together with hepatotoxicity and nephrotoxicity markers. Behavioral responses were recorded for indication of toxicity. Pharmacokinetics was carried out following the 16th dosage of P1 and 17th dosage of P2 when myotoxicity was identified. Multivariable data analysis was employed to explore the relationship between pharmacokinetic parameters and myotoxicity markers. Consequently, myotoxicity occurred in monkey #2 (M2) and M6 in P1, M3 and M4 in P2, M3 and M6 in P3. Data analysis showed T80-150 (sustained time above the given concentration) contributed for myotoxicity discriminance and correlated with myotoxicity risk. This study revealed Cynomolgus monkey may be a good animal model for myotoxicity evaluation with sensitivity, reproducibility and similarities to humans. More interestingly they exhibited a much higher incidence of myotoxicity than that of human. Sustained high drug concentration plays an important role for the occurrence of myotoxicity. This may suggest an influence of drug transport and metabolism on myotoxicity. PMID:19150455

Myotoxicity of gemfibrozil in Cynomolgus monkey model and its relationship to pharmacokinetic properties

International Nuclear Information System (INIS)

Liu Aiming; Xie Shuilin; Sun He; Gonzalez, Frank J.; Wei Xiaoxiong; Dai Renke

2009-01-01

Fibrate drugs are PPARα agonists prescribed for the treatment of dyslipidemia. Severe myotoxicity has been reportedly associated with their use albeit at a low frequency, especially for gemfibrozil. Few studies have investigated the mechanism of fibrate-induced myotoxicity in vivo. Considering the apparent species-related differences in PPARα agonist-induced hepatotoxicity, we studied the myotoxicity of gemfibrozil in a Cynomolgus monkey model and explored the relationship between myotoxicity and pharmacokinetics. Six Cynomolgus monkeys were dosed with gemfibrozil twice daily at 600 mg/kg/day for the first two periods (P1 and P2, 8 days and 9 days respectively) and 300 mg/kg/day for the third period (P3, 14 days). Creatine kinase and myoglobin were measured, together with hepatotoxicity and nephrotoxicity markers. Behavioral responses were recorded for indication of toxicity. Pharmacokinetics was carried out following the 16th dosage of P1 and 17th dosage of P2 when myotoxicity was identified. Multivariable data analysis was employed to explore the relationship between pharmacokinetic parameters and myotoxicity markers. Consequently, myotoxicity occurred in monkey no. 2 (M2) and M6 in P1, M3 and M4 in P2, M3 and M6 in P3. Data analysis showed T80-150 (sustained time above the given concentration) contributed for myotoxicity discriminance and correlated with myotoxicity risk. This study revealed Cynomolgus monkey may be a good animal model for myotoxicity evaluation with sensitivity, reproducibility and similarities to humans. More interestingly, they exhibited a much higher incidence of myotoxicity than that of humans. Sustained high drug concentration plays an important role for the occurrence of myotoxicity. This may suggest an influence of drug transport and metabolism on myotoxicity

Myotoxicity of gemfibrozil in Cynomolgus monkey model and its relationship to pharmacokinetic properties

Energy Technology Data Exchange (ETDEWEB)

Aiming, Liu; Shuilin, Xie [Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510663 (China); He, Sun [School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072 (China); Gonzalez, Frank J [National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Xiaoxiong, Wei [Medpace, Inc., Cincinnati, OH 45212 (United States); Dai Renke [Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510663 (China)], E-mail: dai_renke@gibh.ac.cn

2009-03-15

Fibrate drugs are PPAR{alpha} agonists prescribed for the treatment of dyslipidemia. Severe myotoxicity has been reportedly associated with their use albeit at a low frequency, especially for gemfibrozil. Few studies have investigated the mechanism of fibrate-induced myotoxicity in vivo. Considering the apparent species-related differences in PPAR{alpha} agonist-induced hepatotoxicity, we studied the myotoxicity of gemfibrozil in a Cynomolgus monkey model and explored the relationship between myotoxicity and pharmacokinetics. Six Cynomolgus monkeys were dosed with gemfibrozil twice daily at 600 mg/kg/day for the first two periods (P1 and P2, 8 days and 9 days respectively) and 300 mg/kg/day for the third period (P3, 14 days). Creatine kinase and myoglobin were measured, together with hepatotoxicity and nephrotoxicity markers. Behavioral responses were recorded for indication of toxicity. Pharmacokinetics was carried out following the 16th dosage of P1 and 17th dosage of P2 when myotoxicity was identified. Multivariable data analysis was employed to explore the relationship between pharmacokinetic parameters and myotoxicity markers. Consequently, myotoxicity occurred in monkey no. 2 (M2) and M6 in P1, M3 and M4 in P2, M3 and M6 in P3. Data analysis showed T80-150 (sustained time above the given concentration) contributed for myotoxicity discriminance and correlated with myotoxicity risk. This study revealed Cynomolgus monkey may be a good animal model for myotoxicity evaluation with sensitivity, reproducibility and similarities to humans. More interestingly, they exhibited a much higher incidence of myotoxicity than that of humans. Sustained high drug concentration plays an important role for the occurrence of myotoxicity. This may suggest an influence of drug transport and metabolism on myotoxicity.

New-Onset Diabetes Mellitus After Transplantation in a Cynomolgus Macaque (Macaca fasicularis).

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Matthews, Kristin A; Tonsho, Makoto; Madsen, Joren C

2015-08-01

A 5.5-y-old intact male cynomolgus macaque (Macaca fasicularis) presented with inappetence and weight loss 57 d after heterotopic heart and thymus transplantation while receiving an immunosuppressant regimen consisting of tacrolimus, mycophenolate mofetil, and methylprednisolone to prevent graft rejection. A serum chemistry panel, a glycated hemoglobin test, and urinalysis performed at presentation revealed elevated blood glucose and glycated hemoglobin (HbA1c) levels (727 mg/dL and 10.1%, respectively), glucosuria, and ketonuria. Diabetes mellitus was diagnosed, and insulin therapy was initiated immediately. The macaque was weaned off the immunosuppressive therapy as his clinical condition improved and stabilized. Approximately 74 d after discontinuation of the immunosuppressants, the blood glucose normalized, and the insulin therapy was stopped. The animal's blood glucose and HbA1c values have remained within normal limits since this time. We suspect that our macaque experienced new-onset diabetes mellitus after transplantation, a condition that is commonly observed in human transplant patients but not well described in NHP. To our knowledge, this report represents the first documented case of new-onset diabetes mellitus after transplantation in a cynomolgus macaque.

Comprehensive Evaluation for Substrate Selectivity of Cynomolgus Monkey Cytochrome P450 2C9, a New Efavirenz Oxidase.

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Hosaka, Shinya; Murayama, Norie; Satsukawa, Masahiro; Uehara, Shotaro; Shimizu, Makiko; Iwasaki, Kazuhide; Iwano, Shunsuke; Uno, Yasuhiro; Yamazaki, Hiroshi

2015-07-01

Cynomolgus monkeys are widely used as primate models in preclinical studies, because of their evolutionary closeness to humans. In humans, the cytochrome P450 (P450) 2C enzymes are important drug-metabolizing enzymes and highly expressed in livers. The CYP2C enzymes, including CYP2C9, are also expressed abundantly in cynomolgus monkey liver and metabolize some endogenous and exogenous substances like testosterone, S-mephenytoin, and diclofenac. However, comprehensive evaluation regarding substrate specificity of monkey CYP2C9 has not been conducted. In the present study, 89 commercially available drugs were examined to find potential monkey CYP2C9 substrates. Among the compounds screened, 20 drugs were metabolized by monkey CYP2C9 at a relatively high rates. Seventeen of these compounds were substrates or inhibitors of human CYP2C9 or CYP2C19, whereas three drugs were not, indicating that substrate specificity of monkey CYP2C9 resembled those of human CYP2C9 or CYP2C19, with some differences in substrate specificities. Although efavirenz is known as a marker substrate for human CYP2B6, efavirenz was not oxidized by CYP2B6 but by CYP2C9 in monkeys. Liquid chromatography-mass spectrometry analysis revealed that monkey CYP2C9 and human CYP2B6 formed the same mono- and di-oxidized metabolites of efavirenz at 8 and 14 positions. These results suggest that the efavirenz 8-oxidation could be one of the selective markers for cynomolgus monkey CYP2C9 among the major three CYP2C enzymes tested. Therefore, monkey CYP2C9 has the possibility of contributing to limited specific differences in drug oxidative metabolism between cynomolgus monkeys and humans. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

Biodistribution and safety of a live attenuated tetravalent dengue vaccine in the cynomolgus monkey.

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Ravel, Guillaume; Mantel, Nathalie; Silvano, Jeremy; Rogue, Alexandra; Guy, Bruno; Jackson, Nicholas; Burdin, Nicolas

2017-10-13

The first licensed dengue vaccine is a recombinant, live, attenuated, tetravalent dengue virus vaccine (CYD-TDV; Sanofi Pasteur). This study assessed the biodistribution, shedding, and toxicity of CYD-TDV in a non-human primate model as part of the nonclinical safety assessment program for the vaccine. Cynomolgus monkeys were given one subcutaneous injection of either one human dose (5log 10 CCID 50 /serotype) of CYD-TDV or saline control. Study endpoints included clinical observations, body temperature, body weight, food consumption, clinical pathology, immunogenicity, and post-mortem examinations including histopathology. Viral load, distribution, persistence, and shedding in tissues and body fluids were evaluated by quantitative reverse transcriptase polymerase chain reaction. The subcutaneous administration of CYD-TDV was well tolerated. There were no toxicological findings other than expected minor local reactions at the injection site. A transient low level of CYD-TDV viral RNA was detected in blood and the viral genome was identified primarily at the injection site and in the draining lymph nodes following immunization. These results, together with other data from repeat-dose toxicity and neurovirulence studies, confirm the absence of toxicological concern with CYD-TDV and corroborate clinical study observations. Copyright © 2017 Elsevier Ltd. All rights reserved.

Progression of Pathogenic Events in Cynomolgus Macaques Infected with Variola Virus

Science.gov (United States)

2011-10-01

times, centrifuged, and clarified supernatant was removed for extraction . DNA was extracted from ethylenediaminetetraacetic acid (EDTA) blood to analyze...virus load. All samples were lysed and extracted using the QIAamp Mini Kit (QIAGEN, Valencia, CA) according to the manufacturer’s instructions. qrt-PCR...mesenteric lymph nodes, salivary gland, testis or ovary, liver, gallbladder , spleen, adrenal gland, left and right kidneys, lung, heart, tongue

Genome sequencing and comparison of two nonhuman primate animal models, the cynomolgus and Chinese rhesus macaques

DEFF Research Database (Denmark)

Yan, Guangmei; Zhang, Guojie; Fang, Xiaodong

2011-01-01

The nonhuman primates most commonly used in medical research are from the genus Macaca. To better understand the genetic differences between these animal models, we present high-quality draft genome sequences from two macaque species, the cynomolgus/crab-eating macaque and the Chinese rhesus...

Infectious Chikungunya Virus in the Saliva of Mice, Monkeys and Humans.

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Joy Gardner

Full Text Available Chikungunya virus (CHIKV is a reemerging, ordinarily mosquito-transmitted, alphavirus that occasionally produces hemorrhagic manifestations, such as nose bleed and bleeding gums, in human patients. Interferon response factor 3 and 7 deficient (IRF3/7-/- mice, which are deficient for interferon α/β responses, reliably develop hemorrhagic manifestations after CHIKV infection. Here we show that infectious virus was present in the oral cavity of CHIKV infected IRF3/7-/- mice, likely due to hemorrhagic lesions in the olfactory epithelium that allow egress of infected blood into the nasal, and subsequently, oral cavities. In addition, IRF3/7-/- mice were more susceptible to infection with CHIKV via intranasal and oral routes, with IRF3/7-/- mice also able to transmit virus mouse-to-mouse without an arthropod vector. Cynomolgus macaques often show bleeding gums after CHIKV infection, and analysis of saliva from several infected monkeys also revealed the presence of viral RNA and infectious virus. Furthermore, saliva samples collected from several acute CHIKV patients with hemorrhagic manifestations were found to contain viral RNA and infectious virus. Oral fluids can therefore be infectious during acute CHIKV infections, likely due to hemorrhagic manifestations in the oral/nasal cavities.

A Single Amino Acid Change in the Marburg Virus Glycoprotein Arises during Serial Cell Culture Passages and Attenuates the Virus in a Macaque Model of Disease.

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Alfson, Kendra J; Avena, Laura E; Delgado, Jenny; Beadles, Michael W; Patterson, Jean L; Carrion, Ricardo; Griffiths, Anthony

2018-01-01

Marburg virus (MARV) causes disease with high case fatality rates, and there are no approved vaccines or therapies. Licensing of MARV countermeasures will likely require approval via the FDA's Animal Efficacy Rule, which requires well-characterized animal models that recapitulate human disease. This includes selection of the virus used for exposure and ensuring that it retains the properties of the original isolate. The consequences of amplification of MARV for challenge studies are unknown. Here, we serially passaged and characterized MARV through 13 passes from the original isolate. Surprisingly, the viral genome was very stable, except for a single nucleotide change that resulted in an amino acid substitution in the hydrophobic region of the signal peptide of the glycoprotein (GP). The particle/PFU ratio also decreased following passages, suggesting a role for the amino acid in viral infectivity. To determine if amplification introduces a phenotype in an animal model, cynomolgus macaques were exposed to either 100 or 0.01 PFU of low- and high-passage-number MARV. All animals succumbed when exposed to 100 PFU of either passage 3 or 13 viruses, although animals exposed to the high-passage-number virus survived longer. However, none of the passage 13 MARV-exposed animals succumbed to 0.01-PFU exposure compared to 75% of passage 3-exposed animals. This is consistent with other filovirus studies that show some particles that are unable to yield a plaque in cell culture can cause lethal disease in vivo . These results have important consequences for the design of experiments that investigate MARV pathogenesis and that test the efficacy of MARV countermeasures. IMPORTANCE Marburg virus (MARV) causes disease with a high case fatality rate, and there are no approved vaccines or therapies. Serial amplification of viruses in cell culture often results in accumulation of mutations, but the effect of such cell culture passage on MARV is unclear. Serial passages of MARV

Epidemiologia da infecção pelo vírus da hepatite C Epidemiology of hepatitis C virus infection

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Tatiana Martins

2011-02-01

Full Text Available A hepatite C é uma das principais causas de doença hepática crônica em todo o mundo. Existe grande variação na prevalência da infecção pelo vírus da hepatite C (HCV de acordo com a região geográfica estudada, refletindo não só características epidemiológicas distintas entre as populações, mas diferenças nas metodologias utilizadas para a realização das estimativas. Apesar dos dados escassos, estimativas indicam que o Brasil é um país com prevalência intermediária, variando entre 1% e 2%. Os principais fatores de risco para a infecção pelo HCV são a transfusão de hemoderivados de doadores não rastreados com anti-HCV, uso de drogas intravenosas, transplante de órgãos, hemodiálise, transmissão vertical, exposição sexual e ocupacional. Pela ausência de vacina ou profilaxia pós-exposição eficaz, o foco principal da prevenção está no reconhecimento e controle desses fatores de risco. Neste artigo será feita uma revisão da literatura com enfoque na prevalência da hepatite C, especialmente no Brasil. Além disso, serão discutidos aspectos relacionados à distribuição da infecção pelo HCV de acordo com as faixas etárias e também os principais fatores de risco para a hepatite C.Hepatitis C is a major cause of chronic liver disease worldwide. There is a significant variation in the prevalence of hepatitis C virus (HCV infection according to the geographic region studied. These discrepancies reflect not only distinct epidemiological characteristics among the populations, but also differences in the methodologies used for the estimates. Despite scarce data, estimates indicate that Brazil is a country with an intermediate prevalence of HCV infection, ranging from 1% to 2%. The most important risk factors for HCV acquisition include injection drug use, blood product transfusion, organ transplantation, hemodialysis, occupational injury, sexual transmission and vertical transmission. Because there is no

Detection and Quantification of Male-Specific Fetal DNA in the Serum of Pregnant Cynomolgus Monkeys (Macaca fascicularis)

Science.gov (United States)

Yasmin, Lubna; Takano, Jun-ichiro; Nagai, Yasushi; Otsuki, Junko; Sankai, Tadashi

2015-01-01

Because of their developmental similarities to humans, nonhuman primates are often used as a model to study fetal development for potential clinical applications in humans. The detection of fetal DNA in maternal plasma or serum offers a source of fetal genetic material for prenatal diagnosis. However, no such data have been reported for cynomolgus monkeys (Macaca fascicularis), an important model in biomedical research. We have developed a specific, highly sensitive PCR system for detecting and quantifying male-specific fetal DNA in pregnant cynomolgus monkeys. We used multiplex quantitative real-time PCR to analyze cell-free DNA in maternal blood serum obtained from 46 pregnant monkeys at gestational weeks 5, 12, and 22. The presence of SRY gene and DYS14 Y chromosomal sequences was determined in 28 monkeys with male-bearing pregnancies. According to confirmation of fetal sex at birth, the probe and primers for detecting the Y chromosomal regions at each time point revealed 100% specificity of the PCR test and no false-positive or false-negative results. Increased levels of the SRY-specific sequences (mean, 4706 copies/mL serum DNA; range, 1731 to 12,625) and DYS14-specific sequences (mean, 54,814 copies/mL serum DNA; range, 4175–131,250 copies) were detected at week 22. The SRY- and DYS14-specific probes appear to be an effective combination of markers in a multiplex PCR system. To our knowledge, this report is the first to describe the detection of cell-free DNA in cynomolgus monkeys. PMID:25730760

Subarachnoid administration of iohexol in cynomolgus monkeys

International Nuclear Information System (INIS)

Drobeck, H.P.; Mayes, B.A.; Barbolt, T.A.; Fabian, R.J.; Kimball, J.P.; Slighter, R.R. Jr.

1986-01-01

A non-ionic diagnostic medium, iohexol, was administered by subarachnoid injection to groups of six cynomolgus monkeys and compared with the vehicle, physiologically normal saline, and/or saline of equal osmolality to determine its potential for increasing total protein and leucocyte levels in cerebrospinal fluid. Also investigated was the effect of repeated spinal taps not subsequently followed by the intrathecal injection of test or control articles. In the monkey, unlike man, low-level leucocyte counts were consistently observed following initial withdrawal of spinal fluid. Elevated leucocyte and total protein levels were observed in the present investigations one day to a week after intrathecal injection of radiopaque, vehicle or saline solution. Total protein returned to normal levels earlier than did leucocyte counts. However, repeated needle puncture alone was found to be sufficient to cause an elevation of leucocytes 3 to 4 times the baseline level, while inflammatory effects were observed histologically only when autopsy was performed soon after the final spinal tap. (orig.)

Cynomolgus macaque as an animal model for severe acute respiratory syndrome.

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James V Lawler

2006-05-01

Full Text Available The emergence of severe acute respiratory syndrome (SARS in 2002 and 2003 affected global health and caused major economic disruption. Adequate animal models are required to study the underlying pathogenesis of SARS-associated coronavirus (SARS-CoV infection and to develop effective vaccines and therapeutics. We report the first findings of measurable clinical disease in nonhuman primates (NHPs infected with SARS-CoV.In order to characterize clinically relevant parameters of SARS-CoV infection in NHPs, we infected cynomolgus macaques with SARS-CoV in three groups: Group I was infected in the nares and bronchus, group II in the nares and conjunctiva, and group III intravenously. Nonhuman primates in groups I and II developed mild to moderate symptomatic illness. All NHPs demonstrated evidence of viral replication and developed neutralizing antibodies. Chest radiographs from several animals in groups I and II revealed unifocal or multifocal pneumonia that peaked between days 8 and 10 postinfection. Clinical laboratory tests were not significantly changed. Overall, inoculation by a mucosal route produced more prominent disease than did intravenous inoculation. Half of the group I animals were infected with a recombinant infectious clone SARS-CoV derived from the SARS-CoV Urbani strain. This infectious clone produced disease indistinguishable from wild-type Urbani strain.SARS-CoV infection of cynomolgus macaques did not reproduce the severe illness seen in the majority of adult human cases of SARS; however, our results suggest similarities to the milder syndrome of SARS-CoV infection characteristically seen in young children.

Virus-Like Particle Vaccination Protects Nonhuman Primates from Lethal Aerosol Exposure with Marburgvirus (VLP Vaccination Protects Macaques against Aerosol Challenges

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John M. Dye

2016-04-01

Full Text Available Marburg virus (MARV was the first filovirus to be identified following an outbreak of viral hemorrhagic fever disease in Marburg, Germany in 1967. Due to several factors inherent to filoviruses, they are considered a potential bioweapon that could be disseminated via an aerosol route. Previous studies demonstrated that MARV virus-like particles (VLPs containing the glycoprotein (GP, matrix protein VP40 and nucleoprotein (NP generated using a baculovirus/insect cell expression system could protect macaques from subcutaneous (SQ challenge with multiple species of marburgviruses. In the current study, the protective efficacy of the MARV VLPs in conjunction with two different adjuvants: QS-21, a saponin derivative, and poly I:C against homologous aerosol challenge was assessed in cynomolgus macaques. Antibody responses against the GP antigen were equivalent in all groups receiving MARV VLPs irrespective of the adjuvant; adjuvant only-vaccinated macaques did not demonstrate appreciable antibody responses. All macaques were subsequently challenged with lethal doses of MARV via aerosol or SQ as a positive control. All MARV VLP-vaccinated macaques survived either aerosol or SQ challenge while animals administered adjuvant only exhibited clinical signs and lesions consistent with MARV disease and were euthanized after meeting the predetermined criteria. Therefore, MARV VLPs induce IgG antibodies recognizing MARV GP and VP40 and protect cynomolgus macaques from an otherwise lethal aerosol exposure with MARV.

Correlations between serum levels of beta amyloid, cerebrospinal levels of tau and phospho tau, and delayed response tasks in young and aged cynomolgus monkeys (Macaca fascicularis)

DEFF Research Database (Denmark)

Darusman, Huda Shalahudin; Sajuthi, D; Kalliokoski, O

2013-01-01

In an attempt to explore cynomolgus monkeys as an animal model for Alzheimer's disease, the present study focused on the Alzheimer's biomarkers beta amyloid 1-42 (Aβ42 ) in serum, and total tau (t-tau) and phosphorylated tau (p-tau) levels in cerebrospinal fluid.......In an attempt to explore cynomolgus monkeys as an animal model for Alzheimer's disease, the present study focused on the Alzheimer's biomarkers beta amyloid 1-42 (Aβ42 ) in serum, and total tau (t-tau) and phosphorylated tau (p-tau) levels in cerebrospinal fluid....

Idiopathic New Bone Formation in the Femoral Shafts of a Cynomolgus Monkey (Macaca fascicularis)

OpenAIRE

Lee, Jae-il; Kim, Young-suk; Kim, Myung-Jin; Hong, Sung-Hyeok

2008-01-01

A 6.5-y-old cynomolgus monkey was referred to the Veterinary Medical Teaching Hospital at Chungnam National University for suspected bone fracture. The monkey had been reared singly in a cage at a laboratory facility. An animal caretaker incidentally found a bone fragment protruding through the skin of the right leg. Radiographic examination revealed 2 new bone fragments clearly distinguishable from the original femurs; the fragments seemed to be inserted into both femurs. One of the new bone...

Widespread gene transfer in the central nervous system of cynomolgus macaques following delivery of AAV9 into the cisterna magna

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Christian Hinderer

2014-01-01

Full Text Available Adeno-associated virus serotype 9 (AAV9 vectors have recently been shown to transduce cells throughout the central nervous system of nonhuman primates when injected into the cerebrospinal fluid (CSF, a finding which could lead to a minimally invasive approach to treat genetic and acquired diseases affecting the entire CNS. We characterized the transduction efficiency of two routes of vector administration into the CSF of cynomolgus macaques—lumbar puncture, which is typically used in clinical practice, and suboccipital puncture, which is more commonly used in veterinary medicine. We found that delivery of vector into the cisterna magna via suboccipital puncture is up to 100-fold more efficient for achieving gene transfer to the brain. In addition, we evaluated the inflammatory response to AAV9-mediated GFP expression in the nonhuman primate CNS. We found that while CSF lymphocyte counts increased following gene transfer, there were no clinical or histological signs of immune toxicity. Together these data indicate that delivery of AAV9 into the cisterna magna is an effective method for achieving gene transfer in the CNS, and suggest that adapting this uncommon injection method for human trials could vastly increase the efficiency of gene delivery.

Metabolism by conjugation appears to confer resistance to paracetamol (acetaminophen) hepatotoxicity in the cynomolgus monkey.

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Yu, Hong; Barrass, Nigel; Gales, Sonya; Lenz, Eva; Parry, Tony; Powell, Helen; Thurman, Dale; Hutchison, Michael; Wilson, Ian D; Bi, Luke; Qiao, Junwen; Qin, Qiuping; Ren, Jin

2015-03-01

1. Paracetamol overdose remains the leading cause of acute liver failure in humans. This study was undertaken in cynomolgus monkeys to study the pharmacokinetics, metabolism and the potential for hepatotoxic insult from paracetamol administration as a possible model for human toxicity. 2. No adverse effects were observed for doses of up to 900 mg/kg/d for 14 d. Only minor sporadic increases in alanine aminotransferase, aspartate aminotransferase and glutamate dehydrogenase in a number of animals were observed, with no clear dose response. 3. Toxicokinetic analysis showed good plasma exposure, albeit with less than proportional rises in Cmax and AUC, with increasing dose. The Cmax values in monkey were up to 3.5 times those associated with human liver toxicity and the AUC approx. 1000 times those associated with liver enzyme changes in 31-44% of human subjects. 4. Metabolite profiling of urine by (1)H NMR spectroscopy revealed paracetamol and its glucuronide and sulphate metabolites. Glutathione-derived metabolites, e.g. the cysteinyl conjugate, were only present in very low concentrations whilst the mercapturate was not detected. 5. These in vivo observations demonstrated that the cynomolgus monkey is remarkably resistant to paracetamol-induced toxicity and a poor model for investigating paracetamol-related hepatotoxicity in humans.

The Peptide Vaccine Combined with Prior Immunization of a Conventional Diphtheria-Tetanus Toxoid Vaccine Induced Amyloid β Binding Antibodies on Cynomolgus Monkeys and Guinea Pigs

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Akira Yano

2015-01-01

Full Text Available The reduction of brain amyloid beta (Aβ peptides by anti-Aβ antibodies is one of the possible therapies for Alzheimer’s disease. We previously reported that the Aβ peptide vaccine including the T-cell epitope of diphtheria-tetanus combined toxoid (DT induced anti-Aβ antibodies, and the prior immunization with conventional DT vaccine enhanced the immunogenicity of the peptide. Cynomolgus monkeys were given the peptide vaccine subcutaneously in combination with the prior DT vaccination. Vaccination with a similar regimen was also performed on guinea pigs. The peptide vaccine induced anti-Aβ antibodies in cynomolgus monkeys and guinea pigs without chemical adjuvants, and excessive immune responses were not observed. Those antibodies could preferentially recognize Aβ40, and Aβ42 compared to Aβ fibrils. The levels of serum anti-Aβ antibodies and plasma Aβ peptides increased in both animals and decreased the brain Aβ40 level of guinea pigs. The peptide vaccine could induce a similar binding profile of anti-Aβ antibodies in cynomolgus monkeys and guinea pigs. The peptide vaccination could be expected to reduce the brain Aβ peptides and their toxic effects via clearance of Aβ peptides by generated antibodies.

Nonhuman Primate Models of Chikungunya Virus Infection and Disease (CHIKV NHP Model

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Rebecca Broeckel

2015-09-01

Full Text Available Chikungunya virus (CHIKV is a positive-sense RNA virus transmitted by Aedes mosquitoes. CHIKV is a reemerging Alphavirus that causes acute febrile illness and severe and debilitating polyarthralgia of the peripheral joints. Huge epidemics and the rapid spread of CHIKV seen in India and the Indian Ocean region established CHIKV as a global health concern. This concern was further solidified by the recent incursion of the virus into the Western hemisphere, a region without pre-existing immunity. Nonhuman primates (NHPs serve as excellent animal models for understanding CHIKV pathogenesis and pre-clinical assessment of vaccines and therapeutics. NHPs present advantages over rodent models because they are a natural amplification host for CHIKV and they share significant genetic and physiological homology with humans. CHIKV infection in NHPs results in acute fever, rash, viremia and production of type I interferon. NHPs develop CHIKV-specific B and T-cells, generating neutralizing antibodies and CHIKV-specific CD4+ and CD8+ T-cells. CHIKV establishes a persistent infection in NHPs, particularly in cynomolgus macaques, because infectious virus could be recovered from spleen, liver, and muscle as late as 44 days post infection. NHPs are valuable models that are useful in preclinical testing of vaccines and therapeutics and uncovering the details of CHIKV pathogenesis.

Canine distemper virus infection in a lesser grison (Galictis cuja: first report and virus phylogeny Infecção pelo vírus da cinomose canina em um furão (Galictis cuja: primeiro relato e filogenia viral

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Jane Megid

2013-02-01

Full Text Available Infectious diseases in wild animals have been increasing as a result of their habitat alterations and closer contact with domestic animals. Canine distemper virus (CDV has been reported in several species of wild carnivores, presenting a threat to wildlife conservation. We described the first case of canine distemper virus infection in lesser grison (Galictis cuja. A free-ranging individual, with no visible clinical sigs, presented sudden death after one day in captivity. Molecular diagnosis for CDV infection was performed using whole blood collected by postmortem intracardiac puncture, which resulted positive. The virus phylogeny indicated that domestic dogs were the probable source of infection.Doenças infecciosas em animais selvagens têm aumentado devido às alterações em seu habitat e ao maior contato com animais domésticos. A cinomose já foi descrita em diversas espécies de carnívoros selvagens, representando uma ameaça à conservação da vida selvagem. Nesse estudo é descrito o primeiro caso de infecção pelo vírus da cinomose em um furão (Galictis cuja. Um indivíduo de vida livre, sem sinais clínicos aparentes, apresentou morte súbita após um dia em cativeiro. Foi realizado o diagnóstico molecular para detecção do vírus da cinomose canina, sendo o resultado positivo. A filogenia do vírus indicou que cães domésticos foram a provável fonte de infecção.

Normal Anatomy, Histology, and Spontaneous Pathology of the Nasal Cavity of the Cynomolgus Monkey (Macaca fascicularis).

Science.gov (United States)

Chamanza, Ronnie; Taylor, Ian; Gregori, Michela; Hill, Colin; Swan, Mark; Goodchild, Joel; Goodchild, Kane; Schofield, Jane; Aldous, Mark; Mowat, Vasanthi

2016-07-01

The evaluation of inhalation studies in monkeys is often hampered by the scarcity of published information on the relevant nasal anatomy and pathology. We examined nasal cavities of 114 control cynomolgus monkeys from 11 inhalation studies evaluated 2008 to 2013, in order to characterize and document the anatomic features and spontaneous pathology. Compared to other laboratory animals, the cynomolgus monkey has a relatively simple nose with 2 unbranched, dorsoventrally stacked turbinates, large maxillary sinuses, and a nasal septum that continues into the nasopharynx. The vomeronasal organ is absent, but nasopalatine ducts are present. Microscopically, the nasal epithelium is thicker than that in rodents, and the respiratory (RE) and transitional epithelium (TE) rest on a thick basal lamina. Generally, squamous epithelia and TE line the vestibule, RE, the main chamber and nasopharynx, olfactory epithelium, a small caudodorsal region, while TE is observed intermittently along the passages. Relatively high incidences of spontaneous pathology findings, some resembling induced lesions, were observed and included inflammation, luminal exudate, scabs, squamous and respiratory metaplasia or hyperplasia, mucous cell hyperplasia/metaplasia, and olfactory degeneration. Regions of epithelial transition were the most affected. This information is considered helpful in the histopathology evaluation and interpretation of inhalation studies in monkeys. © The Author(s) 2016.

Neurons in the brain of the male cynomolgus monkey accumulate 3H-medroxyprogesterone acetate (MPA)

International Nuclear Information System (INIS)

Michael, R.P.; Bonsall, R.W.; Rees, H.D.

1986-01-01

MPA is a synthetic progestin with androgen-depleting activity. It is used clinically to reduce sexual motivation and aggression in male sex offenders. The mechanisms for its behavioral effects are not known. The authors used steroid autoradiography to help identify sites where MPA may act in the brain of male primates. Twenty-four hours after castration, two adult male cynomolgus macaques, weighing 4.9 and 6.6 kg, were administered 5 mCi 3 H-MPA (NEN, 47.7 Ci/mmol) i.v., and were killed 1 h later. Left sides of the brains and samples of pituitary glands were frozen and 4-micron sections were cut and processed for thaw-mount autoradiography. Radioactivity was concentrated in the nuclei of many neutrons in the ventromedial hypothalamic nucleus (n.), arcuate n., medial preoptic n., and anterior hypothalamic area. Virtually no labeled cells were seen in the bed n. of stria terminalis, lateral septal n., amygdala, or pituitary gland. Right sides of the brains were analyzed by HPLC which demonstrated that 98% of the radioactivity in cell nuclei from the hypothalamus was in the form of unmetabolized 3 H-MPA. The distribution of labelling in the brain following 3 H-MPA administration resembled that previously seen following 3 H-ORG 2058 in female cynomolgus monkeys. These data indicate that MPA has a circumscribed localization in the brain

Homologous and Heterologous Protection of Nonhuman Primates by Ebola and Sudan Virus-Like Particles

Science.gov (United States)

Warfield, Kelly L.; Dye, John M.; Wells, Jay B.; Unfer, Robert C.; Holtsberg, Frederick W.; Shulenin, Sergey; Vu, Hong; Swenson, Dana L.; Bavari, Sina; Aman, M. Javad

2015-01-01

Filoviruses cause hemorrhagic fever resulting in significant morbidity and mortality in humans. Several vaccine platforms that include multiple virus-vectored approaches and virus-like particles (VLPs) have shown efficacy in nonhuman primates. Previous studies have shown protection of cynomolgus macaques against homologous infection for Ebola virus (EBOV) and Marburg virus (MARV) following a three-dose vaccine regimen of EBOV or MARV VLPs, as well as heterologous protection against Ravn Virus (RAVV) following vaccination with MARV VLPs. The objectives of the current studies were to determine the minimum number of vaccine doses required for protection (using EBOV as the test system) and then demonstrate protection against Sudan virus (SUDV) and Taï Forest virus (TAFV). Using the EBOV nonhuman primate model, we show that one or two doses of VLP vaccine can confer protection from lethal infection. VLPs containing the SUDV glycoprotein, nucleoprotein and VP40 matrix protein provide complete protection against lethal SUDV infection in macaques. Finally, we demonstrate protective efficacy mediated by EBOV, but not SUDV, VLPs against TAFV; this is the first demonstration of complete cross-filovirus protection using a single component heterologous vaccine within the Ebolavirus genus. Along with our previous results, this observation provides strong evidence that it will be possible to develop and administer a broad-spectrum VLP-based vaccine that will protect against multiple filoviruses by combining only three EBOV, SUDV and MARV components. PMID:25793502

Homologous and heterologous protection of nonhuman primates by Ebola and Sudan virus-like particles.

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Kelly L Warfield

Full Text Available Filoviruses cause hemorrhagic fever resulting in significant morbidity and mortality in humans. Several vaccine platforms that include multiple virus-vectored approaches and virus-like particles (VLPs have shown efficacy in nonhuman primates. Previous studies have shown protection of cynomolgus macaques against homologous infection for Ebola virus (EBOV and Marburg virus (MARV following a three-dose vaccine regimen of EBOV or MARV VLPs, as well as heterologous protection against Ravn Virus (RAVV following vaccination with MARV VLPs. The objectives of the current studies were to determine the minimum number of vaccine doses required for protection (using EBOV as the test system and then demonstrate protection against Sudan virus (SUDV and Taï Forest virus (TAFV. Using the EBOV nonhuman primate model, we show that one or two doses of VLP vaccine can confer protection from lethal infection. VLPs containing the SUDV glycoprotein, nucleoprotein and VP40 matrix protein provide complete protection against lethal SUDV infection in macaques. Finally, we demonstrate protective efficacy mediated by EBOV, but not SUDV, VLPs against TAFV; this is the first demonstration of complete cross-filovirus protection using a single component heterologous vaccine within the Ebolavirus genus. Along with our previous results, this observation provides strong evidence that it will be possible to develop and administer a broad-spectrum VLP-based vaccine that will protect against multiple filoviruses by combining only three EBOV, SUDV and MARV components.

Stimulus-Food Pairings Produce Stimulus-Directed Touch Screen Responding in Cynomolgus Monkeys ("Macaca Fascicularis") with or without a Positive Response Contingency

Science.gov (United States)

Bullock, Christopher E.; Myers, Todd M.

2009-01-01

Acquisition and maintenance of touch-screen responding was examined in naive cynomolgus monkeys ("Macaca fascicularis") under automaintenance and classical conditioning arrangements. In the first condition of Experiment 1, we compared acquisition of screen touching to a randomly positioned stimulus (a gray square) that was either stationary or…

Nutrient Intake and Digestibility of Cynomolgus Monkey (Macaca fascicularis Fed with High Soluble Carbohydrate Diet: A Preliminary Study

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DEWI APRI ASTUTI

2009-12-01

Full Text Available High carbohydrate as obese diet is not yet available commercially for monkeys. Therefore, this preliminary study was to carry out nutrient intake and digestibility of cynomolgus monkeys (Macaca fascicularis fed with high soluble carbohydrate diet compared to monkey chow. Five adult female macaques (average body weight 2.67 kg were made to consume freshly diet. Commercial monkey chows (contains 3500 cal/g energy and 35% starch were fed to three adult females (average body weight 3.62 kg. Nutrient intakes and digestibility parameters were measured using modified metabolic cages. Result showed that average of protein, fat, starch, and energy intakes in treatment diet were higher than control diet (T-test. Fat intake in the treatment diet was three times higher, while starch and energy intakes were almost two times higher than monkey chow. Digestibility percentage of all nutrients were the same in both diets except for the protein. The study concludes that the freshly prepared high sugar diet was palatable and digestible for the cynomolgus monkeys. Further studies are in progress to develop obese diet high in energy content based on fat and source of starch treatments.

Retosiban Prevents Stretch-Induced Human Myometrial Contractility and Delays Labor in Cynomolgus Monkeys.

Science.gov (United States)

Aye, Irving L M H; Moraitis, Alexandros A; Stanislaus, Dinesh; Charnock-Jones, D Stephen; Smith, Gordon C S

2018-03-01

Stretch of the myometrium promotes its contractility and is believed to contribute to the control of parturition at term and to the increased risk of preterm birth in multiple pregnancies. To determine the effects of the putative oxytocin receptor (OTR) inverse agonist retosiban on (1) the contractility of human myometrial explants and (2) labor in nonhuman primates. Human myometrial biopsies were obtained at planned term cesarean, and explants were exposed to stretch in the presence and absence of a range of drugs, including retosiban. The in vivo effects of retosiban were determined in cynomolgus monkeys. Prolonged mechanical stretch promoted myometrial extracellular signal-regulated kinase (ERK)1/2 phosphorylation. Moreover, stretch-induced stimulation of myometrial contractility was prevented by ERK1/2 inhibitors. Retosiban (10 nM) prevented stretch-induced stimulation of myometrial contractility and phosphorylation of ERK1/2. Moreover, the inhibitory effect of retosiban on stretch-induced ERK1/2 phosphorylation was prevented by coincubation with a 100-fold excess of a peptide OTR antagonist, atosiban. Compared with vehicle-treated cynomolgus monkeys, treatment with oral retosiban (100 to 150 days of gestational age) reduced the risk of spontaneous delivery (hazard ratio = 0.07, 95% confidence interval 0.01 to 0.60, P = 0.015). The OTR acts as a uterine mechanosensor, whereby stretch increases myometrial contractility through agonist-free activation of the OTR. Retosiban prevents this through inverse agonism of the OTR and, in vivo, reduced the likelihood of spontaneous labor in nonhuman primates. We hypothesize that retosiban may be an effective preventative treatment of preterm birth in high-risk multiple pregnancies, an area of unmet clinical need.

Aspectos funcionais, microbiológicos e morfológicos intestinais em crianças infectadas pelo vírus da imunodeficiência humana Functional, microbiological and morphological intestinal findings among human immunodeficiency virus infected children

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Christiane Araujo Chaves Leite

2006-12-01

Full Text Available RACIONAL: O trato gastrointestinal é freqüentemente acometido nas crianças infectadas pelo vírus da imunodeficiência humana, com importantes repercussões no seu estado nutricional e sobrevida. A maioria dos estudos relacionados a esse tema foi desenvolvida com adultos, sendo menos investigado o problema nas crianças OBJETIVOS: Estudar aspectos digestivo-absortivos, microbiológicos e morfológicos intestinais em crianças infectadas pelo vírus da imunodeficiência humana MATERIAL E MÉTODOS: Onze crianças infectadas pelo vírus da imunodeficiência humana, menores de 13 anos, pertencentes às categorias clínicas A, B ou C, divididas em dois grupos: cinco pacientes com relato atual ou recente de diarréia e seis pacientes sem diarréia nos 30 dias que antecederam à inclusão no estudo. Investigação proposta: biopsia de intestino delgado e reto para análise morfológica e microbiológica, coprocultura, protoparasitológico de fezes, pesquisa de rotavírus, micobactérias e Cryptosporidium; teste da D-xilose RESULTADOS: Todos os pacientes testados (9/11 apresentavam má absorção da D-xilose (8,4-24,4 mg/dL. Os achados histopatológicos de intestino delgado foram inespecíficos, representados em sua maioria, por enteropatia grau I a II (6/10. Em todos os casos foi constatado aumento do infiltrado celular do córion. As alterações histopatológicas do reto também foram inespecíficas, com presença de aumento do infiltrado celular do córion. A pesquisa de microorganismos enteropatogênicos só foi positiva em dois casos, sendo identificado Mycobacterium avium intracellulare e Cryptosporidium nas fezes CONCLUSÕES: Demonstrou-se alta prevalência (100% de má absorção intestinal em crianças infectadas pelo vírus da imunodeficiência humana, com ou sem diarréia. Não foi possível estabelecer correlações quanto à presença de agentes enteropatogênicos, má absorção intestinal, alterações morfológicas intestinais e

Infarto cerebral em duas crianças infectadas pelo HIV-1 Ischaemic stroke in two children with HIV-1

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Cristiane Rocha

2003-12-01

Full Text Available Os quadros vasculares são incomuns não somente nos pacientes adultos (1% como também nas crianças. Nosso objetivo é alertar para a possibilidade da infecção pelo HIV-1 em crianças com manifestações cerebrovasculares. Das 204 crianças infectadas pelo HIV acompanhadas no Ambulatório de SIDA, descrevemos dois pacientes pré-escolares do gênero masculino, com quadro agudo febril, rebaixamento do nível de consciência, status epilepticus e hemiparesia como primeira manifestação de infecção pelo HIV-1. Nos dois casos evidenciou-se extensa isquemia em território da artéria cerebral média. Um dos pacientes evoluiu com tetraparesia espástica grave, sem contactuar com o meio, epilepsia parcial e óbito 4 anos após o diagnóstico, sem melhora do quadro neurológico. O outro paciente apresentou hemiparesia direita e afasia global, evoluindo com regressão completa do quadro neurológico. A infreqüência desses achados torna importante o seu relato, visando a inclusão da infecção pelo HIV-1 no diagnóstico diferencial das quadros cerebrovasculares na criança.Cerebral ischaemia caused by inflammatory vasculopathies has been described as a complication of human immunodeficiency virus (HIV infection. The goal of our study is to report two cases of pediatric human immunodeficiency virus infection and cerebrovascular manifestations. We describe two pre-school boys, from a group of 204 outpatients, who presented fever, seizures, hemiparesis and impairment of conscience level as a first symptom of HIV-1 infection. The serial imaging studies revealed infarction of middle cerebral artery in both cases. The first one child had a severe spastic tetraparesis and partial epilepsy and died four years later without any improvement despite of the antiretroviral therapy. The second patient had a right hemiparesis and global aphasia totally recovered two years later with antiretroviral and rehabilitation therapies. HIV infection should be included

Effects of long-term estrogen replacement therapy on bone turnover in periarticular tibial osteophytes in surgically postmenopausal cynomolgus monkeys.

Science.gov (United States)

Olson, Erik J; Lindgren, Bruce R; Carlson, Cathy S

2008-05-01

The aims of the present study were to assess the effects of long-term estrogen replacement therapy (ERT) on size and indices of bone turnover in periarticular osteophytes in ovariectomized cynomolgus monkeys and to compare dynamic indices of bone turnover in osteophyte bone with those of subchondral bone (SCB) and epiphyseal/metaphyseal cancellous (EMC) bone. One hundred sixty-five adult female cynomolgus macaques were bilaterally ovariectomized and randomly divided into three age- and weight-matched treatment groups for a 36-month treatment period. Group 1 (OVX control) received no treatment, Group 2 (SPE) received soy phytoestrogens, and Group 3 (ERT) received conjugated equine estrogens in the diet; all monkeys were labeled with calcein before necropsy. A midcoronal, plastic-embedded section of the right proximal tibia from 20 randomly selected animals per treatment group was examined histologically. Forty-nine of the sections (OVX control, n=16; SPE, n=16; ERT, n=17) contained lateral abaxial osteophytes, and static and dynamic histomorphometry measurements were taken from osteophyte bone, SCB from the lateral tibial plateau, and EMC bone. Data were analyzed using the ANOVA and Kruskal-Wallis test, correlation and regression methods, and the Friedman and Wilcoxon signed rank test. There was no significant effect of long-term ERT on osteophyte area or on any static or dynamic histomorphometry parameters. The bone volume, trabecular number, and trabecular thickness in osteophyte bone were considerably higher than in EMC bone; whereas, trabecular separation was considerably lower in osteophyte bone. In all three treatment groups, BS/BV was significantly lower in osteophyte bone vs. EMC bone and significantly higher in osteophyte bone vs. lateral SCB. We conclude that osteophyte area and static and dynamic histomorphometry parameters within periarticular tibial osteophytes in ovariectomized cynomolgus monkeys are not significantly influenced by long-term ERT, but

Effects of long-term estrogen replacement therapy on bone turnover in periarticular tibial osteophytes in surgically postmenopausal cynomolgus monkeys

Science.gov (United States)

Olson, Erik J.; Lindgren, Bruce R.; Carlson, Cathy S.

2008-01-01

The aims of the present study were to assess the effects of long-term estrogen replacement therapy (ERT) on size and indices of bone turnover in periarticular osteophytes in ovariectomized cynomolgus monkeys and to compare dynamic indices of bone turnover in osteophyte bone with those of subchondral bone (SCB) and epiphyseal/metaphyseal cancellous (EMC) bone. One hundred sixty-five adult female cynomolgus macaques were bilaterally ovariectomized and randomly divided into three age- and weight-matched treatment groups for a 36-month treatment period. Group 1 (OVX control) received no treatment, Group 2 (SPE) received soy phytoestrogens, and Group 3 (ERT) received conjugated equine estrogens in the diet; all monkeys were labeled with calcein before necropsy. A midcoronal, plastic-embedded section of the right proximal tibia from 20 randomly selected animals per treatment group was examined histologically. Forty-nine of the sections (OVX control, n=16; SPE, n=16; ERT, n=17) contained lateral abaxial osteophytes, and static and dynamic histomorphometry measurements were taken from osteophyte bone, SCB from the lateral tibial plateau, and EMC bone. Data were analyzed using the ANOVA and Kruskal-Wallis test, correlation and regression methods, and the Friedman and Wilcoxon signed rank test. There was no significant effect of long-term ERT on osteophyte area or on any static or dynamic histomorphometry parameters. The bone volume, trabecular number, and trabecular thickness in osteophyte bone were considerably higher than in EMC bone; whereas, trabecular separation was considerably lower in osteophyte bone. In all three treatment groups, BS/BV was significantly lower in osteophyte bone vs. EMC bone and significantly higher in osteophyte bone vs. lateral SCB. We conclude that osteophyte area and static and dynamic histomorphometry parameters within periarticular tibial osteophytes in ovariectomized cynomolgus monkeys are not significantly influenced by long-term ERT, but

Pharmacokinetics of Cefovecin in Cynomolgus Macaques (Macaca fascicularis), Olive Baboons (Papio anubis), and Rhesus Macaques (Macaca mulatto)

Energy Technology Data Exchange (ETDEWEB)

Raabe, Brigitte M.; Lovaglio, Jamie A.; Grover, GScott; Brown, Scott A.; Boucher, Joseph F.; Yuan, Yang; Civil, Jacqueline R.; Gillhouse, Kimberly A.; Stubbs, Makeida N.; Hoggatt, Amber F.; Halliday, Lisa C.; Fortman, Jeffrey D.

2011-05-01

Cefovecin sodium is a long-acting, third-generation, cephalosporin antibiotic approved for the treatment of skin infections in dogs and cats. The pharmacokinetic properties of cefovecin were evaluated in cynomolgus macaques (Macaca fascicularis), olive baboons (Papio anubis), and rhesus macaques (Macaca mulatto) by using a single-dose (8 mg/kg SC) dosing regimen. Plasma cefovecin concentrations were determined by using ultra-performance liquid chromatography with tandem mass spectrometry, and a noncompartmental model was used to determine pharmacokinetic parameters. The half-life of cefovecin was 4.95 {+-} 1.47 h in cynomolgus macaques, 9.17 {+-} 1.84 h in olive baboons, and 8.40 {+-} 2.53 h in rhesus macaques. These values are considerably lower than the half-lives previously published for dogs (133 h) and cats (166 h). The extended half-life of cefovecin in dogs and cats is speculated to be due to active reabsorption of drug in the kidney tubules because plasma clearance is well below the normal glomerular filtration rate. In nonhuman primates, renal clearance rates approximated plasma clearance rates, suggesting that active renal reabsorption of cefovecin does not occur in these species. The pharmacokinetic properties of cefovecin in nonhuman primates are vastly different from the pharmacokinetic properties in dogs and cats, precluding its use as a long-acting antibiotic in nonhuman primates. This study highlights the importance of performing pharmacokinetic studies prior to extralabel drug usage.

Pre-travel health advice for human immunodeficiency virus-infected travelers, from Rio de Janeiro Aconselhamento pré-viagem para os viajantes infectados pelo vírus da imunodeficiência humana no Rio de Janeiro

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Ricardo Pereira Igreja

2009-06-01

Full Text Available Counseling for human immunodeficiency virus infected travelers is becoming increasingly specialized. Previous studies have reported the experience of HIV-infected travelers from temperate-climate countries but little is known about HIV-infected travelers from tropical countries. A retrospective study was conducted on HIV-infected travelers presenting at a travel health clinic in Rio de Janeiro. Eleven journeys by ten people were recorded. Brazil (Amazon region and Northeast was the destination for six journeys. Other destinations were Peru, Angola, Europe and Asia. Nine attendees were undergoing antiretroviral therapy. Few HIV-infected people from Rio de Janeiro consulted a travel medicine specialist before traveling. Since they travel to destinations in Brazil and abroad where there are endemic diseases not encountered in Rio de Janeiro, careful pre-travel planning needs to be undertaken. Strategies for increasing the frequency of pre-travel consultations need to be developed, such as closer collaboration between HIV clinics and travel health clinics.O aconselhamento para os viajantes infectados pelo vírus da imunodeficiência humana está se especializando cada vez mais. Estudos prévios relatam a experiência dos viajantes infectados pelo vírus da imunodeficiência humana dos países de clima temperado, mas pouco se sabe sobre os viajantes infectados pelo vírus da imunodeficiência humana dos países tropicais. Foi realizado um estudo retrospectivo dos viajantes infectados pelo vírus da imunodeficiência humana que consultaram um serviço de medicina de viagem no Rio de Janeiro. Dez viajantes realizaram onze viagens. O Brasil (Amazônia e Nordeste foi o destino de seis viagens. Outros destinos foram Peru, Angola, Europa e Ásia. Nove pacientes estavam sob terapia anti-retroviral. No Rio de Janeiro, poucas pessoas infectadas pelo vírus da imunodeficiência humana consultaram um especialista em medicina de viagem antes de viajar. Como elas

In vitro germ cell differentiation from cynomolgus monkey embryonic stem cells.

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Kaori Yamauchi

Full Text Available BACKGROUND: Mouse embryonic stem (ES cells can differentiate into female and male germ cells in vitro. Primate ES cells can also differentiate into immature germ cells in vitro. However, little is known about the differentiation markers and culture conditions for in vitro germ cell differentiation from ES cells in primates. Monkey ES cells are thus considered to be a useful model to study primate gametogenesis in vitro. Therefore, in order to obtain further information on germ cell differentiation from primate ES cells, this study examined the ability of cynomolgus monkey ES cells to differentiate into germ cells in vitro. METHODS AND FINDINGS: To explore the differentiation markers for detecting germ cells differentiated from ES cells, the expression of various germ cell marker genes was examined in tissues and ES cells of the cynomolgus monkey (Macaca fascicularis. VASA is a valuable gene for the detection of germ cells differentiated from ES cells. An increase of VASA expression was observed when differentiation was induced in ES cells via embryoid body (EB formation. In addition, the expression of other germ cell markers, such as NANOS and PIWIL1 genes, was also up-regulated as the EB differentiation progressed. Immunocytochemistry identified the cells expressing stage-specific embryonic antigen (SSEA 1, OCT-4, and VASA proteins in the EBs. These cells were detected in the peripheral region of the EBs as specific cell populations, such as SSEA1-positive, OCT-4-positive cells, OCT-4-positive, VASA-positive cells, and OCT-4-negative, VASA-positive cells. Thereafter, the effect of mouse gonadal cell-conditioned medium and growth factors on germ cell differentiation from monkey ES cells was examined, and this revealed that the addition of BMP4 to differentiating ES cells increased the expression of SCP1, a meiotic marker gene. CONCLUSION: VASA is a valuable gene for the detection of germ cells differentiated from ES cells in monkeys, and the

Discovery of novel MHC-class I alleles and haplotypes in Filipino cynomolgus macaques (Macaca fascicularis) by pyrosequencing and Sanger sequencing: Mafa-class I polymorphism.

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Shiina, Takashi; Yamada, Yukiho; Aarnink, Alice; Suzuki, Shingo; Masuya, Anri; Ito, Sayaka; Ido, Daisuke; Yamanaka, Hisashi; Iwatani, Chizuru; Tsuchiya, Hideaki; Ishigaki, Hirohito; Itoh, Yasushi; Ogasawara, Kazumasa; Kulski, Jerzy K; Blancher, Antoine

2015-10-01

Although the low polymorphism of the major histocompatibility complex (MHC) transplantation genes in the Filipino cynomolgus macaque (Macaca fascicularis) is expected to have important implications in the selection and breeding of animals for medical research, detailed polymorphism information is still lacking for many of the duplicated class I genes. To better elucidate the degree and types of MHC polymorphisms and haplotypes in the Filipino macaque population, we genotyped 127 unrelated animals by the Sanger sequencing method and high-resolution pyrosequencing and identified 112 different alleles, 28 at cynomolgus macaque MHC (Mafa)-A, 54 at Mafa-B, 12 at Mafa-I, 11 at Mafa-E, and seven at Mafa-F alleles, of which 56 were newly described. Of them, the newly discovered Mafa-A8*01:01 lineage allele had low nucleotide similarities (Filipino macaque population would identify these and other high-frequency Mafa-class I haplotypes that could be used as MHC control animals for the benefit of biomedical research.

Distúrbios causados pelo frio e pelo calor durante corridas de longa distância

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1999-06-01

Full Text Available Muitos corredores amadores e de elite participam todos os anos de corridas de longa distância. Quando estes eventos ocorrem em temperaturas altas ou baixas, aumenta o risco de distúrbios térmicos. Contudo, a hipertermia induzida pelo exercício, a hipotermia, a desidratação e outros problemas relacionados podem ser minimizados através de esclarecimentos e um preparo antes do evento. Este documento fornece recomendações para o diretor médico e outras autoridades da organização das corridas nas seguintes áreas: planejamento, profissionais envolvidos na organização, instalações, suprimentos, equipamento e comunicação; fornecimento de esclarecimentos aos participantes; avaliação do estresse térmico; fornecimento de líquidos; e prevenção de questões legais em potencial. Este posicionamento oficial também descreve as condições predisponentes, as formas de diagnóstico e o tratamento dos quatro distúrbios ambientais mais comuns: exaustão pelo calor, colapso pelo calor, hipotermia e congelamento de extremidades. Os objetivos deste documento são: 1 Educar os organizadores e os participantes de corridas de longa distância a respeito das formas mais comuns de distúrbios térmicos incluindo as condições predisponentes, sinais de alerta, suscetibilidade e a redução de sua incidência; 2 Alertar os organizadores sobre as suas responsabilidades civis em potencial no que concerne à segurança do evento e à prevenção de lesões; 3 Recomendar que os organizadores consultem arquivos locais de meteorologia e planejem eventos em horas que provavelmente causem menos estresse térmico de modo a minimizar os efeitos deletérios sobre os participantes; 4 Estimular os organizadores a alertar os participantes sobre o estresse térmico no dia da corrida e as suas implicações no que tange aos distúrbios causados pelo frio e pelo calor; 5 Informar os organizadores sobre as ações preventivas que podem reduzir a incidência dos

Optimization of HIV-1 Envelope DNA Vaccine Candidates within Three Different Animal Models, Guinea Pigs, Rabbits and Cynomolgus Macaques.

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Borggren, Marie; Vinner, Lasse; Andresen, Betina Skovgaard; Grevstad, Berit; Repits, Johanna; Melchers, Mark; Elvang, Tara Laura; Sanders, Rogier W; Martinon, Frédéric; Dereuddre-Bosquet, Nathalie; Bowles, Emma Joanne; Stewart-Jones, Guillaume; Biswas, Priscilla; Scarlatti, Gabriella; Jansson, Marianne; Heyndrickx, Leo; Grand, Roger Le; Fomsgaard, Anders

2013-07-19

HIV-1 DNA vaccines have many advantageous features. Evaluation of HIV-1 vaccine candidates often starts in small animal models before macaque and human trials. Here, we selected and optimized DNA vaccine candidates through systematic testing in rabbits for the induction of broadly neutralizing antibodies (bNAb). We compared three different animal models: guinea pigs, rabbits and cynomolgus macaques. Envelope genes from the prototype isolate HIV-1 Bx08 and two elite neutralizers were included. Codon-optimized genes, encoded secreted gp140 or membrane bound gp150, were modified for expression of stabilized soluble trimer gene products, and delivered individually or mixed. Specific IgG after repeated i.d. inoculations with electroporation confirmed in vivo expression and immunogenicity. Evaluations of rabbits and guinea pigs displayed similar results. The superior DNA construct in rabbits was a trivalent mix of non-modified codon-optimized gp140 envelope genes. Despite NAb responses with some potency and breadth in guinea pigs and rabbits, the DNA vaccinated macaques displayed less bNAb activity. It was concluded that a trivalent mix of non-modified gp140 genes from rationally selected clinical isolates was, in this study, the best option to induce high and broad NAb in the rabbit model, but this optimization does not directly translate into similar responses in cynomolgus macaques.

Optimization of HIV-1 Envelope DNA Vaccine Candidates within Three Different Animal Models, Guinea Pigs, Rabbits and Cynomolgus Macaques

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Roger Le Grand

2013-07-01

Full Text Available HIV-1 DNA vaccines have many advantageous features. Evaluation of HIV-1 vaccine candidates often starts in small animal models before macaque and human trials. Here, we selected and optimized DNA vaccine candidates through systematic testing in rabbits for the induction of broadly neutralizing antibodies (bNAb. We compared three different animal models: guinea pigs, rabbits and cynomolgus macaques. Envelope genes from the prototype isolate HIV-1 Bx08 and two elite neutralizers were included. Codon-optimized genes, encoded secreted gp140 or membrane bound gp150, were modified for expression of stabilized soluble trimer gene products, and delivered individually or mixed. Specific IgG after repeated i.d. inoculations with electroporation confirmed in vivo expression and immunogenicity. Evaluations of rabbits and guinea pigs displayed similar results. The superior DNA construct in rabbits was a trivalent mix of non-modified codon-optimized gp140 envelope genes. Despite NAb responses with some potency and breadth in guinea pigs and rabbits, the DNA vaccinated macaques displayed less bNAb activity. It was concluded that a trivalent mix of non-modified gp140 genes from rationally selected clinical isolates was, in this study, the best option to induce high and broad NAb in the rabbit model, but this optimization does not directly translate into similar responses in cynomolgus macaques.

Correlation of pharmacodynamic activity, pharmacokinetics, and anti-product antibody responses to anti-IL-21R antibody therapeutics following IV administration to cynomolgus monkeys

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Spaulding Vikki

2010-04-01

Full Text Available Abstract Background Anti-IL-21R antibodies are potential therapeutics for the treatment of autoimmune diseases. This study evaluated correlations between the pharmacodynamic (PD activity, pharmacokinetics, and anti-product antibody responses of human anti-IL-21R antibodies Ab-01 and Ab-02 following IV administration to cynomolgus monkeys. Methods The PD assay was based on the ability of recombinant human IL-21 (rhuIL-21 to induce expression of the IL-2RA gene in cynomolgus monkey whole blood samples ex vivo. Monkeys screened for responsiveness to rhuIL-21 stimulation using the PD assay, were given a single 10 mg/kg IV dosage of Ab-01, Ab-02, or a control antibody (3/group, and blood samples were evaluated for PD activity (inhibition of IL-2RA expression for up to 148 days. Anti-IL-21R antibody concentrations and anti-product antibody responses were measured in serum using immunoassays and flow cytometry. Results Following IV administration of Ab-01 and Ab-02 to cynomolgus monkeys, PD activity was observed as early as 5 minutes (first time point sampled. This PD activity had good correlation with the serum concentrations and anti-product antibody responses throughout the study. The mean terminal half-life (t1/2 was ~10.6 and 2.3 days for Ab-01 and Ab-02, respectively. PD activity was lost at ~5-13 weeks for Ab-01 and at ~2 weeks for Ab-02, when serum concentrations were relatively low. The estimated minimum concentrations needed to maintain PD activity were ~4-6 nM for Ab-01 and ~2.5 nM for Ab-02, and were consistent with the respective KD values for binding to human IL-21R. For Ab-01, there was noticeable inter-animal variability in t1/2 values (~6-14 days and the resulting PD profiles, which correlated with the onset of anti-product antibody formation. While all three Ab-01-dosed animals were positive for anti-Ab-01 antibodies, only one monkey (with the shortest t1/2 and the earliest loss of PD activity had evidence of neutralizing anti-Ab-01

Chromosomal aberrations in Cynomolgus peripheral lymphocytes during and after fractionated whole-body γ-irradiation

International Nuclear Information System (INIS)

Guedeney, G.; Malarbet, J.L.; Doloy, M.T.

1989-01-01

Cynomolgus monkeys (Macaca fascicularis) were exposed to fractionated whole-body γ-irradiation at high and low dose rates for 4 or 5 weeks. The time-dependence of chromosomal aberrations was studied in relation to the number of lymphocytes during irradiation and after exposure for periods of up to about 600 days for chromosomal aberrations and 200 days for lymphocyte counts. Additivity of the daily effects on the number of chromosomal aberrations was observed during the exposures. Immediately after the end of the exposures the number of chromosomal aberrations decreased to reach low values. The disappearance of chromosomal aberrations seemed to be related to recovery of the lymphocyte counts. The data presented here emphasize the different kinetic patterns of chromosomal aberrations after fractionated and acute irradiation. (author)

Infecção experimental em cabritos pelo vírus da artrite encefalite Caprine arthritis encephalitis virus experimental infection in new-born kids

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M.I.M.C. Guedes

2001-02-01

Full Text Available Vinte e quatro caprinos de uma semana de idade, soronegativos pela imunodifusão em gel de agar para artrite encefalite caprina (AEC, foram utilizados para estudo de infecção experimental pelo vírus da AEC. Dezesseis animais foram inoculados com lentivirus caprino, amostra Cork, oito pela via intravenosa e oito por instilação nasal. Oito animais serviram como controle, inoculados pelas vias intranasal ou intravenosa com 1ml de meio de cultura de células não infectadas. Os animais foram sacrificados aos 2, 6, 12 e 20 dias pós-inoculação (PI, e colhidas amostras do sistema nervoso central, articulações, tonsilas, linfonodos, pulmões, rins, timo, baço e intestinos delgado e grosso para histopatologia e imunoistoquímica. Um animal inoculado com o vírus da AEC pela via intranasal e sacrificado aos 20 dias PI apresentou imunomarcação positiva em um macrófago alveolar. Concluiu-se que a via aerógena é uma provável rota de infecção pelo vírus da AEC.The caprine arthritis encephalitis virus (CAEV experimental infection was studied in 24 one-week-old seronegative kids. Sixteen kids were inoculated with CAEV-Cork, with 10(6 TCID50/ml concentration, being eight inoculated intravenously, and eight intranasally. Eight animals were used as controls, being four inoculated intravenously, and four intranasally with non-infected cell culture medium. Since the day of the inoculation, clinical evaluation was performed daily, until the day of the sacrifice. Blood samples were taken for serological tests. The animals were killed in pairs at 2, 6, 12 and 20 days post-inoculation (PI and tissues samples of central nervous system, joints, tonsils, lymphonodes, lungs, kidneys, thymus, spleen, small and large intestine were collected for histopathological and immunohistochemical studies. One animal CAEV inoculated intranasally and killed at 20 days PI showed immunohistochemical positive reaction in an alveolar macrophage. It was concluded that

Evaluation of 89 compounds for identification of substrates for cynomolgus monkey CYP2C76, a new bupropion/nifedipine oxidase.

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Hosaka, Shinya; Murayama, Norie; Satsukawa, Masahiro; Shimizu, Makiko; Uehara, Shotaro; Fujino, Hideki; Iwasaki, Kazuhide; Iwano, Shunsuke; Uno, Yasuhiro; Yamazaki, Hiroshi

2015-01-01

Cynomolgus monkeys are widely used in preclinical studies during drug development because of their evolutionary closeness to humans, including their cytochrome P450s (P450s). Most cynomolgus monkey P450s are almost identical (≥90%) to human P450s; however, CYP2C76 has low sequence identity (approximately 80%) to any human CYP2Cs. Although CYP2C76 has no ortholog in humans and is partly responsible for species differences in drug metabolism between cynomolgus monkeys and humans, a broad evaluation of potential substrates for CYP2C76 has not yet been conducted. In this study, a screening of 89 marketed compounds, including human CYP2C and non-CYP2C substrates or inhibitors, was conducted to find potential CYP2C76 substrates. Among the compounds screened, 19 chemicals were identified as substrates for CYP2C76, including substrates for human CYP1A2 (7-ethoxyresorufin), CYP2B6 (bupropion), CYP2D6 (dextromethorphan), and CYP3A4/5 (dextromethorphan and nifedipine), and inhibitors for CYP2B6 (sertraline, clopidogrel, and ticlopidine), CYP2C8 (quercetin), CYP2C19 (ticlopidine and nootkatone), and CYP3A4/5 (troleandomycin). CYP2C76 metabolized a wide variety of the compounds with diverse structures. Among them, bupropion and nifedipine showed high selectivity to CYP2C76. As for nifedipine, CYP2C76 formed methylhydroxylated nifedipine, which was not produced by monkey CYP2C9, CYP2C19, or CYP3A4, as identified by mass spectrometry and estimated by a molecular docking simulation. This unique oxidative metabolite formation of nifedipine could be one of the selective marker reactions of CYP2C76 among the major CYP2Cs and CYP3As tested. These results suggest that monkey CYP2C76 contributes to bupropion hydroxylation and formation of different nifedipine oxidative metabolites as a result of its relatively large substrate cavity. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

Oral abstracts of the 21st International AIDS Conference 18?22 July 2016, Durban, South Africa

OpenAIRE

Ericsen, A; Lauck, M; Mohns, M; Dinapoli, S; Mutschler, J; Greene, J; Weinfurter, J; Lehrer-Brey, G; Crosno, K; Peterson, E; Reynolds, M; Wiseman, R; Burwitz, B; Sacha, J; Friedrich, T

2016-01-01

Introduction Within the first weeks of human immunodeficiency virus (HIV) infection, virus replication reaches systemic circulation. Despite the critical, causal role of virus replication in determining transmissibility and kinetics of disease progression, there is limited understanding of the conditions required to transform a small localized transmitted founder population into a large and heterogeneous systemic infection. Methods Cynomolgus and rhesus macaques were infected with simian immu...

Laboratory acquired infection by the virus SP H 114202 (Arenavirus: Arenaviridae: clinical and laboratory findings Infecção humana adquirida em laboratório causada pelo virus SP H 114202 (Arenavirus: família Arenaviridae: aspectos clínicos e laboratoriais

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Pedro Fernando da Costa Vasconcelos

1993-12-01

Full Text Available Here in is described the clinical and laboratorial findings of a laboratory-acquired infection caused by the virus SP H 114202 (Arenavirus, family Arenaviridae a recently discovered agent responsible for a viral hemorrhagic fever. The patient was sick for 13 days. The disease had an abrupt onset characterized by high fever (39ºC., headache, chills and myalgias for 8 days. In addition, on the 3rd day, the patient developed nauseas and vomiting, and in the 10th, epigastralgia, diarrheia and gengivorrhagia. Leucopenia was seen within the 1 st week of onset, with counts as low as 2,500 white cells per mm³. Counts performed after the 23th day of the onset were within normal limits. With the exception of moderate lymphocitosis, no changes were observed in differential counts. An increase in the liter of antibodies by complement fixation, neutralization and ELISA (IgM was detected. Suckling mice and baby hamsters were inoculated intracerebrally with 0.02 ml of blood samples collected in the 2nd and 7th days of disease. Attempts to isolate the virus were also made in Vero cells. No virus was isolated. This virus was isolated before in a single occasion in São Paulo State, in 1990, from the blood of a patient with hemorrhagic fever with a fatal outcome. The manipulation of the virus under study, must be done carefully, since the transmission can occur through aerosols.São descritos os achados clínico-laboratoriais da infecção acidental pelo virus SP H 114202 (Arenavirus, família Arenaviridae, um virus novo causador de febre hemorrágica humana. O paciente, técnico de laboratório, apresentou quadro febril por 13 dias. A doença cursou com febre elevada ( 39ºC. diária, cefaléia, calefrios e mialgias por 8 dias. A partir do 3º dia surgiram náuseas, vômitos alimentares e anorexia e no 10º dia, epigastralgia, diarréia e gengivorragia. Laboratorialmente, foram observadas as seguintes alterações: leucopenia gradativa com linfocitose a medida

Discovery of a Cynomolgus Monkey Family With Retinitis Pigmentosa.

Science.gov (United States)

Ikeda, Yasuhiro; Nishiguchi, Koji M; Miya, Fuyuki; Shimozawa, Nobuhiro; Funatsu, Jun; Nakatake, Shunji; Fujiwara, Kohta; Tachibana, Takashi; Murakami, Yusuke; Hisatomi, Toshio; Yoshida, Shigeo; Yasutomi, Yasuhiro; Tsunoda, Tatsuhiko; Nakazawa, Toru; Ishibashi, Tatsuro; Sonoda, Koh-Hei

2018-02-01

To accelerate the development of new therapies, an inherited retinal degeneration model in a nonhuman primate would be useful to confirm the efficacy in preclinical studies. In this study, we describe the discovery of retinitis pigmentosa in a cynomolgus monkey (Macaca fascicularis) pedigree. First, screening with fundus photography was performed on 1443 monkeys at the Tsukuba Primate Research Center. Ophthalmic examinations, such as indirect ophthalmoscopy, ERGs using RETeval, and optic coherent tomography (OCT) measurement, were then performed to confirm diagnosis. Retinal degeneration with cystoid macular edema was observed in both eyes of one 14-year-old female monkey. In her examinations, the full-field ERGs were nonrecordable and the outer layer of the retina in the parafoveal area was not visible on OCT imaging. Moreover, less frequent pigmentary retinal anomalies also were observed in her 3-year-old nephew. His full-field ERGs were almost nonrecordable and the outer layer was not visible in the peripheral retina. His father was her cousin (the son of her mother's older brother) and his mother was her younger half-sibling sister with a different father. The hereditary nature is highly probable (autosomal recessive inheritance suspected). However, whole-exome analysis performed identified no pathogenic mutations in these monkeys.

Multigenic DNA vaccine induces protective cross-reactive T cell responses against heterologous influenza virus in nonhuman primates.

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Merika T Koday

Full Text Available Recent avian and swine-origin influenza virus outbreaks illustrate the ongoing threat of influenza pandemics. We investigated immunogenicity and protective efficacy of a multi-antigen (MA universal influenza DNA vaccine consisting of HA, M2, and NP antigens in cynomolgus macaques. Following challenge with a heterologous pandemic H1N1 strain, vaccinated animals exhibited significantly lower viral loads and more rapid viral clearance when compared to unvaccinated controls. The MA DNA vaccine induced robust serum and mucosal antibody responses but these high antibody titers were not broadly neutralizing. In contrast, the vaccine induced broadly-reactive NP specific T cell responses that cross-reacted with the challenge virus and inversely correlated with lower viral loads and inflammation. These results demonstrate that a MA DNA vaccine that induces strong cross-reactive T cell responses can, independent of neutralizing antibody, mediate significant cross-protection in a nonhuman primate model and further supports development as an effective approach to induce broad protection against circulating and emerging influenza strains.

Seroprevalence for hepatitis E virus (HEV infection among volunteer blood donors of the Regional Blood Bank of Londrina, State of Paraná , Brazil Soroprevalência da infecção pelo virus da hepatite E (VHE em candidatos a doadores de sangue voluntários do Hemocentro Regional de Londrina, Londrina, Estado do Paraná, Brasil

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André Luiz Bortoliero

2006-04-01

Full Text Available A cross-sectional study was carried out among 996 volunteer blood donors enrolled from May 1999 to December 1999 to determine the seroprevalence of hepatitis E virus (HEV infection among volunteer blood donors of the Regional Blood Bank of Londrina, State of Paraná, Brazil, and to evaluate whether the rate of seroprevalence of IgG anti-HEV antibodies is associated with sociodemographic variables and with seropositivity for hepatitis A virus (HAV infection. All participants answered the questionnaire regarding the sociodemographic characterisitcs. Serum samples were tested for IgG antibodies to HEV (anti-HEV by an enzyme linked immunoassay (ELISA. All serum samples positive for anti-HEV IgG and 237 serum samples negative for anti-HEV were also assayed for IgG anti-HAV antibodies by ELISA. Anti-HEV IgG was confirmed in 23/996 samples, resulting in a seroprevalence of 2.3% for HEV infection, similar to previous results obtained in developed countries. No significant association was found between the presence of anti-HEV IgG antibodies and the sociodemographic variables including gender, age, educational level, rural or urban areas, source of water, and sewer system (p > 0.05. Also, no association with seropositivity for anti-HAV IgG antibodies was observed (p > 0.05. Although this study revealed a low seroprevalence of HEV infection in the population evaluated, the results showed that this virus is circulating among the population from Londrina, South Brazil, and point out the need of further studies to define the clinical and epidemiological importance of HEV infection and to identify additional risk factors involved in the epidemiology and pathogenesis of this infection in this population.Os objetivos do estudo foram determinar a soroprevalência da infecção pelo vírus da hepatite E (VHE em candidatos a doadores de sangue voluntários do Hemocentro Regional de Londrina, Paraná, e avaliar se essa soroprevalência está associada com vari

Priming-boosting vaccination with recombinant Mycobacterium bovis bacillus Calmette-Guérin and a nonreplicating vaccinia virus recombinant leads to long-lasting and effective immunity.

Science.gov (United States)

Ami, Yasushi; Izumi, Yasuyuki; Matsuo, Kazuhiro; Someya, Kenji; Kanekiyo, Masaru; Horibata, Shigeo; Yoshino, Naoto; Sakai, Koji; Shinohara, Katsuaki; Matsumoto, Sohkichi; Yamada, Takeshi; Yamazaki, Shudo; Yamamoto, Naoki; Honda, Mitsuo

2005-10-01

Virus-specific T-cell responses can limit immunodeficiency virus type 1 (HIV-1) transmission and prevent disease progression and so could serve as the basis for an affordable, safe, and effective vaccine in humans. To assess their potential for a vaccine, we used Mycobacterium bovis bacillus Calmette-Guérin (BCG)-Tokyo and a replication-deficient vaccinia virus strain (DIs) as vectors to express full-length gag from simian immunodeficiency viruses (SIVs) (rBCG-SIVgag and rDIsSIVgag). Cynomolgus macaques were vaccinated with either rBCG-SIVgag dermally as a single modality or in combination with rDIsSIVgag intravenously. When cynomologus macaques were primed with rBCG-SIVgag and then boosted with rDIsSIVgag, high levels of gamma interferon (IFN-gamma) spot-forming cells specific for SIV Gag were induced. This combination regimen elicited effective protective immunity against mucosal challenge with pathogenic simian-human immunodeficiency virus for the 1 year the macaques were under observation. Antigen-specific intracellular IFN-gamma activity was similarly induced in each of the macaques with the priming-boosting regimen. Other groups receiving the opposite combination or the single-modality vaccines were not effectively protected. These results suggest that a recombinant M. bovis BCG-based vector may have potential as an HIV/AIDS vaccine when administered in combination with a replication-deficient vaccinia virus DIs vector in a priming-boosting strategy.

Fenofibrate Metabolism in the Cynomolgus Monkey using Ultraperformance Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry-Based MetabolomicsS⃞

Science.gov (United States)

Liu, Aiming; Patterson, Andrew D.; Yang, Zongtao; Zhang, Xinying; Liu, Wei; Qiu, Fayang; Sun, He; Krausz, Kristopher W.; Idle, Jeffrey R.; Gonzalez, Frank J.; Dai, Renke

2009-01-01

Fenofibrate, widely used for the treatment of dyslipidemia, activates the nuclear receptor, peroxisome proliferator-activated receptor α. However, liver toxicity, including liver cancer, occurs in rodents treated with fibrate drugs. Marked species differences occur in response to fibrate drugs, especially between rodents and humans, the latter of which are resistant to fibrate-induced cancer. Fenofibrate metabolism, which also shows species differences, has not been fully determined in humans and surrogate primates. In the present study, the metabolism of fenofibrate was investigated in cynomolgus monkeys by ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOFMS)-based metabolomics. Urine samples were collected before and after oral doses of fenofibrate. The samples were analyzed in both positive-ion and negative-ion modes by UPLC-QTOFMS, and after data deconvolution, the resulting data matrices were subjected to multivariate data analysis. Pattern recognition was performed on the retention time, mass/charge ratio, and other metabolite-related variables. Synthesized or purchased authentic compounds were used for metabolite identification and structure elucidation by liquid chromatographytandem mass spectrometry. Several metabolites were identified, including fenofibric acid, reduced fenofibric acid, fenofibric acid ester glucuronide, reduced fenofibric acid ester glucuronide, and compound X. Another two metabolites (compound B and compound AR), not previously reported in other species, were characterized in cynomolgus monkeys. More importantly, previously unknown metabolites, fenofibric acid taurine conjugate and reduced fenofibric acid taurine conjugate were identified, revealing a previously unrecognized conjugation pathway for fenofibrate. PMID:19251819

Biotransformación del pelo residual de curtiembres

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Ruth Viviana Numpaque

2016-12-01

Full Text Available La industria de curtiembres genera una alta carga contaminante representada por residuos líquidos, sólidos y gaseosos. Entre los residuos sólidos, el pelo residual es vertido directamente al río Bogotá y/o en rellenos sanitarios, desencadenando serios conflictos de orden ambiental, social y económico. El objetivo de esta investigación fue evaluar la capacidad de los microorganismos del EM y Agroplux en la transformación del pelo residual en compost. Se evaluaron tres tratamientos con pelo residual y materiales orgánicos de plaza en diferentes porcentajes y dos controles, utilizando el diseño completamente al azar, con tres repeticiones. Durante el compostaje se determinaron las variables temperatura, formación de agregados, pH y conductividad eléctrica. El desarrollo de la temperatura ocurrió en ciclos que concordaron con los volteos y re-inoculaciones. En el tercer ciclo el mayor incremento de temperatura fue obtenido en los tres tratamientos, cuando ya se había agotado la mayor parte de los residuos orgánicos. La formación de agregados indicó que el proceso se llevó a efecto principalmente en el tratamiento con 20% de pelo residual más 80% de residuos orgánicos. Además de su color oscuro y la ausencia de olor y fragmentos, el compost producido mediante dicho tratamiento mostró la conductividad eléctrica más baja y un pH casi neutro. Se concluye que los microorganismos del EM y Agroplux tienen capacidad para transformar el pelo residual en compost y por lo tanto representan una alternativa viable para la continuación del funcionamiento de la industria de curtiembres en Villapinzón (Cundinamarca y en otras regiones de Colombia.

Pedicled Instep Flap and Tibial Nerve Reconstruction in a Cynomolgus Monkey [Macaca fascicularis

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Ruth Weiss

2016-01-01

Full Text Available A male cynomolgus monkey experienced extensive soft tissue trauma to the right caudal calf area. Some weeks after complete healing of the original wounds, the monkey developed a chronic pressure sore on plantar surface of the heel of its right foot. A loss of sensitivity in the sole of the foot was hypothesized. The skin defect was closed by a medial sensate pedicled instep flap followed by counter transplantation of a full thickness graft from the interdigital webspace. The integrity of the tibial nerve was revised and reconstructed by means of the turnover flap technique. Both procedures were successful. This is an uncommon case in an exotic veterinary patient as it demonstrates a reconstructive skin flap procedure for the treatment of a chronic, denervated wound in combination with the successful reconstruction of 2.5 cm gap in the tibial nerve.

Estudo soroepidemiológico da infecção pelo vírus da hepatite B entre portadores do vírus da imunodeficiência humana/sida na cidade de Belém, Pará - Brasil

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Maria Rita de Cassia Costa Monteiro

2004-01-01

Full Text Available O objetivo desta pesquisa foi estudar a prevalência de infecção pelo virus da hepatite B em 406 portadores do virus da imunodeficiência humana, maiores de dezoito anos de idade, atendidos na rede pública de saúde da cidade de Belém, Pará, assim como analisar possíveis fatores de risco para a infecção. A prevalência global de infecção pelo virus da hepatite B foi de 51% (IC: 46,1 - 55,8, com 7,9% (IC: 5,3 - 10,5 para o HBsAg, 45,1% (IC: 40,3 - 49,9 para o anti-HBc e 32,3% (IC: 27,5 - 36,8 para o anti-HBs. Após ajuste por regressão logística, os marcadores sorológicos de infecção pelo vírus da hepatite B apresentaram associação com as seguintes variáveis: idade, situação conjugal e preferência sexual. A prevalência dos marcadores do vírus B nos heterossexuais foi 28,7% e 68,8% nos homossexuais/bissexuais (IC: 3,50 - 9,08; OR: 5,63; p=0,000. Quanto à situação conjugal, a categoria com companheiro fixo/casado apresentou freqüência de 31%, e foi de 58,7% a observada no grupo sem companheiro fixo (IC: 1,29 - 3,63; OR: 2,16; p=0,003. A análise multivariada não mostrou associação do vírus B com o uso de drogas ilícitas injetáveis.

Coexistência de pênfigo vulgar e infecção pelo vírus herpes simples na mucosa oral Coexistence of pemphigus vulgaris and herpes simplex virus infection in oral mucosa

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Adrianna Milagres

2007-12-01

Full Text Available O pênfigo vulgar é uma doença mucocutânea, imunomediada, caracterizada por lesões vesiculobolhosas, enquanto a infecção pelo vírus herpes simples (HSV é comum na cavidade oral. A coexistência das duas doenças tem sido relatada por alguns autores. Este artigo relata o caso de um paciente com múltiplas lesões em várias áreas da mucosa oral, cujo procedimento foi raspagem e biópsia incisional, que resultou no diagnóstico de pênfigo vulgar associado à infecção pelo HSV. Destaca-se a inusitada associação das doenças e a identificação citopatológica de duas populações celulares com aspectos morfológicos distintos e característicos, capazes de determinar o correto diagnóstico, sendo fundamental para a conduta e terapêutica adequada.Pemphigus vulgaris is an autoimmune mucocutaneous disease, characterized by vesiculobullous lesions. Herpes simplex virus (HSV infection is common in the oral cavity and the coexistence of pemphigus vulgaris and HSV infection has been reported by some authors. In this work, we report a case of a patient with multiple lesions involving several areas of the oral mucous membrane. Based on scraping cytology and incisional biopsy findings, the diagnosis was pemphigus vulgaris associated with HSV infection. We call attention to the uncommon association of both diseases and the cytological identification of two cell populations with different and characteristic morphological aspects, able enough to establish the correct diagnosis and define an appropriate therapeutic approach.

The effect of angiotensin receptor neprilysin inhibitor, sacubitril/valsartan, on central nervous system amyloid-β concentrations and clearance in the cynomolgus monkey.

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Schoenfeld, Heidi A; West, Tim; Verghese, Philip B; Holubasch, Mary; Shenoy, Neeta; Kagan, David; Buono, Chiara; Zhou, Wei; DeCristofaro, Marc; Douville, Julie; Goodrich, Geoffrey G; Mansfield, Keith; Saravanan, Chandra; Cumin, Frederic; Webb, Randy L; Bateman, Randall J

2017-05-15

Sacubitril/valsartan (LCZ696) is the first angiotensin receptor neprilysin inhibitor approved to reduce cardiovascular mortality and hospitalization in patients with heart failure with reduced ejection fraction. As neprilysin (NEP) is one of several enzymes known to degrade amyloid-β (Aβ), there is a theoretical risk of Aβ accumulation following long-term NEP inhibition. The primary objective of this study was to evaluate the potential effects of sacubitril/valsartan on central nervous system clearance of Aβ isoforms in cynomolgus monkeys using the sensitive Stable Isotope Labeling Kinetics (SILK™)-Aβ methodology. The in vitro selectivity of valsartan, sacubitril, and its active metabolite sacubitrilat was established; sacubitrilat did not inhibit other human Aβ-degrading metalloproteases. In a 2-week study, sacubitril/valsartan (50mg/kg/day) or vehicle was orally administered to female cynomolgus monkeys in conjunction with SILK™-Aβ. Despite low cerebrospinal fluid (CSF) and brain penetration, CSF exposure to sacubitril was sufficient to inhibit NEP and resulted in an increase in the elimination half-life of Aβ1-42 (65.3%; p=0.026), Aβ1-40 (35.2%; p=0.04) and Aβtotal (29.8%; p=0.04) acutely; this returned to normal as expected with repeated dosing for 15days. CSF concentrations of newly generated Aβ (AUC (0-24h) ) indicated elevations in the more aggregable form Aβ1-42 on day 1 (20.4%; p=0.039) and day 15 (34.7%; p=0.0003) and in shorter forms Aβ1-40 (23.4%; p=0.009), Aβ1-38 (64.1%; p=0.0001) and Aβtotal (50.45%; p=0.00002) on day 15. However, there were no elevations in any Aβ isoforms in the brains of these monkeys on day 16. In a second study cynomolgus monkeys were administered sacubitril/valsartan (300mg/kg) or vehicle control for 39weeks; no microscopic brain changes or Aβ deposition, as assessed by immunohistochemical staining, were present. Further clinical studies are planned to address the relevance of these findings. Copyright �

Preclinical and Clinical Development of a YFV 17 D-Based Chimeric Vaccine against West Nile Virus

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Gustavo H. Dayan

2013-12-01

Full Text Available Substantial success has been achieved in the development and implementation of West Nile (WN vaccines for horses; however, no human WN vaccines are approved. This review focuses on the construction, pre-clinical and clinical characterization of ChimeriVax-WN02 for humans, a live chimeric vaccine composed of a yellow fever (YF 17D virus in which the prM-E envelope protein genes are replaced with the corresponding genes of the WN NY99 virus. Pre-clinical studies demonstrated that ChimeriVax-WN02 was significantly less neurovirulent than YF 17D in mice and rhesus and cynomolgus monkeys. The vaccine elicited neutralizing antibody titers after inoculation in hamsters and monkeys and protected immunized animals from lethal challenge including intracerebral inoculation of high dose of WN NY99 virus. Safety, viremia and immunogenicity of ChimeriVax-WN02 were assessed in one phase I study and in two phase II clinical trials. No safety signals were detected in the three clinical trials with no remarkable differences in incidence of adverse events (AEs between vaccine and placebo recipients. Viremia was transient and the mean viremia levels were low. The vaccine elicited strong and durable neutralizing antibody and cytotoxic T cell responses. WN epidemiology impedes a classical licensure pathway; therefore, innovative licensure strategies should be explored.

Stress-relevant social behaviors of middle-class male cynomolgus monkeys (Macaca fascicularis).

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Cui, Ding; Zhou, Yuan

2015-11-18

Stress from dominance ranks in human societies, or that of other social animals, especially nonhuman primates, can have negative influences on health. Individuals holding different social status may be burdened with various stress levels. The middle class experiences a special stress situation within the dominance hierarchy due to its position between the higher and lower classes. Behaviorally, questions about where middle-class stress comes from and how individuals adapt to middle-class stress remain poorly understood in nonhuman primates. In the present study, social interactions, including aggression, avoidance, grooming and mounting behaviors, between beta males, as well as among group members holding higher or lower social status, were analyzed in captive male-only cynomolgus monkey groups. We found that aggressive tension from the higher hierarchy members was the main origin of stress for middle-class individuals. However, behaviors such as attacking lower hierarchy members immediately after being the recipient of aggression, as well as increased avoidance, grooming and mounting toward both higher and lower hierarchy members helped alleviate middle-class stress and were particular adaptations to middle-class social status.

TALEN-based generation of a cynomolgus monkey disease model for human microcephaly

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Ke, Qiong; Li, Weiqiang; Lai, Xingqiang; Chen, Hong; Huang, Lihua; Kang, Zhuang; Li, Kai; Ren, Jie; Lin, Xiaofeng; Zheng, Haiqing; Huang, Weijun; Ma, Yunhan; Xu, Dongdong; Chen, Zheng; Song, Xinming; Lin, Xinyi; Zhuang, Min; Wang, Tao; Zhuang, Fengfeng; Xi, Jianzhong; Mao, Frank Fuxiang; Xia, Huimin; Lahn, Bruce T; Zhou, Qi; Yang, Shihua; Xiang, Andy Peng

2016-01-01

Gene editing in non-human primates may lead to valuable models for exploring the etiologies and therapeutic strategies of genetically based neurological disorders in humans. However, a monkey model of neurological disorders that closely mimics pathological and behavioral deficits in humans has not yet been successfully generated. Microcephalin 1 (MCPH1) is implicated in the evolution of the human brain, and MCPH1 mutation causes microcephaly accompanied by mental retardation. Here we generated a cynomolgus monkey (Macaca fascicularis) carrying biallelic MCPH1 mutations using transcription activator-like effector nucleases. The monkey recapitulated most of the important clinical features observed in patients, including marked reductions in head circumference, premature chromosome condensation (PCC), hypoplasia of the corpus callosum and upper limb spasticity. Moreover, overexpression of MCPH1 in mutated dermal fibroblasts rescued the PCC syndrome. This monkey model may help us elucidate the role of MCPH1 in the pathogenesis of human microcephaly and better understand the function of this protein in the evolution of primate brain size. PMID:27502025

Animal models for Ebola and Marburg virus infections

Science.gov (United States)

Nakayama, Eri; Saijo, Masayuki

2013-01-01

Ebola and Marburg hemorrhagic fevers (EHF and MHF) are caused by the Filoviridae family, Ebolavirus and Marburgvirus (ebolavirus and marburgvirus), respectively. These severe diseases have high mortality rates in humans. Although EHF and MHF are endemic to sub-Saharan Africa. A novel filovirus, Lloviu virus, which is genetically distinct from ebolavirus and marburgvirus, was recently discovered in Spain where filoviral hemorrhagic fever had never been reported. The virulence of this virus has not been determined. Ebolavirus and marburgvirus are classified as biosafety level-4 (BSL-4) pathogens and Category A agents, for which the US government requires preparedness in case of bioterrorism. Therefore, preventive measures against these viral hemorrhagic fevers should be prepared, not only in disease-endemic regions, but also in disease-free countries. Diagnostics, vaccines, and therapeutics need to be developed, and therefore the establishment of animal models for EHF and MHF is invaluable. Several animal models have been developed for EHF and MHF using non-human primates (NHPs) and rodents, which are crucial to understand pathophysiology and to develop diagnostics, vaccines, and therapeutics. Rhesus and cynomolgus macaques are representative models of filovirus infection as they exhibit remarkably similar symptoms to those observed in humans. However, the NHP models have practical and ethical problems that limit their experimental use. Furthermore, there are no inbred and genetically manipulated strains of NHP. Rodent models such as mouse, guinea pig, and hamster, have also been developed. However, these rodent models require adaptation of the virus to produce lethal disease and do not mirror all symptoms of human filovirus infection. This review article provides an outline of the clinical features of EHF and MHF in animals, including humans, and discusses how the animal models have been developed to study pathophysiology, vaccines, and therapeutics. PMID:24046765

Animal models for Ebola and Marburg virus infections

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Eri eNakayama

2013-09-01

Full Text Available Ebola and Marburg hemorrhagic fevers (EHF and MHF are caused by the Filoviridae family, Ebolavirus and Marburgvirus (ebolavirus and marburgvirus, respectively. These severe diseases have high mortality rates in humans. Although EHF and MHF are endemic to sub-Saharan Africa. A novel filovirus, Lloviu virus, which is genetically distinct from ebolavirus and marburgvirus, was recently discovered in Spain where filoviral hemorrhagic fever had never been reported. The virulence of this virus has not been determined. Ebolavirus and marburgvirus are classified as biosafety level-4 (BSL-4 pathogens and Category A agents, for which the US government requires preparedness in case of bioterrorism. Therefore, preventive measures against these viral hemorrhagic fevers should be prepared, not only in disease-endemic regions, but also in disease-free countries. Diagnostics, vaccines, and therapeutics need to be developed, and therefore the establishment of animal models for EHF and MHF is invaluable. Several animal models have been developed for EHF and MHF using nonhuman primates (NHPs and rodents, which are crucial to understand pathophysiology and to develop diagnostics, vaccines, and therapeutics. Rhesus and cynomolgus macaques are representative models of filovirus infection as they exhibit remarkably similar symptoms to those observed in humans. However, the NHP models have practical and ethical problems that limit their experimental use. Furthermore, there are no inbred and genetically manipulated strains of NHP. Rodent models such as mouse, guinea pig, and hamster, have also been developed. However, these rodent models require adaptation of the virus to produce lethal disease and do not mirror all symptoms of human filovirus infection. This review article provides an outline of the clinical features of EHF and MHF in animals, including humans, and discusses how the animal models have been developed to study pathophysiology, vaccines, and therapeutics.

Ebola Virus Infections in Nonhuman Primates Are Temporally Influenced by Glycoprotein Poly-U Editing Site Populations in the Exposure Material

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Trefry, John C.; Wollen, Suzanne E.; Nasar, Farooq; Shamblin, Joshua D.; Kern, Steven J.; Bearss, Jeremy J.; Jefferson, Michelle A.; Chance, Taylor B.; Kugelman, Jeffery R.; Ladner, Jason T.; Honko, Anna N.; Kobs, Dean J.; Wending, Morgan Q.S.; Sabourin, Carol L.; Pratt, William D.; Palacios, Gustavo F.; Pitt, M. Louise M.

2015-01-01

Recent experimentation with the variants of the Ebola virus that differ in the glycoprotein’s poly-uridine site, which dictates the form of glycoprotein produced through a transcriptional stutter, has resulted in questions regarding the pathogenicity and lethality of the stocks used to develop products currently undergoing human clinical trials to combat the disease. In order to address these concerns and prevent the delay of these critical research programs, we designed an experiment that permitted us to intramuscularly challenge statistically significant numbers of naïve and vaccinated cynomolgus macaques with either a 7U or 8U variant of the Ebola virus, Kikwit isolate. In naïve animals, no difference in survivorship was observed; however, there was a significant delay in the disease course between the two groups. Significant differences were also observed in time-of-fever, serum chemistry, and hematology. In vaccinated animals, there was no statistical difference in survivorship between either challenge groups, with two succumbing in the 7U group compared to 1 in the 8U challenge group. In summary, survivorship was not affected, but the Ebola virus disease course in nonhuman primates is temporally influenced by glycoprotein poly-U editing site populations. PMID:26703716

Ebola Virus Infections in Nonhuman Primates Are Temporally Influenced by Glycoprotein Poly-U Editing Site Populations in the Exposure Material

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John C. Trefry

2015-12-01

Full Text Available Recent experimentation with the variants of the Ebola virus that differ in the glycoprotein’s poly-uridine site, which dictates the form of glycoprotein produced through a transcriptional stutter, has resulted in questions regarding the pathogenicity and lethality of the stocks used to develop products currently undergoing human clinical trials to combat the disease. In order to address these concerns and prevent the delay of these critical research programs, we designed an experiment that permitted us to intramuscularly challenge statistically significant numbers of naïve and vaccinated cynomolgus macaques with either a 7U or 8U variant of the Ebola virus, Kikwit isolate. In naïve animals, no difference in survivorship was observed; however, there was a significant delay in the disease course between the two groups. Significant differences were also observed in time-of-fever, serum chemistry, and hematology. In vaccinated animals, there was no statistical difference in survivorship between either challenge groups, with two succumbing in the 7U group compared to 1 in the 8U challenge group. In summary, survivorship was not affected, but the Ebola virus disease course in nonhuman primates is temporally influenced by glycoprotein poly-U editing site populations.

Recombinant vesicular stomatitis virus vaccine vectors expressing filovirus glycoproteins lack neurovirulence in nonhuman primates.

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Chad E Mire

Full Text Available The filoviruses, Marburg virus and Ebola virus, cause severe hemorrhagic fever with high mortality in humans and nonhuman primates. Among the most promising filovirus vaccines under development is a system based on recombinant vesicular stomatitis virus (rVSV that expresses an individual filovirus glycoprotein (GP in place of the VSV glycoprotein (G. The main concern with all replication-competent vaccines, including the rVSV filovirus GP vectors, is their safety. To address this concern, we performed a neurovirulence study using 21 cynomolgus macaques where the vaccines were administered intrathalamically. Seven animals received a rVSV vector expressing the Zaire ebolavirus (ZEBOV GP; seven animals received a rVSV vector expressing the Lake Victoria marburgvirus (MARV GP; three animals received rVSV-wild type (wt vector, and four animals received vehicle control. Two of three animals given rVSV-wt showed severe neurological symptoms whereas animals receiving vehicle control, rVSV-ZEBOV-GP, or rVSV-MARV-GP did not develop these symptoms. Histological analysis revealed major lesions in neural tissues of all three rVSV-wt animals; however, no significant lesions were observed in any animals from the filovirus vaccine or vehicle control groups. These data strongly suggest that rVSV filovirus GP vaccine vectors lack the neurovirulence properties associated with the rVSV-wt parent vector and support their further development as a vaccine platform for human use.

Aerosol measles vaccination in macaques: Preclinical studies of immune responses and safety

NARCIS (Netherlands)

R.L. de Swart (Rik); T. Kuiken (Thijs); J. Fernandez-de Castro (Jorge); M.J. Papania (Mark); J.V. Bennett (John); J.L. Valdespino (José); P.D. Minor; C.L. Witham (Clyde); S. Yüksel (Selma); H.W. Vos (Helma); G. van Amerongen (Geert); A.D.M.E. Osterhaus (Albert)

2006-01-01

textabstractThe comparative efficacy and safety of measles vaccination via the aerosol route versus subcutaneous injection has not been fully resolved. We vaccinated cynomolgus monkeys (Macaca fascicularis) with the live-attenuated Edmonston-Zagreb measles virus (MV) vaccine and compared different

Contribuições para interação pelo olhar com teclados virtuais

OpenAIRE

Antonio Díaz Tula

2015-01-01

A presente tese de doutorado insere-se na área de interação pelo olhar. A interação pelo olhar é uma forma de comunicação com o computador utilizando os movimentos oculares do usuário. Pessoas com deficiência física, que não conseguem usar dispositivos convencionais como um teclado e um mouse de computador, podem se beneficiar da interação pelo olhar para se comunicarem e se inserirem na sociedade. Para isso a entrada de texto ou digitação pelo olhar é um recurso importante e assunto principa...

Correlation between the concentration of serum polychlorinated biphenyls (PCBs) in pregnant cynomolgus monkeys and their offspring's behavioral scores in eye-contact test and finger maze learning test

Energy Technology Data Exchange (ETDEWEB)

Negishi, T. [Aoyama Gakuin Univ., Kanagawa (Japan); Takasuga, T. [Shimadzu Techno-Research Inc., Kyoto (Japan); Kawasaki, K. [Hoshi Univ., Tokyo (Japan); Kuroda, Y. [CREST Japan Science and Technology Corp., Saitama (Japan); Yoshikawa, Y. [The Univ. of Tokyo (Japan)

2004-09-15

A recent review suggested that pre- or perinatal exposure of developing fetuses to dioxins, the widespread environmental contaminants, such as polychrorinated biphenlys (PCBs), induce the irreversible abnormalities in the functions of central nervous system (CNS) in human. These chemicals can be transferred to each fetus and naonate transplacentally and lactationally in rhesus monkey. Several studies also reported the adverse effect of PCB on CNS development in rodents and monkeys as well as on behavior in rodents and monkeys. In the present study, we show a preliminary data about the correlation between the serum concentrations of PCBs in pregnant cynomolgus monkeys (Macaca fascicularis) and the scores of two behavioral tests, eye-contact test and four-step finger maze test, which evaluate consciousness against human observer and learning ability, respectively, in their offspring. This experimental surveillance system using non-human primates would be useful to predict the risk of PCBs exposure in human fetuses because of the similarities of cynomolgus monkey to human with regard to reproduction, developmental parameter, and others.

Using immunoglobulin Y as an alternative antibody for the detection of hepatitis A virus in frozen liver sections

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Gentil Arthur Bentes

2015-06-01

Full Text Available An increasing amount of research has been conducted on immunoglobulin Y (IgY because the use of IgY offers several advantages with respect to diagnostic testing, including its easy accessibility, low cost and translatability to large-scale production, in addition to the fact that it can be ethically produced. In a previous work, immunoglobulin was produced and purified from egg yolks (IgY reactive to hepatitis A virus (HAV antigens. In the present work, this anti-HAV-specific IgY was used in an indirect immunofluorescence assay to detect viral antigens in liver biopsies that were obtained from experimentally infected cynomolgus monkeys. Fields that were positive for HAV antigen were detected in liver sections using confocal microscopy. In conclusion, egg yolks from immunised hens may be a reliable source for antibody production, which can be employed for immunological studies.

Studies of tolerance induction through mixed chimerism in cynomolgus monkeys. Method for detection of chimeric cells and effect of thymic irradiation on induction of tolerance

International Nuclear Information System (INIS)

Hoshino, Tomoaki; Kawai, Tatsuo; Ota, Kazuo

1996-01-01

To establish the method for the detection of chimerism in cynomologus monkeys, we tested cross reactivity of various anti-HLA monoclonal antibodies (mAb) to cynomolgus monkeys. In 29 mAb we tested, only three monoclonal anti-HLA antibodies crossreacted with lymphocytes of monkeys. With these mAb, chimeric cell can be detected up to 1% by flow cytometric analysis (study 1). Utilizing the method we developed in study 1, we applied the regimen that induces mixed chimerism and skin graft tolerance in mice to renal allotransplantation of cynomolgus monkey. Regimen A includes non-lethal dose of total body irradiation (TBI), administration of anti-thymocyte globulin (ATG) for 3 days, donor bone marrow infusion and 45 days course of cyclosporine (CYA) administration. We added 7 Gy of thymic irradiation on day-6 in regimen B and on day-1 in regimen C. Although all monkeys in regimen A and B consistently developed chimerism, they rejected kidney allografts soon after stopping CYA. In contrast, 4 monkeys out of 5 failed to develop chimerism in regimen C, but renal allograft tolerance was induced in one monkey who developed chimerism in regimen C. In conclusion, the induction of chimerism is considered necessary but not sufficient for tolerance induction. (author)

Studies of tolerance induction through mixed chimerism in cynomolgus monkeys. Method for detection of chimeric cells and effect of thymic irradiation on induction of tolerance

Energy Technology Data Exchange (ETDEWEB)

Hoshino, Tomoaki; Kawai, Tatsuo; Ota, Kazuo [Tokyo Women`s Medical Coll. (Japan)

1996-12-01

To establish the method for the detection of chimerism in cynomologus monkeys, we tested cross reactivity of various anti-HLA monoclonal antibodies (mAb) to cynomolgus monkeys. In 29 mAb we tested, only three monoclonal anti-HLA antibodies crossreacted with lymphocytes of monkeys. With these mAb, chimeric cell can be detected up to 1% by flow cytometric analysis (study 1). Utilizing the method we developed in study 1, we applied the regimen that induces mixed chimerism and skin graft tolerance in mice to renal allotransplantation of cynomolgus monkey. Regimen A includes non-lethal dose of total body irradiation (TBI), administration of anti-thymocyte globulin (ATG) for 3 days, donor bone marrow infusion and 45 days course of cyclosporine (CYA) administration. We added 7 Gy of thymic irradiation on day-6 in regimen B and on day-1 in regimen C. Although all monkeys in regimen A and B consistently developed chimerism, they rejected kidney allografts soon after stopping CYA. In contrast, 4 monkeys out of 5 failed to develop chimerism in regimen C, but renal allograft tolerance was induced in one monkey who developed chimerism in regimen C. In conclusion, the induction of chimerism is considered necessary but not sufficient for tolerance induction. (author)

Teste rápido para detecção da infecção pelo HIV-1 em gestantes Rapid test to detect HIV-1 infection among pregnant women

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Geraldo Duarte

2001-03-01

Full Text Available Objetivos: avaliar os resultados do teste de diagnóstico rápido da infecção pelo HIV-1 disponibilizado pelo Ministério da Saúde, para identificação de gestantes contaminadas por este vírus. Métodos: avaliação prospectiva de 443 gestantes sem teste sorológico para HIV no pré-natal, atendidas no Departamento de Ginecologia e Obstetrícia da Faculdade de Medicina de Ribeirão Preto-Universidade de São Paulo (HCFMRP-USP, entre fevereiro e junho de 2000. As amostras destas pacientes foram submetidas ao teste rápido imunocromatográfico, sendo comparadas com ELISA e confirmadas pela aglutinação. Resultados: dentre as 443 gestantes submetidas ao teste rápido (20,1% dos partos no período, 16 apresentaram resultados positivos (3,6%. Nenhuma amostra negativa pelo teste rápido foi positiva pelo ELISA. Entretanto, das 16 amostras positivas pelo teste rápido, duas foram negativas pelos testes confirmatórios. Logo, a sensibilidade do teste rápido foi de 100,0%, especificidade 99,5%, valor preditivo positivo 87,5% e valor preditivo negativo 100,0%. Conclusões: os resultados obtidos na avaliação do teste para o diagnóstico rápido da infecção pelo HIV-1 em gestantes revelaram sensibilidade, especificidade e valores preditivos que o credenciam como recurso extremamente importante na indicação de medidas que reduzem a transmissão perinatal desse vírus.Purpose: to evaluate the results of a rapid diagnostic test for HIV-1 infection made available by the Health Ministry for the identification of pregnant women contaminated by this virus. Methods: we evaluated prospectively 443 pregnant women with no prenatal serologic anti-HIV test seen at the Department of Gynecology and Obstetrics of the Faculty of Medicine of Ribeirão Preto, University of São Paulo, from February to June, 2000. Samples from these patients were submitted to the rapid immunochromatographic test, which was compared with ELISA and submitted to a confirmatory

The effect of angiotensin receptor neprilysin inhibitor, sacubitril/valsartan, on central nervous system amyloid-β concentrations and clearance in the cynomolgus monkey

International Nuclear Information System (INIS)

Schoenfeld, Heidi A.; West, Tim; Verghese, Philip B.; Holubasch, Mary; Shenoy, Neeta; Kagan, David; Buono, Chiara; Zhou, Wei; DeCristofaro, Marc; Douville, Julie; Goodrich, Geoffrey G.; Mansfield, Keith; Saravanan, Chandra; Cumin, Frederic; Webb, Randy L.; Bateman, Randall J.

2017-01-01

Sacubitril/valsartan (LCZ696) is the first angiotensin receptor neprilysin inhibitor approved to reduce cardiovascular mortality and hospitalization in patients with heart failure with reduced ejection fraction. As neprilysin (NEP) is one of several enzymes known to degrade amyloid-β (Aβ), there is a theoretical risk of Aβ accumulation following long-term NEP inhibition. The primary objective of this study was to evaluate the potential effects of sacubitril/valsartan on central nervous system clearance of Aβ isoforms in cynomolgus monkeys using the sensitive Stable Isotope Labeling Kinetics (SILK™)-Aβ methodology. The in vitro selectivity of valsartan, sacubitril, and its active metabolite sacubitrilat was established; sacubitrilat did not inhibit other human Aβ-degrading metalloproteases. In a 2-week study, sacubitril/valsartan (50 mg/kg/day) or vehicle was orally administered to female cynomolgus monkeys in conjunction with SILK™-Aβ. Despite low cerebrospinal fluid (CSF) and brain penetration, CSF exposure to sacubitril was sufficient to inhibit NEP and resulted in an increase in the elimination half-life of Aβ1-42 (65.3%; p = 0.026), Aβ1-40 (35.2%; p = 0.04) and Aβtotal (29.8%; p = 0.04) acutely; this returned to normal as expected with repeated dosing for 15 days. CSF concentrations of newly generated Aβ (AUC (0–24 h) ) indicated elevations in the more aggregable form Aβ1-42 on day 1 (20.4%; p = 0.039) and day 15 (34.7%; p = 0.0003) and in shorter forms Aβ1-40 (23.4%; p = 0.009), Aβ1-38 (64.1%; p = 0.0001) and Aβtotal (50.45%; p = 0.00002) on day 15. However, there were no elevations in any Aβ isoforms in the brains of these monkeys on day 16. In a second study cynomolgus monkeys were administered sacubitril/valsartan (300 mg/kg) or vehicle control for 39 weeks; no microscopic brain changes or Aβ deposition, as assessed by immunohistochemical staining, were present. Further clinical studies are planned to address the relevance of these

The effect of angiotensin receptor neprilysin inhibitor, sacubitril/valsartan, on central nervous system amyloid-β concentrations and clearance in the cynomolgus monkey

Energy Technology Data Exchange (ETDEWEB)

Schoenfeld, Heidi A., E-mail: heidi.schoenfeld@novartis.com [Novartis Institutes for BioMedical Research, East Hanover, NJ (United States); West, Tim; Verghese, Philip B.; Holubasch, Mary [C2N Diagnostics, St. Louis, MO (United States); Shenoy, Neeta; Kagan, David; Buono, Chiara [Novartis Institutes for BioMedical Research, Cambridge, MA (United States); Zhou, Wei; DeCristofaro, Marc [Novartis Institutes for BioMedical Research, East Hanover, NJ (United States); Douville, Julie [Charles River Laboratories ULC, Montreal, Quebec (Canada); Goodrich, Geoffrey G. [Charles River Laboratories, Inc., Reno, NV (United States); Mansfield, Keith; Saravanan, Chandra [Novartis Institutes for BioMedical Research, Cambridge, MA (United States); Cumin, Frederic [Novartis Institutes for BioMedical Research, Basel (Switzerland); Webb, Randy L. [Novartis Pharmaceuticals Corporation, East Hanover, NJ (United States); Bateman, Randall J. [Department of Neurology, Washington University School of Medicine, St. Louis, MO (United States)

2017-05-15

Sacubitril/valsartan (LCZ696) is the first angiotensin receptor neprilysin inhibitor approved to reduce cardiovascular mortality and hospitalization in patients with heart failure with reduced ejection fraction. As neprilysin (NEP) is one of several enzymes known to degrade amyloid-β (Aβ), there is a theoretical risk of Aβ accumulation following long-term NEP inhibition. The primary objective of this study was to evaluate the potential effects of sacubitril/valsartan on central nervous system clearance of Aβ isoforms in cynomolgus monkeys using the sensitive Stable Isotope Labeling Kinetics (SILK™)-Aβ methodology. The in vitro selectivity of valsartan, sacubitril, and its active metabolite sacubitrilat was established; sacubitrilat did not inhibit other human Aβ-degrading metalloproteases. In a 2-week study, sacubitril/valsartan (50 mg/kg/day) or vehicle was orally administered to female cynomolgus monkeys in conjunction with SILK™-Aβ. Despite low cerebrospinal fluid (CSF) and brain penetration, CSF exposure to sacubitril was sufficient to inhibit NEP and resulted in an increase in the elimination half-life of Aβ1-42 (65.3%; p = 0.026), Aβ1-40 (35.2%; p = 0.04) and Aβtotal (29.8%; p = 0.04) acutely; this returned to normal as expected with repeated dosing for 15 days. CSF concentrations of newly generated Aβ (AUC{sub (0–24} {sub h)}) indicated elevations in the more aggregable form Aβ1-42 on day 1 (20.4%; p = 0.039) and day 15 (34.7%; p = 0.0003) and in shorter forms Aβ1-40 (23.4%; p = 0.009), Aβ1-38 (64.1%; p = 0.0001) and Aβtotal (50.45%; p = 0.00002) on day 15. However, there were no elevations in any Aβ isoforms in the brains of these monkeys on day 16. In a second study cynomolgus monkeys were administered sacubitril/valsartan (300 mg/kg) or vehicle control for 39 weeks; no microscopic brain changes or Aβ deposition, as assessed by immunohistochemical staining, were present. Further clinical studies are planned to address the relevance

Distribution, retention and early cytogenetic damage in Cynomolgus monkeys following inhalation of 239Pu(NO3)4

International Nuclear Information System (INIS)

Brooks, A.L.; Mewhinney, J.A.; Redman, H.C.; Guilmette, R.A.; McClellan, R.O.

1980-01-01

Sixteen Cynomolgus monkeys were exposed by inhalation to an aerosol of 239 Pu(NO 3 ) 4 which resulted in calculated initial lung burdens of 1.0, 0.3 and 0.1 μCi. Four animals were exposed to the carrier aerosol and served as controls. Animals were sacrificed at 4 days and 45 days after exposure to determine the distribution and retention of the aerosol. The amount of plutonium in the liver, skeleton and testes increased as a function of time after exposure. Two monkeys died 155 and 188 days after inhalation exposure from radiation pneumonitis and fibrosis. There was a doubling of the total chromosome aberration frequency in the blood lymphocytes and a significant increase in dicentric chromosomes in the animals exposed for 6 months to initial lung burdens of 1.0 μCi

Allowable warm ischemic time and morphological and biochemical changes in uterine ischemia/reperfusion injury in cynomolgus macaque: a basic study for uterus transplantation.

Science.gov (United States)

Kisu, Iori; Umene, Kiyoko; Adachi, Masataka; Emoto, Katsura; Nogami, Yuya; Banno, Kouji; Itagaki, Iori; Kawamoto, Ikuo; Nakagawa, Takahiro; Narita, Hayato; Yoshida, Atsushi; Tsuchiya, Hideaki; Ogasawara, Kazumasa; Aoki, Daisuke

2017-10-01

How long is the allowable warm ischemic time of the uterus and what morphological and biochemical changes are caused by uterine ischemia/reperfusion injury in cynomolgus macaques? Warm ischemia in the uterus of cynomolgus macaques is tolerated for up to 4 h and reperfusion after uterine ischemia caused no further morphological and biochemical changes. Uterus transplantation is a potential option for women with uterine factor infertility. The allowable warm ischemic time and ischemia/reperfusion injury of the uterus in humans and non-human primates is unknown. This experimental study included 18 female cynomolgus macaques with periodic menstruation. Animals were divided into six groups of three monkeys each: a control group and groups with uterine ischemia for 0.5, 1, 2, 4 and 8 h. Biopsies of uterine tissues were performed before blood flow blockage, after each blockage time, and after reperfusion for 3 h. Blood sampling was performed after each blockage time, and after reperfusion for 5, 15 and 30 min for measurement of biochemical data. Resumption of menstruation was monitored after the surgical procedure. Morphological, physiological and biochemical changes after ischemia and reperfusion were evaluated. Mild muscle degeneration and zonal degeneration were observed in all animals subjected to warm ischemia for 4 or 8 h, but there were no marked differences in the appearance of specimens immediately after ischemia and after reperfusion for 3 h in animals subjected to 4 or 8 h of warm ischemia. There were no significant changes in any biochemical parameters at any time point in each group. Periodical menstruation resumed in all animals with warm ischemia up to 4 h, but did not recover in animals with warm ischemia for 8 h with atrophic uteri. Warm ischemia in actual transplantation was not exactly mimicked in this study because uteri were not perfused, cooled, transplanted or reanastomosed with vessels. Results in non-human primates cannot always be extrapolated to

SHOPPING CENTERS: UMA RELAÇÃO ENTRE OS ATRIBUTOS DE ESCOLHA PELOS CONSUMIDORES VERSUS OS ATRIBUTOS VALORIZADOS PELOS GERENTES

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Vitor Edson Marques Junior

2010-04-01

Full Text Available Embora os shoppings centers estejam em franco processo de ampliação na economia brasileira ainda são poucas as análises envolvendo shoppings centers e atributos motivadores de escolha pelos consumidores. Este trabalho tem por objetivo analisar os fatores motivacionais determinantes para a escolha de um shopping por parte dos consumidores. A amostra deste estudo foi composta por alunos de graduação de cursos de Administração. Adicionalmente, foi realizada uma entrevista em profundidade com os gestores dos três shoppings centers da cidade de Ribeirão Preto. O estudo revelou que os atributos motivadores mais valorizados no processo de escolha foram: limpeza, manutenção, segurança dentro do shopping e qualidade do serviço prestado. Este trabalho pretende contribuir com a compreensão da importância dos fatores valorados pelos consumidores de shoppings centers e assim sendo, fornecer material para a melhoria da gestão destes empreendimentos.

Immunotoxicological Evaluation of Genetically Modified Rice Expressing Cry1Ab/Ac Protein (TT51-1) by a 6-Month Feeding Study on Cynomolgus Monkeys

OpenAIRE

Tan, Xiaoyan; Zhou, Xiaobing; Tang, Yao; Lv, Jianjun; Zhang, Lin; Sun, Li; Yang, Yanwei; Miao, Yufa; Jiang, Hua; Chen, Gaofeng; Huang, Zhiying; Wang, Xue

2016-01-01

The present study was performed to evaluate the food safety of TT51-1, a new type of genetically modified rice that expresses the Cry1Ab/Ac protein (Bt toxin) and is highly resistant to most lepidopteran pests. Sixteen male and 16 female cynomolgus monkeys were randomly divided into four groups: conventional rice (non-genetically modified rice, non-GM rice), positive control, 17.5% genetically modified rice (GM rice) and 70% GM rice. Monkeys in the non-GM rice, positive control, and GM rice g...

Nectin-4 Interactions Govern Measles Virus Virulence in a New Model of Pathogenesis, the Squirrel Monkey (Saimiri sciureus).

Science.gov (United States)

Delpeut, Sébastien; Sawatsky, Bevan; Wong, Xiao-Xiang; Frenzke, Marie; Cattaneo, Roberto; von Messling, Veronika

2017-06-01

In addition to humans, only certain nonhuman primates are naturally susceptible to measles virus (MeV) infection. Disease severity is species dependent, ranging from mild to moderate for macaques to severe and even lethal for certain New World monkey species. To investigate if squirrel monkeys ( Saimiri sciureus ), which are reported to develop a course of disease similar to humans, may be better suited than macaques for the identification of virulence determinants or the evaluation of therapeutics, we infected them with a green fluorescent protein-expressing MeV. Compared to cynomolgus macaques ( Macaca fascicularis ) infected with the same virus, the squirrel monkeys developed more-severe immunosuppression, higher viral load, and a broader range of clinical signs typical for measles. In contrast, infection with an MeV unable to interact with the epithelial receptor nectin-4, while causing immunosuppression, resulted in only a mild and transient rash and a short-lived elevation of the body temperature. Similar titers of the wild-type and nectin-4-blind MeV were detected in peripheral blood mononuclear cells and lymph node homogenates, but only the wild-type virus was found in tracheal lavage fluids and urine. Thus, our study demonstrates the importance of MeV interactions with nectin-4 for clinical disease in the new and better-performing S. sciureus model of measles pathogenesis. IMPORTANCE The characterization of mechanisms underlying measles virus clinical disease has been hampered by the lack of an animal model that reproduces the course of disease seen in human patients. Here, we report that infection of squirrel monkeys ( Saimiri sciureus ) fulfills these requirements. Comparative infection with wild-type and epithelial cell receptor-blind viruses demonstrated the importance of epithelial cell infection for clinical disease, highlighting the spread to epithelia as an attractive target for therapeutic strategies. Copyright © 2017 American Society for

Os dias iniciais da infecção pelo vírus da gripe pandémica (H1N1 2009 na região centro de Portugal

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V. Duque

2010-11-01

Coimbra e da Guarda onde estão as principais estradas de ligação com a Europa. O período de incubação calculado para a infecção pelo vírus da gripe pandémica (H1N1 2009 foi de 2 dias. A duração das manifestações clínicas até os doentes procurarem observação médica teve um valor mediano de 2 dias. Todos os casos foram de gravidade ligeira a moderada, sem casos de morte. Conclusões: Os dias iniciais da infecção pelo vírus da gripe pandémica (H1N1 2009 foram caracterizados na nossa região por casos de doença com gravidade ligeira a moderada. Os mais afectados foram os jovens adultos, com as idades extremas da vida poupadas. O diagnóstico precoce, o isolamento estrito e o tratamento podem ter diminuído a disseminação da infecção. Abstract: Background: The first case of pandemic (H1N1 2009 virus infection was diagnosed in the central region of Portugal on June 16, 2009, in a woman infected in Canada. Methods: The aim of our study was, first to characterize the clinical and epidemiologic aspects of all the patients with clinical manifestations included in the definition of case for investigation with samples submitted to diagnosis of the pandemic (H1N1 2009 virus infection, in the central region of Portugal; second to assess the precision of the case definition of case for investigation considered in the study according to the presence or the absence of fever at the moment of clinical observation. We reviewed the medical records of all the patients presenting with Influenza like-illness classified as case for investigation and the first cases of patients infected with the new pandemic (H1N1 2009 virus, diagnosed in the central region of Portugal during the pandemic period between June and August, 2009, were analyzed. Real-time reverse-transcriptase polymerase-chain-reaction (RT-PCR testing was used to confirm the pandemic (H1N1 2009 virus infection. Data collection was performed on a standardized paper format in agreement with the General Health

Infecção mista pelo Sugarcane mosaic virus e Maize rayado fino virus provoca danos na cultura do milho no estado de São Paulo

OpenAIRE

Gonçalves,Marcos César; Maia,Ivan de Godoy; Galleti,Sílvia Regina; Fantin,Gisèle Maria

2007-01-01

Os dois principais vírus que infectam o milho no Brasil são o Sugarcane mosaic virus (SCMV) e o Maize rayado fino virus (MRFV), cujos principais vetores são o afídeo Rhopalosiphum maidis e a cigarrinha Dalbulus maidis, respectivamente. O MRFV é freqüentemente encontrado em infecções mistas com fitoplasmas e espiroplasmas, causando as doenças denominadas enfezamentos do milho. Em uma lavoura de milho próxima a Santo Antonio da Posse, SP, cercada por campos de cana-de-açúcar, foi encontrada alt...

Nonclinical safety of mavrilimumab, an anti-GMCSF receptor alpha monoclonal antibody, in cynomolgus monkeys: Relevance for human safety

Energy Technology Data Exchange (ETDEWEB)

Ryan, Patricia C., E-mail: ryanp@medimmune.com [MedImmune, LLC, Gaithersburg, MD (United States); Sleeman, Matthew A. [MedImmune, LLC, Cambridge (United Kingdom); Rebelatto, Marlon [MedImmune, LLC, Gaithersburg, MD (United States); Wang, Bing; Lu, Hong [MedImmune, LLC, Moutain View, CA (United States); Chen, Xiaomin [Novartis, East Hanover, NJ (United States); Wu, Chi-Yuan [MedImmune, LLC, Moutain View, CA (United States); Hinrichs, Mary Jane; Roskos, Lorin [MedImmune, LLC, Gaithersburg, MD (United States); Towers, Heidi [MedImmune, LLC, Cambridge (United Kingdom); McKeever, Kathleen; Dixit, Rakesh [MedImmune, LLC, Gaithersburg, MD (United States)

2014-09-01

Mavrilimumab (CAM-3001) is an investigational human IgG4 monoclonal antibody (MAb) targeting GM-CSF receptor alpha which is currently being developed for the treatment of RA. GM-CSF plays a central role in the pathogenesis of rheumatoid arthritis (RA) through the activation, differentiation, and survival of macrophages and neutrophils. To support clinical development, the nonclinical safety of mavrilimumab was evaluated in several studies with cynomolgus monkeys as the pharmacologically relevant species. Comprehensive toxicity parameters were assessed in each study, and treatment duration ranged from 4 to 26 weeks. Mavrilimumab has an acceptable safety profile in monkeys with no changes in any parameters other than microscopic findings in lung. In several studies, minimal accumulation of foamy alveolar macrophages was observed. This finding was only seen in studies of at least 11 weeks duration, was reversible following a dose-free recovery period and was considered non-adverse. At higher dose levels (≥ 30 mg/kg/week), in a 26-week repeat-IV dose study, the presence of lung foreign material, cholesterol clefts, and granulomatous inflammation was also observed in a few animals and was considered adverse. The dose- and time-related accumulation of foamy macrophages in lung following exposure to mavrilimumab observed in several NHP studies was expected based upon the known role of GM-CSFRα signaling in the function of alveolar macrophages. Overall, a clean no-observed-adverse-effect-level (NOAEL) without any effects in lung was established and provided adequate clinical safety margins. In clinical studies in RA patients, mavrilimumab has demonstrated good clinical activity with adequate safety to support further clinical development. A Phase 2b study of mavrilimumab in subjects with RA is in progress. - Highlights: • Mavrilimumab is a MAB targeting GM-CSFRα being developed for RA therapy. • Mavrilimumab has an acceptable safety profile in cynomolgus monkeys. �

Nonclinical safety of mavrilimumab, an anti-GMCSF receptor alpha monoclonal antibody, in cynomolgus monkeys: Relevance for human safety

International Nuclear Information System (INIS)

Ryan, Patricia C.; Sleeman, Matthew A.; Rebelatto, Marlon; Wang, Bing; Lu, Hong; Chen, Xiaomin; Wu, Chi-Yuan; Hinrichs, Mary Jane; Roskos, Lorin; Towers, Heidi; McKeever, Kathleen; Dixit, Rakesh

2014-01-01

Mavrilimumab (CAM-3001) is an investigational human IgG4 monoclonal antibody (MAb) targeting GM-CSF receptor alpha which is currently being developed for the treatment of RA. GM-CSF plays a central role in the pathogenesis of rheumatoid arthritis (RA) through the activation, differentiation, and survival of macrophages and neutrophils. To support clinical development, the nonclinical safety of mavrilimumab was evaluated in several studies with cynomolgus monkeys as the pharmacologically relevant species. Comprehensive toxicity parameters were assessed in each study, and treatment duration ranged from 4 to 26 weeks. Mavrilimumab has an acceptable safety profile in monkeys with no changes in any parameters other than microscopic findings in lung. In several studies, minimal accumulation of foamy alveolar macrophages was observed. This finding was only seen in studies of at least 11 weeks duration, was reversible following a dose-free recovery period and was considered non-adverse. At higher dose levels (≥ 30 mg/kg/week), in a 26-week repeat-IV dose study, the presence of lung foreign material, cholesterol clefts, and granulomatous inflammation was also observed in a few animals and was considered adverse. The dose- and time-related accumulation of foamy macrophages in lung following exposure to mavrilimumab observed in several NHP studies was expected based upon the known role of GM-CSFRα signaling in the function of alveolar macrophages. Overall, a clean no-observed-adverse-effect-level (NOAEL) without any effects in lung was established and provided adequate clinical safety margins. In clinical studies in RA patients, mavrilimumab has demonstrated good clinical activity with adequate safety to support further clinical development. A Phase 2b study of mavrilimumab in subjects with RA is in progress. - Highlights: • Mavrilimumab is a MAB targeting GM-CSFRα being developed for RA therapy. • Mavrilimumab has an acceptable safety profile in cynomolgus monkeys. �

Immunotoxicological Evaluation of Genetically Modified Rice Expressing Cry1Ab/Ac Protein (TT51-1) by a 6-Month Feeding Study on Cynomolgus Monkeys

Science.gov (United States)

Tan, Xiaoyan; Zhou, Xiaobing; Tang, Yao; Lv, Jianjun; Zhang, Lin; Sun, Li; Yang, Yanwei; Miao, Yufa; Jiang, Hua; Chen, Gaofeng; Huang, Zhiying; Wang, Xue

2016-01-01

The present study was performed to evaluate the food safety of TT51-1, a new type of genetically modified rice that expresses the Cry1Ab/Ac protein (Bt toxin) and is highly resistant to most lepidopteran pests. Sixteen male and 16 female cynomolgus monkeys were randomly divided into four groups: conventional rice (non-genetically modified rice, non-GM rice), positive control, 17.5% genetically modified rice (GM rice) and 70% GM rice. Monkeys in the non-GM rice, positive control, and GM rice groups were fed on diets containing 70% non-GM rice, 17.5% GM rice or 70% GM rice, respectively, for 182 days, whereas animals in the positive group were intravenously injected with cyclophosphamide every other day for a total of four injections before the last treatment. Six months of treatment did not yield abnormal observations. Specifically, the following parameters did not significantly differ between the non-GM rice group and GM rice groups: body weight, food consumption, electrocardiogram, hematology, immuno-phenotyping of lymphocytes in the peripheral blood, mitogen-induced peripheral blood lymphocyte proliferation, splenocyte proliferation, KLH-T cell-dependent antibody response, organ weights and ratios, and histological appearance (p>0.05). Animals from the GM rice group differed from animals in the non-GM rice group (pGM rice. In conclusion, a 6-month feeding study of TT51-1 did not show adverse immunotoxicological effects on cynomolgus monkeys. PMID:27684490

Caracterização de um vírus baciliforme isolado de Solanum violaefolium transmitido pelos ácaros Brevipalpus phoenicis e Brevipalpus obovatus (Acari: Tenuipalpidae Characterization of a bacilliform virus isolated from Solanum violaefolium transmitted by the tenuipalpid mites Brevipalpus phoenicis and Brevipalpus obovatus

Directory of Open Access Journals (Sweden)

Paulo de Tarso Oliveira Ferreira

2007-09-01

Full Text Available Solano-violeta (Solanum violaefolium é uma planta ornamental rasteira usada para cobrir solos de áreas sombreadas. Um vírus que induz manchas anelares nas folhas desta planta, tentativamente designado Solanum violaefolium ringspot virus - SvRSV, transmitido pelo ácaro Brevipalpus phoenicis (Acari: Tenuipalpidae foi encontrado em Piracicaba, SP. Trata-se de um vírus baciliforme que se assemelha a outros vírus do tipo citoplasmático transmitidos por Brevipalpus sp. Este trabalho teve como objetivo relatar propriedades biológicas e estabelecer uma caracterização molecular parcial do SvRSV. O vírus pode ser transmitido mecanicamente a várias outras espécies botânicas, causando lesões localizadas. Entre as espécies avaliadas, Datura stramonium mostrou-se a melhor hospedeira experimental. Observou-se também a manifestação de sintomas nestas plantas após infestação das mesmas por B. obovatus previamente alimentado em lesões de SvRSV, confirmando esta outra espécie de ácaro como vetor do vírus. Suas propriedades físicas in vitro foram: temperatura de inativação 40-45 ºC; ponto final de diluição 10-3-10-4; longevidade in vitro 12 dias. Em secções ultrafinas, as partículas do SvRSV mostraram-se levemente mais delgadas e mais longas que as de outros vírus do mesmo grupo. A partir do dsRNA do SvRSV foi construída uma biblioteca de cDNA e foram identificadas duas possíveis regiões codificadoras das proteínas de movimento e replicase viral. Baseado nestas regiões foram desenhados "primers" para amplificação do RNA do SvRSV por RT-PCR. Sondas baseadas nas seqüências obtidas hibridizaram com ss- e dsRNA de D. stramonium infectadas pelo vírus. Ensaios preliminares de RT-PCR e hibridização não resultaram em reação com o vírus da leprose dos citros, tipo citoplasmático (CiLV-C.Solanum violaefolium is an ornamental plant, with prostrate, trailing growth habit and is cultivated in shaded areas. A virus that causes

Utility of finger maze test for learning and memory abilities in infants of cynomolgus monkeys exposed to thiamazole.

Science.gov (United States)

Inoue, Ayumi; Arima, Akihiro; Kato, Hirohito; Ebihara, Shizufumi

2014-11-01

A new type of learning and memory test using a finger maze was conducted in infant cynomolgus monkeys that were exposed to thiamazole (2 and 3.5 mg/kg per day to pregnant animals orally) during the fetal period (gestational days 120 to 150). We modified Tsuchida's original finger maze test method by reducing the number of trials per day and simplifying the criteria for achievement of training, and we added a long-term memory test. In the memory test, thiamazole-exposed infants required greater time to complete the finger maze test than the control infants although no effect was noted in the training or learning test. The results suggest that an impaired long-term memory could be detected by our modified finger maze test. © 2014 Japanese Teratology Society.

Simultaneous Assessment of Transporter-Mediated Drug-Drug Interactions Using a Probe Drug Cocktail in Cynomolgus Monkey.

Science.gov (United States)

Kosa, Rachel E; Lazzaro, Sarah; Bi, Yi-An; Tierney, Brendan; Gates, Dana; Modi, Sweta; Costales, Chester; Rodrigues, A David; Tremaine, Larry M; Varma, Manthena V

2018-06-07

We aim to establish an in vivo preclinical model to enable simultaneous assessment of inhibition potential of an investigational drug on clinically relevant drug transporters, organic anion transporting polypeptide (OATP)1B, breast cancer resistance protein (BCRP), P-glycoprotein (P-gp) and organic anion transporter (OAT)3. Pharmacokinetics of substrate cocktail consisting of pitavastatin (OATP1B substrate), rosuvastatin (OATP1B/BCRP/OAT3), sulfasalazine (BCRP) and talinolol (P-gp) were obtained in cynomolgus monkey - alone or in combination with transporter inhibitors. Single dose rifampicin (30 mg/kg) significantly (pdrugs, with a marked effect on pitavastatin and rosuvastatin (AUC ratio ~21-39). Elacridar, BCRP/P-gp inhibitor, increased the AUC of sulfasalazine, talinolol, as well as rosuvastatin and pitavastatin. An OAT1/3 inhibitor (probenecid) significantly (pdrug-drug interaction risk assessment, before advancing a new molecular entity into clinical development, as well as providing mechanistic insights on transporter-mediated interactions. The American Society for Pharmacology and Experimental Therapeutics.

Hepatite crônica por vírus C: Parte 1. Considerações gerais Hepatitis C virus: Part 1. General considerations

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Vinício Paride CONTE

2000-07-01

Full Text Available O vírus da hepatite C foi identificado em 1989 como sendo o principal agente causador das hepatites não-A não-B e o seu reconhecimento como agente de alta prevalência nas infecções pós-tranfusionais e/ou uso de derivados do sangue ou em associação com o abuso de drogas endovenosas. A descoberta e a maior disponibilidade de novas técnicas para a seleção adequada de doadores de sangue, reduziu sensivelmente a incidência das hepatites pós-transfusionais. Cerca de 95% dos indivíduos infectados pelo vírus da hepatite C podem ser identificados pelos testes anti-vírus da hepatite C de terceira geração. Os estudos retrospectivos de infecções pelo vírus da hepatite C iatrogênicas, são as principais fontes de reconhecimento da história natural da doença. A distribuição dos diferentes genótipos do vírus da hepatite C varia de acordo com as regiões geográficas. Na América do Sul, Europa, Estados Unidos e Japão 1, 2, e 3 representam a maioria das infecções, sendo o subtipo 1-b o mais prevalente. Os parâmetros epidemiológicos (idade, fatores de risco e duração da infecção podem estar associados com os genótipos do vírus da hepatite C, sendo os tipos 1-a e 3-a mais freqüentes nos drogaditos endovenosos e o 1-b nas hepatites pós-transfusionais. O subtipo 1-b ocasiona lesões hepáticas mais graves e prolongadas, com alterações ultraestruturais mitocondriais freqüentes e grande comprometimento dos processos de fosforilização oxidativa. A produção aumentada de radicais livres pode influenciar negativamente a evolução da doença hepática pelo reforço da ação citopática do vírus da hepatite C que provoca. O significado clínico dos níveis de vírus C no interior do fígado, nesses pacientes, não é determinado pelos fatores hospedeiro (idade, tipo e duração da infecção ou pelos fatores virais (genótipos e os repetidamente vírus da hepatite C RNA RT-PCR negativos no soro, não indicam

Collagen-induced arthritis in nonhuman primates: multiple epitopes of type II collagen can induce autoimmune-mediated arthritis in outbred cynomolgus monkeys.

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Shimozuru, Y; Yamane, S; Fujimoto, K; Terao, K; Honjo, S; Nagai, Y; Sawitzke, A D; Terato, K

1998-03-01

To define which regions of the type II collagen (CII) molecule result in anticollagen antibody production and the subsequent development of autoantibodies in a collagen-induced arthritis (CIA) nonhuman primate model. Male and female cynomolgus monkeys (2-6 of each sex per group) were immunized with either chicken (Ch), human, or monkey (Mk) CII, or with cyanogen bromide (CB)-generated peptide fragments of ChCII emulsified in Freund's complete adjuvant. Monkeys were observed for the development of arthritis, and sera were collected and analyzed for anticollagen antibody specificity by enzyme-linked immunosorbent assay. Overt arthritis developed in all groups of monkeys immunized with intact CII and with all major CB peptide fragments of ChCII except CB8. Onset and severity of arthritis correlated best with serum anti-MkCII antibody levels. The levels of IgG autoantibody to MkCII were a result of the cross-reactivity rate of anti-heterologous CII antibodies with MkCII, which was based on the genetic background of individual monkeys rather than on sex differences. CII from several species and disparate regions of the CII molecule were able to induce autoantibody-mediated arthritis in outbred cynomolgus monkeys. The strong anti-MkCII response suggests that epitope spreading or induction of broad-based CII cross-reactivity occurred in these animals. Autoantibody levels to MkCII were higher in CIA-susceptible monkeys than in resistant monkeys, despite comparable antibody levels in response to the various immunizations of CII. These results closely parallel the type of anticollagen responses found in sera from rheumatoid arthritis patients. Perhaps this can be accounted for by similar major histocompatibility complex heterogenicity associated with an outbred population, or maybe this is a primate-specific pattern of reactivity to CII.

Características epidemiológicas e genéticas associadas à gravidade da bronquiolite viral aguda pelo vírus sincicial respiratório

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Alfonso E. Alvarez

2013-12-01

Full Text Available OBJETIVO: avaliar os fatores epidemiológicos e genéticos associados à gravidade da Bronquiolite Viral Aguda (BVA pelo Vírus Sincicial Respiratório (VSR. FONTE DOS DADOS: foram utilizados descritores "bronchiolitis", "risk factor", "genetics" e "respiratory syncytial virus" e todas as combinações entre eles, nas bases de dados PubMed, SciELO e Lilacs publicados após o ano de 2000 e que incluíram indivíduos menores de dois anos de idade. SÍNTESE DOS DADOS: foram encontrados 1.259 artigos e lidos seus respectivos resumos. Destes foram selecionados 81 que avaliaram fatores de risco para a gravidade da BVA para leitura na íntegra, e foram incluídos os 60 estudos mais relevantes. Os fatores epidemiológicos associados com a gravidade da BVA pelo VSR foram: prematuridade, tabagismo passivo, baixa idade, ausência de aleitamento materno, doença pulmonar crônica, cardiopatia congênita, sexo masculino, etnia, coinfecção viral, baixo peso na admissão hospitalar, tabagismo materno na gestação, dermatite atópica, ventilação mecânica no período neonatal, antecedente materno de atopia e/ou asma na gestação, estação do nascimento, baixo nível socioeconômico, síndrome de Down, poluição ambiental, morar em altitude acima de 2.500 metros do nível do mar e parto cesariana. Em contrapartida, algumas crianças com BVA grave não apresentam nenhum desses fatores de risco. Neste sentido, estudos recentes têm verificado a influência de fatores genéticos relacionados à gravidade da BVA pelo VSR. Polimorfismos dos genes TLRs, RANTES, JUN, IFNA5, NOS2, CX3CR1, ILs e VDR têm-se mostrado associados com a evolução mais grave da BVA pelo VSR. CONCLUSÃO: a gravidade da BVA pelo VSR é um fenômeno dependente da interação entre variáveis epidemiológicas, ambientais e genéticas em seus diferentes graus de interação.

Infecção pelo vírus Influenza A (H1N1 de origem suína: como reconhecer, diagnosticar e prevenir How to prevent, recognize and diagnose infection with the swine-origin Influenza A (H1N1 virus in humans

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Alcyone Artioli Machado

2009-05-01

Full Text Available Em março de 2009, houve o início de uma epidemia de gripe no México que, em pouco tempo, levou ao surgimento de casos semelhantes em outros países, alertando as autoridades sanitárias para o risco de uma pandemia. Neste artigo, descrevemos os principais sinais e sintomas da infecção pelo vírus Influenza A (H1N1 de origem suína, as medidas a serem tomadas para os casos suspeitos ou confirmados e como proceder em relação aos contactantes. Comentamos também quais drogas são utilizadas para o tratamento e profilaxia.In March of 2009, a flu epidemic began in Mexico. Shortly thereafter, similar cases appeared in other countries, alerting authorities to the risk of a pandemic. This article details the principal signs and symptoms of infection with the swine-origin Influenza A (H1N1 virus. In addition, the measures to be taken in suspected or confirmed cases are addressed, as are the procedures to follow in relation to contacts. Furthermore, the drugs used in the prophylaxis against and the treatment of infection with the H1N1 virus are described.

Influência da infecção pregressa pelo vírus da hepatite B na fibrose hepática em portadores de hepatite C crônica: avaliação retrospectiva de uma série de casos Influence of previous hepatitis B virus infection on liver fibrosis in patients with chronic hepatitis C: a retrospective case series evaluation

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Gaspar Lisboa Neto

2010-08-01

Full Text Available INTRODUCÃO: A hepatite C é uma das principais causas de doença hepática em todo mundo. Apresenta um curso evolutivo dinâmico e influenciável por diversos co-fatores. Dentre eles, a infecção pregressa pelo vírus B (anti-HBcAg [+] e HBsAg [-] tem se associado a pior prognóstico histológico e terapêutico. Este trabalho teve como objetivo analisar a associação entre a infecção pregressa pelo vírus B e fibrose hepática em portadores de hepatite C crônica, de maneira independente. MÉTODOS: Foram revistos retrospectivamente prontuários médicos de pacientes infectados cronicamente pelo vírus C, atendidos consecutivamente durante um ano no ambulatório de Doenças Infecciosas e Parasitárias - HC FMUSP, quanto aos dados epidemiológicos, clínicos, laboratoriais e histológicos. A análise de independência do impacto da infecção pregressa pelo vírus B foi realizada através de modelo estatístico de regressão logística multivariado, considerando a detecção do anti-HBcAg como variável de exposição, sendo o desfecho a alteração estrutural histopatológica graus 3 e 4 (septos com formação de nódulos e cirrose.0 RESULTADOS: 145 indivíduos foram avaliados pelo estudo, 47.2% com anti-HBcAg (+. O fator de risco mais comumente relatado foi transfusão de sangue e hemoderivados (35,9%. Embora necrose em saca-bocado tenha sido encontrada com maior frequência no grupo de infecção pregressa, a sorologia anti-HBcAg (+ não se associou à fibrose hepática avançada. CONCLUSÕES: A infecção pregressa pelo vírus B não parece acentuar a lesão estrutural desencadeada pela hepatite C crônica, após controle estatístico para outros co-fatores sabidamente capazes de influenciar a história natural desta infecção.INTRODUCTION: Hepatitis C is a major cause of liver disease worldwide. Its evolutionary course is dynamics and may be influenced by several cofactors. Among them, previous hepatitis B virus infection (anti

Pharmacokinetics of 2 Formulations of Transdermal Fentanyl in Cynomolgus Macaques (Macaca fascicularis)

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Carlson, Amy M; Kelly, Richard; Fetterer, David P; Rico, Pedro J; Bailey, Emily J

2016-01-01

Fentanyl is a μ-opioid agonist that often is used as the analgesic component for balanced anesthesia in both human and veterinary patients. Minimal information has been published regarding appropriate dosing, and the pharmacokinetics of fentanyl are unknown in NHP. The pharmacokinetic properties of 2 transdermal fentanyl delivery methods, a solution (2.6 and 1.95 mg/kg) and a patch (25 µg/h), were determined when applied topically to the dorsal scapular area of cynomolgus macaques (Macaca fascicularis). Serum fentanyl concentrations were analyzed by using liquid chromatography–mass spectrometry. Compared with the patch, the transdermal fentanyl solution generated higher drug concentrations over longer time. Adverse reactions occurred in the macaques that received the transdermal fentanyl solution at 2.6 mg/kg. Both preparations showed significant interanimal variability in the maximal serum drug levels, time to achieve maximal fentanyl levels, elimination half-life, and AUC values. Both the maximal concentration and the time at which this concentration occurred were increased in macaques compared with most other species after application of the transdermal fentanyl patch and compared with dogs after application of the transdermal fentanyl solution. The pharmacokinetic properties of transdermal fentanyl in macaques are markedly different from those in other veterinary species and preclude its use as a long-acting analgesic drug in NHP. PMID:27423151

Experimental infection of macaques with a wild water bird-derived highly pathogenic avian influenza virus (H5N1.

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Tomoko Fujiyuki

Full Text Available Highly pathogenic avian influenza virus (HPAIV continues to threaten human health. Non-human primate infection models of human influenza are desired. To establish an animal infection model with more natural transmission and to determine the pathogenicity of HPAIV isolated from a wild water bird in primates, we administered a Japanese isolate of HPAIV (A/whooper swan/Hokkaido/1/2008, H5N1 clade 2.3.2.1 to rhesus and cynomolgus monkeys, in droplet form, via the intratracheal route. Infection of the lower and upper respiratory tracts and viral shedding were observed in both macaques. Inoculation of rhesus monkeys with higher doses of the isolate resulted in stronger clinical symptoms of influenza. Our results demonstrate that HPAIV isolated from a water bird in Japan is pathogenic in monkeys by experimental inoculation, and provide a new method for HPAIV infection of non-human primate hosts, a good animal model for investigation of HPAIV pathogenicity.

Linear pharmacokinetic parameters for monoclonal antibodies are similar within a species and across different pharmacological targets: A comparison between human, cynomolgus monkey and hFcRn Tg32 transgenic mouse using a population-modeling approach.

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Betts, Alison; Keunecke, Anne; van Steeg, Tamara J; van der Graaf, Piet H; Avery, Lindsay B; Jones, Hannah; Berkhout, Jan

2018-04-10

The linear pharmacokinetics (PK) of therapeutic monoclonal antibodies (mAbs) can be considered a class property with values that are similar to endogenous IgG. Knowledge of these parameters across species could be used to avoid unnecessary in vivo PK studies and to enable early PK predictions and pharmacokinetic/pharmacodynamic (PK/PD) simulations. In this work, population-pharmacokinetic (popPK) modeling was used to determine a single set of 'typical' popPK parameters describing the linear PK of mAbs in human, cynomolgus monkey and transgenic mice expressing the human neonatal Fc receptor (hFcRn Tg32), using a rich dataset of 27 mAbs. Non-linear PK was excluded from the datasets and a 2-compartment model was applied to describe mAb disposition. Typical human popPK estimates compared well with data from comparator mAbs with linear PK in the clinic. Outliers with higher than typical clearance were found to have non-specific interactions in an affinity-capture self-interaction nanoparticle spectroscopy assay, offering a potential tool to screen out these mAbs at an early stage. Translational strategies were investigated for prediction of human linear PK of mAbs, including use of typical human popPK parameters and allometric exponents from cynomolgus monkey and Tg32 mouse. Each method gave good prediction of human PK with parameters predicted within 2-fold. These strategies offer alternative options to the use of cynomolgus monkeys for human PK predictions of linear mAbs, based on in silico methods (typical human popPK parameters) or using a rodent species (Tg32 mouse), and call into question the value of completing extensive in vivo preclinical PK to inform linear mAb PK.

Measles vaccination of nonhuman primates provides partial protection against infection with canine distemper virus.

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de Vries, Rory D; Ludlow, Martin; Verburgh, R Joyce; van Amerongen, Geert; Yüksel, Selma; Nguyen, D Tien; McQuaid, Stephen; Osterhaus, Albert D M E; Duprex, W Paul; de Swart, Rik L

2014-04-01

Measles virus (MV) is being considered for global eradication, which would likely reduce compliance with MV vaccination. As a result, children will grow up without MV-specific immunity, creating a potential niche for closely related animal morbilliviruses such as canine distemper virus (CDV). Natural CDV infection causing clinical signs has never been reported in humans, but recent outbreaks in captive macaques have shown that CDV can cause disease in primates. We studied the virulence and tropism of recombinant CDV expressing enhanced green fluorescent protein in naive and measles-vaccinated cynomolgus macaques. In naive animals CDV caused viremia and fever and predominantly infected CD150(+) lymphocytes and dendritic cells. Virus was reisolated from the upper and lower respiratory tracts, but infection of epithelial or neuronal cells was not detectable at the time points examined, and the infections were self-limiting. This demonstrates that CDV readily infects nonhuman primates but suggests that additional mutations are necessary to achieve full virulence in nonnatural hosts. Partial protection against CDV was observed in measles-vaccinated macaques, as demonstrated by accelerated control of virus replication and limited shedding from the upper respiratory tract. While neither CDV infection nor MV vaccination induced detectable cross-reactive neutralizing antibodies, MV-specific neutralizing antibody levels of MV-vaccinated macaques were boosted by CDV challenge infection, suggesting that cross-reactive VN epitopes exist. Rapid increases in white blood cell counts in MV-vaccinated macaques following CDV challenge suggested that cross-reactive cellular immune responses were also present. This study demonstrates that zoonotic morbillivirus infections can be controlled by measles vaccination. Throughout history viral zoonoses have had a substantial impact on human health. Given the drive toward global eradication of measles, it is essential to understand the

EXPRESSÕES ORAIS POPULARES UTILIZADAS PELO POVO DO LAVRADO EM RORAIMA

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Sebastião Pereira Nascimento

2016-08-01

Full Text Available São apresentadas 564 expressões orais populares utilizadas pelos habitantes do lavrado em Roraima. A maioria dos significados dos termos é originária da herança cultural trazida pelo povo nordestino radicado nos Campos do Rio Branco desde o século XIX. As línguas indígenas também têm influência nestas expressões orais locais, com destaque para as famílias linguísticas Karib e Aruak. Alguns termos têm influências culturais de outras regiões brasileiras e fragmentos de línguas estrangeiras.

Immune response to the West Nile virus in aged non-human primates.

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Anne M Wertheimer

2010-12-01

Full Text Available Risk of encephalitis from West Nile virus (WNV infection increases dramatically with age. Understanding the basis of this susceptibility requires development of suitable animal models. Here, we investigated the immune response to WNV in old non-human primates.We investigated clinical, immunological and virological correlates of WNV infection in aging non-human primates. Aged (17-30 yrs and adult (6-9 yrs Rhesus macaques (RM were challenged with WNV in the presence or the absence of the mosquito salivary gland extract (SGE to approximate natural infection. None of the 26 animals exhibited clinical signs of the disease. Quantitative PCR suggested discrete and short-lived viremia, but infectious virus was never isolated. There was markedly increased, age-independent, proliferation of CD3(- non-B cells, followed by B-cell proliferation, which correlated to the loss of detectable WNV genomes. Moreover, animals primed with mosquito salivary gland extract exhibited reduced circulating WNV RNA. While we found the expected age-associated reduction in T cell proliferation, adaptive immunity did not correlate with infection outcome. That was further confirmed in a cohort of thymectomized and/or CD8 T-cell depleted Cynomolgus macaques (CM; N = 15, who also failed to develop WNV disease.Results are consistent with strong and age-independent innate resistance of macaques against WNV challenge. This animal model is therefore not suitable for vaccine and therapeutic testing against WNV. However, understanding the basis of their innate resistance against WNV in macaques could provide helpful clues to improve anti-WNV protection of older adults.

The concept of ’Musa-pelo and the medicinal use of shrubby legumes (Fabaceae in Lesotho

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A. Moteetee

2007-08-01

Full Text Available In the Kingdom of Lesotho, 20 plant species are commonly known as  'Musa-pelo. The term literally means ‘the one who brings back or tums around the heart’.  'Musa-pelo is traditionally used as a sedative and is given as a first aid treatment to bereaved people who are under severe psychological duress or stress. Of the 20 species known as  'Musa-pelo, 17 belong to nine genera of the Fabaceae  (Argyrolobium, Crotalaria, Indigofera, Lessertia, Lotononis, Melolobium, Sutherlandia, Tephrosia and  Trifolium. The three remaining species namely Cleome monophylla, Heliophila carnosa and  Cysticapnos pruinosa, belong to the families Capparaceae, Brassicaceae and Fumariaceae, respectively. In this paper, the concept of 'Musa-pelo in traditional medicine is explored.

Transcriptome Analysis of Circulating Immune Cell Subsets Highlight the Role of Monocytes in Zaire Ebola Virus Makona Pathogenesis

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Andrea R. Menicucci

2017-10-01

Full Text Available Existing models of Ebola virus disease (EVD suggest antigen-presenting cells are initial targets of Zaire ebolavirus (ZEBOV. In vitro studies have shown that ZEBOV infection of monocytes and macrophages results in the production of inflammatory mediators, which may cause lymphocyte apoptosis. However, these findings have not been corroborated by in vivo studies. In this study, we report the first longitudinal analysis of transcriptional changes in purified monocytes, T-cells, and B-cells isolated from cynomolgus macaques following infection with ZEBOV-Makona. Our data reveal monocytes as one of the major immune cell subsets that supports ZEBOV replication in vivo. In addition, we report a marked increase in the transcription of genes involved in inflammation, coagulation, and vascular disease within monocytes, suggesting that monocytes contribute to EVD manifestations. Further, genes important for antigen presentation and regulation of immunity were downregulated, potentially subverting development of adaptive immunity. In contrast, lymphocytes, which do not support ZEBOV replication, showed transcriptional changes limited to a small number of interferon-stimulated genes (ISGs and a failure to upregulate genes associated with an antiviral effector immune response. Collectively, these data suggest that ZEBOV-infected monocytes play a significant role in ZEBOV-Makona pathogenesis and strategies to suppress virus replication or modify innate responses to infection in these cells should be a priority for therapeutic intervention.

Immune Response to Marburg Virus Angola Infection in Nonhuman Primates.

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Fernando, Lisa; Qiu, Xiangguo; Melito, P Leno; Williams, Kinola J N; Feldmann, Friederike; Feldmann, Heinz; Jones, Steven M; Alimonti, Judie B

2015-10-01

The 2005 outbreak of Marburg virus (MARV) infection in Angola was the most lethal MARV infection outbreak in history, with a case-fatality rate (90%) similar to that for Zaire ebolavirus (EBOV) infection. However, very little is known about the pathogenicity of MARV Angola, as few studies have been conducted to date. Therefore, the immune response was examined in MARV Angola-infected nonhuman primates. Cynomolgus macaques were infected with MARV Angola and monitored for survival. The effect of MARV Angola on the immune system was examined by immunophenotyping whole-blood and by analyzing cytokine and chemokine levels in plasma and spleen specimens, using flow cytometry. The prominent clinical findings were rapid onset of disease and death (mean time after infection, 6.7 days), fever, depression, anorexia, petechial rash, and lymphopenia. Specifically, T, B, and natural killer cells were severely depleted in the blood by day 6. The typical cytokine storm was present, with levels of interferon γ, tumor necrosis factor, interleukin 6, and CCL2 rising in the blood early during infection. MARV Angola displayed the same virulence and disease pathology as EBOV. MARV Angola appears to cause a more rapid onset and severe outcome of infection than other MARV strains. © Crown copyright 2015.

Influence of human t-cell lymphotropic virus type 1 (HTLV-1 Infection on laboratory parameters of patients with chronic hepatitis C virus Influência da infecção pelo vírus linfotrópico humano tipo 1 (HTLV-1 em parâmetros laboratoriais de pacientes com hepatite C crônica

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Daniela Fernandes Cardoso

2009-12-01

Full Text Available Hepatitis C virus (HCV and human T-cell lymphotropic virus type 1 (HTLV-1 share routes of transmission and some individuals have dual infection. Although some studies point to a worse prognosis of hepatitis C virus in patients co-infected with HTLV-1, the interaction between these two infections is poorly understood. This study evaluated the influence of HTLV-1 infection on laboratory parameters in chronic HCV patients. Twelve HTLV-1/HCV-coinfected patients were compared to 23 patients infected only with HCV, in regard to demographic data, risk factors for viral acquisition, HCV genotype, presence of cirrhosis, T CD4+ and CD8+ cell counts and liver function tests. There was no difference in regard to age, gender, alcohol consumption, smoking habits, HCV genotype or presence of cirrhosis between the groups. Intravenous drug use was the most common risk factor among individuals co-infected with HTLV-1. These patients showed higher TCD8+ counts (p = 0.0159 and significantly lower median values of AST and ALT (p = 0.0437 and 0.0159, respectively. In conclusion, we have shown that HCV/HTLV-1 co-infected patients differs in laboratorial parameters involving both liver and immunological patterns. The meaning of these interactions in the natural history of these infections is a matter that deserves further studies.O vírus da hepatite C (VHC e vírus linfotrópico humano tipo 1 (HTLV-1 compartilham formas de transmissão e algumas pessoas apresentam coinfecção. Embora alguns estudos apontem para um pior prognóstico da infecção pelo VHC em pacientes coinfectados com HTLV-1, a interação entre estas infecções é mal compreendida. Este estudo avaliou a influência da infecção pelo HTLV-1 em parâmetros laboratoriais de pacientes com VHC. 12 coinfectados VHC/HTLV-1 foram comparados com 23 pacientes monoinfectados com VHC, no que diz respeito aos dados demográficos, fatores de risco para aquisição viral, genótipo do VHC, presença de cirrose

Infecção pelo vírus da hepatite B em hemofílicos em Goiás: soroprevalência, fatores de risco associados e resposta vacinal Seroprevalence, vaccination response and risk factors for hepatitis B virus infection in hemophiliacs in Goiás

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Renato S. Tavares

2004-01-01

Full Text Available Objetivando determinar a prevalência da infecção pelo vírus da hepatite B (HBV em hemofílicos em Goiás, analisar os fatores de risco associados e avaliar a resposta vacinal contra hepatite B, 102 pacientes foram entrevistados e amostras sangüíneas coletadas para detecção dos seguintes marcadores sorológicos: HBsAg, anti-HBs e anti-HBc. Uma prevalência global de 43,7% (IC 95%: 33,5-54,2 para infecção pelo HBV foi encontrada. A análise multivariada dos fatores de risco mostrou que o número de episódios transfusionais e sorologia positiva para o vírus da hepatite C estiveram significantemente associados à positividade ao HBV. Foram identificados 49 (48,1% hemofílicos susceptíveis a esta infecção, sendo imunizados 30 pacientes com a vacina recombinante Euvax-B. Destes, 28 (93,3% indivíduos apresentaram títulos de anti-HBs maiores que 10 UI/L, o que mostra uma boa resposta à vacina. Os achados deste estudo ressaltam a importância das medidas de controle e prevenção da hepatite B nesta população.In order to study the prevalence and risk factors for hepatitis B in hemophiliacs in Goiás, 102 patients were interviewed and blood samples collected and screened for the following serological markers: HBsAg, anti-HBs and anti-HBc. An overall prevalence of 43.7% (95% IC: 33.5-54.2 was found to hepatitis B virus (HBV infection. Multivariate analysis of risk factors showed that the number of transfusions and positive serology for hepatitis C virus were significantly associated with HBV positivity. There were 48 (48.1% susceptible patients for this infection, of whom 30 were immunized with the Euvax-B vaccine. Among them, 28 (93.3% individuals developed anti-HBs titers higher than 10 IU/L. Thus, a good response was observed in the studied population. The findings of this study emphasize the importance of strategies of control and prevention of hepatitis B in this population.

Respuesta reproductiva de ovejas de pelo sincronizadas con progesterona o prostaglandinas

OpenAIRE

Arroyo-Ledezma, Jaime; De La Torre-Barrera, Jannette; Ávila-Serrano, N. Ysac

2013-01-01

La sincronización ajusta los estros a tiempos específicos y permite usar tecnologías reproductivas. El objetivo de este estudio fue evaluar la respuesta reproductiva de 30 ovejas de pelo sincronizadas con progesterona (P4) o prostaglandinas. Las ovejas de pelo eran 5/8 Pelibuey x 2/8 Black Belly x 1/8 Dorper, de 3.5 a 4.0 años de edad, con peso promedio de 37.8 ±3.0 kg; el último parto fue 8 meses previos al experimento. Los tratamientos fueron; 1) aplicación por 11 d de 300 mg de P4 impregna...

Vesicular stomatitis virus-based vaccines protect nonhuman primates against Bundibugyo ebolavirus.

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Chad E Mire

Full Text Available Ebola virus (EBOV causes severe and often fatal hemorrhagic fever in humans and nonhuman primates (NHPs. Currently, there are no licensed vaccines or therapeutics for human use. Recombinant vesicular stomatitis virus (rVSV-based vaccine vectors, which encode an EBOV glycoprotein in place of the VSV glycoprotein, have shown 100% efficacy against homologous Sudan ebolavirus (SEBOV or Zaire ebolavirus (ZEBOV challenge in NHPs. In addition, a single injection of a blend of three rVSV vectors completely protected NHPs against challenge with SEBOV, ZEBOV, the former Côte d'Ivoire ebolavirus, and Marburg virus. However, recent studies suggest that complete protection against the newly discovered Bundibugyo ebolavirus (BEBOV using several different heterologous filovirus vaccines is more difficult and presents a new challenge. As BEBOV caused nearly 50% mortality in a recent outbreak any filovirus vaccine advanced for human use must be able to protect against this new species. Here, we evaluated several different strategies against BEBOV using rVSV-based vaccines. Groups of cynomolgus macaques were vaccinated with a single injection of a homologous BEBOV vaccine, a single injection of a blended heterologous vaccine (SEBOV/ZEBOV, or a prime-boost using heterologous SEBOV and ZEBOV vectors. Animals were challenged with BEBOV 29-36 days after initial vaccination. Macaques vaccinated with the homologous BEBOV vaccine or the prime-boost showed no overt signs of illness and survived challenge. In contrast, animals vaccinated with the heterologous blended vaccine and unvaccinated control animals developed severe clinical symptoms consistent with BEBOV infection with 2 of 3 animals in each group succumbing. These data show that complete protection against BEBOV will likely require incorporation of BEBOV glycoprotein into the vaccine or employment of a prime-boost regimen. Fortunately, our results demonstrate that heterologous rVSV-based filovirus vaccine

Systemic gene delivery transduces the enteric nervous system of guinea pigs and cynomolgus macaques.

Science.gov (United States)

Gombash, S E; Cowley, C J; Fitzgerald, J A; Lepak, C A; Neides, M G; Hook, K; Todd, L J; Wang, G-D; Mueller, C; Kaspar, B K; Bielefeld, E C; Fischer, A J; Wood, J D; Foust, K D

2017-10-01

Characterization of adeno-associated viral vector (AAV) mediated gene delivery to the enteric nervous system (ENS) was recently described in mice and rats. In these proof-of-concept experiments, we show that intravenous injections of clinically relevant AAVs can transduce the ENS in guinea pigs and non-human primates. Neonatal guinea pigs were given intravenous injections of either AAV8 or AAV9 vectors that contained a green fluorescent protein (GFP) expression cassette or phosphate-buffered saline. Piglets were euthanized three weeks post injection and tissues were harvested for immunofluorescent analysis. GFP expression was detected in myenteric and submucosal neurons along the length of the gastrointestinal tract in AAV8 injected guinea pigs. GFP-positive neurons were found in dorsal motor nucleus of the vagus and dorsal root ganglia. Less transduction occurred in AAV9-treated tissues. Gastrointestinal tissues were analyzed from young cynomolgus macaques that received systemic injection of AAV9 GFP. GFP expression was detected in myenteric neurons of the stomach, small and large intestine. These data demonstrate that ENS gene delivery translates to larger species. This work develops tools for the field of neurogastroenterology to explore gut physiology and anatomy using emerging technologies such as optogenetics and gene editing. It also provides a basis to develop novel therapies for chronic gut disorders.

Distribution and excretion of arsenic in cynomolgus monkey following repeated administration of diphenylarsinic acid

Energy Technology Data Exchange (ETDEWEB)

Kobayashi, Yayoi [National Institute for Environmental Studies, Environmental Health Sciences Division, Tsukuba, Ibaraki (Japan); Negishi, Takayuki [Aoyama Gakuin University, Department of Chemistry and Biological Science, Tokyo (Japan); Mizumura, Ayano; Watanabe, Takayuki [Chiba University, Graduate School of Pharmaceutical Sciences, Chiba (Japan); Hirano, Seishiro [Chiba University, Graduate School of Pharmaceutical Sciences, Chiba (Japan); National Institute for Environmental Studies, Research Center for Environmental Risk, Tsukuba, Ibaraki (Japan)

2008-08-15

Diphenylarsinic acid (DPAA), a possible product of degradation of arsenic-containing chemical weapons, was detected in well water in Kamisu City, Ibaraki Prefecture, Japan, in 2003. Although some individuals in this area have been affected by drinking DPAA-containing water, toxicological findings on DPAA are limited. To elucidate the mechanism of its toxicity, it is necessary to determine the metabolic behavior of DPAA in the body. In this study, pregnant cynomolgus monkeys at the 50th day of pregnancy were used. The monkeys were treated daily with 1.0 mg DPAA/kg body weight using a nasogastric tube, and the distribution and excretion of arsenic were examined after the repeated administration and 198-237 days after the last administration of DPAA. Fecal excretion was higher than urinary excretion (ca. 3:2 ratio), and arsenic accumulated in the hair and erythrocytes. Distribution of DAPP to plasma and hemolyzed erythrocytes was also examined by high-performance liquid chromatography-inductively coupled argon plasma mass spectrometry (HPLC-ICP MS). Two peaks were found in the elution profile of arsenic, due to free and probably protein-bound DPAA. The protein-bound arsenic compounds were presumably trivalent diphenylarsenic compounds, since free DPAA was recovered after treatment of heat-denatured samples with hydrogen peroxide. (orig.)

A toxicity profile of osteoprotegerin in the cynomolgus monkey.

Science.gov (United States)

Smith, Brenda B; Cosenza, Mary Ellen; Mancini, Audrey; Dunstan, Colin; Gregson, Richard; Martin, Steven W; Smith, Susan Y; Davis, Harold

2003-01-01

Osteoprotegerin (OPG) is a novel secreted glycoprotein of the tumor necrosis factor (TNF) receptor superfamily that acts as an antiresorptive agent inhibiting osteoclast maturation. OPG acts by competitively inhibiting the association of the OPG ligand with the RANK receptor on osteoclasts and osteoclast precursors. This inhibition of osteoclasts can lead to excess accumulation of newly synthesized bone and cartilage in vivo. The purpose of this study was to investigate the potential toxicity of a human recombinant form of OPG in the young cynomolgus monkey. OPG was administered by intravenous (i.v.) or subcutaneous (s.c.) injection three times per week for either 4 or 13 weeks. There were no deaths during the study, no clinical signs related to treatment, no effect on body weight, appetence, or ophthalmology. No toxicologically relevant changes in routine laboratory investigations, organ weights, or gross or histopathological findings were observed. Serum ionized calcium and phosphorus were decreased at all dose levels. Evaluations were performed to monitor biochemical markers of bone resorption (N-telopeptide [NTx], deoxypyridinoline [DPD]), bone formation (skeletal alkaline phosphatase [sALP], osteocalcin [OC]), parathyroid hormone [PTH], and bone density of the proximal tibia and distal radius in vivo. Dose-related decreases in NTx and/or DPD were observed at each dose level, with up to a 90% decrease in NTx noted for animals treated i.v. or s.c. at 15 mg/kg. Similar decreases were observed for sALP and OC. PTH was increased for animals treated at 5 and 15 mg/kg (i.v. or s.c.). Trabecular bone density was increased for the majority of males and females treated i.v. or s.c. at 15 mg/kg and males treated i.v. at 5 mg/kg. Microscopic examination of the sternebrae revealed corresponding increases in bone. Decreases in markers of bone turnover, and corresponding increases in bone density, were consistent with the pharmacological action of OPG as an osteoclast

Obtenção de plantas de feijão-caupi resistentes ao Cowpea severe mosaic virus e ao Cowpea aphid-borne mosaic virus

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Gislanne Brito Barros

2013-06-01

Full Text Available Dentre os vírus que infectam o feijão-caupi (Vigna unguiculata L. Walp. destacam-se, respectivamente, pela severidade e ampla ocorrência o Cowpea severe mosaic virus (CPSMV e o Cowpea aphid-borne mosaic virus (CABMV. Portanto, objetivaram-se, no presente trabalho, obter e avaliar plantas de feijão-caupi com resistência ao CPSMV e ao CABMV, visando ao desenvolvimento de cultivares essencialmente derivadas e novas cultivares. Realizaram-se oito cruzamentos seguidos de retrocruzamentos, utilizando a linhagem TE 97-309G-9 e a cultivar Patativa como genitores resistentes, e as cultivares BR3-Tracuateua, BRS-Urubuquara, BRS-Novaera, BRS-Guariba e Pretinho como genitores suscetíveis. As gerações F2 e F2RC1 foram desafiadas quanto à resistência por meio de inoculação mecânica com isolados do CPSMV e do CABMV. Nas gerações F2RC1, além da resistência foram avaliados os caracteres: número de dias para o início da floração, comprimento das vagens, número de grãos. vagem-1, peso de cem grãos e produção de grãos.planta-1. Todos os indivíduos F2 e F2RC1 foram analisados pelo teste χ² e se ajustaram à frequência esperada de 15 plantas suscetíveis 1 planta resistente a ambos os vírus. As médias das plantas F2RC1 resistentes, de cada retrocruzamento, foram comparadas com a média do seu respectivo genitor recorrente pelo teste 't' e as médias dos retrocruzamentos foram comparadas pelo teste de Scott-Knott. Foi detectada variabilidade genética entre os retrocruzamentos para todos os caracteres. Todos os retrocruzamentos foram considerados promissores para produção de cultivares essencialmente derivadas resistentes ao CPSMV e ao CABMV e as plantas selecionadas possuem características que possibilitam a seleção de linhagens com grãos de bom padrão comercial e altamente produtivas.

High prevalence of hepatitis B virus among female sex workers in Nigeria Alta prevalência de hepatite pelo vírus B entre trabalhadoras do sexo feminino na Nigéria

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J. C. Forbi

2008-08-01

Full Text Available Hepatitis B virus (HBV infection is endemic in Nigeria and constitutes a public health menace. The prevalence of HBV infection in many professional groups has been described in Nigeria. However, literature on HBV infection among female sex workers (FSW in Nigeria is scanty. FSW in Nigeria are not subjected to a preventive control of HBV infection. This study assesses the extent of spread of HBV among FSW in Nigeria. Seven hundred and twenty (n = 720 FSW (mean age = 26.7 years were tested for hepatitis B surface antigen (HBsAg by a double antibody sandwich ELISA method. The overall HBV prevalence among the FSW was 17.1%. FSWs between the ages of 31-35 year (20.5% and those with 'age-at-first-sex' below 10 years of age (28% were most affected. This high prevalence of a vaccine preventable disease is unacceptable, therefore, vaccination of this high risk HBV reservoir group should be considered worthwhile.A hepatite pelo vírus B (HBV é infecção endêmica na Nigéria e constitui problema de saúde pública. A prevalência da infecção HBV em muitos grupos profissionais foi descrito na Nigéria. No entanto, a literatura da infecção HBV entre trabalhadoras do sexo feminino (FSW na Nigéria é escasso. FSW na Nigéria não são submetidas a um controle preventivo de infecção de HBV. Este estudo avalia a extensão da disseminação de HBV entre FSW na Nigéria. Setecentos e vinte (n = 720 FSW (média de idade = 26,7 anos foram testadas para antígeno de superfície da hepatite B (HBsAg pelo método ELISA usando sandwich de duplos anticorpos. A prevalência total de HBV entre o FSW foi 17,1%. FSWs entre as idades de 31-35 anos (20,5% e abaixo de 10 anos de idade (28% foram mais afetadas. Esta alta prevalência de doença evitável pela vacinação é inaceitável, portanto, vacinação deste grupo de alto risco de HBV deve ser considerada fundamental.

Gene therapy strategy to reduced bone marrow aplasia: evaluation in cynomolgus macaque exposed to a gamma total body irradiation

International Nuclear Information System (INIS)

Becard, N.

2003-01-01

The aim of this work was to assess whether direct intra-marrow injection of an adeno-viral vector expressing human IL-1α gene stimulates hematopoiesis in healthy non-irradiated and gamma irradiated cynomolgus macaques. In the first hand, we have evaluated the feasibility of this gene therapy strategy in two healthy non-irradiated macaques. In this work, we have observed an increase of neutrophil, monocyte and platelets in the two animals treated with the therapeutic construct. This effect was associated with no abnormal clinical side effect. On the other hand, we have evaluated this strategy in non-human primate exposed to a sublethal gamma irradiation. Two of three animals treated by the therapeutic construct reduced significantly the neutropenia, thrombocytopenia and anemia radio-induced. In conclusion, this gene therapy strategy gave a similar clinical benefit comparatively to systemic administration of huIL-1α but without severe side effect. (author) [fr

Associantion between leprosy and hepatitis B infecion: a survey in Goiânia, Central Brazil Associação entre hanseniase e infecção pelo virus da hepatite B: estudo de prevalência realizado em Goiânia, Brasil Central

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Heitor Rosa

1992-10-01

Full Text Available This investigation presents the results of Hepatitis B virus screening among leprosy patients conducted in Central Brazil as a preliminary information for a HBV vaccination programme. The main objectives were to assess the seroprevalence of HBV serum markers among lepromatous patients and to analyse institutionalization as risk factor for HBV infection in this population. Two groups of lepromatous patients were studied, 83 outpatients and 171 institutionalized ones. Screening for HBV serum markers included the detection of HBsAg, anti-HBc by radioimmune assay (RIA. The prevalence of carrier state (HBsAg was 4.8% and 8.8% among outpatients and institutionalized, respectively, (p>0.05. Seroprevalence of exposure (all markers was statistically significant different between outpatients (16.9% and institutionalized ones (50.3%. Institutionalized patients had an almost four fold risk of HBV infection when compared to the outpatients, and the highest risks were among patients with more than 21 years of residence in the colony, after adjusting for age and sex.Este estudo apresenta os resultados de investigação sorológica para o virus da hepatite B (VHB entre pacientes hansenianos como etapa inicial para um programa de vacinação contra Hepatite B na cidade de Goiânia - Brasil Central. Os principais objetivos foram determinar a soroprevalência dos marcadores sorológicos para hepatite B entre pacientes com hanseníase do polo lepromatoso da doença, e avaliar a institucionalização como fator de risco para a infecção pelo VHB. Foram estudados 83 pacientes ambulatoriais e 171 pacientes institucionalizados e os marcadores testados foram AgHBs, anti-HBs e anti-HBc, utilizando-se a técnica de radioimuno ensaio. A prevalência de portadores virais (HBsAg foi de 4,8% e 8,8% para os pacientes ambulatoriais e institucionalizados, respectivamente (P>0,05. A prevalência de exposição ao VHB (todos os marcadores foi estatisticamente diferente entre os

Redistribuição da gordura corporal induzida pelos inibidores de protease em pacientes com Aids Redistribution of body fat induced by HIV protease inhibitors in patients with AIDS

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Cristina Mansur

2006-10-01

Full Text Available Apresentam-se quatro pacientes com infecção pelo vírus da imunodeficiência humana em tratamento com inibidores de proteases há oito meses e três semanas em média. Ressaltam-se o acúmulo de gordura na região dorsocervical e fáscies de lua cheia, semelhante à que ocorre na síndrome de Cushing.Four patients with Human Immunodeficiency Virus Infection in treatment with protease inhibitors for an average of 8 months and 3 weeks are reported. Fat accumulation in the cervical-dorsal region (buffalo hump and moon face, similar to that of Cushing's Syndrome, are highlighted.

Aerosol exposure to Zaire ebolavirus in three nonhuman primate species: differences in disease course and clinical pathology.

Science.gov (United States)

Reed, Douglas S; Lackemeyer, Matthew G; Garza, Nicole L; Sullivan, Lawrence J; Nichols, Donald K

2011-10-01

There is little known concerning the disease caused by Zaire ebolavirus (ZEBOV) when inhaled, the likely route of exposure in a biological attack. Cynomolgus macaques, rhesus macaques, and African green monkeys were exposed to aerosolized ZEBOV to determine which species might be the most relevant model of the human disease. A petechial rash was noted on cynomolgus and rhesus macaques after fever onset but not on African green monkeys. Fever duration was shortest in rhesus macaques (62.7 ± 16.3 h) and longest in cynomolgus macaques (82.7 ± 22.3h) and African green monkeys (88.4 ± 16.7h). Virus was first detectable in the blood 3 days after challenge; the level of viremia was comparable among all three species. Hematological changes were noted in all three species, including decreases in lymphocyte and platelet counts. Increased blood coagulation times were most pronounced in African green monkeys. Clinical signs and time to death in all three species were comparable to what has been reported previously for each species after parenteral inoculation with ZEBOV. These data will be useful in selection of an animal model for efficacy studies. Published by Elsevier Masson SAS.

A single amino acid of human immunodeficiency virus type 2 capsid protein affects conformation of two external loops and viral sensitivity to TRIM5α.

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Tadashi Miyamoto

Full Text Available We previously reported that human immunodeficiency virus type 2 (HIV-2 carrying alanine or glutamine but not proline at position 120 of the capsid protein (CA could grow in the presence of anti-viral factor TRIM5α of cynomolgus monkey (CM. To elucidate details of the interaction between the CA and TRIM5α, we generated mutant HIV-2 viruses, each carrying one of the remaining 17 possible amino acid residues, and examined their sensitivity to CM TRIM5α-mediated restriction. Results showed that hydrophobic residues or those with ring structures were associated with sensitivity, while those with small side chains or amide groups conferred resistance. Molecular dynamics simulation study revealed a structural basis for the differential TRIM5α sensitivities. The mutations at position 120 in the loop between helices 6 and 7 (L6/7 affected conformation of the neighboring loop between helices 4 and 5 (L4/5, and sensitive viruses had a common L4/5 conformation. In addition, the common L4/5 structures of the sensitive viruses were associated with a decreased probability of hydrogen bond formation between the 97th aspartic acid in L4/5 and the 119th arginine in L6/7. When we introduced aspartic acid-to-alanine substitution at position 97 (D97A of the resistant virus carrying glutamine at position 120 to disrupt hydrogen bond formation, the resultant virus became moderately sensitive. Interestingly, the virus carrying glutamic acid at position 120 showed resistance, while its predicted L4/5 conformation was similar to those of sensitive viruses. The D97A substitution failed to alter the resistance of this particular virus, indicating that the 120th amino acid residue itself is also involved in sensitivity regardless of the L4/5 conformation. These results suggested that a hydrogen bond between the L4/5 and L6/7 modulates the overall structure of the exposed surface of the CA, but the amino acid residue at position 120 is also directly involved in CM TRIM5�

Ocorrência de Manifestações Bucais em indivíduos infectados pelo vírus da imunodeficiência humana em hospital de referência de Goiânia-Goiás

OpenAIRE

Silva, Solange Moreira da

2012-01-01

As manifestações bucais em indivíduos infectados pelo Virus da Imunodeficiência Humana (HIV) são comuns e estão presentes em algum momento da infecção. Causadas por germes oportunistas como fungos, bactérias e vírus, podem resultar até mesmo em lesões malignas. Este estudo objetivou realizar uma revisão sistemática da literatura científica para investigar a prevalência das manifestações bucais relacionadas ao HIV em pacientes infectados por este vírus e verificar a ocorrência das mesmas em pa...

Chlorotic spots on Clerodendrum, a disease caused by a nuclear type of Brevipalpus (Acari:Tenuipalpidae transmitted virus Mancha clorótica do Clerodendrum, uma enfermidade causada por um vírus do tipo nuclear, transmitido pelo ácaro Brevipalpus phoenicis (Acari:Tenuipalpidae

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Elliot Watanabe Kitajima

2008-02-01

Full Text Available Chlorotic spots have been observed in plants of Clerodendrum x speciosum growing in residential gardens and parks in Piracicaba, SP, Brazil. Thin sections of diseased tissues revealed characteristic cytopathic effects of the nuclear type of the Brevipalpus (Acari: Tenuipalpidae mite-transmitted viruses (BTrV. Brevipalpus mites, identified as B. phoenicis, infesting symptomatic C. x speciosum plants transmitted the pathogen to healthy C. x speciosum and to C. thomsonae, Gomphrena globosa, Hibiscus cannabinus, H. coccineus, H. schizopetalus, Salvia leucantha, Spathiphyllum wallasi and Tetragonia expansa causing chlorotic spots on their leaves. Mechanical inoculation using leaf extracts from infected C. x speciosum resulted in chlorotic spots on inoculated C. x speciosum, Chenopodium quinoa, C. amaranticolor, G. globosa, H. cannabinus, H. coccineus and T. expansa leaves. C. amaranticolor and C. quinoa kept at 28 - 30°C became systemically infected. The same cytopathic effects caused by the nuclear type of BTrV were seen in tissues from all infected test plants by electron microscopy. The virus was purified from systemically infected leaves of C. amaranticolor and C. quinoa. A polyclonal antiserum obtained from an immunized rabbit presented a strong reaction with the homologous antigen in ELISA tests. The results suggest that this chlorotic spot disease of C. x speciosum is caused by a new species of the nuclear type of BTrV, tentatively named Clerodendrum chlorotic spot virus (ClCSV.Manchas cloróticas e necróticas foram observadas em folhas de várias plantas de coração-sangrento (Clerodendrum x speciosum cultivadas em parques e jardins em Piracicaba, SP, associadas à infestação pelo ácaro tenuipalpídeo Brevipalpus phoenicis. Exames preliminares de secções de tecido das manchas cloróticas ao microscópio eletrônico revelaram a ocorrência de efeitos citopáticos característicos dos induzidos pelos vírus do tipo nuclear, transmitido

Asma induzida pelo exercício: aspectos atuais e recomendações

OpenAIRE

Laitano,Orlando; Meyer,Flávia

2007-01-01

OBJETIVO: Descrever os mecanismos da asma induzida pelo exercício (AIE), bem como os efeitos de diferentes tipos de treinamento físico na função pulmonar e nas capacidades aeróbia e anaeróbia. Destaca-se a importância de um diagnóstico correto mediante o teste de exercício e, no manejo, o uso de drogas beta-adrenérgicas e anticolinérgicas. FONTE DOS DADOS: Os artigos foram criteriosamente escolhidos utilizando as bases de dados PubMed e Scielo pelo ano de publicação e dando preferência a ensa...

PET CT Identifies Reactivation Risk in Cynomolgus Macaques with Latent M. tuberculosis.

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Philana Ling Lin

2016-07-01

Full Text Available Mycobacterium tuberculosis infection presents across a spectrum in humans, from latent infection to active tuberculosis. Among those with latent tuberculosis, it is now recognized that there is also a spectrum of infection and this likely contributes to the variable risk of reactivation tuberculosis. Here, functional imaging with 18F-fluorodeoxygluose positron emission tomography and computed tomography (PET CT of cynomolgus macaques with latent M. tuberculosis infection was used to characterize the features of reactivation after tumor necrosis factor (TNF neutralization and determine which imaging characteristics before TNF neutralization distinguish reactivation risk. PET CT was performed on latently infected macaques (n = 26 before and during the course of TNF neutralization and a separate set of latently infected controls (n = 25. Reactivation occurred in 50% of the latently infected animals receiving TNF neutralizing antibody defined as development of at least one new granuloma in adjacent or distant locations including extrapulmonary sites. Increased lung inflammation measured by PET and the presence of extrapulmonary involvement before TNF neutralization predicted reactivation with 92% sensitivity and specificity. To define the biologic features associated with risk of reactivation, we used these PET CT parameters to identify latently infected animals at high risk for reactivation. High risk animals had higher cumulative lung bacterial burden and higher maximum lesional bacterial burdens, and more T cells producing IL-2, IL-10 and IL-17 in lung granulomas as compared to low risk macaques. In total, these data support that risk of reactivation is associated with lung inflammation and higher bacterial burden in macaques with latent Mtb infection.

Seleção de linhagens de melancia resistentes ao Watermelon mosaic virus e ao Papaya ringspot virus Selection of resistant watermelon lines to Watermelon mosaic virus and Papaya ringspot virus

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José Evando Aguiar Beserra Júnior

2007-10-01

Full Text Available Foram avaliadas 20 linhagens de melancia, provenientes do cruzamento da cultivar comercial suscetível Crimson Sweet e da introdução PI 595201 resistente ao Watermelon mosaic virus (WMV e Papaya ringspot virus (PRSV-W. As linhagens, e os parentais foram inoculados com o WMV ou com o PRSV-W em casa-de-vegetação distintas. Aos 35 e 49 dias após a primeira inoculação (DAI, as plantas foram avaliadas por meio de uma escala de notas, em que 1 (ausência de sintomas a 5 (intenso mosaico e deformações foliares. Pelos resultados infere-se que, aos 35 DAI, as linhagens 1, 2 e 20 apresentaram resistência tanto para o WMV como para o PRSV-W, com médias de 1,95, 1,80 e 2,25 para o WMV, e de 2,50, 2,30 e 2,50 para o PRSV-W, respectivamente. As linhagens 5, 7 e 13 foram resistentes somente ao WMV e as plantas das linhagens 3, 10 e 18 para o PRSV-W. A reação das linhagens permaneceu em geral pouco alterada aos 49 DAI. A existência de linhagens resistentes somente ao WMV e somente ao PRSV-W, ao lado de linhagens resistentes a ambos os vírus, é indicativo de que as resistências ao WMV e ao PRSV-W não são controladas pelos mesmos genes.Twenty advanced watermelon breeding lines, derived from the cross between cv. Crimson Sweet (susceptible and PI 595201 (resistant to WMV and PRSV-W, were screened for resistance to both potyviruses. The twenty lines, among with Crimson Sweet and PI 595201, were inoculated with either WMV or PRSV-W, in two different greenhouse trials. Plants were evaluated for symptoms 35 and 49 days after the first inoculation (DAI, using a scale from 1 (no symptoms to 5 (severe mosaic and foliar distortion. Evaluations at 35 DAI indicated that lines 1, 2 and 20 had good levels of resistance to both WMV and PRSV-W, with ratings of 1,95, 1,80 and 2,25 for WMV, and of 2,50, 2,30 and 2,50 for PRSV-W, respectively. Lines 5, 7 and 13 were resistant to WMV only, whereas lines 3, 10 and 18 were resistant to PRSV-W only. The reaction of

Comparative proteomic analyses of macular and peripheral retina of cynomolgus monkeys (Macaca fascicularis).

Science.gov (United States)

Okamoto, Haru; Umeda, Shinsuke; Nozawa, Takehiro; Suzuki, Michihiro T; Yoshikawa, Yasuhiro; Matsuura, Etsuko T; Iwata, Takeshi

2010-01-01

The central region of the primate retina is called the macula. The fovea is located at the center of the macula, where the photoreceptors are concentrated to create a neural network adapted for high visual acuity. Damage to the fovea, e.g., by macular dystrophies and age-related macular degeneration, can reduce central visual acuity. The molecular mechanisms leading to these diseases are most likely dependent on the proteins in the macula which differ from those in the peripheral retina in expression level. To investigate whether the distribution of proteins in the macula is different from the peripheral retina, proteomic analyses of tissues from these two regions of cynomolgus monkeys were compared. Two-dimensional gel electrophoresis and mass spectrometry identified 26 proteins that were present only in the macular gel spots. The expression levels of five proteins, cone photoreceptor specific arrestin-C, gamma-synuclein, epidermal fatty acid binding protein, tropomyosin 1alpha chain, and heterogeneous nuclear ribonucleoproteins A2/B1, were significantly higher in the macula than in the peripheral retina. Immunostaining of macula sections by antibodies to each identified protein revealed unique localization in the retina, retinal pigment epithelial cells and the choroidal layer. Some of these proteins were located in cells with higher densities in the macula. We suggest that it will be important to study these proteins to determine their contribution to the pathogenesis and progression of macula diseases.

Respiratory complications in Brazilian patients infected with human immunodeficiency virus Complicações respiratórias em pacientes brasileiros infectados pelo vírus da imunodeficiência humana

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Adriana Weinberg

1993-04-01

Full Text Available PURPOSE: To determine how often and by what means an indentifiable pulmonary pathogen can be recognized in human immunodeficiency virus (HIV infected patients with respiratory disorders in Brazil, which are the most frequently observed microorganisms and what impact specific therapy has on these agents. PATIENTS AND METHODS: Thirty-five HIV seroposiüve subjects with respiratory complaints were studied. All patients had a complete history, physical examination and blood counts. The pulmonary assessment included chest radiograms; sputum examination for bacterial and fungal pathogens; bronchoscopy with bronchoalveolar lavage and transbronchial biopsy. Patients with treatable complications received standard antimicrobial therapy. RESULTS: One or more microorganisms were found in 24 subjects and another 3 individuals showed nonspecific interstitial pneumonitis. The sputum examination identified the pulmonary pathogens in 7 cases. The bronchoalveolar lavage and the histopathologic examination were diagnostic in 14% and 83%, respectively, of the 28 individuals that were submitted to bronchoscopy. The most frequently identified microorganism was P. carinii (55%, followed by M. tuberculosis (41% and cytomegalovirus (8%. The clinical, laboratory and radiographic findings failed to distinguish the specific pulmonary pathogens. Twenty-three individuals with P. carinii pneumonitis and/or tuberculosis received specific therapy; among the evaluable patients the therapeutic response rates were 79% for PCP and 100% for TB. CONCLUSIONS: We have determined that tuberculosis, P. carinii and cytomegalovirus pneumonitis are the most common respiratory opportunistic diseases in Brazilian patients infected with HIV. The histologic evaluation was crucial in order to identify the pulmonary pathogens. Tuberculosis in AIDS individuals displayed clinical and radiographic findings atypical for reactivation disease. However, most of the features observed in HIV infected

Arremessar por cima do ombro e a distância percorrida pelo implemento

OpenAIRE

Silva,Samuel Bento da; Vilela Junior,Guanis de Barros; Toloka,Rute Estanislava

2009-01-01

A habilidade de arremessar por cima do ombro tem sido bastante estudada, observando-se a velocidade do implemento, porém enquanto muitas tarefas têm como objetivo arremessar o mais longe possível, a distância percorrida pelo objeto ainda não tem sido investigada. O objetivo deste estudo foi verificar se existe relação entre o estágio de desenvolvimento motor nesta habilidade e a distância percorrida pelo implemento e observar diferenças entre os gêneros masculino e feminino; 50 crianças, com ...

Infecção pelo vírus da hepatite C em gestantes em Mato Grosso do Sul, 2005-2007 Infección por el virus de la hepatitis C en gestantes en Mato Grosso do Sul, Centro-Oeste de Brasil, 2005-2007 Hepatitis C virus infection among pregnant women in Central-Western Brazil, 2005-2007

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Clarice Souza Pinto

2011-10-01

Full Text Available O estudo teve por objetivo estimar a prevalência da infecção e genótipo do vírus da hepatite C (HCV, bem como determinar a subnotificação de casos. O total de 115.386 gestantes atendidas pelo Programa Estadual de Proteção à Gestante de Mato Grosso do Sul foi submetido à coleta de sangue para a detecção de anti-HCV, de 2005 a 2007. A prevalência da infecção pelo HCV foi de 1,07 casos/1.000. As amostras positivas foram submetidas à detecção do HCV-RNA e genotipadas. O genótipo 1 foi encontrado em 73% das amostras, 24,3% pertenciam ao genótipo 3 e 2,7% ao genótipo 2. A subnotificação de casos de hepatite C foi de 35,5%.El estudio tuvo por objetivo estimar la prevalencia de la infección y genotipo del virus de la hepatitis C (HCV, así como determinar la subnotificación de casos. El total de 115.386 gestantes atendidas por el Programa Estatal de Protección a la Gestante de Mato Grosso do Sul (Centro-Oeste de Brasil fueron sometidas a la colecta de sangre para la detección de anti-HCV, de 2005 a 2007. La prevalencia de la infección por el HCV fue de 1,07 casos/1000. Las muestras positivas fueron sometidas a la detección del HCV-RNA y genotipadas. El genotipo 1 fue encontrado en 73% de las muestras, 24,3% pertenecían al genotipo 3 y 2,7% al genotipo 2. La subnotificación de casos de hepatitis C fue de 35,5%.The study was aimed at estimating the prevalence of infection with and the genotype of hepatitis C virus (HCV, and to determine the extent of underreporting of HCV cases. A total of 115,386 pregnant women seen by the Program for Protection of Pregnancy [Programa Estadual de Proteção à Gestante] of the state of Mato Grosso do Sul, Central-Western Brazil, were tested for anti-HCV antibodies between 2005 and 2007. Prevalence of HCV infection was 1.07 cases per thousand. Positive samples were tested for HCV RNA and genotyped. Genotype 1 was detected in 73% of samples, genotype 3 in 24.3%, and genotype 2 in 2

Preparation of highly specific radioactivity [18F]flumazenil and its evaluation in cynomolgus monkey by positron emission tomography

International Nuclear Information System (INIS)

Ryzhikov, Nikolaj N.; Seneca, Nicholas; Krasikova, Raisa N.; Gomzina, Natalia A.; Shchukin, Evgeny; Fedorova, Olga S.; Vassiliev, Dmitrij A.; Gulyas, Balazs; Hall, Hakan; Savic, Ivanka; Halldin, Christer

2005-01-01

A straightforward method for the preparation of no-carrier-added (n.c.a.) [ 18 F]flumazenil via standard nucleophilic radiofluorination of the corresponding nitro-analog Ro 15-2344 has been developed. The labeling was performed by employing the K 18 F/kryptofix complex in DMF at 160 deg. C for 30 min and equimolar ratio [K/K2.2.2] +18 F - /precursor. Under these conditions, an 18 F incorporation rate into flumazenil was in the range of 55-60%. The final product was isolated by HPLC purification within a total synthesis time of 75 min and a radiochemical yield of about 30% (EOB). Human post-mortem whole-hemisphere autoradiography of brain sections demonstrated selective uptake of the radioligand in the areas of high density of the central benzodiazepine receptors (BZR). PET studies in a cynomolgus monkey and metabolite studies by HPLC demonstrated similar results by [ 18 F]flumazenil as for [ 11 C]flumazenil. In blocking experiments, almost all radioactivity was inhibited by the addition of unlabeled flumazenil. [ 18 F]Flumazenil is a suitable radioligand for PET assessment of the BZR

Poor Memory Performance in Aged Cynomolgus Monkeys with Hippocampal Atrophy, Depletion of Amyloid Beta 1-42 and Accumulation of Tau Proteins in Cerebrospinal Fluid

DEFF Research Database (Denmark)

Darusman, Huda S; Pandelaki, Jacub; Mulyadi, Rahmad

2014-01-01

, aged cynomolgus monkeys were divided into two groups to compare high-performing (n=6) and low-performing (n=6) subjects. Both groups were tested for biomarkers related to Alzheimer's disease and their brains were scanned using structural magnetic resonance imaging. RESULTS: The subjects with poor DRT......BACKGROUND: Due to their similarities in behavior and disease pathology to humans, non-human primate models are desirable to complement small animals as models for the study of age-related dementia. MATERIALS AND METHODS: Based on their performance on delayed response task (DRT) tests of memory...... performance had evidence of atrophy in the hippocampus and cortical areas, significantly lower cerebrospinal fluid levels of amyloid beta amino acid 1-42 (pperforming well on the DRT tests. CONCLUSION: Old, memory...

Infestaçao humana pelo Dipylidium caninum

OpenAIRE

Carlos Henrique Lemos; Clarice de Resende Oliveira

1985-01-01

Os autores descrevem um caso de infestação pelo Dipylidium caninum numa criança residente em Araguari, Minas Gerais, que apresentou lesões cutâneas, insônia, irritabilidade, vômitos eperda do apetite. Relatam a eliminação abundante deproglotes quando a paciente foi tratada com medicamentos caseiros e a remissão dos sintomas, após dois tratamentos com mebendazol. Contudo não puderam concluir sobre a eficiência das drogas, devido à medicação empírica e ã administração de 200 mg/dia de mebendazo...

O virus do mixoma no coelho do mato (Sylvilagus minenses, sua transmissão pelos Aedes scapularis e aegypti

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Henrique Beaurepaire Aragão

1943-01-01

Full Text Available The brazilian wild rabbit (Sylvilagus minensis is sensible to the virus of the mixomatosis but the desease takes on it a mild character, lasts for long time and generally do not kill the animal. The tumors are generally smaller and less numerous than those of the domestic rabbit, but sometimes there were noted large and flat lesions (fig. 3. The natural infection of the wild rabbit may be quite common not only because many rabbits caught in the country were found to be immune as also because it was found among the animals caught in the country near Rio, one that was infected with mixomatosis. The experimental infection of the Sylvilagus may be easily obtained by cutan, subcutan or conjuntival way and also when a health wild rabbit is placed in the same cage with a sick domestic animal. It is also possible to obtain the infection of the wild and domestic rabbits by the bite of infected blood sucking insects as fleas and mosquitoes. The infected mosquito can transmit the disease 2 or 3 times til 17 days after an infective meal on a sick rabbit. The transmission is a mecanical one and only the proboscis of the insect contains the virus as it was shown by the inoculation of emulsions of the proboscis, thorax and abdomen of the mosquito. Though mecanical this kind of transmission acts as an important epidemiological mean of dissemination of the deseasse and splains the suddendly outbreaks of mixomatosis in rabbits breedings where no new rabbits were introduced since very long time. The transmition of mixomatosis by fleas (Slenopsylla was at first demonstrated by us, then S. Torres pointed out the capacity of Culex fatigans to transmit the desease and now we have proved that Aedes scapularis and Aedes aegypti were also able to transmit it (Foto 1 and 2. The virus of the mixomatosis (Chlamidozoon mixoma is seen on the smeavs of the tumors of the wild reabbit with the same morphology, as in the material of the domestic animal.

Virus isolation and molecular characterization of canine distemper virus by RT-PCR from a mature dog with multifocal encephalomyelit Isolamento e caracterização molecular do vírus da cinomose canina por RT-PCR a partir de um cão adulto com encefalomielite multifocal

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Alexandre Mendes Amude

2007-06-01

Full Text Available A case of multifocal distemper encephalomyelitis in a mature dog is described. In the presented case the ante mortem clinical diagnosis of canine distemper virus (CDV infection could not be ideally performed due to the absence of typical signs of distemper, such as myoclonus and systemic signs accompanying the nervous signs. The definitive diagnosis of distemper encephalomyelitis was only carried out at post mortem through virus isolation in cell culture from fresh central nervous system (CNS fragments and CDV nucleoprotein gene detection in the CNS by RT-PCR.Descreve-se um caso de encefalomielite multifocal pela cinomose em um cão adulto. No caso apresentado o diagnóstico clínico da infecção pelo vírus da cinomose canina (CDV não pode ser adequadamente realizado devido à ausência de sinais típicos da enfermidade, tais como mioclonia e sinais sistêmicos. O diagnóstico definitivo somente foi possível post mortem pelo isolamento do CDV em cultivo celular a partir dos fragmentos frescos do sistema nervoso central (SNC e pela detecção do gene da nucleoproteína do CDV em fragmentos do SNC por meio da RT-PCR.

Opção pelo curso de Medicina em Angola: o caso da Universidade Agostinho Neto

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Maria Fernanda Afonso Dias Monteiro

Full Text Available O presente trabalho pretende: (i identificar os motivos que conduzem os jovens a optar pelo curso de Medicina na Faculdade de Medicina da Universidade Agostinho Neto (FMUAN; (ii identificar como é percebida a profissão médica; (iii determinar se existe influência das características sociodemográficas sobre os fatores identificados como determinantes que os orientam para a pretensão de ser médico. O estudo contou com uma amostra de 1.815 candidatos (96,2%. Os dados recolhidos correspondem a uma amostra obtida por intermédio de inquéritos de opinião. Os candidatos identificaram como principais razões de opção pelo curso de Medicina as seguintes: Altruísmo (mediana = 87,5; Vocação (mediana = 81,3; Influência Familiar (mediana = 75,0; Prestígio Social (mediana = 75,0; Interesse Científico (mediana = 68,7; Pessoas na Família Exercendo a Profissão (mediana = 62,5; Mercado de Trabalho (mediana = 50,0. Não consideraram como razões de opção pelo curso: Benefício Econômico (mediana = 45,0, Sucesso (mediana = 43,8 e os Problemas de Saúde na Família (mediana = 37,5. Podemos concluir que os candidatos ao curso de Medicina se distinguem pela dedicação aos outros e pelo compromisso com as pessoas, constituindo a Vocação e o Altruísmo as principais forças impulsionadoras da opção pelo curso.

Impact of intravenous infusion time on AAV8 vector pharmacokinetics, safety, and liver transduction in cynomolgus macaques

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Jenny A Greig

2016-01-01

Full Text Available Systemically delivered adeno-associated viral (AAV vectors are now in early-phase clinical trials for a variety of diseases. While there is a general consensus on inclusion and exclusion criteria for each of these trials, the conditions under which vectors are infused vary significantly. In this study, we evaluated the impact of intravenous infusion rate of AAV8 vector in cynomolgus macaques on transgene expression, vector clearance from the circulation, and potential activation of the innate immune system. The dose of AAV8 vector in terms of genome copies per kilogram body weight and its concentration were fixed, while the rate of infusion varied to deliver the entire dose over different time periods, including 1, 10, or 90 minutes. Analyses during the in-life phase of the experiment included sequential evaluation of whole blood for vector genomes and appearance of proinflammatory cytokines. Liver tissues were analyzed at the time of necropsy for enhanced green fluorescent protein (eGFP expression and vector genomes. The data were remarkable with a relative absence of any statistically significant effect of infusion time on vector transduction, safety, and clearance. However, some interesting and unexpected trends did emerge.

ESCOAMENTO DA ÁGUA DA CHUVA PELO TRONCO DAS ÁRVORES EM UMA FLORESTA ESTACIONAL SEMIDECIDUAL

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Alexandre Simões Lorenzon

2015-06-01

Full Text Available RESUMOEste trabalho foi desenvolvido na Estação de Pesquisas, Treinamento e Educação Ambiental Mata do Paraíso, situada no Município de Viçosa, na Zona da Mata de Minas Gerais, Brasil, e teve como objetivo avaliar o escoamento pelo tronco em um fragmento de Mata Atlântica, no período de agosto de 2009 a março de 2011. Para quantificar esse escoamento, foram demarcadas seis parcelas de 10 x 10 m, sendo em cada parcela adaptados coletores à base de poliuretano nos troncos das árvores com circunferência 15,0 cm. Um pluviômetro foi instalado em local aberto para quantificar a água diretamente da chuva. Além disso, realizou-se uma análise qualitativa dos indivíduos do escoamento pelo troco, avaliando a qualidade do fuste e da copa, posição no estrato da floresta e infestação de cipó. Em todo o período de análises, foram realizadas 75 medições. Nas parcelas de escoamento pelo tronco foram amostrados 126 indivíduos, distribuídos em 29 famílias e 59 espécies. A precipitação em aberto foi de 2.391,63 mm, e o escoamento pelo tronco somou 31,59 mm, ou 1,32% da precipitação em aberto. A espécie com maior escoamento pelo tronco foi a Euterpe edulis, com um volume médio de água escoado de 637,00 L. Das espécies com maior escoamento pelo tronco, 73,91% encontravam-se no estrato inferior da floresta, evidenciando que algumas espécies possuem algum tipo de adaptação morfológica para captação da água da chuva.

Freqüência das infecções pelo HIV-1, rubéola, sífilis, toxoplasmose, citomegalovírus, herpes simples, hepatite B, hepatite C, doença de Chagas e HTLV I/II em gestantes, do Estado de Mato Grosso do Sul Frequency of HIV-1, rubella, syphilis, toxoplasmosis, cytomegalovirus, simple herpes virus, hepatitis B, hepatitis C, Chagas’ disease and HTLV I/II infection in pregnant women of State of Mato Grosso do Sul

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Ernesto Antonio Figueiró-Filho

2007-04-01

Full Text Available Objetivou-se avaliar a freqüência das infecções por sífilis, rubéola, hepatite B, hepatite C, toxoplasmose, doença de Chagas, HTLV I/II, herpes simples, HIV-1 e citomegalovírus em gestantes e relacionar a faixa etária das pacientes com a freqüência das infecções. Estudo transversal de 32.512 gestantes submetidas à triagem pré-natal no período de novembro de 2002 a outubro de 2003. As freqüências encontradas foram de 0,2% para infecção pelo vírus HIV-1, 0,03% para rubéola, 0,8% para sífilis, 0,4% para toxoplasmose, 0,05% para infecção aguda pelo citomegalovírus, 0,02% pelo vírus herpes simples, 0,3% para hepatite B (HBsAg, 0,1% para hepatite C, 0,1% para HTLV I/II e 0,1% para doença de Chagas. Houve associação significativa entre faixa etária e infecções por rubéola, citomegalovírus, doença de Chagas e herpes vírus. As freqüências de rubéola, sífilis, toxoplasmose, doença de Chagas e citomegalovírus nas gestantes encontram-se abaixo dos valores descritos na literatura.It was aimed to estimate the frequency of syphilis, rubella, hepatitis B, hepatitis C, toxoplasmosis, Chagas’ disease, HTLV I/II, simple herpes virus, HIV-1 and cytomegalovirus in pregnant women and to evaluate the relationship between age and the frequency of the infections studied. A transversal study of 32,512 pregnant women submitted to pre-natal sreening in the period of November 2002 to October 2003. The frequency of the tried infections among the pregnant women were 0.2% of HIV-1, 0.03% of rubella, 0.8% of syphilis, 0.4% of toxoplasmosis, 0.05% of cytomegalovirus, 0.02% of simple herpes virus, 0.3% of HBsAg, 0.1% of hepatitis C, 0.1% of HTLV and 0.1% of Chagas’ disease. There was significative statistical association between age and prenatal infection of rubella, cytomegalovirus, Chagas’ disease and herpes virus. The rates of frequency of rubella, syphilis, toxoplasmosis, Chagas’ disease and cytomegalovirus in pregnant women

Behavioural profiles in captive-bred cynomolgus macaques: towards monkey models of mental disorders?

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Sandrine M J Camus

Full Text Available BACKGROUND: To date, experimental and preclinical studies on neuropsychiatric conditions have almost exclusively been performed in experimentally-induced animal models and have only rarely relied upon an ethological approach where animals have been observed in more naturalistic settings. The laboratory species of choice has been the rodent while the potential of more closely-related non-human primates have remained largely underexplored. METHODS: The present study, therefore, aimed at investigating the possible existence of spontaneous atypical/abnormal behaviours displayed by 40 cynomolgus macaques in captive conditions using an unbiased ethological scan-sampling analysis followed by multifactorial correspondence analysis and a hierarchical clustering. RESULTS: The study identified five distinct profiles (groups A to E that significantly differed on several behaviours, body postures, body orientations, gaze directions and locations in the cage environment. We suggest that animals from the low n groups (D and E present depressive-like and anxious-like symptoms, reminiscent of depressive and generalized anxiety disorders. Inter-individual differences were highlighted through unbiased ethological observations of spontaneous behaviours and associated parameters, although these were not associated with differences in plasma or cerebrospinal fluid levels of either stress-related hormones or monoamines, i.e. in accordance with the human situation. CONCLUSIONS: No interventional behavioural testing was required to discriminate between 3 typical and 2 atypical ethologically-defined behavioural profiles, reminiscent of certain depressive-like and anxiety-like symptoms. The use of unbiased behavioural observations might, thus, allow the identification of animal models of human mental/behavioural disorders and their most appropriate control groups.

Gene expression profiling in the Cynomolgus macaque Macaca fascicularis shows variation within the normal birth range

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Vickers Mark H

2011-10-01

Full Text Available Abstract Background Although an adverse early-life environment has been linked to an increased risk of developing the metabolic syndrome, the molecular mechanisms underlying altered disease susceptibility as well as their relevance to humans are largely unknown. Importantly, emerging evidence suggests that these effects operate within the normal range of birth weights and involve mechanisms of developmental palsticity rather than pathology. Method To explore this further, we utilised a non-human primate model Macaca fascicularis (Cynomolgus macaque which shares with humans the same progressive history of the metabolic syndrome. Using microarray we compared tissues from neonates in the average birth weight (50-75th centile to those of lower birth weight (5-25th centile and studied the effect of different growth trajectories within the normal range on gene expression levels in the umbilical cord, neonatal liver and skeletal muscle. Results We identified 1973 genes which were differentially expressed in the three tissue types between average and low birth weight animals (P Conclusion These differences in gene expression levels between animals in the upper and lower percentiles of the normal birth weight range may point towards early life metabolic adaptations that in later life result in differences in disease risk.

Sex and the stimulus-movement effect: Differences in acquisition of autoshaped responding in cynomolgus monkeys.

Science.gov (United States)

Rice, Nathaniel C; Makar, Jennifer R; Myers, Todd M

2017-03-15

The stimulus-movement effect refers to the phenomenon in which stimulus discrimination or acquisition of a response is facilitated by moving stimuli as opposed to stationary stimuli. The effect has been found in monkeys, rats, and humans, but the experiments conducted did not provide adequate female representation to investigate potential sex differences. The current experiment analyzed acquisition of stimulus touching in a progressive series of classical conditioning procedures in cynomolgus monkeys (Macaca fascicularis) as a function of sex and stimulus movement. Classical conditioning tasks arrange two or more stimuli in relation to each other with different temporal and predictive relations. Autoshaping procedures overlay operant contingencies onto a classical-conditioning stimulus arrangement. In the present case, a neutral stimulus (a small gray square displayed on a touchscreen) functioned as the conditional stimulus and a food pellet functioned as the unconditional stimulus. Although touching is not required to produce food, with repeated stimulus pairings subjects eventually touch the stimulus. Across conditions of increasing stimulus correlation and temporal contiguity, male monkeys acquired the response faster with a moving stimulus. In contrast, females acquired the response faster with a stationary stimulus. These results demonstrate that the stimulus-movement effect may be differentially affected by sex and indicate that additional experiments with females are needed to determine how sex interacts with behavioral phenomena discovered and elaborated almost exclusively using males. Published by Elsevier Inc.

IND-directed safety and biodistribution study of intravenously injected cetuximab-IRDye800 in cynomolgus macaques.

Science.gov (United States)

Zinn, Kurt R; Korb, Melissa; Samuel, Sharon; Warram, Jason M; Dion, David; Killingsworth, Cheryl; Fan, Jinda; Schoeb, Trenton; Strong, Theresa V; Rosenthal, Eben L

2015-02-01

The use of receptor-targeted antibodies conjugated to fluorophores is actively being explored for real-time imaging of disease states; however, the toxicity of the bioconjugate has not been assessed in non-human primates. To this end, the in vivo toxicity and pharmacokinetics of IRDye800 conjugated to cetuximab (cetuximab-IRDye800; 21 mg/kg; equivalent to 250 mg/m(2) human dose) were assessed in male cynomolgus monkeys over 15 days following intravenous injection and compared with an unlabeled cetuximab-dosed control group. Cetuximab-IRDye800 was well tolerated. There were no infusion reactions, adverse clinical signs, mortality, weight loss, or clinical histopathology findings. The plasma half-life for the cetuximab-IRDye800 and cetuximab groups was equivalent (2.5 days). The total recovered cetuximab-IRDye800 in all tissues at study termination was estimated to be 12 % of the total dose. Both cetuximab-IRDye800 and cetuximab groups showed increased QTc after dosing. The QTc for the cetuximab-dosed group returned to baseline by day 15, while the QTc of the cetuximab-IRDye800 remained elevated compared to baseline. IRDye800 in low molar ratios does not significantly impact cetuximab half-life or result in organ toxicity. These studies support careful cardiac monitoring (ECG) for human studies using fluorescent dyes.

Validation of a Pan-Orthopox Real-Time PCR Assay for the Detection and Quantification of Viral Genomes from Nonhuman Primate Blood

Science.gov (United States)

2017-06-19

Validation of a pan-orthopox real-time PCR assay for the detection and quantification of viral genomes from nonhuman primate blood. Eric...medical countermeasures by the U.S. FDA, the assay was designed to quantitate poxvirus genomic DNA in a nonhuman primate (cynomolgus macaque) blood...monkeypox virus into nonhuman primate blood, we chose to use the HA standard after considering the potential biological safety and logistical issues with

Comparative morpho-anatomical studies of the lesions caused by citrus leprosis virus on sweet orange

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João P.R. Marques

2010-06-01

Full Text Available The leprosis disease shows a viral etiology and the citrus leprosis virus is considered its etiologic agent. The disease may show two types of cytopatologic symptom caused by two virus: nuclear (CiLV-N and cytoplasmic (CiLV-C types. The aim of this study was to compare the morpho-anatomical differences in the lesions caused by leprosis virus-cytoplasmic and nuclear types in Citrus sinensis (L. Osbeck 'Pêra'. Leaf and fruit lesions were collected in Piracicaba/São Paulo (cytoplasmic type and Monte Alegre do Sul/São Paulo and Amparo/São Paulo (nuclear type. The lesions were photographed and then fixed in Karnovsky solution, dehydrated in a graded ethylic series, embedded in hydroxy-ethyl methacrylate resin (Leica Historesin, sectioned (5 μm thick, stained and mounted in synthetic resin. The digital images were acquired in a microscope with digital video camera. Leaf and fruit lesions caused by the two viruses were morphologically distinct. Only the lesion caused by CiLV-N virus presented three well-defined regions. In both lesions there was the accumulation of lipidic substances in necrotic areas that were surrounded by cells with amorphous or droplets protein. Only leaf and fruit lesions caused by CiLV-N virus exhibited traumatic gum ducts in the vascular bundles.A doença leprose dos citros tem etiologia viral sendo o citrus leprosis virus seu agente etiológico. Demonstrou-se que há dois vírus distintos que causam sintomas de leprose em ci-tros: citoplasmático (CiLV-C e o nuclear (CiLV-N. O objetivo desse estudo foi comparar as diferenças morfo-anatômicas nas lesões causadas por CiLV-C e por CiLV-N em laranjeira doce (Citrus sinensis (L. Osbeck 'Pêra'. As lesões foliares e dos frutos foram coletadas em Piracicaba/SP (tipo citoplas-mático e em Monte Alegre do Sul/SP e Amparo/SP (tipo nuclear. As lesões foram fotografadas e em seguida fixadas em solução Karnovsky, desidratadas em série etílica, incluídas em historesina e

A 52-week safety study in cynomolgus macaques for genetically modified rice expressing Cry1Ab/1Ac protein.

Science.gov (United States)

Mao, Jie; Sun, Xing; Cheng, Jian-Hua; Shi, Yong-Jie; Wang, Xin-Zheng; Qin, Jun-Jie; Sang, Zhi-Hong; He, Kun; Xia, Qing

2016-09-01

A 52-week feeding study in cynomolgus macaques was carried out to evaluate the safety of Bt rice Huahui 1 (HH1), a transgenic rice line expressing Cry1Ab/1Ac protein. Monkeys were fed a diet with 20% or 60% HH1 rice, 20% or 60% parental rice (Minghui 63, MH63), normal diet, normal diet spiked with purified recombinant Cry1Ab/1Ac fusion protein or bovine serum albumin (BSA) respectively. During the feeding trail, clinical observations were conducted daily, and multiple parameters, including body weight, body temperature, electrocardiogram, hematology, blood biochemistry, serum metabolome and gut microbiome were examined at regular intervals. Upon sacrifice, the organs were weighted, and the macroscopic, microscopic and electron microscopic examinations were performed. The results show no adverse or toxic effects of Bt rice HH1 or Cry1Ab/1Ac fusion protein on monkeys. Therefore, the present 52-week primate feeding study suggests that the transgenic rice containing Cry 1Ab/1Ac is equivalent to its parental rice line MH63. Copyright © 2016 Elsevier Ltd. All rights reserved.

Os encantos da Veneza Americana e da propaganda pelo cinema: os filmes financiados pelo governo Sergio Loreto em Pernambuco (1922-1926

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Luciana Corrêa de Araújo

2013-06-01

Full Text Available Este artigo aborda a produção cinematográfica financiada pelo governo Sergio Loreto em Pernambuco (1922-1926. Por meio de textos históricos, pesquisa em periódicos e análise fílmica, pretendemos destacar a relevância do estímulo oficial ao incipiente meio cinematográfico local e analisar como se constroem, nos filmes, as relações entre estratégias de propaganda e procedimentos estéticos e narrativos.

The early days of pandemic (H1N1 2009 virus infection in the central region of Portugal

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V. Duque

2010-11-01

period for the for pandemic (H1N1 2009 virus infection was 2 days. The length of the clinical manifestations until the patients sough for medical observation had a median time of 2 days. All the cases were of mild to moderate severity. No deaths were observed. Conclusions: The early days of pandemic (H1N1 2009 virus infection were characterized by cases of disease of mild to moderate severity, in our region. Most affected patients were young adults, with the extreme ages of life being spared. An early diagnosis, strict isolation and treatment procedures could have slowed the spread of the infection. Resumo: Introdução: O primeiro caso de infecção pelo vírus da gripe pandémica (H1N1 2009, foi diagnosticado na região centro de Portugal no dia 16 de Junho de 2009, numa mulher infectada no Canadá. Métodos: O nosso estudo tem por objectivos, em primeiro lugar caracterizar os aspectos clínicos e epidemiológicos de todos os doentes que tiveram manifestações clínicas incluídas na definição de caso para investigação com amostras submetidas para diagnóstico da infecção pelo vírus da gripe pandémica (H1N1 2009; em segundo lugar, avaliar a precisão da definição de caso para investigação de acordo com a presença ou ausência de febre no momento da observação clínica. Efectuámos a revisão dos registos médicos de todos os doentes classificados como caso para investigação e analisaram-se os primeiros casos de doentes infectados com o novo vírus da gripe pandémica (H1N1 2009, diagnosticados na região centro de Portugal durante o período pandémico compreendido entre Junho e Agosto de 2009. Foi utilizado o método da reacção em cadeia da polimerase de retrotranscripção em tempo real para confirmação da infecção pelo vírus da gripe pandémica (H1N1 2009. A colheita de dados foi efectuada de forma padronizada em suporte de papel de acordo com as normas da Direcção Geral de Saúde. Resultados e discussão: A infecção pelo vírus da gripe

Epidemiologia, fisiopatogenia e diagnóstico laboratorial da infecção pelo HTLV-I Epidemiology, physiopathogenesis and laboratorial diagnosis of the HTLV-I infection

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Fred Luciano Neves Santos

2005-04-01

Full Text Available O HTLV-I foi descoberto no início dos anos 1980 e associado a leucemia/linfoma de células T (LLTA e paraparesia espástica tropical (PET. O HTLV pertence à família Retroviridae e tem um genoma de RNA de fita simples com uma estrutura genética similar à dos demais retrovírus, possuindo os genes gag, pol, env e pX. Este último contém os genes reguladores tax e rex. Tax e Rex são as principais proteínas reguladoras do genoma viral, sendo que Tax regula a transcrição do genoma proviral indiretamente ao interagir com diferentes proteínas regulatórias celulares, principalmente genes de citocinas e protoncogenes, e Rex atua como um regulador pós-transcricional do genoma do HTLV-I ao controlar o processamento (splicing do RNAm viral. Essa infecção é endêmica em diversas regiões do mundo, tais como Japão, vários países da África, Caribe e América do Sul. No Brasil, Salvador é a cidade de maior prevalência, atingindo 1,7% da população geral. A maioria dos indivíduos infectados pelo HTLV-I permanece assintomática no decorrer de suas vidas, correspondendo a aproximadamente 95%. Dos indivíduos sintomáticos, alguns desenvolvem PET e outros, LLTA, sem que suas fisiopatogenias estejam perfeitamente esclarecidas. O diagnóstico rotineiro da infecção causada pelo HTLV-I baseia-se na detecção sorológica de anticorpos específicos para antígenos das diferentes porções do vírus ou através da pesquisa de seqüências genômicas provirais em células mononucleares periféricas. Ainda não existe nenhum estudo epidemiológico com bases populacionais e com metodologias adequadas sobre a infecção pelo HTLV-I que permita conhecer sua real prevalência no Brasil.Human T-cell lymphotropic virus type I (HTLV-I has been identified as the causative agent of both adult T-cell leukemia (ATL and HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP. Similar to other retroviruses, HTLV-I has a positive strand RNA diploid

Efeito do Soursop yellow blotch virus no desenvolvimento vegetativo e na produção da gravioleira

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Santos,Antonio A. dos; Cardoso,José Edmilson; Viana,Francisco Marto Pinto; Vidal,Júlio Cal; Souza,Raimundo Nonato Martins de

2007-01-01

Os danos causados no desenvolvimento vegetativo e na produção de frutos da gravioleira pelo vírus da mancha-amarela da gravioleira (Soursop yellow blotch virus, SYBV), foram estudados durante os anos de 2000 a 2004 em um experimento com dois tratamentos: plantas sadias e plantas doentes, dispostos em blocos ao acaso, com oito repetições e quatro plantas por parcela. Foram avaliados, anualmente, a altura da planta, diâmetro do caule, número e peso de frutos, sendo que a produção foi monitorada...

Infecção mista pelo Sugarcane mosaic virus e Maize rayado fino virus provoca danos na cultura do milho no estado de São Paulo Mixed infection by Sugarcane mosaic virus and Maize rayado fino virus causing breaking yields in maize in São Paulo state

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Marcos César Gonçalves; Ivan de Godoy Maia; Sílvia Regina Galleti; Gisèle Maria Fantin

2007-01-01

Os dois principais vírus que infectam o milho no Brasil são o Sugarcane mosaic virus (SCMV) e o Maize rayado fino virus (MRFV), cujos principais vetores são o afídeo Rhopalosiphum maidis e a cigarrinha Dalbulus maidis, respectivamente. O MRFV é freqüentemente encontrado em infecções mistas com fitoplasmas e espiroplasmas, causando as doenças denominadas enfezamentos do milho. Em uma lavoura de milho próxima a Santo Antonio da Posse, SP, cercada por campos de cana-de-açúcar, foi encontrada alt...

AS VIOLAÇÕES SOFRIDAS PELO POVO KRENAK E O DANO CAUSADO AO PROJETO DE VIDA

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Rodrigo de Medeiros Silva

2017-06-01

Full Text Available Este artigo versa sobre as violações cometidas pelo Regime Militar ao povo Krenak e o possível dano ao projeto de vida. Conceituando esta espécie de dano como violação de direitos humanos, irá discorrer sobre a criação da Guarda Rural Indígena (GRIN, a instalação do presídio indígena em suas terras chamado “Reformatório Krenak” e o deslocamento forçado para outro centro de detenção indígena, denominado fazenda Guarani, no município de Carmésia/MG. Procurará se demonstrar que as ações cometidas a este povo, pelo Estado Brasileiro, devem ser reparadas também por atingir o modo e a expectativa de vida que possuíam a época. Para melhor identificar estes danos causados, o trabalho recorrerá à peça inicial da Ação Civil Pública nº 64483-95.2015.4.01.3800, impetrada pelo Ministério Público Federal, que trata das violações sofridas pelos Krenak e o Relatório da Comissão Nacional da Verdade, Volume II. Também se demostrará que a Corte Interamericana de Direitos Humanos já vem entendendo que este tipo de dano deve ser reparado.

PROGRESSION OF LIVER FIBROSIS IN MONOINFECTED PATIENTS BY HEPATITIS C VIRUS AND COINFECTED BY HCV AND HUMAN IMMUNODEFICIENCY VIRUS

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Cristiane Valle TOVO

2013-03-01

Full Text Available Context The progression of liver fibrosis in patients coinfected by hepatitis C virus and human immunodeficiency virus (HCV/HIV has been increasingly studied in the past decade. Studies made before the highly active antiretroviral therapy suggest that HIV can change the natural history of the HCV infection, leading to a faster progression of the liver fibrosis. Objective To evaluate and compare the fibrosis progression in two groups of patients (HCV/HIV coinfected and HCV monoinfected Methods Seventy patients HCV monoinfected and 26 patients HCV/HIV coinfected who had not undertaken HCV treatment and were submitted to serial percutaneous liver biopsies were retrospectively evaluated. There was no difference in the fibrosis progression between the two groups. Conclusion The fibrosis grade evolution was not worse in the coinfected patients. The immunosuppression absence and the shortest time period between the biopsies in the coinfected group are possible explanations. Contexto A progressão da fibrose hepática em pacientes coinfectados pelos vírus da hepatite C (VHC e da imunodeficiência humana (VHC/HIV tem sido mais estudada na última década. Estudos realizados antes da terapia antiretroviral de alta potência (HAART sugerem que o HIV pode mudar a história natural da infecção pelo VHC, levando a uma progressão mais rápida da fibrose hepática. Objetivo Avaliar e comparar a progressão de fibrose em duas populações de pacientes (coinfectados VHC/HIV e monoinfectados VHC. Métodos Foram avaliados retrospectivamente 70 pacientes monoinfectados VHC e 26 coinfectados VHC/HIV nunca tratados para o VHC e que haviam realizado duas biopsias hepáticas seriadas. Não houve diferença na progressão de fibrose entre os dois grupos. Conclusão A evolução do grau de fibrose não foi pior nos pacientes coinfectados. A ausência de imunodepressão e o menor intervalo de tempo entre as biopsias no grupo de coinfectados são poss

Aspectos histopatológicos das lesões renais em gatos experimentalmente infectados pelo vírus da imunodeficiência felina

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Leonardo P. Mesquita

2014-09-01

Full Text Available A infecção pelo vírus da imunodeficiência felina (FIV em gatos domésticos é caracterizada por distúrbios imunológicos, que geralmente se manifestam tardiamente na doença. Semelhante à infecção pelo vírus da imunodeficiência humana (HIV em humanos, a infecção pelo FIV geralmente está associada a infecções oportunistas e ao desenvolvimento progressivo de nefropatia. Portanto, o objetivo do presente estudo foi avaliar as alterações histopatológicas em rins de 10 gatos experimentalmente infectados pelo FIV submetidos a eutanásia 60 meses após a inoculação viral. Nos rins de 100% dos gatos infectados pelo FIV foram visualizadas lesões glomerulares e tubulointersticiais. As lesões glomerulares eram caracterizadas principalmente por espessamento global ou segmentar da membrana basal glomerular (glomerulonefrite membranosa. Glomeruloesclerose e, em dois casos, proliferação de células epiteliais intraglomerulares (crescente glomerular, também foram observados. Nefrite intersticial linfoplasmocítica foi a alteração tubulointersticial mais frequente, visualizada em diferentes intensidades nos rins de 100% dos gatos. Os resultados do presente estudo demonstram que o tempo prolongado entre a infecção e a avaliação histopatológica pode ter sido decisivo para o surgimento das lesões renais em todos os gatos infectados pelo FIV e para o agravamento dessas lesões em alguns gatos.

Ocorrência do vírus da imunodeficiência felina e do vírus da leucemia felina em gatos domésticos mantidos em abrigos no município de Belo Horizonte Occurrence of feline immunodeficiency virus and feline leukemia virus in Sheltered domestic cats of Belo Horizonte

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B.M. Teixeira

2007-08-01

Full Text Available Investigou-se a ocorrência da infecção pelo vírus da imunodeficiência felina (FIV e pelo vírus da leucemia felina (FeLV em gatos domésticos, provenientes de dois abrigos, no município de Belo Horizonte. Amostras de sangue de 145 animais foram coletadas e testadas para detecção do FIV pela reação em cadeia da polimerase (PCR. Destas amostras, 40 foram testadas para o antígeno p26 de FeLV por meio de ELISA. Observaram-se duas fêmeas (1,4% e quatro machos (2,8% positivos para FIV e nove fêmeas (22,5% e quatro machos (10,0% positivos para FeLV.The occurrence of the feline immunodeficiency virus (FIV and feline leukemia virus (FeLV was investigated in domestic cats from two shelters of Belo Horizonte. Samples from 145 cats were collected and tested for FIV by the polymerase chain reaction (PCR. Forty out of 145 samples were tested for FeLV p27 antigen by a commercial ELISA kit. Two females (1.4% and four males (2.8% were positive for FIV. For FeLV tests, 13 cats (32.5% were positive, being nine females (22.5% and four males (10.0%.

Ebola Virus and Marburg Virus

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Ebola virus and Marburg virus Overview Ebola virus and Marburg virus are related viruses that cause hemorrhagic fevers — illnesses marked by severe bleeding (hemorrhage), organ failure and, in many ...

Ação do radium sôbre o vírus da Coriomeningite linfocitária benigna Radium effect upon the lymphocytic choriomeningitis virus

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J. Guilherme Lacorte

1968-01-01

Full Text Available O presente trabalho faz parte de uma seqüência iniciada em 1953 com a verificação do efeito dos raios X sôbre o vírus da gripe em que observamos que os mesmos, em doses fracas, tem aumentado o seu poder patogênico para camundongos. Posteriormente, verificamos a ação do radium sôbre o vírus da gripe e da poliomielite. Neste último caso, o vírus irradiado mostrou-se ativo durante maior número de dias. Nas pesquisas aqui referidas, submetemos o vírus da coriomeningite linfocitária benigna a ação do radium, usando quatro agulhas de 1 mg desse elemento em dispositivo que idealizamos para êste fim. Depois de irradiada, foi a suspensão de vírus diluida a 10*-1, 10*-2 e 10*-3 para as inoculações em camundongos, juntamente com as diluições testemunhas. Observamos que o vírus resistiu pelo menos 264 dias, à temperatura de 4ºC. Quanto às alterações do poder patogênico provocadas pelo radium verificamos que o mesmo não se altera após 24 horas de irradiação. Diminue após 8 dias para aumentar, de modo seguro, após 20 e 33 dias. Iguala-se ao testemunha depois de 78 dias.In the present paper the authors refered the experiments made with the lymphocytic chriomeningitis virus. We strain, after exposition to 4 tubes of 1 mg of radium. The virus suspension was put into the Carrel flask in a layer of 0,1 cm. The titrations of the irradiated virus suspension were made after 24 hours, 8, 20, 33, 78, 85, 120, 264, 292, 387 and 535 days. the virus was still active after 264 days, not after 292 days. The virus irradiated during 24 hours presented the same pathogenicity form mice than the control but after 8 days it was lesser and after 20 and 33 days it was enchanced (Graphic 10. After 78 days the pathogenic power was the same for the irradiated virus and the control.

“12 ANOS DE ESCRAVIDÃO” E A PAIXÃO PELO REAL

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Luís Gustavo Finger de Oliveira

2015-12-01

Full Text Available Este artigo propõe uma reflexão sobre as narrativas audiovisuais contemporâneas marcadas pelo choque do real ou pela paixão pelo real. Em perspectivas semelhantes, os autores defendem a ideia de que, diante da experiência virtualizada e fragmentada atual, as produções audiovisuais construídas a partir da estética realista buscam ofertar um real mais real do que o real, portanto, explícito e contundente, buscando reduzir as mediações e artifícios em seu narrar. A observação deste fenômeno, bem como o estudo das estratégias de autenticação da linguagem audiovisual foram feitas no filme “12 Anos de Escravidão”, de Steve McQueen, vencedor de três Oscars e integrante de uma safra de filmes oscarizados que, em boa parte, foram resultantes da retratação de histórias reais de anônimos.

Discovery and Validation of Pyridoxic Acid and Homovanillic Acid as Novel Endogenous Plasma Biomarkers of Organic Anion Transporter (OAT) 1 and OAT3 in Cynomolgus Monkeys.

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Shen, Hong; Nelson, David M; Oliveira, Regina V; Zhang, Yueping; Mcnaney, Colleen A; Gu, Xiaomei; Chen, Weiqi; Su, Ching; Reily, Michael D; Shipkova, Petia A; Gan, Jinping; Lai, Yurong; Marathe, Punit; Humphreys, W Griffith

2018-02-01

Perturbation of organic anion transporter (OAT) 1- and OAT3-mediated transport can alter the exposure, efficacy, and safety of drugs. Although there have been reports of the endogenous biomarkers for OAT1/3, none of these have all of the characteristics required for a clinical useful biomarker. Cynomolgus monkeys were treated with intravenous probenecid (PROB) at a dose of 40 mg/kg in this study. As expected, PROB increased the area under the plasma concentration-time curve (AUC) of coadministered furosemide, a known substrate of OAT1 and OAT3, by 4.1-fold, consistent with the values reported in humans (3.1- to 3.7-fold). Of the 233 plasma metabolites analyzed using a liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based metabolomics method, 29 metabolites, including pyridoxic acid (PDA) and homovanillic acid (HVA), were significantly increased after either 1 or 3 hours in plasma from the monkeys pretreated with PROB compared with the treated animals. The plasma of animals was then subjected to targeted LC-MS/MS analysis, which confirmed that the PDA and HVA AUCs increased by approximately 2- to 3-fold by PROB pretreatments. PROB also increased the plasma concentrations of hexadecanedioic acid (HDA) and tetradecanedioic acid (TDA), although the increases were not statistically significant. Moreover, transporter profiling assessed using stable cell lines constitutively expressing transporters demonstrated that PDA and HVA are substrates for human OAT1, OAT3, OAT2 (HVA), and OAT4 (PDA), but not OCT2, MATE1, MATE2K, OATP1B1, OATP1B3, and sodium taurocholate cotransporting polypeptide. Collectively, these findings suggest that PDA and HVA might serve as blood-based endogenous probes of cynomolgus monkey OAT1 and OAT3, and investigation of PDA and HVA as circulating endogenous biomarkers of human OAT1 and OAT3 function is warranted. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

Dificuldades enfrentadas pelos pais de crianças com doença do refluxo gastroesofágico

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Cordeiro,Jacqueline Andréia Bernardes Leão; Gualberto,Sacha Martins; Brasil,Virginia Visconde; Oliveira,Grazielle Borges de; Silva,Antonio Márcio Teodoro Cordeiro

2014-01-01

Objetivo Identificar as dificuldades enfrentadas pelos pais de crianças com doença do refluxo gastroesofágico.Métodos Pesquisa qualitativa realizada com 16 familiares de crianças com doença do refluxo gastroesofágico. Foi utilizada uma questão norteadora, as entrevistas foram gravadas e transcritas. Utilizou-se a técnica de análise de conteúdo.Resultados Emergiram oito categorias relacionadas às dificuldades enfrentadas pelos pais: v...

High Expression of UGT1A1/1A6 in Monkey Small Intestine: Comparison of Protein Expression Levels of Cytochromes P450, UDP-Glucuronosyltransferases, and Transporters in Small Intestine of Cynomolgus Monkey and Human.

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Akazawa, Takanori; Uchida, Yasuo; Miyauchi, Eisuke; Tachikawa, Masanori; Ohtsuki, Sumio; Terasaki, Tetsuya

2018-01-02

Cynomolgus monkeys have been widely used for the prediction of drug absorption in humans. The purpose of this study was to clarify the regional protein expression levels of cytochromes P450 (CYPs), UDP-glucuronosyltransferases (UGTs), and transporters in small intestine of cynomolgus monkey using liquid chromatography-tandem mass spectrometry, and to compare them with the corresponding levels in human. UGT1A1 in jejunum and ileum were >4.57- and >3.11-fold and UGT1A6 in jejunum and ileum were >16.1- and >8.57-fold, respectively, more highly expressed in monkey than in human. Also, jejunal expression of monkey CYP3A8 (homologue of human CYP3A4) was >3.34-fold higher than that of human CYP3A4. Among apical drug efflux transporters, BCRP showed the most abundant expression in monkey and human, and the expression levels of BCRP in monkey and human were >1.74- and >1.25-fold greater than those of P-gp and >2.76- and >4.50-fold greater than those of MRP2, respectively. These findings should be helpful to understand species differences of the functions of CYPs, UGTs, and transporters between monkey and human. The UGT1A1/1A6 data would be especially important because it is difficult to identify isoforms responsible for species differences of intestinal glucuronidation by means of functional studies due to overlapping substrate specificity.

Respostas cardiovasculares agudas em ambiente virtualmente simulado pelo Nintendo Wii

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Renato Aparecido de Souza

2013-01-01

Full Text Available DOI: http://dx.doi.org/10.5007/1980-0037.2013v15n1p60 Recentemente, tem sido verificada a utilização do Nintendo Wii no contexto da saúde. O objetivo do presente estudo foi analisar as respostas cardiovasculares agudas monitoradas por meio do comportamento da frequência cardíaca, pressão arterial sistólica, pressão arterial diastólica e duplo produto, em ambiente virtualmente simulado pelo console Nintendo Wii. A amostra foi composta por 18 universitários saudáveis, com média de idade de 22,07 ± 1,34 anos. As variáveis foram observadas com uso de deltas (valor final - inicial após 25 arremessos de basquetebol em duas situações experimentais: (I com o voluntário sentado e, (II com o voluntário saltando verticalmente. Os resultados sugerem que a prática de atividade física em ambiente virtual emulado pelo Nintendo Wii é capaz de alterar as respostas cardiovasculares agudas, especialmente, quando realizada em associação a saltos verticais. Assim, os resultados sustentam a viabilidade do uso do Nintendo Wii em programas de treinamento e favorecem sua indicação de forma mais segura.

Preparation of highly specific radioactivity [{sup 18}F]flumazenil and its evaluation in cynomolgus monkey by positron emission tomography

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Ryzhikov, Nikolaj N. [Institute of Human Brain, Russian Academy of Science, 9, Pavlov str, 197376, Saint Petersburg (Russian Federation); Seneca, Nicholas [Department of Clinical Neuroscience, Karolinska Institutet, Psychiatry Section, Karolinska Hospital, S-17176 Stockholm (Sweden); National Institute of Mental Health, National Institutes of Health, Molecular Imaging Branch, Bethesda, MD 20892 (United States); Krasikova, Raisa N. [Institute of Human Brain, Russian Academy of Science, 9, Pavlov str, 197376, Saint Petersburg (Russian Federation); Gomzina, Natalia A. [Institute of Human Brain, Russian Academy of Science, 9, Pavlov str, 197376, Saint Petersburg (Russian Federation); Shchukin, Evgeny [Department of Clinical Neuroscience, Karolinska Institutet, Psychiatry Section, Karolinska Hospital, S-17176 Stockholm (Sweden); Fedorova, Olga S. [Institute of Human Brain, Russian Academy of Science, 9, Pavlov str, 197376, Saint Petersburg (Russian Federation); Vassiliev, Dmitrij A. [Institute of Human Brain, Russian Academy of Science, 9, Pavlov str, 197376, Saint Petersburg (Russian Federation); Gulyas, Balazs [Department of Clinical Neuroscience, Karolinska Institutet, Psychiatry Section, Karolinska Hospital, S-17176 Stockholm (Sweden); Hall, Hakan [Department of Clinical Neuroscience, Karolinska Institutet, Psychiatry Section, Karolinska Hospital, S-17176 Stockholm (Sweden); Savic, Ivanka [Department of Clinical Neuroscience, Karolinska Institutet, Psychiatry Section, Karolinska Hospital, S-17176 Stockholm (Sweden); Halldin, Christer [Department of Clinical Neuroscience, Karolinska Institutet, Psychiatry Section, Karolinska Hospital, S-17176 Stockholm (Sweden)]. E-mail: christer.halldin@cns.ki.se

2005-02-01

A straightforward method for the preparation of no-carrier-added (n.c.a.) [{sup 18}F]flumazenil via standard nucleophilic radiofluorination of the corresponding nitro-analog Ro 15-2344 has been developed. The labeling was performed by employing the K{sup 18}F/kryptofix complex in DMF at 160 deg. C for 30 min and equimolar ratio [K/K2.2.2]{sup +18}F{sup -}/precursor. Under these conditions, an {sup 18}F incorporation rate into flumazenil was in the range of 55-60%. The final product was isolated by HPLC purification within a total synthesis time of 75 min and a radiochemical yield of about 30% (EOB). Human post-mortem whole-hemisphere autoradiography of brain sections demonstrated selective uptake of the radioligand in the areas of high density of the central benzodiazepine receptors (BZR). PET studies in a cynomolgus monkey and metabolite studies by HPLC demonstrated similar results by [{sup 18}F]flumazenil as for [{sup 11}C]flumazenil. In blocking experiments, almost all radioactivity was inhibited by the addition of unlabeled flumazenil. [{sup 18}F]Flumazenil is a suitable radioligand for PET assessment of the BZR.

Effects of altered FcγR binding on antibody pharmacokinetics in cynomolgus monkeys

Science.gov (United States)

Leabman, Maya K; Meng, Y Gloria; Kelley, Robert F; DeForge, Laura E; Cowan, Kyra J; Iyer, Suhasini

2013-01-01

Antibody interactions with Fcγ receptors (FcγRs), like FcγRIIIA, play a critical role in mediating antibody effector functions and thereby contribute significantly to the biologic and therapeutic activity of antibodies. Over the past decade, considerable work has been directed towards production of antibodies with altered binding affinity to FcγRs and evaluation of how the alterations modulate their therapeutic activity. This has been achieved by altering glycosylation status at N297 or by engineering modifications in the crystallizable fragment (Fc) region. While the effects of these modifications on biologic activity and efficacy have been examined, few studies have been conducted to understand their effect on antibody pharmacokinetics (PK). We present here a retrospective analysis in which we characterize the PK of three antibody variants with decreased FcγR binding affinity caused by amino acid substitutions in the Fc region (N297A, N297G, and L234A/L235A) and three antibody variants with increased FcγRIIIA binding affinity caused by afucosylation at N297, and compare their PK to corresponding wild type antibody PK in cynomolgus monkeys. For all antibodies, PK was examined at a dose that was known to be in the linear range. Since production of the N297A and N297G variants in Chinese hamster ovary cells results in aglycosylated antibodies that do not bind to FcγRs, we also examined the effect of expression of an aglycosylated antibody, without sequence change(s), in E. coli. All the variants demonstrated similar PK compared with that of the wild type antibodies, suggesting that, for the six antibodies presented here, altered FcγR binding affinity does not affect PK. PMID:24492343

Infecção pelo HIV: descritores de mortalidade em pacientes hospitalizados

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Luiz Claudio Santos Thuler

1998-12-01

Full Text Available OBJETIVO: Estudar os descritores clínico-epidemiológicos da mortalidade em pacientes internados por condições clínicas associadas à infecção pelo HIV. MÉTODO: Estudo retrospectivo de todos os pacientes adultos hospitalizados em 1990, 1992 e 1994 em hospital universitário. Os resultados foram descritos como números absolutos, percentagens e médias, sendo a significância estatística entre as diferenças avaliada pelos testes do qui-quadrado, exato de Fisher ou t de Student, conforme o caso. Um modelo de regressão logística foi elaborado visando a identificar os principais fatores associados ao risco de evolução para o óbito. RESULTADOS: Foram incluídos no estudo 240 pacientes. Entre 1990 e 1994 a idade média dos pacientes aumentou de 35,0 para 36,9 anos, a razão entre os sexos masculino e feminino caiu de 9,8 para 2,0, a proporção de não brancos cresceu de 18,5 para 41,3 e registrou-se um aumento do tempo médio entre a descoberta da infecção pelo HIV e a hospitalização de 0,7 para 2,5 anos. Observou-se a redução do número médio de dias de hospitalização de 31,3 para 25,3 e aumento da proporção de pacientes em acompanhamento ambulatorial de 47,8 para 83,3%. As infecções respiratórias representaram a principal causa de hospitalização (58% e as infecções oportunistas apresentadas com maior freqüência foram: candidíase oral (27,1%, tuberculose (18,3%, pneumonia por Pneumocystis carinii (15,4% e neurotoxoplasmose (10,4%. Na análise multivariada, apenas o tempo de hospitalização menor ou igual a 7 dias (Odds Ratio [OR]=3,88; p=0,02 e a ausência de acompanhamento ambulatorial (OR=3,29; p=0,01 mostraram-se associados a um maior risco de evolução para óbito. CONCLUSÃO: O conhecimento dos fatores associados a um risco aumentado de morte pode ser útil na tomada de decisão frente a pacientes hospitalizados com infecção pelo HIV.

Clinical patterns and seasonal trends in respiratory syncytial virus hospitalizations in São Paulo, Brazil Padrões clínicos e sazonalidade das hospitalizações causadas pelo vírus respiratório sincicial em São Paulo, Brasil

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Sandra E. VIEIRA

2001-06-01

Full Text Available The respiratory viruses are recognized as the most frequent lower respiratory tract pathogens for infants and young children in developed countries but less is known for developing populations. The authors conducted a prospective study to evaluate the occurrence, clinical patterns, and seasonal trends of viral infections among hospitalized children with lower respiratory tract disease (Group A. The presence of respiratory viruses in children's nasopharyngeal was assessed at admission in a pediatric ward. Cell cultures and immunofluorescence assays were used for viral identification. Complementary tests included blood and pleural cultures conducted for bacterial investigation. Clinical data and radiological exams were recorded at admission and throughout the hospitalization period. To better evaluate the results, a non- respiratory group of patients (Group B was also constituted for comparison. Starting in February 1995, during a period of 18 months, 414 children were included- 239 in Group A and 175 in Group B. In Group A, 111 children (46.4% had 114 viruses detected while only 5 children (2.9% presented viruses in Group B. Respiratory Syncytial Virus was detected in 100 children from Group A (41.8%, Adenovirus in 11 (4.6%, Influenza A virus in 2 (0.8%, and Parainfluenza virus in one child (0.4%. In Group A, aerobic bacteria were found in 14 cases (5.8%. Respiratory Syncytial Virus was associated to other viruses and/or bacteria in six cases. There were two seasonal trends for Respiratory Syncytial Virus cases, which peaked in May and June. All children affected by the virus were younger than 3 years of age, mostly less than one year old. Episodic diffuse bronchial commitment and/or focal alveolar condensation were the clinical patterns more often associated to Respiratory Syncytial Virus cases. All children from Group A survived. In conclusion, it was observed that Respiratory Syncytial Virus was the most frequent pathogen found in hospitalized

Adolescentes e crack: pelo caminho das pedras

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Eduardo Tomm

2013-12-01

Full Text Available Nos últimos anos, a sociedade tem observado uma rápida expansão no uso de crack, especialmente por adolescentes e jovens. É evidente a necessidade de ouvir esses sujeitos de para melhor compreender sua situação. Para atender a essa necessidade, desenvolvemos uma pesquisa qualitativa descritivo-exploratória cujo foco foi um grupo terapêutico para adolescentes usuários de crack que ocorreu no Centro de Atenção Psicossocial Infanto-Juvenil (CAPSi em uma cidade do interior do Rio Grande do Sul, Brasil. Amparados na modalidade expost-facto, analisamos documentos produzidos nessa instituição. O resultado foi uma cartografia que acompanhou discursivamente os adolescentes pelo "caminho das pedras": os lugares, tratamentos, pessoas, ideias e momentos dos quais falam.

Concentrações séricas de proteína total, albumina e gamaglobulinas em gatos infectados pelo vírus da imunodeficiência felina Serum protein, albumin and gamaglobulin concentrations in cats infected with feline immunodeficiency virus

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Angela Manetti Armentano Rodrigues

2007-02-01

Full Text Available A infecção pelo vírus da imunodeficiência dos felinos (VIF apresenta um curso prolongado, caracterizado por uma fase aguda, em que ocorre a replicação viral no organismo hospedeiro, seguida de um período de menor replicação, no qual o animal é praticamente assintomático. Anos depois, no estádio final da infecção, desenvolve-se a síndrome da imunodeficiência dos felinos. Alguns animais infectados podem desenvolver hipergamaglobulinemia do tipo policlonal, principalmente na fase crônica ou final da infecção. Este fato tem sido atribuído a um distúrbio na produção de citocinas, causado pela infecção viral de linfócitos T CD4+. Não obstante, pouco se sabe a respeito das concentrações de proteínas séricas, especificamente gamaglobulinas, na fase aguda da infecção pelo VIF. Objetivando esclarecer isto, procedeu-se à determinação das proteínas séricas de dez felinos, SRD de ambos os sexos, infectados aos 7 meses de idade com o VIF (clade B, antes da infecção e 4, 8 e 12 meses após. A infecção pelo VIF foi confirmada pela soroconversão, com a presença de anticorpos específicos, pesquisados por meio da técnica de imunoadsorção enzimática (ELISA e pela demonstração de material genético do vírus (PCR. Outros dez felinos VIF-, da mesma faixa etária foram mantidos como controle. Previamente à infecção experimental, todos os felinos eram negativos ao VIF, fato comprovado pela ausência de anticorpos específicos. A proteína sérica total foi determinada pelo método do buireto e as frações protéicas foram obtidas por eletroforese em tiras de acetato de celulose lidas por densitometria. Verificou-se aumento de gamaglobulinas (2,01 ±0,27g dL-1, PFeline immunodeficiency virus (FIV infection is known as a lifelong infection of cats. The acute phase corresponds to the period of viral replication in the host organism, followed by a period of lower replication when the animal is asymptomatic. Some years

Characterization of a Cynomolgus Macaque Model of Pneumonic Plague for Evaluation of Vaccine Efficacy.

Science.gov (United States)

Fellows, Patricia; Price, Jessica; Martin, Shannon; Metcalfe, Karen; Krile, Robert; Barnewall, Roy; Hart, Mary Kate; Lockman, Hank

2015-09-01

The efficacy of a recombinant plague vaccine (rF1V) was evaluated in cynomolgus macaques (CMs) to establish the relationship among vaccine doses, antibody titers, and survival following an aerosol challenge with a lethal dose of Yersinia pestis strain Colorado 92. CMs were vaccinated with a range of rF1V doses on a three-dose schedule (days 0, 56, and 121) to provide a range of survival outcomes. The humoral immune response following vaccination was evaluated with anti-rF1, anti-rV, and anti-rF1V bridge enzyme-linked immunosorbent assays (ELISAs). Animals were challenged via aerosol exposure on day 149. Vaccine doses and antibody responses were each significantly associated with the probability of CM survival (P plague in a dose-dependent manner. There were statistically significant correlations between the vaccine dose and the time to onset of fever (P < 0.0001), the time from onset of fever to death (P < 0.0001), the time to onset of elevated respiratory rate (P = 0.0003), and the time to onset of decreased activity (P = 0.0251) postinfection in animals exhibiting these clinical signs. Delays in the onset of these clinical signs of disease were associated with larger doses of rF1V. Immunization with ≥ 12 μg of rF1V resulted in 100% CM survival. Since both the vaccine dose and anti-rF1V antibody titers correlate with survival, rF1V bridge ELISA titers can be used as a correlate of protection. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Prevalence of oral hairy leukoplakia in 120 pediatric patients infected with HIV-1 Prevalência da leucoplasia pilosa oral em 120 pacientes pediátricos infectados pelo HIV-1

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Eliane Pedra Dias

2006-04-01

Full Text Available Oral hairy leukoplakia (OHL is an EBV (Epstein-Barr virus opportunistic infection found in HIV-infected patients. It is an asymptomatic lesion that has an important prognostic value in AIDS. Differently from what takes place with HIV adult patients, OHL has been described in the literature as having a very small prevalence in pediatric patients. Therefore, the aim of this study was to investigate the prevalence of OHL in HIV pediatric patients using cytopathology. The sample consisted of 120 patients who were submitted to oral examination and had material scraped from both sides of their tongues. The diagnostic criterion was based on the identification of nuclear alterations. Clinical OHL was identified in two (1.67% patients. The cytopathology revealed twenty (16.7% cases of subclinical OHL. Our results show that in pediatric patients the prevalence of OHL may be larger than that described in the literature.A leucoplasia pilosa oral (OHL é uma infecção oportunista causada pelo Vírus Epstein-Barr (EBV encontrada em pacientes infectados pelo HIV. É uma lesão assintomática que tem um importante valor prognóstico na AIDS. Diferentemente de pacientes adultos, a OHL tem sido descrita na literatura como tendo uma prevalência muito pequena em pacientes pediátricos. Logo, o objetivo deste estudo foi investigar a prevalência da OHL em pacientes pediátricos positivos para o HIV através do uso da citopatologia. A amostra consistiu-se de 120 pacientes, que foram submetidos a exame oral e coleta de material de ambos os lados da língua. O critério diagnóstico foi baseado na identificação de alterações nucleares. A OHL clínica foi identificada em dois (1,67% pacientes. A citopatologia revelou vinte casos (16,7% de OHL subclínica. Nossos resultados mostram que a prevalência de OHL em pacientes pediátricos infectados pelo HIV deve ser maior que a relatada na literatura.

RESPONSABILIDADE PELO FATO DO PRODUTO E DO SERVIÇO

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Michele Romero da Costa*

2007-12-01

Full Text Available Este trabalho tem ênfase em apresentar a espécie de responsabilidade adotada pelo Código Brasileiro de Defesa do Consumidor para os fornecedores de produtos e serviços,  qual seja a responsabilidade objetiva, demonstrando uma inovação trazida por este diploma para responsabilidade civil do Direito pátrio. Bem como a sua fundamentação e noções gerais a fim de que se identifiquem as relações em que deve ser o código aplicado, entendidas essas como relações de consumo.

Infestaçao humana pelo Dipylidium caninum

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Carlos Henrique Lemos

1985-12-01

Full Text Available Os autores descrevem um caso de infestação pelo Dipylidium caninum numa criança residente em Araguari, Minas Gerais, que apresentou lesões cutâneas, insônia, irritabilidade, vômitos eperda do apetite. Relatam a eliminação abundante deproglotes quando a paciente foi tratada com medicamentos caseiros e a remissão dos sintomas, após dois tratamentos com mebendazol. Contudo não puderam concluir sobre a eficiência das drogas, devido à medicação empírica e ã administração de 200 mg/dia de mebendazol, contrariando a dosagem recomendada para Cestodas, que é de 400 mg/dia. Relatam, ainda, que exames das fezes do cão de propriedade da família revelaram apenas a presença de ancilostomídeos.

Virus-Vectored Influenza Virus Vaccines

Science.gov (United States)

Tripp, Ralph A.; Tompkins, S. Mark

2014-01-01

Despite the availability of an inactivated vaccine that has been licensed for >50 years, the influenza virus continues to cause morbidity and mortality worldwide. Constant evolution of circulating influenza virus strains and the emergence of new strains diminishes the effectiveness of annual vaccines that rely on a match with circulating influenza strains. Thus, there is a continued need for new, efficacious vaccines conferring cross-clade protection to avoid the need for biannual reformulation of seasonal influenza vaccines. Recombinant virus-vectored vaccines are an appealing alternative to classical inactivated vaccines because virus vectors enable native expression of influenza antigens, even from virulent influenza viruses, while expressed in the context of the vector that can improve immunogenicity. In addition, a vectored vaccine often enables delivery of the vaccine to sites of inductive immunity such as the respiratory tract enabling protection from influenza virus infection. Moreover, the ability to readily manipulate virus vectors to produce novel influenza vaccines may provide the quickest path toward a universal vaccine protecting against all influenza viruses. This review will discuss experimental virus-vectored vaccines for use in humans, comparing them to licensed vaccines and the hurdles faced for licensure of these next-generation influenza virus vaccines. PMID:25105278

A preliminary PET evaluation of the new dopamine D2 receptor agonist [11C]MNPA in cynomolgus monkey

International Nuclear Information System (INIS)

Finnema, Sjoerd J.; Seneca, Nicholas; Farde, Lars; Shchukin, Evgeny; Sovago, Judit; Gulyas, Balazs; Wikstroem, Hakan V.; Innis, Robert B.; Neumeyer, John L.; Halldin, Christer

2005-01-01

This study describes the preliminary positron emission tomography (PET) evaluation of a dopamine D 2 -like receptor agonist (R)-2- 11 CH 3 O-N-n-propylnorapomorphine ([ 11 C]MNPA), as a potential new radioligand for in vivo imaging of the high-affinity state of the dopamine D 2 receptor (D 2 R). MNPA is a selective D 2 -like receptor agonist with a high affinity (K i =0.17 nM). [ 11 C]MNPA was successfully synthesized by direct O-methylation of (R)-2-hydroxy-NPA using [ 11 C]methyl iodide and was evaluated in cynomolgus monkeys. This study included baseline PET experiments and a pretreatment study using unlabeled raclopride (1 mg/kg). High uptake of radioactivity was seen in regions known to contain high D 2 R, with a maximum striatum-to-cerebellum ratio of 2.23±0.21 at 78 min and a maximum thalamus-to-cerebellum ratio of 1.37±0.06 at 72 min. The pretreatment study demonstrated high specific binding to D 2 R by reducing the striatum-to-cerebellum ratio to 1.26 at 78 min. This preliminary study indicates that the dopamine agonist [ 11 C]MNPA has potential as an agonist radioligand for the D 2 -like receptor and has potential for examination of the high-affinity state of the D 2 R in human subjects and patients with neuropsychiatric disorders

Biodistribution of Idursulfase Formulated for Intrathecal Use (Idursulfase-IT in Cynomolgus Monkeys after Intrathecal Lumbar Administration.

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Jou-Ku Chung

Full Text Available Enzyme replacement therapy with intravenous idursulfase (recombinant iduronate-2-sulfatase is approved for the treatment of Hunter syndrome. Intravenous administration does not, however, treat the neurological manifestations, due to its low central nervous system bioavailability. Using intrathecal-lumbar administration, iduronate-2-sulfatase is delivered directly to the central nervous system. This study investigates the central nervous system biodistribution of intrathecal-lumbar administered iduronate-2-sulfatase in cynomolgus monkeys. Twelve monkeys were administered iduronate-2-sulfatase in one 30 mg intrathecal-lumbar injection. Brain, spinal cord, liver, and kidneys were collected for iduronate-2-sulfatase concentration (measured by an enzyme linked immunosorbent assay and enzyme activity measurement (via a method utilizing 4-methylumbelliferyl-α-iduronate-2-sulfate at 1, 2, 5, 12, 24, and 48 hours following administration. The tissue enzyme linked immunosorbent assay confirmed iduronate-2-sulfatase uptake to the brain, spinal cord, kidneys, and liver in a time-dependent manner. In spinal cord and brain, iduronate-2-sulfatase appeared as early as 1 hour following administration, and peak concentrations were observed at ~2 and ~5 hours. Iduronate-2-sulfatase appeared in liver and kidneys 1 hour post intrathecal-lumbar dose with peak concentrations between 5 and 24 hours. Liver iduronate-2-sulfatase concentration was approximately 10-fold higher than kidney. The iduronate-2-sulfatase localization and enzyme activity in the central nervous system, following intrathecal administration, demonstrates that intrathecal-lumbar treatment with iduronate-2-sulfatase may be considered for further investigation as a treatment for Hunter syndrome patients with neurocognitive impairment.

Quantitative control of Lettuce mosaic virus fitness and host defence inhibition by P1-HCPro P1-HC Pro do Lettuce mosaic virus atua de forma quantitativa na inibição da resposta de defesa do hospedeiro e adaptação viral

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Renate Krause-Sakate

2007-06-01

Full Text Available Two Lettuce mosaic virus isolates capable of overcoming the resistance afforded by the resistance gene mo1² in lettuce, LMV-AF199 from Brazil, and LMV-E, an European isolate, were evaluated for the rapidity and severity of symptoms induced on the lettuce variety Salinas 88 (mo1². The mosaic symptoms on Salinas 88 plants inoculated with LMV-AF199 appeared 7 days post-inoculation (dpi and 15 dpi for LMV-E. The symptoms induced by LMV-AF199 in this cultivar were also more severe than those induced by LMV-E. In order to identify the region of the viral genome responsible for this phenotype, recombinant viruses were constructed between these isolates and the phenotype of each recombinant was analysed. The region encoding proteins P1 and HcPro from LMV-AF199 was associated with the increased virulence in Salinas 88.Dois isolados de Lettuce mosaic virus capazes de contornar a resistência conferida pelo gene mo1² em alface, LMV-AF199 proveniente do Brasil e LMV-E um isolado europeu, foram avaliados quanto à rapidez e à severidade dos sintomas induzidos em alface variedade Salinas 88 (mo1². Os sintomas de mosaico induzidos pelo isolado LMV-AF-199 em Salinas 88 são mais severos e aparecem aos 7 dias após a inoculação (dpi, enquanto que para o isolado LMV-E os sintomas são visíveis somente a partir dos 15 dpi. Com o intuito de identificar a região do genoma viral responsável por este fenótipo, vírus recombinantes foram construídos entre estes dois isolados, e o fenótipo avaliado quanto a rapidez e severidade dos sintomas em Salinas-88. A região codificadora para as proteínas P1 e Hc-Pro do LMV-AF199 foi associada com o aumento da virulência deste isolado em Salinas-88.

Movimentos sociais pelo transporte coletivo no Brasil manifestações, estratégias de luta e desafios

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Kader Carvalho Assad

2015-12-01

Full Text Available O artigo trata dos movimentos sociais pelo transporte coletivo no Brasil, enfatizando suas trajetórias, agendas e estratégias de luta pelo acesso ao transporte, entendido como condição imprescindível não apenas para a democratização do espaço urbano, mas também para o acesso aos direitos civis, políticos, sociais, econômicos, culturais e ambientais. A revisão de literatura revela que na trajetória analisada os movimentos pelo transporte recorreram a diferentes estratégias: de manifestações espontâneas como os quebra-quebras e interdição de vias públicas à organização em coletivos abertos e descentralizados; de reivindicações contra o aumento no preço das passagens e protestos contra as péssimas condições de manutenção dos veículos à luta pela gratuidade e estatização do sistema, revelando assim o caráter radical e anticapitalista que adquiriram as lutas desencadeadas nos últimos anos.

Low prevalence of hepatitis B virus, hepatitis D virus and hepatitis C virus among patients with human immunodeficiency virus or acquired immunodeficiency syndrome in the Brazilian Amazon basin Baixa prevalência do vírus da hepatite B, vírus da hepatite D e vírus da hepatite C entre pacientes com o vírus da imunodeficiência humana ou síndrome da imunodeficiência adquirida na Amazônia Brasileira

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Wornei Silva Miranda Braga

2006-12-01

Full Text Available Comorbidities in human immunodeficiency virus infection are of great interest due to their association with unfavorable outcomes and failure of antiretroviral therapy. This study evaluated the prevalence of coinfection by human immunodeficiency virus and viral hepatitis in an endemic area for hepatitis B in the Western Amazon basin. Serological markers for hepatitis B virus, hepatitis C virus and hepatitis D virus were tested in a consecutive sample of all patients referred for treatment of human immunodeficiency virus or acquired immunodeficiency syndrome. The variables sex, age, origin and exposure category were obtained from medical records and from the sexually transmitted diseases and acquired immunodeficiency syndrome surveillance database. Among 704 subjects, the prevalence of chronic hepatitis B carriage was 6.4% and past infection 40.2%. The presence of hepatitis B was associated with birth in hyperendemic areas of the Amazon basin, male sex and illegal drug use. The overall prevalence of hepatitis C was 5% and was associated with illegal drug use. The prevalence of hepatitis B and C among human immunodeficiency virus or acquired immunodeficiency syndrome patients in the Western Amazon basin was lower than seen elsewhere and is probably associated with the local epidemiology of these viruses and the degree of overlap of their shared risk factors. An opportunity presents itself to evaluate the prevention of hepatitis C through harm reduction policies and hepatitis B through vaccination programs among human immunodeficiency virus or acquired immunodeficiency syndrome patients.Co-morbidades na infecção pelo vírus da imunodeficiência humana são de grande interesse devido à associação com desfechos desfavoráveis e falhas na terapia anti-retroviral. Este estudo avalia a prevalência de co-infecção entre o vírus da imunodeficiência humana e hepatites virais, em uma área endêmica de hepatite B, na Amazônia Ocidental. Marcadores

Tratamento da criptococose do sistema nervoso pelo Amphotericin B

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Dante Giorgi

1959-12-01

Full Text Available Os autores descrevem a evolução dos conhecimentos sôbre a meningoen-cefalite produzida pelo Criptococcus neoformans, analisando as dificuldades anteriormente havidas para o diagnóstico em vida, as quais foram superadas depois que se usou rotineiramente a pesquisa do cogumelo no LCR pelo método de coloração de tinta da China e pela cultura. Assinalam, a seguir, o aparecimento do Amphotericin B, novo antibiótico fungicida que veio modificar o prognóstico desta afecção. Apresentam sua experiência com 14 casos de meningite por criptococos diagnosticados em vida e referem pormenorizadamente 2 casos tratados com o Amphotericin B. O primeiro, de paciente portadora desta afecção, evoluindo de maneira crônica, com períodos de exacerbação que melhoram nitidamente com o Amphotericin B e que está com uma sobrevida de 20 meses. O segundo, de paciente portadora de forma aguda desta afecção que teve cura clínica e está com LCR absolutamente normal, com seguimento de 11 meses. Em ambos os casos foi usada a via endovenosa, sendo feitas séries de 10 injeções, cada uma de 50 mg de Amphotericin B em 500 ml de sôro glicosado a 5%. No primeiro caso foram feitas 4 séries e no segundo apenas duas. Não foram registradas reações colaterais de importância. Os autores terminam considerando o Amphotericin B como um elemento que veio tornar muito mais favorável o prognóstico desta afecção até então mortal.

The anti emetic effect of oral administration of ondansetron or granisetron in macacus cynomolgus exposed to mixed neutron-gamma irradiation

International Nuclear Information System (INIS)

Martin, C.; Roman, V.; Martin, S.; Janodet, D.; Fatome, M.

1995-01-01

Nausea and vomiting are the most often observed symptoms in the course of the early radiation syndrome. Their prevention has long been difficult because of the low effectiveness and side-effects of most antiemetics. There is a clear evidence that 5HT 3 receptor antagonists such as ondansetron and granisetron are highly effective to prevent radiation-induced emesis without any side-effect. We studied the prophylactic effectiveness of their oral administration to macacus cynomolgus, for mixed neutron-gamma whole-body exposure, tat high dose rates. Doses of 4 mg of ondansetron or 1 mg of granisetron were administered before, or after, or both before and after irradiation. The treatment was effective when administered both before and after radiation exposure. It was significant but incomplete if administered once. Post-irradiation administration is interesting, particularly in case of accident. Both antiemetic drugs were well tolerated. Their effectiveness and tolerance are apparently comparable. The 5HT 3 receptor antagonists represent a much improved treatment for radiation-induced nausea and vomiting by completely inhibiting emesis, if administered before and after irradiation. Unwanted sedation and extra-pyramidal side-effects, usually associated with the clinical use of D 2 receptor antagonists, were not observed. (authors). 40 refs., 5 tabs

Restabelecimento ("recovery" em plantas de fumo atacadas pelo virus de "vira-cabeça"

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R. Forster

1942-12-01

Full Text Available Observations were made with tobacco plants which, after being naturally infected in the field by the virus of "vira-cabeça", a disease identical to spotted wilt (3, not only resisted to it, but exhibited complete recovery. Several trials were carried out in order to ascertain the following points : 1 whether the recovery means a greater degree of individual constitutional resistance ; 2 whether it represents an acquired immunity or ; 3 whether it is just of pure accidental nature. Plants showing recovery were selfed and seeds collected from them sown in separate rows. The same procedure was always applied with the new recovered plants. Thus, strains of plants were obtained representing several succeeding generations of recovered plants. In 1940-41 recovery progenies were planted at two different transplanting periods. During the next season 1941-42 these progenies, which represented already one more generation in comparison with those of 1940-41, were planted in two districts where the average occurrence of "vira-cabeça" was different. The percentages of "vira-cabeça", observed in all trials, were submitted to statistical analysis, comparing the errors obtained for difference of districts, transplanting time, varieties and progenies representing several generations of recovered plants. Comparing the calculated errors it was found that the greatest effect in the occurrence of ' Vira-cabeça" observed should be attributed to different transplanting times or different districts. The selection of recovered plants showed no influence in lowering the incidence of * vira-cabeça" : hence the impossibility of getting types of tobacco resistant to "vira-cabeça" through selection of recovered plants. Plants were observed in the field that after the first recovery exhibited symptoms of the disease, and then completely recovered from it again. This is in accordance with the results of Smith (11 in the reinoculation of tobacco plants after recovery from

Protection from pulmonary tissue damage associated with infection of cynomolgus macaques by highly pathogenic avian influenza virus (H5N1) by low dose natural human IFN-α administered to the buccal mucosa.

Science.gov (United States)

Strayer, David R; Carter, William A; Stouch, Bruce C; Stittelaar, Koert J; Thoolen, Robert J M M; Osterhaus, Albert D M E; Mitchell, William M

2014-10-01

Using an established nonhuman primate model for H5N1 highly pathogenic influenza virus infection in humans, we have been able to demonstrate the prophylactic mitigation of the pulmonary damage characteristic of human fatal cases from primary influenza virus pneumonia with a low dose oral formulation of a commercially available parenteral natural human interferon alpha (Alferon N Injection®). At the highest oral dose (62.5IU/kg body weight) used there was a marked reduction in the alveolar inflammatory response with minor evidence of alveolar and interstitial edema in contrast to the hemorrhage and inflammatory response observed in the alveoli of control animals. The mitigation of severe damage to the lower pulmonary airway was observed without a parallel reduction in viral titers. Clinical trial data will be necessary to establish its prophylactic human efficacy for highly pathogenic influenza viruses. Copyright © 2014. Published by Elsevier B.V.

Vascular origin of vildagliptin-induced skin effects in Cynomolgus monkeys: pathomechanistic role of peripheral sympathetic system and neuropeptide Y.

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Hoffmann, Peter; Bentley, Phil; Sahota, Pritam; Schoenfeld, Heidi; Martin, Lori; Longo, Linda; Spaet, Robert; Moulin, Pierre; Pantano, Serafino; Dubost, Valerie; Lapadula, Dan; Burkey, Bryan; Kaushik, Virendar; Zhou, Wei; Hayes, Michael; Flavahan, Nick; Chibout, Salah-Dine; Busch, Steve

2014-06-01

The purpose of this article is to characterize skin lesions in cynomolgus monkeys following vildagliptin (dipeptidyl peptidase-4 inhibitor) treatment. Oral vildagliptin administration caused dose-dependent and reversible blister formation, peeling and flaking skin, erosions, ulcerations, scabs, and sores involving the extremities at ≥5 mg/kg/day and necrosis of the tail and the pinnae at ≥80 mg/kg/day after 3 weeks of treatment. At the affected sites, the media and the endothelium of dermal arterioles showed hypertrophy/hyperplasia. Skin lesion formation was prevented by elevating ambient temperature. Vildagliptin treatment also produced an increase in blood pressure and heart rate likely via increased sympathetic tone. Following treatment with vildagliptin at 80 mg/kg/day, the recovery time after lowering the temperature in the feet of monkeys and inducing cold stress was prolonged. Ex vivo investigations showed that small digital arteries from skin biopsies of vildagliptin-treated monkeys exhibited an increase in neuropeptide Y-induced vasoconstriction. This finding correlated with a specific increase in NPY and in NPY1 receptors observed in the skin of vildagliptin-treated monkeys. Present data provide evidence that skin effects in monkeys are of vascular origin and that the effects on the NPY system in combination with increased peripheral sympathetic tone play an important pathomechanistic role in the pathogenesis of cutaneous toxicity. © 2014 by The Author(s).

Long-term blood glucose monitoring with implanted telemetry device in conscious and stress-free cynomolgus monkeys.

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Wang, B; Sun, G; Qiao, W; Liu, Y; Qiao, J; Ye, W; Wang, H; Wang, X; Lindquist, R; Wang, Y; Xiao, Y-F

2017-09-01

Continuous blood glucose monitoring, especially long-term and remote, in diabetic patients or research is very challenging. Nonhuman primate (NHP) is an excellent model for metabolic research, because NHPs can naturally develop Type 2 diabetes mellitus (T2DM) similarly to humans. This study was to investigate blood glucose changes in conscious, moving-free cynomolgus monkeys (Macaca fascicularis) during circadian, meal, stress and drug exposure. Blood glucose, body temperature and physical activities were continuously and simultaneously recorded by implanted HD-XG telemetry device for up to 10 weeks. Blood glucose circadian changes in normoglycemic monkeys significantly differed from that in diabetic animals. Postprandial glucose increase was more obvious after afternoon feeding. Moving a monkey from its housing cage to monkey chair increased blood glucose by 30% in both normoglycemic and diabetic monkeys. Such increase in blood glucose declined to the pre-procedure level in 30 min in normoglycemic animals and >2 h in diabetic monkeys. Oral gavage procedure alone caused hyperglycemia in both normoglycemic and diabetic monkeys. Intravenous injection with the stress hormones, angiotensin II (2 μg/kg) or norepinephrine (0.4 μg/kg), also increased blood glucose level by 30%. The glucose levels measured by the telemetry system correlated significantly well with glucometer readings during glucose tolerance tests (ivGTT or oGTT), insulin tolerance test (ITT), graded glucose infusion (GGI) and clamp. Our data demonstrate that the real-time telemetry method is reliable for monitoring blood glucose remotely and continuously in conscious, stress-free, and moving-free NHPs with the advantages highly valuable to diabetes research and drug discovery.

Responsabilidade civil das empresas de construção civil pelos vícios e defeitos do produto

OpenAIRE

Guedes Júnior, Alberto Augusto

2013-01-01

Responsabilidade civil das empresas de construção civil pelos vícios e defeitos do produto. A discussão ocorre através da análise rápida da evolução do sistema da responsabilidade civil o ordenamento geral e na legislação do consumidor, considerando o afastamento da teoria da culpa e o fortalecimento da responsabilização objetiva com fundamento a boa-fé. Este conflito e interação entre os códigos no que tange a responsabilização civil pelos acidentes de consumo traça a base dos ...

Ocorrência generalizada do Lettuce mottle virus em três regiões produtoras de alface comercial do Estado de São Paulo Occurrence of Lettuce mottle virus on three lettuce producing areas from São Paulo State

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Renate Krause-Sakate

2008-02-01

Full Text Available Os sequivírus são vírus isométricos transmitidos por afídeos. Lettuce mottle virus (LeMoV, um provável sequivirus foi descrito no Brasil em 1982 e causa sintomas de mosaico semelhantes aos observados pelo Lettuce mosaic virus (LMV. Um levantamento para ocorrência do LeMoV nos campos de produção de alface de três diferentes regiões do Estado de São Paulo (Mogi das Cruzes, Campinas e Bauru foi realizado durante 2002 a 2005. RNA total foi extraído e utilizado na detecção, em RT-PCR, com oligonucleotídeos específicos para o LeMoV. Do total de 1362 amostras, 137 (10,05% foram positivas para o LeMoV. Infecção mista com o LMV foi verificada em 43 amostras (31,4%. Foi verificada a ocorrência do LeMoV nas três diferentes regiões analisadas, porém sua ocorrência foi baixa nas diferentes épocas do ano.Sequiviruses are isometric aphid-borne plant viruses. Lettuce mottle virus (LeMoV, a putative sequivirus was first described in Brazil on 1982 causing similar mosaic symptoms as Lettuce mosaic virus (LMV. A survey for the occurrence of LeMoV on open field conditions was carried out during 2002 to 2005 on Mogi das Cruzes, Campinas and Bauru in São Paulo state. Total RNA was extracted and used on RT-PCR with specific LeMoV primers. On 1362 samples tested, 137 (10,05% were positive for LeMoV. Mixed infections with LMV was observed on 43 samples (31,4%. The presence of LeMoV was observed in the three different regions, but with low incidence during the year.

Transplantation of micro- and macroencapsulated piglet islets into mice and monkeys.

Science.gov (United States)

Elliott, R B; Escobar, L; Calafiore, R; Basta, G; Garkavenko, O; Vasconcellos, A; Bambra, C

2005-01-01

Neonatal porcine islets within alginate microcapsules transplanted intraperitoneally (IP) or within semi-permeable macrocapsules (TheraCyte) and transplanted subcutaneously (SC) survive and reverse diabetes for up to 16 weeks in diabetic autoimmune nonobese diabetic (NOD) mice. The islets in microcapsules transplanted IP into nondiabetic cynomolgus monkeys survived for 8 weeks. Similar results were shown with islets transplanted in TheraCytes. Neither species showed adverse effects or evidence of infection with porcine endogenous retroviruses or other endemic pig viruses. Proof of principle is illustrated for successful xenotransplantation in humans.

Efeito do Soursop yellow blotch virus no desenvolvimento vegetativo e na produção da gravioleira Effect of the Soursop yellow blotch virus on the growth and yield of soursop diseased plants

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Antonio A. dos Santos

2007-03-01

Full Text Available Os danos causados no desenvolvimento vegetativo e na produção de frutos da gravioleira pelo vírus da mancha-amarela da gravioleira (Soursop yellow blotch virus, SYBV, foram estudados durante os anos de 2000 a 2004 em um experimento com dois tratamentos: plantas sadias e plantas doentes, dispostos em blocos ao acaso, com oito repetições e quatro plantas por parcela. Foram avaliados, anualmente, a altura da planta, diâmetro do caule, número e peso de frutos, sendo que a produção foi monitorada a partir do segundo ano de plantio. As médias relativas à altura de planta, diâmetro do caule, número e peso de frutos das parcelas foram computadas, analisadas estatisticamente e comparadas pelo teste F. As plantas de ambos tratamentos foram originadas de mudas enxertadas, sendo as plantas doentes obtidas por meio de enxertias com propágulos de plantas infectadas com o SYBV. A doença reduziu em 65,11% e 46,72% a altura e o diâmetro do caule, respectivamente, e em 94,7 % e 99,2 % o número e o peso de frutos em relação às plantas sadias.Growth and yield losses on soursop plants due the Soursop yellow blotch virus (SYBV disease were studied during the years 2000 to 2004 in an experiment with two treatments: healthy and SYBV diseased plants. The experiment was disposed in a completely randomized block design with 8 replications with 4 plants per plot. Plant height, trunk diameter, number and weight of fruits were evaluated annually. Data, as plot means, was computed, statistically analyzed and compared by F test. Plants of both treatments were obtained by grafting with buds from healthy and SYBV infected plants. The disease caused percent reductions of 65.11, 46.72, 94.7 and 99.2 in plant height, trunk diameter, in fruit number and fruit weight, respectively.

Valores de referência para macronutrientes em eucalipto obtidos pelos métodos DRIS e chance matemática

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P. G. S. Wadt

1998-12-01

Full Text Available Informações de 1.213 árvores de plantios comerciais foram obtidas, entre os anos de 1988 a 1994, de híbridos de Eucalyptus grandis x E. urophylla, da Aracruz Celulose S.A., cultivados no estado do Espírito Santo, Brasil. Os resultados da produtividade e concentração dos macronutrientes em quatro órgãos das árvores foram utilizados na obtenção dos valores de referência para a concentração dos nutrientes, pelos métodos da Chance Matemática e do DRIS. Empregou-se, no cálculo dos índices DRIS, a fórmula de Jones (1981, a divisão da população-base em estratos de idade e a seleção das relações entre os nutrientes pelo teste F. O nível crítico dos nutrientes foi atingido pelo DRIS por meio de dois critérios: pela concentração média dos nutrientes nos talhões nutricionalmente balanceados e produtivos (NCO e pelo critério gráfico (NCG. O primeiro critério mostrou-se mais promissor, inclusive em relação ao método da Chance Matemática, o qual foi adequado principalmente para a determinação de faixa ótima que poderia ser adotada como referência para o limite inferior e o superior de árvores com níveis adequados dos nutrientes.

Espíritos cheios de bichos: A fauna nas viagens de Louis Agassiz e Richard Francis Burton pelo Brasil oitocentista

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Janaina Zito Losada

2015-04-01

Full Text Available O Brasil do século XIX foi alvo de inúmeras viagens realizadas por cientistas estrangeiros. O objetivo deste artigo é analisar as impressões sobre a fauna brasileira presentes nos relatos das viagens realizadas pelo naturalista suíço Louis Agassiz, em 1865, e pelo explorador inglês Richard Francis Burton, em 1868. Destes relatos privilegiam-se as descrições do meio natural de diferentes regiões brasileiras e das particularidades da fauna silvestre por eles encontrada.

Nairobi sheep disease virus/Ganjam virus.

Science.gov (United States)

M D, Baron; B, Holzer

2015-08-01

Nairobi sheep disease virus (NSDV) is a tick-borne virus which causes a severe disease in sheep and goats, and has been responsible for several outbreaks of disease in East Africa. The virus is also found in the Indian subcontinent, where it is known as Ganjam virus. The virus only spreads through the feeding of competent infected ticks, and is therefore limited in its geographic distribution by the distribution of those ticks, Rhipicephalus appendiculata in Africa and Haemaphysalis intermedia in India. Animals bred in endemic areas do not normally develop disease, and the impact is therefore primarily on animals being moved for trade or breeding purposes. The disease caused by NSDV has similarities to several other ruminant diseases, and laboratory diagnosis is necessary for confirmation. There are published methods for diagnosis based on polymerase chain reaction, for virus growth in cell culture and for other simple diagnostic tests, though none has been commercialised. There is no established vaccine against NSDV, although cell-culture attenuated strains have been developed which show promise and could be put into field trials if it were deemed necessary. The virus is closely related to Crimean-Congo haemorrhagic fever virus, and studies on NSDV may therefore be useful in understanding this important human pathogen.

Hepatites pós-transfusionais na cidade de Campinas, SP, Brasil: II. Presença dos anticorpos anti-HBc e anti-HCV em candidatos a doadores de sangue e ocorrência de hepatites pós-transfusionais pelo vírus C nos receptores de sangue ou derivados Post-transfusional hepatitis in the city of Campinas, SP, Brazil: II- Presence of anti-HBc and anti-HCV antibodies in blood donors and occurrence of post-transfusional hepatitis C virus in recipients of blood or derivates

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Fernando Lopes Gonçales Júnior

1993-02-01

Full Text Available Pesquisamos os anticorpos anti-HBc e anti-HCV em amostras de soros provenientes de 799 candidatos a doadores, que tiveram suas unidades de sangue ou derivados transfundidas a 111 receptores. O anti-HBc e o anti-HCV foram reagentes, em respectivamente 9 e 2,1% dos doadores testados. Observamos que entre os 111 receptores, 44 haviam recebido pelo menos uma unidade anti-HBc positiva e 67 haviam sido transfundidos somente com unidades anti-HBc negativas. Houve um risco 4,5 vezes maior de aquisição de hepatite por vírus C pelos receptores que receberam pelo menos uma unidade anti-HBc positiva Se a pesquisa do anti-HBc fosse realizada na triagem sorológica dos doadores de sangue, cerca de 56% dos casos de HVC nos receptores saiam evitados. A população de receptores que recebeu pelo menos uma unidade anti-HCV reagente, apresentou um risco 29 vezes maior de adquirir esta hepatite, quando comparada aos receptores transfundidos com todas as unidades anti-HCV negativas. A realização do teste para a pesquisa do anti-HCV na triagem dos doadores de sangue, preveniria 79% dos casos de HVC pós-transfusionais. Os candidatos a doadores brasileiros parecem ser acometidos simultânea ou sequencialmente, pelos vírus B e C das hepatites, pois, 44,4% dos doadores anti-HCV positivos, também foram anti-HBc positivos. A realização dos testes para as pesquisas dos anticorpos anti-HBc e anti-HCV, nas triagens hemoterápicas, está indicada para prevenir a transmissão de hepatites pós-transfusionais, em nosso meio.We have analysed anti-HBc and anti-HCV antibodies in serum samples from 799 donors which had their blood or derivates transfused to 111 recipients. Anti-HBc and anti-HCV were reactive in respectively 9 and 2.1% of the donors tested. We have observed that among the 111 recipients, 44 had received at least one positive anti-HBc unit and 67 had been transfused only with negative anti-HBc, units. The risk of developing hepatitis C virus was 4.5 times

DIAGNOSTICS OF VIRUS PHYTOPATHOGENS FRUIT TREE PLUM POX VIRUS, PRUNUS NECROTIC RINGSPOT VIRUS AND PRUNUS DWARF VIRUS BY BIOLOGICAL AND MOLECULAR DIAGNOSTICS

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Július Rozák

2013-02-01

Full Text Available The aim of this study was to determine the incidence of viral phytopathogen Plum pox virus, Prunus necrotic ringspot virus and Prunus dwarf virus in selected localities of Slovakia and diagnose them using a molecular and biological methods. Forty samples of fruit trees of the genus Prunus, twenty samples from intensive plantings and twenty samples from wild subject were analysed. Biological diagnostic by using biological indicators Prunus persica cv. GF 305, Prunus serrulata cv. Schirofugen and molecular diagnostic by mRT-PCR were applied. Five samples with Plum pox virus were infected. The two samples positive for Prunus necrotic ringspot virus and one sample for Prunus dwarf virus were confirmed. The two samples were found to be infected with two viruses Prunus necrotic ringspot virus and Prunus dwarf virus. This work focuses on two techniques, their application to the diagnosis of stone fruit viruses and their routinely used for sanitary and certification programmes.

Somatic cell nuclear transfer using transported in vitro-matured oocytes in cynomolgus monkey.

Science.gov (United States)

Chen, N; Liow, S-L; Abdullah, R Bin; Embong, W Khadijah Wan; Yip, W-Y; Tan, L-G; Tong, G-Q; Ng, S-C

2007-02-01

Somatic cell nuclear transfer (SCNT) is not successful so far in non-human primates. The objective of this study was to investigate the effects of stimulation cycles (first and repeat) on oocyte retrieval and in vitro maturation (IVM) and to evaluate the effects of stimulation cycles and donor cell type (cumulus and fetal skin fibroblasts) on efficiency of SCNT with transported IVM oocytes. In this study, 369 immature oocytes were collected laparoscopically at 24 h following human chorionic gonadotrophin (hCG) treatment from 12 cynomolgus macaque (Macaca fascicularis) in 24 stimulation cycles, and shipped in pre-equilibrated IVM medium for a 5 h journey, placed in a dry portable incubator (37 degrees C) without CO(2) supplement. A total of 70.6% (247/350) of immature oocytes reached metaphase II (MII) stage at 36 h after hCG administration, MII spindle could be seen clearly in 80.6% (104/129) of matured IVM oocytes under polarized microscopy. A total of 50.0% (37/74) of reconstructive SCNT embryos cleaved after activation; after cleavage, 37.8% (14/37) developed to the 8-cell stage and 8.1% (3/37) developed to morula, but unfortunately none developed to the blastocyst stage. Many more oocytes could be retrieved per cycle from monkeys in the first cycle than in repeated cycles (19.1 vs. 11.7, p vs. 71.4%, p > 0.05) and MII spindle rate under polarized microscopy (76.4 vs. 86.0%, p > 0.05) between the first and repeat cycles. There were also no significant differences in the cleavage rate, and the 4-cell, 8-cell and morula development rate of SCNT embryos between the first and repeat cycles. When fibroblast cells and cumulus cells were used as the donor cells for SCNT, first cleavage rate was not significantly different, but 4-cell (50.0 vs. 88.9%, p vs. 51.9%, p < 0.01) development rate were significantly lower for the former. In conclusion, the number of stimulation cycles has a significant effect on oocyte retrieval, but has no effect on maturation and SCNT embryo

Estimativa do risco de infecção tuberculosa em populações vacinadas pelo BCG

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Arantes Gilberto Ribeiro

1992-01-01

Full Text Available A revacinação de escolares com BCG, capaz de restaurar a alergia remanescente de vacinação realizada nos primeiros meses de vida, porém incapaz de modificar a alergia devida à infecção pelo M. tuberculosis, possibilitaria a quantificação da parcela dessa população infectada pelo bacilo de Koch. Foi desenvolvida pesquisa com o objetivo de avaliar a aplicabilidade desses pressupostos na estimativa do risco de infecção tuberculosa em áreas sob elevada cobertura com BCG. A população de estudo foi constituída por escolares com 6 a 9 anos de idade freqüentando escolas municipais da zona leste da cidade de São Paulo, durante o primeiro semestre letivo de 1988. De 11.455 vacinados, apenas 7.470 foram submetidos ao teste tuberculínico, revacinados em seguida e retestados dez semanas depois. Destes, 3.314 tinham sido vacinados no primeiro trimestre de vida com meia dose e os demais 4.156 receberam dose plena acima dessa idade (75% no primeiro ano de vida, 20% no segundo e 5% no terceiro. A contagem dos infectados, pelo confronto dos resultados pré e pós vacinais em tabelas de correlação, foi realizada segundo os critérios do método original e modificação introduzida pelos autores, separadamente para os vacinados no primeiro trimestre de vida e após essa idade. O risco de infecção foi, respectivamente, 0,35% e 0,37% com o critério original e 0,45% e 0,49% com o modificado. O referencial médio disponível para a área estudada, estimado por outros métodos, foi 0,55%. As diferenças entre critérios e idades e destes com o referencial não foram significantes (P > 0,05. Os resultados sugerem que o método é aplicável para a estimativa do risco de infecção tuberculosa na idade escolar, em vacinados com BCG no primeiro ano de vida, com dose plena de vacina.

Estimativa do risco de infecção tuberculosa em populações vacinadas pelo BCG

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Gilberto Ribeiro Arantes

1992-04-01

Full Text Available A revacinação de escolares com BCG, capaz de restaurar a alergia remanescente de vacinação realizada nos primeiros meses de vida, porém incapaz de modificar a alergia devida à infecção pelo M. tuberculosis, possibilitaria a quantificação da parcela dessa população infectada pelo bacilo de Koch. Foi desenvolvida pesquisa com o objetivo de avaliar a aplicabilidade desses pressupostos na estimativa do risco de infecção tuberculosa em áreas sob elevada cobertura com BCG. A população de estudo foi constituída por escolares com 6 a 9 anos de idade freqüentando escolas municipais da zona leste da cidade de São Paulo, durante o primeiro semestre letivo de 1988. De 11.455 vacinados, apenas 7.470 foram submetidos ao teste tuberculínico, revacinados em seguida e retestados dez semanas depois. Destes, 3.314 tinham sido vacinados no primeiro trimestre de vida com meia dose e os demais 4.156 receberam dose plena acima dessa idade (75% no primeiro ano de vida, 20% no segundo e 5% no terceiro. A contagem dos infectados, pelo confronto dos resultados pré e pós vacinais em tabelas de correlação, foi realizada segundo os critérios do método original e modificação introduzida pelos autores, separadamente para os vacinados no primeiro trimestre de vida e após essa idade. O risco de infecção foi, respectivamente, 0,35% e 0,37% com o critério original e 0,45% e 0,49% com o modificado. O referencial médio disponível para a área estudada, estimado por outros métodos, foi 0,55%. As diferenças entre critérios e idades e destes com o referencial não foram significantes (P > 0,05. Os resultados sugerem que o método é aplicável para a estimativa do risco de infecção tuberculosa na idade escolar, em vacinados com BCG no primeiro ano de vida, com dose plena de vacina.

Effect of Agaricus brasiliensis and Lentinula edodes mushrooms on the infection of passionflower with Cowpea aphid-borne mosaic virus

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Robson Marcelo Di Piero

2010-04-01

Full Text Available The objective of the present study was to evaluate the protection of passion fruit plants against CABMV by using preparations from Agaricus brasiliensis and Lentinula edodes mushrooms. In experiments carried out in the greenhouse, the fruiting body extracts from some of the isolates of both mushrooms significantly reduced CABMV incidence in passion fruit plants. This protective effect occurred when the plant leaves, pre-treated with extracts, were later inoculated mechanically with the virus. However, the extracts did not protect the plants in experiments involving CABMV transmission by aphid vectors. An inhibitory effect of mushroom extracts on the virus particles was also demonstrated on Chenopodium quinoa, a CABMV local lesion host, by inoculating the plants with a mixture of extracts and virus suspension. Still in C. quinoa, the mushroom extracts from some isolates induced systemic resistance against the virus. These results showed that aqueous extracts from A. brasiliensis and L. edodes fruiting bodies had CABMV infectivity inhibitors, but that was not enough to control the viral disease on passion fruit plants at all, considering they were infected through a vector.O endurecimento dos frutos do maracujazeiro, causado pelo Cowpea aphid-borne mosaic virus (CABMV, é um dos problemas mais sérios que atingem a cultura. Tentativas de se obter plantas resistentes ao vírus ou estirpes fracas premunizantes não apresentaram sucesso até o momento. O objetivo do presente estudo foi o de avaliar a proteção das plantas de maracujá contra o CABMV, utilizando preparações dos cogumelos Lentinula edodes e Agaricus blazei, através da indução de resistência. Em experimentos conduzidos no interior de casa de vegetação, os extratos de basidiocarpos de ambos os cogumelos reduziram significativamente a incidência da virose em plantas de maracujá que tiveram as folhas pré-tratadas com esses extratos e que foram posteriormente inoculadas

Oncogenic Viruses and Breast Cancer: Mouse Mammary Tumor Virus (MMTV, Bovine Leukemia Virus (BLV, Human Papilloma Virus (HPV, and Epstein–Barr Virus (EBV

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James S. Lawson

2018-01-01

Full Text Available BackgroundAlthough the risk factors for breast cancer are well established, namely female gender, early menarche and late menopause plus the protective influence of early pregnancy, the underlying causes of breast cancer remain unknown. The development of substantial recent evidence indicates that a handful of viruses may have a role in breast cancer. These viruses are mouse mammary tumor virus (MMTV, bovine leukemia virus (BLV, human papilloma viruses (HPVs, and Epstein–Barr virus (EBV-also known as human herpes virus type 4. Each of these viruses has documented oncogenic potential. The aim of this review is to inform the scientific and general community about this recent evidence.The evidenceMMTV and human breast cancer—the evidence is detailed and comprehensive but cannot be regarded as conclusive. BLV and human breast cancer—the evidence is limited. However, in view of the emerging information about BLV in human breast cancer, it is prudent to encourage the elimination of BLV in cattle, particularly in the dairy industry. HPVs and breast cancer—the evidence is substantial but not conclusive. The availability of effective preventive vaccines is a major advantage and their use should be encouraged. EBV and breast cancer—the evidence is also substantial but not conclusive. Currently, there are no practical means of either prevention or treatment. Although there is evidence of genetic predisposition, and cancer in general is a culmination of events, there is no evidence that inherited genetic traits are causal.ConclusionThe influence of oncogenic viruses is currently the major plausible hypothesis for a direct cause of human breast cancer.

Oncogenic Viruses and Breast Cancer: Mouse Mammary Tumor Virus (MMTV), Bovine Leukemia Virus (BLV), Human Papilloma Virus (HPV), and Epstein-Barr Virus (EBV).

Science.gov (United States)

Lawson, James S; Salmons, Brian; Glenn, Wendy K

2018-01-01

Although the risk factors for breast cancer are well established, namely female gender, early menarche and late menopause plus the protective influence of early pregnancy, the underlying causes of breast cancer remain unknown. The development of substantial recent evidence indicates that a handful of viruses may have a role in breast cancer. These viruses are mouse mammary tumor virus (MMTV), bovine leukemia virus (BLV), human papilloma viruses (HPVs), and Epstein-Barr virus (EBV-also known as human herpes virus type 4). Each of these viruses has documented oncogenic potential. The aim of this review is to inform the scientific and general community about this recent evidence. MMTV and human breast cancer-the evidence is detailed and comprehensive but cannot be regarded as conclusive. BLV and human breast cancer-the evidence is limited. However, in view of the emerging information about BLV in human breast cancer, it is prudent to encourage the elimination of BLV in cattle, particularly in the dairy industry. HPVs and breast cancer-the evidence is substantial but not conclusive. The availability of effective preventive vaccines is a major advantage and their use should be encouraged. EBV and breast cancer-the evidence is also substantial but not conclusive. Currently, there are no practical means of either prevention or treatment. Although there is evidence of genetic predisposition, and cancer in general is a culmination of events, there is no evidence that inherited genetic traits are causal. The influence of oncogenic viruses is currently the major plausible hypothesis for a direct cause of human breast cancer.

Reactivation of organophosphate-inhibited human, Cynomolgus monkey, swine and guinea pig acetylcholinesterase by MMB-4: A modified kinetic approach

International Nuclear Information System (INIS)

Worek, Franz; Wille, Timo; Aurbek, Nadine; Eyer, Peter; Thiermann, Horst

2010-01-01

Treatment of poisoning by highly toxic organophosphorus compounds (OP, nerve agents) is a continuous challenge. Standard treatment with atropine and a clinically used oxime, obidoxime or pralidoxime is inadequate against various nerve agents. For ethical reasons testing of oxime efficacy has to be performed in animals. Now, it was tempting to investigate the reactivation kinetics of MMB-4, a candidate oxime to replace pralidoxime, with nerve agent-inhibited acetylcholinesterase (AChE) from human and animal origin in order to provide a kinetic basis for the proper assessment of in vivo data. By applying a modified kinetic approach, allowing the use of necessary high MMB-4 concentrations, it was possible to determine the reactivation constants with sarin-, cyclosarin-, VX-, VR- and tabun-inhibited AChE. MMB-4 exhibited a high reactivity and low affinity towards OP-inhibited AChE, except of tabun-inhibited enzyme where MMB-4 had an extremely low reactivity. Species differences between human and animal AChE were low (Cynomolgus) to moderate (swine, guinea pig). Due to the high reactivity of MMB-4 a rapid reactivation of inhibited AChE can be anticipated at adequate oxime concentrations which are substantially higher compared to HI-6. Additional studies are necessary to determine the in vivo toxicity, tolerability and pharmacokinetics of MMB-4 in humans in order to enable a proper assessment of the value of this oxime as an antidote against nerve agent poisoning.

Reactivation of organophosphate-inhibited human, Cynomolgus monkey, swine and guinea pig acetylcholinesterase by MMB-4: a modified kinetic approach.

Science.gov (United States)

Worek, Franz; Wille, Timo; Aurbek, Nadine; Eyer, Peter; Thiermann, Horst

2010-12-15

Treatment of poisoning by highly toxic organophosphorus compounds (OP, nerve agents) is a continuous challenge. Standard treatment with atropine and a clinically used oxime, obidoxime or pralidoxime is inadequate against various nerve agents. For ethical reasons testing of oxime efficacy has to be performed in animals. Now, it was tempting to investigate the reactivation kinetics of MMB-4, a candidate oxime to replace pralidoxime, with nerve agent-inhibited acetylcholinesterase (AChE) from human and animal origin in order to provide a kinetic basis for the proper assessment of in vivo data. By applying a modified kinetic approach, allowing the use of necessary high MMB-4 concentrations, it was possible to determine the reactivation constants with sarin-, cyclosarin-, VX-, VR- and tabun-inhibited AChE. MMB-4 exhibited a high reactivity and low affinity towards OP-inhibited AChE, except of tabun-inhibited enzyme where MMB-4 had an extremely low reactivity. Species differences between human and animal AChE were low (Cynomolgus) to moderate (swine, guinea pig). Due to the high reactivity of MMB-4 a rapid reactivation of inhibited AChE can be anticipated at adequate oxime concentrations which are substantially higher compared to HI-6. Additional studies are necessary to determine the in vivo toxicity, tolerability and pharmacokinetics of MMB-4 in humans in order to enable a proper assessment of the value of this oxime as an antidote against nerve agent poisoning. Copyright © 2010 Elsevier Inc. All rights reserved.

Evolutionary relationship of alfalfa mosaic virus with cucumber mosaic virus and brome mosaic virus

OpenAIRE

Savithri, HS; Murthy, MRN

1983-01-01

The amino acid sequences of the non-structural protein (molecular weight 35,000; 3a protein) from three plant viruses - cucumber mosaic, brome mosaic and alfalfa mosaic have been systematically compared using the partial genomic sequences for these three viruses already available. The 3a protein of cucumber mosaic virus has an amino acid sequence homology of 33.7% with the corresponding protein of brome mosaic virus. A similar protein from alfalfa mosaic virus has a homology of 18.2% and 14.2...

Riscos percebidos pelo consumidor e estratégias para minimizá-los no consumo de saladas de horataliças cruas em restaurantes à la carte

OpenAIRE

Mariana Schievano Danelon

2012-01-01

Resumo: O padrão alimentar da população brasileira tem sido caracterizado, entre outros aspectos, pelo reduzido consumo de hortaliças e pelo crescimento do número de refeições realizadas fora do domicílio. A utilização dos serviços de alimentação pode representar oportunidade para a inclusão de variedade de hortaliças na dieta. Tem sido pouco estudado, no Brasil, o comportamento do consumidor quando se alimenta fora de casa. Este pode ser influenciado pelos riscos percebidos em uma situação d...

Alternative Splicing of AMPA subunits in Prefrontal Cortical Fields of Cynomolgus Monkeys following Chronic Ethanol Self-Administration

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Glen eAcosta

2012-01-01

Full Text Available Functional impairment of the orbital and medial prefrontal cortex underlies deficits in executive control that characterize addictive disorders, including alcohol addiction. Previous studies indicate that alcohol alters glutamate neurotransmission and one substrate of these effects may be through the reconfiguration of the subunits constituting ionotropic glutamate receptor (iGluR complexes. Glutamatergic transmission is integral to cortico-cortical and cortico-subcortical communication and alcohol-induced changes in the abundance of the receptor subunits and/or their splice variants may result in critical functional impairments of prefrontal cortex in alcohol dependence. To this end, the effects of chronic ethanol self-administration on glutamate receptor ionotropic AMPA (GRIA subunit variant and kainate (GRIK subunit mRNA expression were studied in the orbitofrontal cortex (OFC, dorsolateral prefrontal cortex (DLPFC and anterior cingulate cortex (ACC of male cynomolgus monkeys. In DLPFC, total AMPA splice variant expression and total kainate receptor subunit expression were significantly decreased in alcohol drinking monkeys. Expression levels of GRIA3 flip and flop and GRIA4 flop mRNAs in this region were positively correlated with daily ethanol intake and blood ethanol concentrations averaged over the six months prior to necropsy. In OFC, AMPA subunit splice variant expression was reduced in the alcohol treated group. GRIA2 flop mRNA levels in this region were positively correlated with daily ethanol intake and blood ethanol concentrations averaged over the six months prior to necropsy. Results from these studies provide further evidence of transcriptional regulation of iGluR subunits in the primate brain following chronic alcohol self-administration. Additional studies examining the cellular localization of such effects in the framework of primate prefrontal cortical circuitry are warranted.

A Disputa pelo sentido: o jogo de poder na Comunicação Organizacional

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Márcia Maria Garçon

2013-12-01

Full Text Available Este trabalho adotou como aporte teórico, os clássicos de Blumer (1980, Bakhtin (1995, Foucalt (1996 e Galbraith (1986 e os estudos contemporâneos da Comunicação Organizacional pautados no paradigma da produção de sentido (OLIVEIRA; PAULA, 2008 e da gestão sistêmica (YANAZE, 2011 com o objetivo de identificar as relações de poder e luta pelo sentido do projeto social Comunidade Educativa, promovido pela Fundação Bunge na E.E. Henrique Dumont Villares, na capital paulista. Foram realizadas entrevistas qualitativas, em profundidade, com os representantes da Fundação e da Escola e suas narrativas, classificadas em categorias léxico-semânticas de semelhança, complementaridade, diversidade e divergência, sendo posteriormente confrontadas, a fim de identificar o embate dos sentidos. Os resultados apontaram que os interesses particulares pautaram a luta pelo sentido e o poder, que a princípio esteve de posse da Fundação, migrou para o campo dos professores, sendo o significado construído entre estes sujeitos, o hegemônico nesta interação.

Regulatory T cells participation in the infection immunopathogenesis by the Human Immunodeficiency Virus (HIV-1 Participação de células T regulatórias (Tregs na imunopatogênese da infecção pelo vírus da imunodeficiência humana 1 (HIV-1

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Isabele Kazahaya Borges

2010-12-01

Full Text Available The survival of patients infected with human immunodeficiency virus (HIV-1 is related to the prevention and effective treatment of opportunistic infections. It is known that the main parameters to evaluate the progression of disease caused by HIV-1 is the counting of CD4 + T cells and viral load of HIV-1. Regulatory T cells has been considered the focus of intense research within the immune system as well as in the pathogenesis of several diseases. Natural regulatory T cells (Tregs CD4+CD25+ act in the modulation of immune activation, functioning as critical mediators of immune homeostasis and self-tolerance. Furthermore, recent studies has shown that the function of Tregs cells is not limited to the prevention of autoimmunity, but is also important to control all forms of immune responses in the context of inflammation, infection, allergy, transplantation and tumor immunity. Many authors have identified Tregs as beneficial effector cells in the context of AIDS, but other researchers disagree. Tregs can exert an important role in the immunopathology of HIV infection due to the suppressor activity on cellular activation and effector function. Thus, this review discusses the molecular and immunological aspects of Tregs in the HIV system. A sobrevivência de pacientes infectados pelo vírus da imunodeficiência humana (HIV-1 é relacionada à prevenção e ao tratamento eficaz de infecções oportunistas. É conhecido que os principais parâmetros para avaliar a progressão da doença causada pelo HIV-1 são contagem de células T CD4+ e carga viral do HIV-1. Células T regulatórias têm sido foco de intensas investigações dentro do sistema imunológico como também na patogênese de diversas doenças. Sabe-se que as células T reguladoras (Tregs CD4+CD25+FoxP3+ atuam na modulação da ativação imune, funcionando como mediadores críticos da homeostasia imune e da auto-tolerância. Além disso, recentes estudos têm demonstrado que as c

OS BENEFÍCIOS PERCEBIDOS PELOS PRINCIPAIS STAKEHOLDERS DE UMA REDE DE EMPRESAS

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Caroline Metzger

2008-01-01

Full Text Available O presente artigo retrata um estudo relacionado aos benefícios percebidos pelos principais stakeholders de uma rede de empresas. Para tanto, desenvolveu-se uma pesquisa bibliográfica sobre a pequena empresa, os antecedentes históricos das redes de empresas, os conceitos relacionados, as tipologias e características estruturais, os benefícios proporcionados pelas redes e apresentou-se o Programa Redes de Cooperação no Estado do Rio Grande do Sul. Descreveram-se também os conceitos de stakeholders, as suas classificações e os benefícios do relacionamento destes grupos. Considerando este contexto, o objetivo deste artigo foi identificar e analisar os benefícios percebidos pelos principais stakeholders envolvidos com a rede de cooperação Hipereletro. A metodologia utilizada foi o estudo de caso a partir dos dados coletados através da pesquisa de campo, por meio de um questionário aplicado a quatro grupos envolvidos com a Hipereletro. Após a análise dos dados, identificaram-se os benefícios percebidos por cada stakeholder. Os associados perceberam benefícios nas ações de marketing, nas negociações em conjunto e no relacionamento entre as empresas, destacam-se as promoções realizadas pelo grupo, obtenção de melhores preços nas compras e troca de informações, conhecimentos e experiências. Já os funcionários apontaram a melhora na apresentação da empresa, realização de eventos e a troca de informações entre as lojas. Para os fornecedores, os primeiros reflexos da parceria com a rede foram o aumento das vendas, a garantia de pagamento e a fidelidade das empresas. E, quanto aos clientes, destacaram-se a percepção em relação à mudança da fachada da loja, as promoções e a diferença nos preços dos produtos. Pela pesquisa, concluiu-se que todos percebem benefícios ao se relacionarem com a rede, alguns mais, outros menos. Porém, devido ao pouco tempo de existência da Hipereletro, todos acreditam no

Comparative analysis of chrysanthemum transcriptome in response to three RNA viruses: Cucumber mosaic virus, Tomato spotted wilt virus and Potato virus X.

Science.gov (United States)

Choi, Hoseong; Jo, Yeonhwa; Lian, Sen; Jo, Kyoung-Min; Chu, Hyosub; Yoon, Ju-Yeon; Choi, Seung-Kook; Kim, Kook-Hyung; Cho, Won Kyong

2015-06-01

The chrysanthemum is one of popular flowers in the world and a host for several viruses. So far, molecular interaction studies between the chrysanthemum and viruses are limited. In this study, we carried out a transcriptome analysis of chrysanthemum in response to three different viruses including Cucumber mosaic virus (CMV), Tomato spotted wilt virus (TSWV) and Potato virus X (PVX). A chrysanthemum 135K microarray derived from expressed sequence tags was successfully applied for the expression profiles of the chrysanthemum at early stage of virus infection. Finally, we identified a total of 125, 70 and 124 differentially expressed genes (DEGs) for CMV, TSWV and PVX, respectively. Many DEGs were virus specific; however, 33 DEGs were commonly regulated by three viruses. Gene ontology (GO) enrichment analysis identified a total of 132 GO terms, and of them, six GO terms related stress response and MCM complex were commonly identified for three viruses. Several genes functioning in stress response such as chitin response and ethylene mediated signaling pathway were up-regulated indicating their involvement in establishment of host immune system. In particular, TSWV infection significantly down-regulated genes related to DNA metabolic process including DNA replication, chromatin organization, histone modification and cytokinesis, and they are mostly targeted to nucleosome and MCM complex. Taken together, our comparative transcriptome analysis revealed several genes related to hormone mediated viral stress response and DNA modification. The identified chrysanthemums genes could be good candidates for further functional study associated with resistant to various plant viruses.

Depressão, estresse e alexitimia em pacientes com infecção pelo vírus HIV = Depression, stress and alexitimy in patients with infection by the HIV virus

OpenAIRE

Verônica da Silveira Leite; Daniela Darce Motta; Miguel Spack Junior; Silvana Marques Araujo; Áurea Regina Telles Pupulin

2007-01-01

Durante o curso da infecção pelo HIV, é comum a depressão; um alto nível de estresse pode derivar em uma menor competência imunitária. Alexitimia é uma reação "estado" para os efeitos de doenças físicas sérias. Este trabalho teve como objetivo avaliar níveis de depressão, estresse e alexitimia em pacientes portadores de HIV correlacionandoosao nível de células TCD4+ e ocorrência de infecções oportunistas. Foram selecionados 50 pacientes portadores de HIV. Escalas para avaliação dos níveis de ...

Birth origin differentially affects depressive-like behaviours: are captive-born cynomolgus monkeys more vulnerable to depression than their wild-born counterparts?

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Sandrine M J Camus

Full Text Available BACKGROUND: Adverse early-life experience might lead to the expression of abnormal behaviours in animals and the predisposition to psychiatric disorder (e.g. major depressive disorder in Humans. Common breeding processes employ weaning and housing conditions different from what happens in the wild. METHODS: The present study, therefore, investigated whether birth origin impacts the possible existence of spontaneous atypical/abnormal behaviours displayed by 40 captive-born and 40 wild-born socially-housed cynomolgus macaques in farming conditions using an unbiased ethological scan-sampling analysis followed by multifactorial correspondence and hierarchical clustering analyses. RESULTS: We identified 10 distinct profiles (groups A to J that significantly differed on several behaviours, body postures, body orientations, distances between individuals and locations in the cage. Data suggest that 4 captive-born and 1 wild-born animals (groups G and J present depressive-like symptoms, unnatural early life events thereby increasing the risk of developing pathological symptoms. General differences were also highlighted between the captive- and wild-born populations, implying the expression of differential coping mechanisms in response to the same captive environment. CONCLUSIONS: Birth origin thus impacts the development of atypical ethologically-defined behavioural profiles, reminiscent of certain depressive-like symptoms. The use of unbiased behavioural observations might allow the identification of animal models of human mental/behavioural disorders and their most appropriate control groups.

Avaliação do ventrículo direito pelo ecocardiograma com doppler tecidual na embolia pulmonar aguda

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Ana Clara Tude Rodrigues

2013-06-01

Full Text Available FUNDAMENTO: A avaliação da função Ventricular Direita (VD pelo ecocardiograma em pacientes com Tromboembolismo Pulmonar (TEP é complexa, frequentemente qualitativa; o Doppler tecidual tem sido utilizado para avaliação semiquantitativa dessa câmara, com algumas limitações. OBJETIVO: Avaliar a função do VD no TEP pelo ecocardiograma com Doppler tecidual, complementando com o peptídeo atrial natriurético (BNP. MÉTODOS: Foram estudados pacientes com TEP pelo ecocardiograma com Doppler tecidual e BNP até 24 horas do diagnóstico, obtendo-se as velocidades miocárdicas (s', strain, strain rate e índice de performance miocárdica do VD; disfunção do VD foi iagnosticada por hipocinesia da câmara, movimento anormal septal e relação VD/VE >1. De acordo com o BNP os pacientes foram divididos em Grupo I, BNP 50 pg/mL. RESULTADOS: De 118 pacientes, 100 (60 homens, idade = 55 ± 17 anos foram analisados; observou-se disfunção do VD em 28%, mais frequentemente no grupo II (19 vs. 9 pacientes, p < 0,001. O grupo II era mais idoso (64 ± 19 vs. 50 ± 15 anos, apresentava menor velocidade de s' (10,5 ± 3,5 vs. 13,2 ± 3,1 cm/s e maior pressão pulmonar (48 ± 11 vs. 35 ± 11 mmHg, p < 0,001 para todos. O ponto de corte de s' para disfunção do VD foi de 10,8 cm/s (especificidade = 85%, sensibilidade = 54%, com moderada correlação entre o BNP e a onda s'(r = -0,39. CONCLUSÃO: No TEP, a disfunção do VD pelo ecocardiograma se acompanha de elevação do BNP; apesar confirmar adequadamente a presença de disfunção do VD, o Doppler tecidual apresenta sensibilidade limitada para este diagnóstico.

Democracia digital? Os usos da Internet pelos sindicatos da saúde

OpenAIRE

Marques Alves, P.

2015-01-01

Os movimentos sindicais dos países capitalistas desenvolvidos vêm enfrentando uma crise profunda desde os anos 70. As suas causas são múltiplas, nelas se mesclando fatores que lhes são exógenos com outros endógenos, remetendo para a sua burocratização. Visando revitalizar-se, eles têm vindo a implementar ações diversificadas, onde se conta a adoção das TIC e da Internet. Este artigo apresenta os resultados de um estudo sobre a adoção e os usos da Internet pelos sindicatos da saúde. Visou-se c...

Resistência à corrosão de junta dissimilar soldada pelo processo TIG composta pelos aços inoxidáveis AISI 316L e AISI 444

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Luis Henrique Guilherme

2014-03-01

Full Text Available O aço inoxidável AISI 444 tornou-se uma opção para substituir a liga AISI 316L devido ao seu menor custo e satisfatória resistência à corrosão. Entretanto, o uso da liga AISI 444 no feixe tubular de trocadores de calor acarreta na soldagem de uma junta dissimilar. O presente estudo teve por objetivo avaliar a resistência à corrosão da junta tubo-espelho soldada pelo processo TIG composta pelas ligas AISI 316L e AISI 444. A manufatura das amostras consistiu em replicar o projeto da junta tubo-espelho de trocadores de calor. Realizou-se em juntas soldadas ensaios de sensitização, perda de massa por imersão desde a temperatura ambiente até 90 ºC, e ensaios eletroquímicos de polarização potenciodinâmica nos eletrólitos 0,5 mol/L de HCl e 0,5 mol/L de H2SO4. Os resultados mostraram que a junta dissimilar sofreu corrosão galvânica com maior degradação na zona afetada pelo calor (ZAC do tubo AISI 444. Porém, os mecanismos de corrosão localizada (pite e intergranular demonstraram ser mais ativos para a liga AISI 316L. Conclui-se que a junta dissimilar apresentou melhor resistência à corrosão do que a junta soldada composta unicamente pela liga AISI 316L em temperaturas de até 70 ºC, conforme as condições observadas neste trabalho.

Nota Fiscal Paulista: principais características percebidas pelos cidadãos paulistas

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Sérgio Roberto da Silva

2018-03-01

Full Text Available Estima-se que 60% dos valores de tributos são sonegados pelo varejo (ROLLI e FERNANDES, 2008. Como resposta o governo Paulista criou o projeto NFP-Nota Fiscal Paulista. Nesse projeto a identificação do contribuinte através do CPF gera créditos (benefícios financeiros ao comprador/contribuinte e assegura o pagamento dos tributos por parte do fornecedor/ comerciante. O objetivo deste trabalho foi identificar as  principais características percebidas pelos cidadãos paulistas com relação ao projeto.  A pesquisa envolveu 132 pessoas em um formulário com 25 assertivas no estilo Likert.  Os resultados indicam que os contribuintes aceitam e participam do projeto. No entanto desconhecem outras características do projeto, por exemplo, doação de créditos a instituições filantrópicas. A maior forma de ressarcimento dos créditos é o depósito em conta corrente. Parte dos contribuintes acredita que as informações referentes aos valores de credito não são repassados a Receita Federal. Dessa forma busca-se contribuir com um estudo sob a ótica dos contribuintes em relação a esse projeto.Nota Fiscal Paulista, análise fatorial, sonegação de tributos

ANALISIS DE LOS MECANISMOS INVOLUCRADOS EN LA LOCALIZACION ASIMETRICA DE TPRP1 Y ATPRP3 EN EL PELO RADICULAR DE ARABIDOPSIS THALIANA

OpenAIRE

RODRIGUEZ FURLAN, CECILIA

2012-01-01

Las proteínas ricas en prolinas (PRPs) son proteínas estructurales involucradas en el ensamblaje de la pared celular. En Arabidopsis dos miembros de esta familia de genes, ATPRP1 y ATPRP3, se expresan específicamente en células de pelo radicular. Los pelos radiculares elongan mediante crecimiento por el ápice a partir de células epidermales especializadas denominadas tricoblastos. El crecimiento por el ápice involucra la secreción polarizada de los materiales necesarios para formar la memb...

Uptake and metabolism of [3H]testosterone in the brain, pituitary gland and genital tract of the male cynomolgus monkey

International Nuclear Information System (INIS)

Bonsall, R.W.; Rees, H.D.; Micheal, R.P.

1986-01-01

To study the mechanism by which testosterone restores the sexual potency of castrated cynomolgus monkeys, two males (body weights 5.2 and 5.3 kg) were castrated and, 3 days later, injected with 3 mCi [ 3 H]testosterone ([ 3 H]T) as an intravenous bolus. After 30 min, males were killed and brains and samples of other tissues were rapidly removed and placed on ice. Samples were dissected from the right halves of the brain and homogenized. Purified cell nuclei were prepared and ether extracts were analyzed by reverse-phase HPCL. Generally, unchanged [ 3 H]T was the major form of radioactivity in brain and pituitary gland, but in cell nuclei from hypothalamus, preoptic area and amygdala, a large proportion (34 - 61%) was in the form of [ 3 H]estradiol ([ 4 H]E 2 ). Little or no [ 3 H]dihydrotestosterone ([ 3 H]DHT) was detected in cell nuclei from any brain region or from pituitary gland. However, [ 3 H]DHT was the major form (61 - 95%) of radioactivity in cell nuclei from glans penis, prostrate and seminal vesicles. In autoradiograms of the left halves of the same brains, the percentage of cells that accumulated radioactivity in their nuclei was high in specific regions of the hypothalamus, preoptic areas and amygdala. The authors conclude that the peripheral actions of T are mediated via DHT, but its central actions are dependent on unchanged T or on E 2 formed locally by aromatization

Competitive virus assay method for titration of noncytopathogenic bovine viral diarrhea viruses (END⁺ and END⁻ viruses).

Science.gov (United States)

Muhsen, Mahmod; Ohi, Kota; Aoki, Hiroshi; Ikeda, Hidetoshi; Fukusho, Akio

2013-03-01

A new, reliable and secure virus assay method, named the competitive virus assay (CVA) method, has been established for the titration of bovine viral diarrhea viruses (BVDVs) that either show the exaltation of Newcastle disease virus (END) phenomenon or heterologous interference phenomenon (but not the END phenomenon). This method is based on the principle of (1) homologous interference between BVDVs, by using BVDV RK13/E(-) or BVDV RK13/E(+) strains as competitor virus, and (2) END phenomenon and heterologous interference, by using attenuated Newcastle disease virus (NDV) TCND strain as challenge virus. In titration of BVDV END(+) and BVDV END(-) viruses, no significant difference in estimated virus titer was observed between CVA and conventional methods. CVA method demonstrated comparable levels of sensitivity and accuracy as conventional END and interference methods, which require the use of a velogenic Miyadera strain of NDV and vesicular stomatitis virus (VSV), both of which are agents of high-risk diseases. As such, the CVA method is a safer alternative, with increased bio-safety and bio-containment, through avoidance of virulent strains that are commonly employed with conventional methods. Copyright © 2012 Elsevier B.V. All rights reserved.

Tat protein vaccination of cynomolgus macaques influences SHIV-89.6P cy243 epitope variability.

Science.gov (United States)

Ridolfi, Barbara; Genovese, Domenico; Argentini, Claudio; Maggiorella, Maria Teresa; Sernicola, Leonardo; Buttò, Stefano; Titti, Fausto; Borsetti, Alessandra; Ensoli, Barbara

2008-02-01

In a previous study we showed that vaccination with the native Tat protein controlled virus replication in five out of seven monkeys against challenge with the simian human immunodeficiency virus (SHIV)-89.6P cy243 and that this protection correlated with T helper (Th)-1 response and cytotoxic T lymphocyte (CTL) activity. To address the evolution of the SHIV-89.6P cy243 both in control and vaccinated infected monkeys, the sequence of the human immunodeficiency virus (HIV)-1 Tat protein and the C2-V3 Env region of the proviral-DNA-derived clones were analyzed in both control and vaccinated but unprotected animals. We also performed analysis of the T cell epitope using a predictive epitope model taking into consideration the phylogeny of the variants. Our results suggest that even though the viral evolution observed in both groups of monkeys was directed toward variations in the major histocompatibility complex (MHC)-I epitopes, in the control animals it was associated with mutational escape of such epitopes. On the contrary, it is possible that viral evolution in the vaccinated monkeys was linked to mutations that arose to keep high the viral fitness. In the vaccinated animals the reduction of epitope variability, obtained prompting the immune system by vaccination and inducing a specific immunological response against virus, was able to reduce the emergence of escape mutants. Thus the intervention of host's selective forces in driving CTL escape mutants and in modulating viral fitness appeared to be different in the two groups of monkeys. We concluded that in the vaccinated unprotected animals, vaccination with the Tat protein induced a broad antiviral response, as demonstrated by the reduced ability to develop escape mutants, which is known to help in the control of viral replication.

O adoecimento pelo cancer de laringe The illness narrative for larynx cancer

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Márcia Maria Fontão Zago

2001-06-01

Full Text Available Com a finalidade de aprimorar a assistência ao laringectomizado, este estudo teve o objetivo de compreender o adoecimento pelo câncer de laringe na visão do paciente e sua família. Participaram do estudo 14 pacientes laringectomizados e familiares, em diferentes períodos pós-operatórios. Na análise das narrativas identificamos categorias que foram interpretadas sob a visão antropológica da cultura. Na interpretação dos participantes, o processo é permeado pelo sofrimento, pela busca de estratégias de enfrentamento, pela valorização de sobreviver à cirurgia, ou seja, pressupostos culturais que diferem do modelo biomédico dos profissionais e que devem ser considerados na sua reabilitação.With the purpose of improving the care of laryngectomized patients, the aim is to understand the illness experience of patients and families of having larynx cancer. The participants were 14 laryngectomized patients and their families, in different post-surgical periods. The narrative analysis searched for categories which were understood on the basis of an anthropological focusing the culture. The understanding that the participants had of the illness experience of having a larynx cancer shows us that this process is one of suffering, of searching of strategies of coping, of evaluating the survival to the surgical treatment, which were based on the cultural system, which is different from the biomedical model of the health professionals and they must be considered in the approach for the rehabilitation.

Phylogenetic analysis of Tomato mosaic virus from Hemerocallis sp. and Impatiens hawkeri Análise filogenética de Tomato mosaic virus isolado de Hemerocallis sp. e Impatiens hawkeri

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Lígia Maria Lembo Duarte

2007-12-01

, respectivamente, assim como estabelecer relações filogenéticas entre os isolados e outras espécies de Tobamovirus, foram realizados extrações do RNA, RT-PCR, seqüenciamento do gene da capa protéica e análises filogenéticas. Quando foram comparadas seqüências homólogas de tobamovirus, valores superiores a 98,5% de identidade, ao nível de nucleotídeos, foram obtidos com isolados do Tomato mosaic virus (ToMV. Em relação ao tobamo-H, foi encontrado 100% de identidade com o ToMV isolado de tomateiro da Austrália e do Peru. Com base em análise de máxima verossimilhança (MV, sugere-se que o tobamo-H e tobamo-I compartilham um ancestral comum com ToMV, Tobacco mosaic virus, Odontoglossum ringspot virus e Pepper mild mottle virus. A topologia da árvore reconstruída a partir de MV mostra um grupo monofilético, sustentado por 100% de "bootstrap", formado por vários isolados de ToMV de diferentes hospedeiras, incluindo ornamentais, a partir de diferentes localizações geográficas. Os resultados indicam que Hemerocallis sp.e I. hawkeri estão infectados pelo ToMV, sendo esse o primeiro relato desse vírus em ornamentais, no Brasil.

Normocyte-binding protein required for human erythrocyte invasion by the zoonotic malaria parasitePlasmodium knowlesi

KAUST Repository

Moon, Robert W.; Sharaf, Hazem; Hastings, Claire H.; Ho, Yung Shwen; Nair, Mridul; Rchiad, ‍ Zineb; Knuepfer, Ellen; Ramaprasad, Abhinay; Mohring, Franziska; Amir, Amirah; Yusuf, Noor A.; Hall, Joanna; Almond, Neil; Lau, Yee Ling; Pain, Arnab; Blackman, Michael J.; Holder, Anthony A.

2016-01-01

The dominant cause of malaria in Malaysia is now Plasmodium knowlesi, a zoonotic parasite of cynomolgus macaque monkeys found throughout South East Asia. Comparative genomic analysis of parasites adapted to in vitro growth in either cynomolgus or human RBCs identified a genomic deletion that includes the gene encoding normocyte-binding protein Xa (NBPXa) in parasites growing in cynomolgus RBCs but not in human RBCs. Experimental deletion of the NBPXa gene in parasites adapted to growth in human RBCs (which retain the ability to grow in cynomolgus RBCs) restricted them to cynomolgus RBCs, demonstrating that this gene is selectively required for parasite multiplication and growth in human RBCs. NBPXa-null parasites could bind to human RBCs, but invasion of these cells was severely impaired. Therefore, NBPXa is identified as a key mediator of P. knowlesi human infection and may be a target for vaccine development against this emerging pathogen.

Normocyte-binding protein required for human erythrocyte invasion by the zoonotic malaria parasitePlasmodium knowlesi

KAUST Repository

Moon, Robert W.

2016-06-15

The dominant cause of malaria in Malaysia is now Plasmodium knowlesi, a zoonotic parasite of cynomolgus macaque monkeys found throughout South East Asia. Comparative genomic analysis of parasites adapted to in vitro growth in either cynomolgus or human RBCs identified a genomic deletion that includes the gene encoding normocyte-binding protein Xa (NBPXa) in parasites growing in cynomolgus RBCs but not in human RBCs. Experimental deletion of the NBPXa gene in parasites adapted to growth in human RBCs (which retain the ability to grow in cynomolgus RBCs) restricted them to cynomolgus RBCs, demonstrating that this gene is selectively required for parasite multiplication and growth in human RBCs. NBPXa-null parasites could bind to human RBCs, but invasion of these cells was severely impaired. Therefore, NBPXa is identified as a key mediator of P. knowlesi human infection and may be a target for vaccine development against this emerging pathogen.

A diversidade de lagartos na Caatinga é mediada pelos térmitas?

OpenAIRE

Souza, Heitor Bruno de Araujo

2012-01-01

Ao tentar explicar a extraordinária taxa de coexistência de lagartos em desertos Australianos, Morton & James (1988) formularam uma hipótese em que a diversidade de térmitas promoveria uma diversificação dos lagartos. O presente estudo visa verificar se essa hipótese é válida para as taxocenoses de lagartos da Caatinga. Objetiva-se também verificar se os mecanismos de defesa dos térmitas influenciam a taxa com que esses são consumidos pelos lagartos e se esse padrão difere entre diferentes li...

Virus wars: using one virus to block the spread of another

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Matthew L. Paff

2016-06-01

Full Text Available The failure of traditional interventions to block and cure HIV infections has led to novel proposals that involve treating infections with therapeutic viruses–infectious viruses that specifically inhibit HIV propagation in the host. Early efforts in evaluating these proposals have been limited chiefly to mathematical models of dynamics, for lack of suitable empirical systems. Here we propose, develop and analyze an empirical system of a therapeutic virus that protects a host cell population against a lethal virus. The empirical system uses E. coli bacteria as the host cell population, an RNA phage as the lethal virus and a filamentous phage as the therapeutic virus. Basic dynamic properties are established for each virus alone and then together. Observed dynamics broadly agree with those predicted by a computer simulation model, although some differences are noted. Two cases of dynamics are contrasted, differing in whether the therapeutic virus is introduced before the lethal virus or after the lethal virus. The therapeutic virus increases in both cases but by different mechanisms. With the therapeutic virus introduced first, it spreads infectiously without any appreciable change in host dynamics. With the therapeutic virus introduced second, host abundance is depressed at the time therapy is applied; following an initial period of therapeutic virus spread by infection, the subsequent rise of protection is through reproduction by hosts already protected. This latter outcome is due to inheritance of the therapeutic virus state when the protected cell divides. Overall, the work establishes the feasibility and robustness to details of a viral interference using a therapeutic virus.

Zika virus disease

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Adel I Al-Afaleq

2017-01-01

Full Text Available The Zika virus is an arbovirus belonging to the virus family Flaviviridae. The virus was isolated in 1947 from a rhesus monkey in the Zika Forest of Uganda. The virus causes sporadic mild human infections in Africa and later in Asia. However, by 2007 a major shift in its infection pattern was noticed and thousands of human infections were reported in the State of Yap and Federated States of Micronesia. In the last 3 years, major outbreaks have continued to occur and the virus has spread to several Pacific and American countries. These outbreaks were mostly asymptomatic; however, there were more severe clinical signs associated with the infections. Those signs included microcephaly and Guillain–Barre syndrome. It is believed that various species of mosquitoes can biologically transmit the virus. However, Aedes aegypti is most widely associated with the Zika virus. Recently, new modes of virus transmission have been reported, including mother-to-fetus, sexual, blood transfusion, animal bites, laboratory exposure and breast milk. Differential diagnosis is very important as some other arboviruses such as yellow fever virus, West Nile virus, dengue virus, and chikungunya virus have similar clinical manifestations to the Zika virus infection as well as relating serologically to some of these viruses. Established laboratory diagnostic tests to detect the Zika virus are limited, with reverse transcription polymerase chain reaction being the most widely used test. Taking into consideration the quickness of the spread of infection, size of the infected population and change of the infection severity pattern, the Zika virus infection merits collective efforts on all levels to prevent and control the disease. Limited research work and data, concurrent infection with other arboviruses, involvement of biological vectors, mass crowd events, human and trade movements and lack of vaccines are some of the challenges that we face in our efforts to prevent and

Dengue virus receptor

OpenAIRE

Hidari, Kazuya I.P.J.; Suzuki, Takashi

2011-01-01

Dengue virus is an arthropod-borne virus transmitted by Aedes mosquitoes. Dengue virus causes fever and hemorrhagic disorders in humans and non-human primates. Direct interaction of the virus introduced by a mosquito bite with host receptor molecule(s) is crucial for virus propagation and the pathological progression of dengue diseases. Therefore, elucidation of the molecular mechanisms underlying the interaction between dengue virus and its receptor(s) in both humans and mosquitoes is essent...

ALTERAÇÕES CITOLÓGICAS ASSOCIADAS A INFECÇÃO PELO PAPILOMAVIRUS HUMANO EM MULHERES ATENDIDAS EM UM HOSPITAL

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Emilly de Oliveira Silva

2016-01-01

Full Text Available O Papilomavírus Humano (HPV é atualmente a principal causa de virose sexualmente transmissível, sendo sua principal consequência o câncer de colo de útero. Neste contexto, este estudo teve como objetivo avaliar as alterações citológicas em mulheres atendidas em um hospital. Tratou-se de uma pesquisa do tipo quantitativa, de caráter documental, composta por 198 mulheres que apresentaram lesão devido à infecção pelo HPV e atendidas no Hospital Alpheu de Quadros. Os dados foram coletados por meio de registros arquivados no computador do hospital. Das mulheres infectadas pelo HPV, 66,7% tinham entre 20 e 39 anos e das que relataram sua iniciação sexual 61,6% tinham entre 16 e 20 anos. A maioria dessas mulheres foi diagnosticada com lesão intraepitelial de alto grau (HSIL seja na citologia ou na biópsia. O resultado pós Cirurgia de Alta Frequência apresentou-se positivo, pois houve diminuição de HSIL das mulheres. Ações de saúde pública podem prevenir a incidência e mortalidade pelo câncer de colo de útero quase que totalmente, desde que o planejamento destas ações esteja em concordância com o conhecimento científico atual.

Conhecimento dos obstetras sobre a transmissão vertical da hepatite B Knowledge of obstetricians about the vertical transmission of hepatitis B virus

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Joseni Santos da Conceição

2009-03-01

profissionais (P = 0,018; P = 0,001 e P = 0,002, respectivamente. CONCLUSÕES: Observou-se a inadequação do conhecimento dos obstetras sobre as medidas eficazes para a detecção da infecção pelo vírus da hepatite B na gravidez e prevenção da transmissão vertical desse vírus para os recém-nascidos e a necessidade de educação continuada sobre as infecç��es passíveis de transmissão vertical.CONTEXT: Vertical transmission is responsible for 35%-40% of the new cases of hepatitis B worldwide and it is associated with an increased risk of chronic hepatitis B, cirrhosis and hepatocellular carcinoma. OBJECTIVE: To describe obstetricians' knowledge on the recommended measures to the diagnosis of the infection by the hepatitis virus B in pregnant women and to prevent the transmission of this infection to the babies of infected mothers. METHODS: Obstetricians registered at the "Sociedade de Ginecologia e Obstetrícia da Bahia", Salvador, BA, Brazil were randomly selected and invited to answer a questionnaire with questions regarding their academic formation, workplace, contact with medical students and their practices about the hepatitis virus B. Individuals who were not currently working as obstetricians or were not living in the state of Bahia were excluded from the study. Data were analyzed with the EpiInfo software with a 95% confidence interval. RESULTS: Three hundred and one obstetricians answered the questionnaire: 90.3% of them recognized that the hepatitis virus B could be transmitted vertically and 81.7% routinely screened their patients for hepatitis virus B infection during prenatal consultations; 66.0% considered HBsAg the best serological marker to be employed on the screening. Only 13.0% systematically recommended the vaccination against hepatitis virus B and the administration of immunoglobulin to the newborns of infected mothers in the first 12 hours of life. The frequency of correct answers about the vertical transmission of hepatitis virus B, the best

Pesquisa de anticorpos contra o sarampo em crianças infectadas pelo HIV, após a imunização básica Search of antimeasles antibodies in HIV-infected children after basic immunization

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Claudia R. Lindgren-Alves

2001-12-01

Full Text Available OBJETIVO: verificar a presença de anticorpos contra o sarampo em crianças com infecção perinatal pelo HIV e devidamente imunizadas. MÉTODOS: estudo de coorte retrospectivo realizado em Belo Horizonte, entre 1995 e 1996. Foram incluídas 21 crianças com infecção perinatal pelo HIV e 29 crianças imunocompetentes não-infectadas. Informações acerca da vacina contra o sarampo foram obtidas do cartão de imunizações dos pacientes. A pesquisa de anticorpos contra o sarampo foi realizada pelos testes de neutralização por redução de placa e dosagem de IgM pela técnica de ELISA. Adotou-se nível de significância de 5% em todas as análises estatísticas realizadas. RESULTADOS: a mediana de idade dos pacientes infectados pelo HIV foi de 44,5 meses, e das crianças não-infectadas, de 62,0 meses (P=0,64.Os grupos receberam em média 2 doses da vacina contra o sarampo. Todos os pacientes soronegativos para o HIV apresentaram títulos de anticorpos contra o sarampo superiores a 50 mUI/ml, enquanto 57,1% das crianças infectadas apresentaram títulos acima deste valor (P=0,0001. O título geométrico médio de anticorpos neutralizantes foi significativamente menor no grupo de crianças com infecção pelo HIV (433,5 mUI/ml do que no grupo de não-infectados(1668,1 mUI/ml, P=0,001. Todos os pacientes dos dois grupos foram negativos para a pesquisa de IgM contra o sarampo. CONCLUSÃO: as crianças infectadas pelo HIV apresentaram menor soroprevalência de anticorpos contra o sarampo após a imunização do que as crianças não-infectadas. Esses resultados alertam para o risco potencial de aquisição do vírus do sarampo, e apontam a necessidade de avaliar alternativas para a imunização das crianças infectadas pelo HIV, no sentido de maximizar a proteção contra o sarampo nesse grupo de pacientes.OBJECTIVE: to determine the presence of antimeasles antibodies in children perinatally infected with HIV and properly immunized. METHODS: a

ECHO virus

Science.gov (United States)

... page: //medlineplus.gov/ency/article/001340.htm ECHO virus To use the sharing features on this page, please enable JavaScript. Enteric cytopathic human orphan (ECHO) viruses are a group of viruses that can lead ...

Hepatitis C virus and human T-lymphotropic virus coinfection: epidemiological, clinical, laboratory and histopathological features Coinfecção vírus da hepatite C-vírus linfotrópico de células T humanas: aspectos epidemiológicos, clínicos, laboratoriais e histopatológicos

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Flávio Augusto Pádua Milagres

2009-08-01

Full Text Available Twenty-four hepatitis C virus patients coinfected with human T-lymphotropic virus type 1 were compared with six coinfected with HTLV-2 and 55 with HCV alone, regarding clinical, epidemiological, laboratory and histopathological data. Fischer's discriminant analysis was applied to define functions capable of differentiating between the study groups (HCV, HCV/HTLV-1 and HCV/HTLV-2. The discriminant accuracy was evaluated by cross-validation. Alcohol consumption, use of intravenous drugs or inhaled cocaine and sexual partnership with intravenous drug users were more frequent in the HCV/HTLV-2 group, whereas patients in the HCV group more often reported abdominal pain or a sexual partner with hepatitis. Coinfected patients presented higher platelet counts, but aminotransferase and gamma-glutamyl transpeptidase levels were higher among HCV-infected subjects. No significant difference between the groups was seen regarding liver histopathological findings. Through discriminant analysis, classification functions were defined, including sex, age group, intravenous drug use and sexual partner with hepatitis. Cross-validation revealed high discriminant accuracy for the HCV group.Compararam-se 24 pacientes coinfectados pelos vírus da hepatite C/vírus linfotrópico de células T humanas do tipo 1 com 6 coinfectados por VHC/HTLV-2 e 55 infectados pelo VHC, no tocante a dados clínico-epidemiológicos, laboratoriais e histopatológicos. A análise discriminante de Fischer foi utilizada para definir funções capazes de diferenciar os grupos de estudo (VHC, VHC/HTLV-1 e VHC/HTLV-2. A acurácia discriminatória foi avaliada pelo por validação cruzada. O uso de álcool, drogas endovenosas, cocaína inalatória e a parceria sexual com UDEV foram mais freqüentes no grupo VHC/HTLV-2, enquanto queixa de dor abdominal e parceiro sexual com hepatite predominaram no grupo VHC. Os coinfectados apresentaram número maior de plaquetas, enquanto as aminotransferases e

Requerimientos energéticos de ovinos de pelo en las regiones tropicales de Latinoamérica. Revisión

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Alfonso Juventino Chay-Canul

2016-01-01

Full Text Available Los ovinos de pelo juegan un papel importante en la producción animal en las regiones tropicales; sin embargo, sus requerimientos nutricionales no se han determinado en la misma medida que los de las razas de lana. Debido a las condiciones ambientales de las regiones tropicales (clima, calidad y disponibilidad de alimentos, es razonable la hipótesis de que los requerimientos de energía metabolizable (EM y la eficiencia de utilización de la EM pueden ser diferentes entre los ovinos de razas de pelo y de lana. La información disponible en ovinos de pelo muestra una gran discrepancia en cuanto a las necesidades de energía. Con base en datos de la literatura disponible para hembras ovinas, el requerimiento de EM para mantenimiento (EMm fue de 419±129 kJ/kg PC0.75 (media ± desviación estándar y para machos fue 388±123 kJ/kg BW0.75. El requerimiento de energía neta para la ganancia de peso (ENg varió de 8.75 a 14.06 kJ/g (11.63±1.86 kJ/g. Las eficiencias de utilización de la EM para el mantenimiento (km y la ganancia de peso (kg fueron de 0.66±0.023 y 0.42±0.044, respectivamente. Esta revisión también indicó que la información es escasa para ovejas adultas en diferentes etapas fisiológicas (mantenimiento, lactancia y gestación. Se requiere más trabajo de investigación con relación a la estimación de las necesidades de energía de los ovinos de pelo, con el fin de hacer ajustes a los modelos existentes de alimentación, con el objetivo de predecir la respuesta de los animales con la condición que prevalece en los trópicos (tipo de animal, medio ambiente y alimentos disponibles.

Hepatitis E virus coinfection with hepatotropic viruses in Egyptian children.

Science.gov (United States)

Zaki, Maysaa El Sayed; Salama, Osama Saad; Mansour, Fathy Awaad; Hossein, Shaimaa

2008-06-01

Major hepatotropic viruses continue to be important causes of acute viral hepatitis in developing countries. This work was carried out to detect the seroprevalence of hepatitis E virus (HEV) markers in children with acute viral hepatitis due to hepatotropic viruses (A, B and C) and non-A, non-B, non-C acute hepatitis, and to ascertain the influence of HEV superinfection in individuals infected with hepatitis viruses (A, B and C). We studied prospectively 162 children with sporadic acute hepatitis who reported to our hospital. Thirteen healthy controls were also included in the study. Laboratory investigations were performed, including complete liver function tests. Complete serological profiles for hepatitis viruses A, B, C and E were evaluated. HEV immunoglobulin G was detected with highest percentage among patients with hepatitis B (56.7%), followed by patients with hepatitis C virus (52.0%), hepatitis A virus (34.1%) and combined hepatitis B and C viruses (30.0%). The detection rate among patients with non-A, non-B, non-C hepatitis was 7.1%. HEV immunoglobulin M was found in 4.5% of hepatitis A virus patients and in 3.3% of hepatitis B patients. The prevalence of HEV immunoglobulin G and immunoglobulin M correlated with the levels of hepatic aspartate aminotransferase and alanine aminotransferase in patients with dual markers of infection with hepatitis E and other viruses compared to patients with acute hepatitis due to A and C viruses. HEV serological markers are common among children with acute viral hepatitis, especially from hepatitis C and B viruses. There may be increased sensitivity to HEV coinfection in association with hepatitis B and C infections. Dual infection with HEV and other hepatotropic viruses was associated with greater elevation of aspartate and alanine aminotransferases.

A GESTÃO DO TERRITÓRIO PELO CAPITAL SUCROALCOOLEIRO NO NORTE DO PARANÁ

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Marcos Antonio de Souza

2013-02-01

Full Text Available Toda produção econômica possui uma determinada territorialidade, cuja gestão deste território está orientada no desenvolvimento de estratégias que primem pela rentabilidade da produção, prioritariamente em patamares diferenciais. Partindo-se da premissa de que o território não é uma mera localização, a agroindústria canavieira não se localiza pura e simplesmente em uma base física qualquer. Antes, há uma seletividade espacial marcada pelas disputas territoriais e a partir destas há o exercício do controle sob os elementos necessários para realizar a sua produção, subordinando a terra, a força de trabalho, os recursos naturais ao seu negócio que prima pela reprodução ampliada do capital. Trata-se na verdade de um conjunto de estratégias espaciais, onde o poder econômico ao controlar o território, reserva para si a gestão deste no âmbito do pacto social engendrado pelos grupos hegemônicos, resultando em um território gerido e ordenado pelo capital que aí se territorializou. Nesse contexto, este trabalho busca apresentar as principais estratégias espaciais dos agroindustriais do setor canavieiro desenvolvidas nas últimas três décadas no Norte do Paraná.

Avaliação da determinação da fibra em detergente neutro e da fibra em detergente ácido pelo sistema ANKOM

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Berchielli Telma Teresinha

2001-01-01

Full Text Available O objetivo do trabalho foi comparar os valores de fibra em detergente neutro (FDN e os de fibra em detergente ácido (FDA obtidos com o equipamento ANKOM e pelo método convencional (Van Soest. No primeiro ensaio foram analisados cinco materiais diferentes (cana-de-açúcar, capim-braquiária, silagem de milho, polpa cítrica e fezes bovina e testados quatro tipos de saquinhos para filtragem de amostra. O delineamento experimental foi em blocos casualizados, em um fatorial 5x4 (cinco materiais diferentes e quatro tipos de saquinhos de filtragem, com três repetições. As médias obtidas foram comparadas àquelas obtidas com método convencional. No segundo ensaio procurou-se avaliar o efeito da quantidade de amostra por saquinho (0,5; 0,8 e 1,0 g sobre os teores de FDN e FDA em três tipos de alimentos, utilizando o ANKOM. Neste ensaio, o delineamento experimental foi em blocos casualizados em esquema fatorial 3x3 (três alimentos x três quantidades, com três repetições. Os tipos de saquinhos de filtragem utilizados não influenciaram os teores de FDN nos diferentes alimentos, com exceção das fezes, cujos saquinhos de náilon resultaram em concentrações de FDN inferiores. Não houve diferença entre os valores de FDN e FDA, obtidos pelo equipamento ANKOM ou pelo convencional, para os alimentos estudados, com exceção da polpa cítrica, cujo valor médio de FDA pelo ANKOM foi inferior àquele obtido pelo método convencional. A quantidade não exerceu efeito sobre a concentração de FDN dos alimentos analisados no equipamento ANKOM.

Phytophthora viruses.

Science.gov (United States)

Cai, Guohong; Hillman, Bradley I

2013-01-01

Phytophthora sp. is a genus in the oomycetes, which are similar to filamentous fungi in morphology and habitat, but phylogenetically more closely related to brown algae and diatoms and fall in the kingdom Stramenopila. In the past few years, several viruses have been characterized in Phytophthora species, including four viruses from Phytophthora infestans, the late blight pathogen, and an endornavirus from an unnamed Phytophthora species from Douglas fir. Studies on Phytophthora viruses have revealed several interesting systems. Phytophthora infestans RNA virus 1 (PiRV-1) and PiRV-2 are likely the first members of two new virus families; studies on PiRV-3 support the establishment of a new virus genus that is not affiliated with established virus families; PiRV-4 is a member of Narnaviridae, most likely in the genus Narnavirus; and Phytophthora endornavirus 1 (PEV1) was the first nonplant endornavirus at the time of reporting. Viral capsids have not been found in any of the above-mentioned viruses. PiRV-1 demonstrated a unique genome organization that requires further examination, and PiRV-2 may have played a role in late blight resurgence in 1980s-1990s. Copyright © 2013 Elsevier Inc. All rights reserved.

Viruses infecting reptiles.

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Marschang, Rachel E

2011-11-01

A large number of viruses have been described in many different reptiles. These viruses include arboviruses that primarily infect mammals or birds as well as viruses that are specific for reptiles. Interest in arboviruses infecting reptiles has mainly focused on the role reptiles may play in the epidemiology of these viruses, especially over winter. Interest in reptile specific viruses has concentrated on both their importance for reptile medicine as well as virus taxonomy and evolution. The impact of many viral infections on reptile health is not known. Koch's postulates have only been fulfilled for a limited number of reptilian viruses. As diagnostic testing becomes more sensitive, multiple infections with various viruses and other infectious agents are also being detected. In most cases the interactions between these different agents are not known. This review provides an update on viruses described in reptiles, the animal species in which they have been detected, and what is known about their taxonomic positions.

Viruses Infecting Reptiles

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Rachel E. Marschang

2011-11-01

Full Text Available A large number of viruses have been described in many different reptiles. These viruses include arboviruses that primarily infect mammals or birds as well as viruses that are specific for reptiles. Interest in arboviruses infecting reptiles has mainly focused on the role reptiles may play in the epidemiology of these viruses, especially over winter. Interest in reptile specific viruses has concentrated on both their importance for reptile medicine as well as virus taxonomy and evolution. The impact of many viral infections on reptile health is not known. Koch’s postulates have only been fulfilled for a limited number of reptilian viruses. As diagnostic testing becomes more sensitive, multiple infections with various viruses and other infectious agents are also being detected. In most cases the interactions between these different agents are not known. This review provides an update on viruses described in reptiles, the animal species in which they have been detected, and what is known about their taxonomic positions.

Seleção de progênies de eucalipto pelo índice Z por MQM e Blup

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Cristiane Aparecida Fioravante Reis

2011-05-01

Full Text Available O objetivo deste trabalho foi avaliar a eficiência do índice Z (índice somatório das variáveis padronizadas na seleção de progênies de irmãos completos entre Eucalyptus grandis e Eucalyptus urophylla via método dos quadrados mínimos (MQM e da melhor predição linear não viesada (Blup. Os experimentos foram realizados em dois tipos de solo e de ambiente, em blocos ao acaso com cinco repetições, oito plantas por parcela e espaçamento de 3x2 m. Aos três anos de idade, as plantas foram avaliadas quanto ao incremento médio anual de madeira, à densidade básica, ao rendimento de celulose e ao álcali efetivo. Para a comparação da eficiência da seleção das melhores progênies, pelos procedimentos MQM e Blup, foi obtido o índice Z para cada indivíduo. Posteriormente, foram obtidas as médias preditas das progênies para o índice Z, ranqueadas em sentido favorável ao melhoramento. O índice clássico também foi utilizado. A coincidência entre as melhores progênies selecionadas pelos índices clássico e Z foi boa. No entanto, o índice Z permite visualização gráfica, o que possibilita verificar em quais caracteres uma determinada progênie apresenta alguma deficiência. Não há diferença entre as melhores progênies selecionadas pelo índice Z via MQM e Blup.

A centralidade ocupada pelos sujeitos que participam das pesquisas do Serviço Social = The centrality occupied by the subjects who participate in researches from Social Work

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Bourguignon, Jussara Ayres

2008-01-01

Full Text Available Com este texto temos por objetivo debater a posição ocupada pelos sujeitos participantes das pesquisas desenvolvidas pelo Serviço Social. Como fundamento, entendemos que a pesquisa é constitutiva e constituinte da prática profissional do Serviço Social, sendo determinada pela sua natureza interventiva e pela sua inserção histórica na divisão sociotécnica do trabalho. Este pressuposto tem como interface a preocupação com a centralidade que as pesquisas desenvolvidas pelo Serviço Social garantem aos sujeitos que delas são participantes, bem como com o alcance social dos seus resultados

Characterization of uncultivable bat influenza virus using a replicative synthetic virus.

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Bin Zhou

2014-10-01

Full Text Available Bats harbor many viruses, which are periodically transmitted to humans resulting in outbreaks of disease (e.g., Ebola, SARS-CoV. Recently, influenza virus-like sequences were identified in bats; however, the viruses could not be cultured. This discovery aroused great interest in understanding the evolutionary history and pandemic potential of bat-influenza. Using synthetic genomics, we were unable to rescue the wild type bat virus, but could rescue a modified bat-influenza virus that had the HA and NA coding regions replaced with those of A/PR/8/1934 (H1N1. This modified bat-influenza virus replicated efficiently in vitro and in mice, resulting in severe disease. Additional studies using a bat-influenza virus that had the HA and NA of A/swine/Texas/4199-2/1998 (H3N2 showed that the PR8 HA and NA contributed to the pathogenicity in mice. Unlike other influenza viruses, engineering truncations hypothesized to reduce interferon antagonism into the NS1 protein didn't attenuate bat-influenza. In contrast, substitution of a putative virulence mutation from the bat-influenza PB2 significantly attenuated the virus in mice and introduction of a putative virulence mutation increased its pathogenicity. Mini-genome replication studies and virus reassortment experiments demonstrated that bat-influenza has very limited genetic and protein compatibility with Type A or Type B influenza viruses, yet it readily reassorts with another divergent bat-influenza virus, suggesting that the bat-influenza lineage may represent a new Genus/Species within the Orthomyxoviridae family. Collectively, our data indicate that the bat-influenza viruses recently identified are authentic viruses that pose little, if any, pandemic threat to humans; however, they provide new insights into the evolution and basic biology of influenza viruses.

Characterization of uncultivable bat influenza virus using a replicative synthetic virus.

Science.gov (United States)

Zhou, Bin; Ma, Jingjiao; Liu, Qinfang; Bawa, Bhupinder; Wang, Wei; Shabman, Reed S; Duff, Michael; Lee, Jinhwa; Lang, Yuekun; Cao, Nan; Nagy, Abdou; Lin, Xudong; Stockwell, Timothy B; Richt, Juergen A; Wentworth, David E; Ma, Wenjun

2014-10-01

Bats harbor many viruses, which are periodically transmitted to humans resulting in outbreaks of disease (e.g., Ebola, SARS-CoV). Recently, influenza virus-like sequences were identified in bats; however, the viruses could not be cultured. This discovery aroused great interest in understanding the evolutionary history and pandemic potential of bat-influenza. Using synthetic genomics, we were unable to rescue the wild type bat virus, but could rescue a modified bat-influenza virus that had the HA and NA coding regions replaced with those of A/PR/8/1934 (H1N1). This modified bat-influenza virus replicated efficiently in vitro and in mice, resulting in severe disease. Additional studies using a bat-influenza virus that had the HA and NA of A/swine/Texas/4199-2/1998 (H3N2) showed that the PR8 HA and NA contributed to the pathogenicity in mice. Unlike other influenza viruses, engineering truncations hypothesized to reduce interferon antagonism into the NS1 protein didn't attenuate bat-influenza. In contrast, substitution of a putative virulence mutation from the bat-influenza PB2 significantly attenuated the virus in mice and introduction of a putative virulence mutation increased its pathogenicity. Mini-genome replication studies and virus reassortment experiments demonstrated that bat-influenza has very limited genetic and protein compatibility with Type A or Type B influenza viruses, yet it readily reassorts with another divergent bat-influenza virus, suggesting that the bat-influenza lineage may represent a new Genus/Species within the Orthomyxoviridae family. Collectively, our data indicate that the bat-influenza viruses recently identified are authentic viruses that pose little, if any, pandemic threat to humans; however, they provide new insights into the evolution and basic biology of influenza viruses.

Longitudinal changes in reproductive hormones and menstrual cyclicity in cynomolgus monkeys during strenuous exercise training: abrupt transition to exercise-induced amenorrhea.

Science.gov (United States)

Williams, N I; Caston-Balderrama, A L; Helmreich, D L; Parfitt, D B; Nosbisch, C; Cameron, J L

2001-06-01

Cross-sectional studies of exercise-induced reproductive dysfunction have documented a high proportion of menstrual cycle disturbances in women involved in strenuous exercise training. However, longitudinal studies have been needed to examine individual susceptibility to exercise-induced reproductive dysfunction and to elucidate the progression of changes in reproductive function that occur with strenuous exercise training. Using the female cynomolgus monkey (Macaca fascicularis), we documented changes in menstrual cyclicity and patterns of LH, FSH, estradiol, and progesterone secretion as the animals developed exercise-induced amenorrhea. As monkeys gradually increased running to 12.3 +/- 0.9 km/day, body weight did not change significantly although food intake remained constant. The time spent training until amenorrhea developed varied widely among animals (7-24 months; mean = 14.3 +/- 2.2 months) and was not correlated with initial body weight, training distance, or food intake. Consistent changes in function of the reproductive axis occurred abruptly, one to two menstrual cycles before the development of amenorrhea. These included significant declines in plasma reproductive hormone concentrations, an increase in follicular phase length, and a decrease in luteal phase progesterone secretion. These data document a high level of interindividual variability in the development of exercise-induced reproductive dysfunction, delineate the progression of changes in reproductive hormone secretion that occur with exercise training, and illustrate an abrupt transition from normal cyclicity to an amenorrheic state in exercising individuals, that is not necessarily associated with weight loss.

Prevalence of human immunodeficiency virus, hepatitis C virus ...

African Journals Online (AJOL)

Background. Human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) and syphilis remain major infections around the world. In Angola, about 166 000 individuals are living with HIV, representing a prevalence of 1.98% in adults between 15 and 49 years of age. In a 2003 study in Luanda, 4.5% ...

Socio-demographic and epidemiological characteristics associated with human immunodeficiency virus type I (HIV-1 infection in HIV-1-explosed but uninfected individuals, and in HIV-1-infected patients from a southern brasilian population Características sociodemográficas e epidemiológicas associadas com a infecção pelo vírus da imunodeficiência humana tipo 1 (HIV-1 em indivíduos expostos ao HIV-1 mas não infectados e em pacientes infectados pelo HIV-1, provenientes da população da região Sul do Brasil

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Edna Maria Vissoci Reiche

2005-10-01

Full Text Available The ability to control human immunodeficiency virus type 1 (HIV-1 infection and progression of the disease is regulated by host and viral factors. This cross-sectional study describes the socio-demographic and epidemiological characteristics associated with HIV-1 infection in 1,061 subjects attended in Londrina and region, south of Brazil: 136 healthy individuals (Group 1, 147 HIV-1-exposed but uninfected individuals (Group 2, 161 HIV-1-infected asymptomatic patients (Group 3, and 617 patients with AIDS (Group 4. Data were obtained by a standardized questionnaire and serological tests. The age of the individuals ranged from 15.1 to 79.5 years, 54.0% and 56.1% of the Groups 3 and 4 patients, respectively, were men. The major features of groups 2, 3, and 4 were a predominance of education level up to secondary school (55.8%, 60.2% and 62.4%, respectively, sexual route of exposure (88.4%, 87.0% and 82.0%, respectively, heterosexual behavior (91.8%, 75.2% and 83.7%, respectively, and previous sexually transmitted diseases (20.4%, 32.5%, and 38.1%, respectively. The patients with AIDS showed the highest rates of seropositivity for syphilis (25.6%, of anti-HCV (22.3%, and anti-HTLV I/II obtained by two serological screening tests (6.2% and 6.8%, respectively. The results documenting the predominant characteristics for HIV-1 infection among residents of Londrina and region, could be useful for the improvement of current HIV-1 prevention, monitoring and therapeutic programs targeted at this population.Este estudo transversal descreve as principais características sociodemográficas e epidemiológicas associadas com a infecção pelo HIV-1 em 1.061 indivíduos atendidos em Londrina e região, Sul do Brasil: 136 indivíduos saudáveis (Grupo 1, 147 indivíduos expostos ao HIV-1 mas não infectados (Grupo 2, 161 pacientes infectados pelo HIV-1 assintomáticos (Grupo 3 e 617 pacientes com aids (Grupo 4. Os dados foram obtidos pela aplicação de um

Epstein - Barr Virus

OpenAIRE

Štorkánová, Lenka

2011-01-01

Epstein-Barr virus Bachelor thesis summarizes the findings of Epstein-Barr virus (EBV), its general characteristics, transmission and spread of the virus, symptoms of disease and subsequent therapy and recovery. More specifically, it focuses on infectious mononucleosis, as well as more generally to other diseases, which the Epstein-Barr virus causes. It includes details of the vaccine against EB virus. There are the statistics on the incidence of infectious mononucleosis.

Dismorfia muscular: A busca pelo corpo hiper musculoso

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Andréa Pires Azevedo

2012-03-01

Full Text Available A dismorfia muscular tem sido identificada tanto em homens quanto em mulheres, provocando alterações da perceção da autoimagem e prejuízos socioculturais, e na saúde e bem-estar dos indivíduos. Nesse sentido, o objetivo deste estudo é analisar os aspetos socioculturais, psicológicos e o uso de recursos ergogênicos relacionados à dismorfia muscular, bem como, identificar os riscos promovidos pelo transtorno. Participaram 20 indivíduos, inscritos na rede mundial de computadores. Utilizou-se um questionário para coleta de dados e a análise documental para interpretação das respostas. Os resultados demonstram que as preocupações com a imagem corporal geram insegurança social, baixa autoestima e sentimentos de inferioridade, que seriam resolvidos se a pessoa tivesse corpos belos e fortes. A dismorfia muscular pode aumentar o risco de uso dos esteroides anabolizantes e o uso indiscriminado de suplementos alimentares. Conclui-se que a dismorfia muscular causa sofrimentos e prejuízos psicológicos, socioculturais e, desse modo, compromete a saúde das pessoas.

Is West Nile virus a potential cause of central nervous system infection in Brazil? Seria o vírus do Oeste do Nilo causa potencial de infecção no sistema nervoso central no Brasil?

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Cristiane N Soares

2010-10-01

Full Text Available Meningitis and encephalitis are complications of West Nile virus (WNV infection. Although WNV is endemic in North America, the virus has recently been reported in Colombia and Argentina. Investigation of WNV in Brazil is important since this virus has never been studied previously in this country. OBJECTIVE: To investigate the presence of WNV infection in viral encephalitis/meningitis cases of unknown etiology in the city of Rio de Janeiro, Brazil. METHOD: Thirty-seven adults with viral meningitis/encephalitis had their serum and CSF tested for WNV antibodies using the ELISA method. RESULTS: Only one case was WNV-positive, but this case was also positive for dengue. The plaque reduction neutralization test distinguished infections, and was negative for WNV. CONCLUSION: WNV can be confused with dengue infection. Their symptoms and neurological picture are similar. We did not find WNV in any patients with encephalitis and meningitis in the city of Rio de Janeiro. Up to now, it has not been detected in BrazilMeningite e encefalite são complicações da infecção pelo vírus do Oeste do Nilo (VON. Embora o VON seja endêmico na América do Norte, recentemente o vírus foi descrito na Colômbia e Argentina. Sua pesquisa no Brasil é importante uma vez que o vírus nunca fora estudado antes em nosso país. OBJETIVO: Investigar a presença do VON em casos de meningite e encefalite viral de etiologia desconhecida, na cidade no Rio de Janeiro, Brasil. MéTODO: Trinta e sete adultos com quadro de meningite/encefalite tiveram seu LCR e soro testados para anticorpos anti-VON, pelo método ELISA. RESULTADOS: Apenas um caso obteve sorologia positiva para VON, mas a sorologia para dengue também fora positiva. O teste da neutralização por redução de placa foi utilizado para distinção entre as infecções, sendo negativo para VON. CONCLUSÃO: A infecção por VON pode ser confundida com a infecção pelo vírus da dengue, seus sintomas e quadro neurol

Emerging influenza viruses and the prospect of a universal influenza virus vaccine.

Science.gov (United States)

Krammer, Florian

2015-05-01

Influenza viruses cause annual seasonal epidemics and pandemics at irregular intervals. Several cases of human infections with avian and swine influenza viruses have been detected recently, warranting enhanced surveillance and the development of more effective countermeasures to address the pandemic potential of these viruses. The most effective countermeasure against influenza virus infection is the use of prophylactic vaccines. However, vaccines that are currently in use for seasonal influenza viruses have to be re-formulated and re-administered in a cumbersome process every year due to the antigenic drift of the virus. Furthermore, current seasonal vaccines are ineffective against novel pandemic strains. This paper reviews zoonotic influenza viruses with pandemic potential and technological advances towards better vaccines that induce broad and long lasting protection from influenza virus infection. Recent efforts have focused on the development of broadly protective/universal influenza virus vaccines that can provide immunity against drifted seasonal influenza virus strains but also against potential pandemic viruses. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Virus-host interaction in feline immunodeficiency virus (FIV) infection.

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Taniwaki, Sueli Akemi; Figueiredo, Andreza Soriano; Araujo, João Pessoa

2013-12-01

Feline immunodeficiency virus (FIV) infection has been the focus of several studies because this virus exhibits genetic and pathogenic characteristics that are similar to those of the human immunodeficiency virus (HIV). FIV causes acquired immunodeficiency syndrome (AIDS) in cats, nevertheless, a large fraction of infected cats remain asymptomatic throughout life despite of persistent chronic infection. This slow disease progression may be due to the presence of factors that are involved in the natural resistance to infection and the immune response that is mounted by the animals, as well as due to the adaptation of the virus to the host. Therefore, the study of virus-host interaction is essential to the understanding of the different patterns of disease course and the virus persistence in the host, and to help with the development of effective vaccines and perhaps the cure of FIV and HIV infections. Copyright © 2013 Elsevier Ltd. All rights reserved.

Systematic analysis of protein identity between Zika virus and other arthropod-borne viruses.

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Chang, Hsiao-Han; Huber, Roland G; Bond, Peter J; Grad, Yonatan H; Camerini, David; Maurer-Stroh, Sebastian; Lipsitch, Marc

2017-07-01

To analyse the proportions of protein identity between Zika virus and dengue, Japanese encephalitis, yellow fever, West Nile and chikungunya viruses as well as polymorphism between different Zika virus strains. We used published protein sequences for the Zika virus and obtained protein sequences for the other viruses from the National Center for Biotechnology Information (NCBI) protein database or the NCBI virus variation resource. We used BLASTP to find regions of identity between viruses. We quantified the identity between the Zika virus and each of the other viruses, as well as within-Zika virus polymorphism for all amino acid k -mers across the proteome, with k ranging from 6 to 100. We assessed accessibility of protein fragments by calculating the solvent accessible surface area for the envelope and nonstructural-1 (NS1) proteins. In total, we identified 294 Zika virus protein fragments with both low proportion of identity with other viruses and low levels of polymorphisms among Zika virus strains. The list includes protein fragments from all Zika virus proteins, except NS3. NS4A has the highest number (190 k -mers) of protein fragments on the list. We provide a candidate list of protein fragments that could be used when developing a sensitive and specific serological test to detect previous Zika virus infections.

Blueberry (Vaccinium corymbosum)-Virus Diseases

Science.gov (United States)

At least six viruses have been found in highbush blueberry plantings in the Pacific Northwest: Blueberry mosaic virus, Blueberry red ringspot virus, Blueberry scorch virus, Blueberry shock virus, Tobacco ringspot virus, and Tomato ringspot virus. Six other virus and virus-like diseases of highbush b...

Pharmacokinetics and immunogenicity investigation of a human anti-interleukin-17 monoclonal antibody in non-naïve cynomolgus monkeys.

Science.gov (United States)

Han, Chao; Gunn, George R; Marini, Joseph C; Shankar, Gopi; Han Hsu, Helen; Davis, Hugh M

2015-05-01

The pharmacokinetics (PK) of biologic therapeutics, especially monoclonal antibodies (mAbs), in monkeys generally presents the most relevant predictive PK information for humans. However, human mAbs, xenogeneic proteins to monkeys, are likely to be immunogenic. Monkeys previously treated with a human mAb (non-naïve) may have developed antidrug antibodies (ADAs) that cross-react with another test mAb in subsequent studies. Unlike PK studies for small-molecule therapeutics, in which animals may be reused, naïve monkeys have been used almost exclusively for preclinical PK studies of biologic therapeutics to avoid potential pre-existing immunologic cross-reactivity issues. The propensity and extent of pre-existing ADAs have not been systematically investigated to date. In this study, the PK and immunogenicity of mAb A, a human anti-human interkeukin-17 mAb, were investigated in a colony of 31 cynomolgus monkeys previously exposed to other human mAbs against different targets. We screened the monkeys for pre-existing antibodies to mAb A prior to the PK study and showed that 44% of the monkeys had pre-existing cross-reactive antibodies to mAb A, which could affect the PK characterization of the antibody. In the subcolony of monkeys without measurable pre-existing ADAs, PK and immunogenicity of mAb A were successfully characterized. The impact of ADAs on mAb A PK was also demonstrated in the monkeys with pre-existing ADAs. Here we report the results and propose a pragmatic approach for the use of non-naïve monkeys when conducting PK studies of biologic therapeutics. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

Single virus genomics: a new tool for virus discovery.

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Lisa Zeigler Allen

Full Text Available Whole genome amplification and sequencing of single microbial cells has significantly influenced genomics and microbial ecology by facilitating direct recovery of reference genome data. However, viral genomics continues to suffer due to difficulties related to the isolation and characterization of uncultivated viruses. We report here on a new approach called 'Single Virus Genomics', which enabled the isolation and complete genome sequencing of the first single virus particle. A mixed assemblage comprised of two known viruses; E. coli bacteriophages lambda and T4, were sorted using flow cytometric methods and subsequently immobilized in an agarose matrix. Genome amplification was then achieved in situ via multiple displacement amplification (MDA. The complete lambda phage genome was recovered with an average depth of coverage of approximately 437X. The isolation and genome sequencing of uncultivated viruses using Single Virus Genomics approaches will enable researchers to address questions about viral diversity, evolution, adaptation and ecology that were previously unattainable.

Resistance to Two Heterologous Neurotropic Oncolytic Viruses, Semliki Forest Virus and Vaccinia Virus, in Experimental Glioma

Science.gov (United States)

Le Boeuf, Fabrice; Lemay, Chantal; De Silva, Naomi; Diallo, Jean-Simon; Cox, Julie; Becker, Michelle; Choi, Youngmin; Ananth, Abhirami; Sellers, Clara; Breton, Sophie; Roy, Dominic; Falls, Theresa; Brun, Jan; Hemminki, Akseli; Hinkkanen, Ari; Bell, John C.

2013-01-01

Attenuated Semliki Forest virus (SFV) may be suitable for targeting malignant glioma due to its natural neurotropism, but its replication in brain tumor cells may be restricted by innate antiviral defenses. We attempted to facilitate SFV replication in glioma cells by combining it with vaccinia virus, which is capable of antagonizing such defenses. Surprisingly, we found parenchymal mouse brain tumors to be refractory to both viruses. Also, vaccinia virus appears to be sensitive to SFV-induced antiviral interference. PMID:23221568

Detection of sweet potato virus C, sweet potato virus 2 and sweet potato feathery mottle virus in Portugal.

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Varanda, Carla M R; Santos, Susana J; Oliveira, Mônica D M; Clara, Maria Ivone E; Félix, Maria Rosário F

2015-06-01

Field sweet potato plants showing virus-like symptoms, as stunting, leaf distortion, mosaic and chlorosis, were collected in southwest Portugal and tested for the presence of four potyviruses, sweet potato virus C (SPVC), sweet potato virus 2 (SPV2), sweet potato feathery mottle virus (SPFMV), sweet potato virus G (SPVG), and the crinivirus sweet potato chlorotic stunt virus (SPCSV). DsRNA fractions were extracted from symptomatic leaves and used as templates in single and multiplex RT-PCR assays using previously described specific primers for each analyzed virus. The amplified reaction products for SPVC, SPV2 and SPFMV were of expected size, and direct sequencing of PCR products revealed that they correspond to the coat protein gene (CP) and showed 98%, 99% and 99% identity, respectively, to those viruses. Comparison of the CP genomic and amino acid sequences of the Portuguese viral isolates recovered here with those of ten other sequences of isolates obtained in different countries retrieved from the GenBank showed very few differences. The application of the RT-PCR assays revealed for the first time the presence of SPVC and SPFMV in the sweet potato crop in Portugal, the absence of SPVG and SPCSV in tested plants, as well as the occurrence of triple virus infections under field conditions.

Estimulação cognitiva para idoso com Doença de Alzheimer realizada pelo cuidador

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Thiara Joanna Peçanha da Cruz

2015-06-01

Full Text Available RESUMOObjetivo:conhecer a influência da estimulação cognitiva no domicílio, realizada pelo cuidador de idosos com Doença de Alzheimer.Método:realizado estudo de caso com cinco idosos com Doença de Alzheimer e seus cuidadores. As etapas de desenvolvimento da pesquisa foram: orientação aos cuidadores, seleção dos idosos e cuidadores; abordagem dos sujeitos no domicílio, encontros semanais e reaplicação dos testes para acompanhamento da função cognitiva do idoso.Resultados:no período de três meses foi possível identifi car melhora da cognição, verificada pelo resultado do Mini Exame do Estado Mental (MEEM. Os demais testes (KATZ, LAWTON, TDR e TFV mantiveram os escores iniciais.Conclusões:esta estratégia pode ser considerada uma tecnologia leve do cuidado de enfermagem para idosos com demência. Quando o cuidador realiza este cuidado, após o suporte do enfermeiro, sente-se menos ansioso e com maior compreensão da doença.

Effect of P/S ratio (0.5 vs 0.9) on hepatic LDL transport at three levels of dietary cholesterol in cynomolgus macaques

International Nuclear Information System (INIS)

Hunt, C.E.; Funk, G.M.; Turley, S.D.; Spady, D.K.; Dietschy, J.M.

1990-01-01

Interaction between dietary polyunsaturated to saturated (P/S) fatty acid ratio and cholesterol (C) was studied in 6 groups of male cynomolgus macaques fed diets (oleic acid constant) for 72 weeks as follows (C mg/Cal-P/S): (1), 0.06 - 0.5; (2), 0.06-0.9, (3), 0.28-0.5; (4), 0.28-0.9; (5), 2,35-0.5; (6), 2,35-0.9. Plasma C was proportional to dietary C and was affected significantly by P/S in 1 and 2 only. Mean plasma C (mg/dl) at 72 weeks was: (1) 158; (2) 117; (3) 320; (4) 284; (5) 602; (6) 601. LDL-C was significantly higher in (1) than in (2) (90 vs 65 mg/dl). In vivo LDL turnover studies showed that LDL clearance was suppressed by excess dietary C and by saturated fats in low C diets. Receptor-independent clearance was relatively constant. Hepatic LDL transport was determined after injection of 125I-cellobiose-LDL. Hepatic LDL-C uptake was greater in (2) than in (1). LDL-C synthesis was reduced in (4) and (6) compared to (3) and (5), respectively. The authors conclude that (i) hepatic LDL receptor activity is altered by degree of saturation in dietary triglycerides when dietary C is minimal and (ii) saturated triglycerides enhance LDL-C synthesis when dietary C is ample in this model

O Goodwill gerado pelo Passivo

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Eliseu Martins

2017-01-01

Full Text Available Objetivo: O objetivo deste estudo está relacionado à figura do Goodwill originado do Passivo de uma empresa, ou seja, não é a do Goodwill normalmente constituído pelos Ativos Intangíveis capazes de produzir uma rentabilidade anormal e que fazem com que o valor da entidade como um todo, em funcionamento, seja maior do que a soma algébrica dos valores justos de seus elementos patrimoniais. Trata-se de uma visão que se pode entender como novidade para muitos, ou seja, a do Goodwill originado do Passivo e, não, dos Ativos de uma empresa. Existem empresas que sequer conseguem remunerar o risco que seus Ativos carregam, mas podem apresentar Goodwill devido à forma com que suas atividades são financiadas. Método: Como ensaio, são apresentados conceitos básicos e de formulação, normalmente utilizados em avaliações de empresas. Na sequência, são apresentadas simulações que demonstram, de forma objetiva, o verdadeiro sentido técnico da formulação. Resultados: Sabendo-se que determinadas agências estatais de desenvolvimento e o próprio BNDES acabam financiando determinadas atividades com taxas de juros generosas, este estudo apresenta ainda um caso real de existência de Goodwill originado do Passivo de uma empresa brasileira. Contribuições: Este trabalho tem como uma de suas principais contribuições a exposição de um tema que é praticamente desconhecido no mundo acadêmico, totalmente desconsiderado pelas normas e legislações contábeis, mas presente no mundo dos analistas e investidores mais bem preparados, e o faz pela não disseminação desse conceito, com apresentação e redação acessíveis a todos os níveis de leitores.

Hepatitis E virus and fulminant hepatitis--a virus or host-specific pathology?

Science.gov (United States)

Smith, Donald B; Simmonds, Peter

2015-04-01

Fulminant hepatitis is a rare outcome of infection with hepatitis E virus. Several recent reports suggest that virus variation is an important determinant of disease progression. To critically examine the evidence that virus-specific factors underlie the development of fulminant hepatitis following hepatitis E virus infection. Published sequence information of hepatitis E virus isolates from patients with and without fulminant hepatitis was collected and analysed using statistical tests to identify associations between virus polymorphisms and disease outcome. Fulminant hepatitis has been reported following infection with all four hepatitis E virus genotypes that infect humans comprising multiple phylogenetic lineages within genotypes 1, 3 and 4. Analysis of virus sequences from individuals infected by a common source did not detect any common substitutions associated with progression to fulminant hepatitis. Re-analysis of previously reported associations between virus substitutions and fulminant hepatitis suggests that these were probably the result of sampling biases. Host-specific factors rather than virus genotype, variants or specific substitutions appear to be responsible for the development of fulminant hepatitis. © 2014 The Authors. Liver International Published by John Wiley & Sons Ltd.

Stock indexing and Potato virus Y elimination from potato plants cultivated in vitro Indexação de matrizes e eliminação do Potato virus Y em plantas de batata cultivadas in vitro

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Luciana Cordeiro Nascimento

2003-01-01

Full Text Available Potato cultivars (Solanum tuberosum L. have shown degeneration or run out caused by viruses after several cycles of propagation using seed tubers from commercial fields. This work reports the occurrence of single and mixed infections of four potato viruses in Paraíba-Brazil and presents a method for Potato virus Y (PVY elimination, by using thermo-and chemotherapies. Plants of potato cv. Baraka were tested by direct antigen coating ELISA. Antisera against PVY, Potato virus X (PVX, Potato virus S (PVS, and Potato leafroll virus (PLRV were used. Materials with positive reaction to PVY were treated for virus elimination. Single node cuttings (1.0 cm length were excised and inoculated in Murashige & Skoog (MS medium, supplemented with 1.0 mg L-1 of kinetin, 0.001 mg L-1 of naphthalene acetic acid (NAA and 0.1 mg L-1 of gibberellic acid (GA3. The thermotherapy at approximately 37ºC, during 30 and 40 days, resulted in 20.0 and 37.5% PVY elimination, respectively. Chemotherapy was undertaken with Ribavirin (RBV, 5-Azacytidine (AZA, and 3-Deazauridine (DZD. The RBV showed the highest rate of virus eradication, with 55.5% virus-free plants. Simultaneous thermo and chemotherapy had higher efficiency for the elimination of PVY, reaching rates of healthy plants of 83.3% with RBV, 70.0% with AZA, and 50.0% with DZD.Cultivares de batata (Solanum tuberosum L. têm mostrado degenerescência causada por vírus após ciclos sucessivos do uso de tubérculos de campos comerciais como material propagativo. Este trabalho verifica a ocorrência de infecção simples e mista de quatro vírus da batata na Paraíba e apresenta adequação da técnica de cultivo in vitro para obtenção de material livre de Potato virus Y (PVY, incluindo uso de microestacas, termo e quimioterapia. Plantas de batata do cv. Baraka foram submetidas à indexação sorológica pelo teste "direct antigen coating" ELISA. Utilizaram-se antissoros contra o PVY, Potato virus X (PVX, Potato virus

Circulating avian influenza viruses closely related to the 1918 virus have pandemic potential

Science.gov (United States)

Watanabe, Tokiko; Zhong, Gongxun; Russell, Colin A.; Nakajima, Noriko; Hatta, Masato; Hanson, Anthony; McBride, Ryan; Burke, David F.; Takahashi, Kenta; Fukuyama, Satoshi; Tomita, Yuriko; Maher, Eileen A.; Watanabe, Shinji; Imai, Masaki; Neumann, Gabriele; Hasegawa, Hideki; Paulson, James C.; Smith, Derek J.; Kawaoka, Yoshihiro

2014-01-01

Summary Wild birds harbor a large gene pool of influenza A viruses that have the potential to cause influenza pandemics. Foreseeing and understanding this potential is important for effective surveillance. Our phylogenetic and geographic analyses revealed the global prevalence of avian influenza virus genes whose proteins differ only a few amino acids from the 1918 pandemic influenza virus, suggesting that 1918-like pandemic viruses may emerge in the future. To assess this risk, we generated and characterized a virus composed of avian influenza viral segments with high homology to the 1918 virus. This virus exhibited higher pathogenicity in mice and ferrets than an authentic avian influenza virus. Further, acquisition of seven amino acid substitutions in the viral polymerases and the hemagglutinin surface glycoprotein conferred respiratory droplet transmission to the 1918-like avian virus in ferrets, demonstrating that contemporary avian influenza viruses with 1918 virus-like proteins may have pandemic potential. PMID:24922572

Lack of Durable Cross-Neutralizing Antibodies Against Zika Virus from Dengue Virus Infection.

Science.gov (United States)

Collins, Matthew H; McGowan, Eileen; Jadi, Ramesh; Young, Ellen; Lopez, Cesar A; Baric, Ralph S; Lazear, Helen M; de Silva, Aravinda M

2017-05-01

Cross-reactive antibodies elicited by dengue virus (DENV) infection might affect Zika virus infection and confound serologic tests. Recent data demonstrate neutralization of Zika virus by monoclonal antibodies or human serum collected early after DENV infection. Whether this finding is true in late DENV convalescence (>6 months after infection) is unknown. We studied late convalescent serum samples from persons with prior DENV or Zika virus exposure. Despite extensive cross-reactivity in IgG binding, Zika virus neutralization was not observed among primary DENV infections. We observed low-frequency (23%) Zika virus cross-neutralization in repeat DENV infections. DENV-immune persons who had Zika virus as a secondary infection had distinct populations of antibodies that neutralized DENVs and Zika virus, as shown by DENV-reactive antibody depletion experiments. These data suggest that most DENV infections do not induce durable, high-level Zika virus cross-neutralizing antibodies. Zika virus-specific antibody populations develop after Zika virus infection irrespective of prior DENV immunity.

Ganjam virus.

Science.gov (United States)

Sudeep, A B; Jadi, R S; Mishra, A C

2009-11-01

Ganjam virus (GANV), a member of genus Nairovirus of family Bunyavirdae is of considerable veterinary importance in India. Though, predominantly tick borne, GANV was also isolated from mosquitoes, man and sheep. Neutralizing and complement fixing antibodies to GANV have been detected in animal and human sera collected from different parts of the country. Thirty three strains of GANV have been isolated from India, mainly from Haemaphysalis ticks. The virus replicated in certain vertebrate and mosquito cell lines and found pathogenic to laboratory animals. One natural infection and five laboratory-acquired infections in men were also reported. GANV is antigenically related to Nairobi sheep disease virus (NSDV) of Africa, which is highly pathogenic for sheep and goats causing 70-90 per cent mortality among the susceptible population. Recent molecular studies have demonstrated that GANV is an Asian variant of NSDV and both these viruses are related to the dreaded Crimean Congo haemorrhagic fever (CCHF) group viruses. The versatility of the virus to replicate in different arthropod species, its ability to infect sheep, goat and man makes it an important zoonotic agent.

The Drosophila Nora virus is an enteric virus, transmitted via feces.

Science.gov (United States)

Habayeb, Mazen S; Cantera, Rafael; Casanova, Gabriela; Ekström, Jens-Ola; Albright, Shannon; Hultmark, Dan

2009-04-01

The biology of the Drosophila viruses has not been intensely investigated. Here we have investigated the biology of the Nora virus, a persistent Drosophila virus. We find that injected Nora virus is able to replicate in the files, reaching a high titer that is maintained in the next generation. There is a remarkable variation in the viral loads of individual flies in persistently infected stocks; the titers can differ by three orders of magnitude. The Nora virus is mainly found in the intestine of infected flies, and the histology of these infected intestines show increased vacuolization. The virus is excreted in the feces and is horizontally transmitted. The Nora virus infection has a very mild effect on the longevity of the flies, and no significant effect on the number of eggs laid and the percent of eggs that develop to adults.

Identification of putative substrates for cynomolgus monkey cytochrome P450 2C8 by substrate depletion assays with 22 human P450 substrates and inhibitors.

Science.gov (United States)

Hosaka, Shinya; Murayama, Norie; Satsukawa, Masahiro; Uehara, Shotaro; Shimizu, Makiko; Iwasaki, Kazuhide; Iwano, Shunsuke; Uno, Yasuhiro; Yamazaki, Hiroshi

2016-07-01

Cynomolgus monkeys are widely used in drug developmental stages as non-human primate models. Previous studies used 89 compounds to investigate species differences associated with cytochrome P450 (P450 or CYP) function that reported monkey specific CYP2C76 cleared 19 chemicals, and homologous CYP2C9 and CYP2C19 metabolized 17 and 30 human CYP2C9 and/or CYP2C19 substrates/inhibitors, respectively. In the present study, 22 compounds selected from viewpoints of global drug interaction guidances and guidelines were further evaluated to seek potential substrates for monkey CYP2C8, which is highly homologous to human CYP2C8 (92%). Amodiaquine, montelukast, quercetin and rosiglitazone, known as substrates or competitive inhibitors of human CYP2C8, were metabolically depleted by recombinant monkey CYP2C8 at relatively high rates. Taken together with our reported findings of the slow eliminations of amodiaquine and montelukast by monkey CYP2C9, CYP2C19 and CYP2C76, the present results suggest that these at least four chemicals may be good marker substrates for monkey CYP2C8. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Herpes viruses and human papilloma virus in nasal polyposis and controls

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Dimitrios Ioannidis

2015-12-01

Full Text Available ABSTRACT INTRODUCTION: Chronic rhinosinusitis with nasal polyps is a multifactorial disease entity with an unclear pathogenesis. Contradictory data exist in the literature on the potential implication of viral elements in adult patients with chronic rhinosinusitis. OBJECTIVE: To compare the prevalence of human herpes viruses (1-6 and Human Papilloma Virus in adult patients with chronic rhinosinusitis with nasal polyps and healthy controls. METHODS: Viral DNA presence was evaluated by real-time polymerase chain reaction application to nasal polyps specimens from 91 chronic rhinosinusitis with nasal polyps patients and nasal turbinate mucosa from 38 healthy controls. RESULTS: Epstein-Barr virus positivity was higher in nasal polyps (24/91; 26.4% versus controls (4/38; 10.5%, but the difference did not reach significance (p = 0.06. Human herpes virus-6 positivity was lower in nasal polyps (13/91; 14.29% versus controls (10/38; 26.32%,p = 0.13. In chronic rhinosinusitis with nasal polyps group, 1 sample was herpes simplex virus-1-positive (1/91; 1.1%, and another was cytomegalovirus-positive (1/91; 1.1%, versus none in controls. No sample was positive for herpes simplex virus-2, varicella-zoster virus, high-risk-human papilloma viruses (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and low-risk-human papilloma viruses (6, 11. CONCLUSION: Differences in Epstein-Barr virus and human herpes virus-6 positivity among patients with chronic rhinosinusitis with nasal polyps and healthy controls are not statistically significant, weakening the likelihood of their implication in chronic rhinosinusitis with nasal polyps pathogenesis.

Evaluation of recombinant influenza virus-simian immunodeficiency virus vaccines in macaques.

Science.gov (United States)

Sexton, Amy; De Rose, Robert; Reece, Jeanette C; Alcantara, Sheilajen; Loh, Liyen; Moffat, Jessica M; Laurie, Karen; Hurt, Aeron; Doherty, Peter C; Turner, Stephen J; Kent, Stephen J; Stambas, John

2009-08-01

There is an urgent need for human immunodeficiency virus (HIV) vaccines that induce robust mucosal immunity. Influenza A viruses (both H1N1 and H3N2) were engineered to express simian immunodeficiency virus (SIV) CD8 T-cell epitopes and evaluated following administration to the respiratory tracts of 11 pigtail macaques. Influenza virus was readily detected from respiratory tract secretions, although the infections were asymptomatic. Animals seroconverted to influenza virus and generated CD8 and CD4 T-cell responses to influenza virus proteins. SIV-specific CD8 T-cell responses bearing the mucosal homing marker beta7 integrin were induced by vaccination of naïve animals. Further, SIV-specific CD8 T-cell responses could be boosted by recombinant influenza virus-SIV vaccination of animals with already-established SIV infection. Sequential vaccination with influenza virus-SIV recombinants of different subtypes (H1N1 followed by H3N2 or vice versa) produced only a limited boost in immunity, probably reflecting T-cell immunity to conserved internal proteins of influenza A virus. SIV challenge of macaques vaccinated with an influenza virus expressing a single SIV CD8 T cell resulted in a large anamnestic recall CD8 T-cell response, but immune escape rapidly ensued and there was no impact on chronic SIV viremia. Although our results suggest that influenza virus-HIV vaccines hold promise for the induction of mucosal immunity to HIV, broader antigen cover will be needed to limit cytotoxic T-lymphocyte escape.

Schmallenberg virus – et nyt virus hos drøvtyggere

DEFF Research Database (Denmark)

Lohse, Louise

undersøgelser på laboratoriet, blev alle prøver i en længere periode testet negative for kendte patogener, der evt. kunne tænkes at knytte sig til disse sygdomsudbrud. Efterfølgende fandt man ved sekvensanalyse på DNA/RNA oprenset fra prøvematerialet lighed med virus fra orthobunyavirusgruppen. Disse virus er...... normalt vektorbårne og er kendt som årsag til sygdom i drøvtyggere i Australien, Asien, Afrika og Mellemøsten. Det nye virus blev kaldt Schmallenberg virus (SBV) efter stedet hvor det første tilfælde blev påvist. Siden har Schmallenberg virus spredt sig og er nu påvist i får, kvæg og geder i Tyskland......, Holland, Belgien, Luxembourg, Frankrig, Spanien, Italien og Storbritannien (status april 2012). Det antages, at virus overføres med mitter og myg og inkubationstiden har fra eksperimentelle forsøg vist sig at være kort (1-4 dage). Virus cirkulerer få dage i blodet og manifesterer sig ved milde uspecifikke...

Etoposide-induced apoptosis in murine neuroblastoma (N2A cells infected with Paramyxoviruses Apoptose induzida por etoposídeo em células de neuroblastoma murino (N2A infectadas por paramixovírus

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L. Moro

2003-02-01

Full Text Available The present study aimed to determine whether measles virus can induce apoptosis in murine neuroblastoma cells and the behavior of these cells under acute infection with measles virus or persistent infection with canine distemper virus upon treatment with etoposide. Measles virus induced necrosis in murine neuroblastoma cells. Canine distemper virus-persistent infection did not alter murine neuroblastoma cells behavior when treated with etoposide.O presente trabalho foi realizado tendo como objetivo determinar se o vírus de sarampo induz apoptose em células de neuroblastoma murino e avaliar o comportamento de células de neuroblastoma murino agudamente infectadas com vírus do sarampo ou persistentemente infectadas com o vírus da cinomose canina quando tratadas com etoposídeo. A infecção pelo vírus de sarampo induziu principalmente necrose em células de neuroblastoma murino. A infecção persistente pelo vírus de cinomose canina não alterou o comportamento de células de neuroblastoma murino tratadas com etoposídeo.

Sensitive radioimmunosorbent assay for the detection of plant viruses. [Cauliflower mosaic virus, lettuce mosaic virus

Energy Technology Data Exchange (ETDEWEB)

Ghabrial, S A; Shepherd, R J [Kentucky Univ., Lexington (USA); California Univ., Davis (USA))

1980-06-01

A simple and highly sensitive radioimmunosorbent assay (RISA) for the detection of plant viruses is described. The RISA procedure is a microplate method based on the principle of 'double-antibody sandwich' and follows essentially the protocol of the enzyme-linked immunosorbent assay (ELISA) (Clark and Adams, 1977), with the exception that /sup 125/I-labelled ..gamma..-globulin is substituted for the ..gamma..-globulin enzyme conjugate; the bound /sup 125/I-..gamma..-globulin is dissociated by acidification from the double-antibody sandwich. The radioactivity is proportional to virus concentration, and cauliflower mosaic virus (CaMV) and lettuce mosaic virus (LMV) could be detected at concentrations as low as 5 and 2 ng/ml, respectively. Direct evidence of the adverse effects of conjugation with enzyme on the binding abilities of antibodies is presented. The RISA procedure should prove valuable with viruses for which the ELISA values are too low to be dependable.

Malformações detectadas pelo ultrassom abdominal em crianças com cardiopatia congênita

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Rosana Cardoso Manique Rosa

Full Text Available FUNDAMENTO: Malformações extracardíacas podem estar presentes em pacientes com cardiopatia congênita (CC, trazendo maior risco de comorbidade e mortalidade. OBJETIVO: Verificar a frequência e os tipos de anormalidades abdominais detectadas em crianças com e sem CC através do ultrassom abdominal (USA, comparar os pacientes quanto a seus achados dismórficos/citogenéticos e realizar uma estimativa do custo-benefício da triagem pelo USA. MÉTODOS: Foi realizado um estudo transversal com controle. Os casos consistiram de pacientes com CC admitidos pela primeira vez em uma unidade de terapia intensiva pediátrica; os controles consistiram de crianças sem CC submetidas ao USA no hospital logo após cada caso. Todos os pacientes com CC foram submetidos ao USA, ao cariótipo de alta resolução e à hibridização in situ fluorescente (FISH para microdeleção 22q11.2. RESULTADOS: USA identificou anormalidades clinicamente significativas em 12,2% dos casos e em 5,2% dos controles (p = 0,009, com um poder de significância de 76,6%. A maioria das malformações com significado clínico foi de anomalias renais (10,4% nos casos e 4,9% nos controles, p = 0,034. No Brasil, o custo de um exame de USA pelo Sistema Único de Saúde é de 21 dólares. Uma vez que anormalidades clinicamente significativas foram observadas em um a cada 8,2 pacientes com CC, o custo para identificar uma criança afetada foi de 176 dólares. CONCLUSÃO: Pacientes com CC apresentam uma frequência significativa de anomalias detectadas pelo USA, um método diagnóstico barato e não invasivo, com boa sensibilidade. O custo da triagem para esses defeitos é consideravelmente menor que o custo para tratar as complicações do diagnóstico tardio de malformações abdominais, como a doença renal.

A escolha da unidade de atuação pelo docente da Escola Pública Estadual do Ensino Médio: Fatores relevantes

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Carlos Vital Giordano

2015-11-01

Full Text Available Este artigo pesquisou sobre quais são os fatores que levam o professor a escolher a escola de atuação, e relacionar se esses fatores possuem alguma associação com a formação ou, se a escolha apresenta outros aspectos, além dos pedagógicos. Por meio de entrevistas com os docentes, utilizando-se questionários, a pesquisa mostra o cenário de uma escola da Diretoria Regional de Ensino Sul I, que no ano de 2014 alcançou as metas de Ensino Médio estabelecidas pelo IDESP. Os resultados apresentados no artigo indicam quais os fatores considerados pelos docentes a atuar na escola, em seus variados graus de importância.

Nascent VLDL from liver perfusions of cynomolgus monkeys are preferentially enriched in RRR- compared with SRR-alpha-tocopherol: Studies using deuterated tocopherols

International Nuclear Information System (INIS)

Traber, M.G.; Rudel, L.L.; Burton, G.W.; Hughes, L.; Ingold, K.U.; Kayden, H.J.

1990-01-01

The transport and secretion of vitamin E in lipoproteins have been studied in cynomolgus monkeys fed tocopherols labeled with different amounts of deuterium. The animals were fed a single dose of vitamin E containing 60 mumol of each 2R,4'R,8'R-alpha-(5,7-(C2H3)2)tocopheryl acetate (d6-RRR-alpha-tocopheryl acetate; alpha-tocopherol with natural stereochemistry), 2S,4'R,8'R-alpha-5-(C2H3)tocopheryl acetate (d3-SRR-alpha-tocopheryl acetate; alpha-tocopherol with unnatural stereochemistry), and 2R,4'R,8'R-gamma-(3,4-2H)tocopherol (d2-RRR-gamma-tocopherol; gamma-tocopherol with natural stereochemistry). Chylomicrons, as well as the other plasma lipoproteins, contained equal concentrations of all three tocopherols at the earliest time points after feeding suggesting that all three tocopherols were absorbed equally. At later times plasma lipoproteins became preferentially enriched in d6-RRR-alpha-tocopherol. This is likely to be due to hepatic secretion of VLDL (very low density lipoproteins) and other lipoproteins, which were enriched in d6-RRR-alpha-tocopherol, as demonstrated in the lipoproteins isolated from perfused livers that had been obtained 24 h following the administration of the deuterated tocopherols. Taken together these data demonstrate that the liver, not the intestine, is the likely site of discrimination between tocopherol isomers and that the liver secretes nascent lipoproteins preferentially enriched in d6-RRR-alpha-tocopherol

Cartografia do lugar de moradia dos adolescentes com passagem pelo CENSE I de Londrina

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Claudemir Zulim

2011-07-01

Full Text Available Este artigo apresenta os resultados da análise dos dados documentais obtidos na pesquisa realizada no Centro de Socioeducação I - CENSE I, de Londrina, que objetiva identificar, mapear e analisar as condições sócio-espaciais dos bairros de origem dos adolescentes com passagem pela Unidade. O CENSE I é uma unidade de internação provisória por onde passam todos os adolescentes apreendidos em flagrante de ato infracional e encaminhados à autoridade policial competente, que avalia se eles serão liberados para seus familiares ou se de acordo com a gravidade dos fatos que eles sejam ouvidos pelo representante do Ministério Público, enquanto aguardam as entrevistas para a realização das oitivas junto ao Juizado da Vara da Infância e Adolescência. Analisa os dados sobre o lugar de moradia dos adolescentes com passagem pela Unidade no ano de 2009. Utiliza as técnicas de Cartografia e de programas específicos com os quais foram produzidos gráficos e mapas onde são facilmente visualizados os locais de residência desses adolescentes. Verifica que os locais de maior concentração de adolescentes com passagem pelo CENSE I também concentram graves problemas sócio-espaciais, geralmente ligados a ocupações irregulares e em fundos de vale.

Release of Virus from Lymphoid Tissue Affects Human Immunodeficiency Virus Type 1 and Hepatitis C Virus Kinetics in the Blood

NARCIS (Netherlands)

Müller, Viktor; Marée, Athanasius F.M.; Boer, R.J. de

2000-01-01

Kinetic parameters of human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) infections have been estimated from plasma virus levels following perturbation of the chronically infected (quasi-) steady state. We extend previous models by also considering the large pool of virus

Hepatitis E Virus and Related Viruses in Animals.

Science.gov (United States)

Thiry, D; Mauroy, A; Pavio, N; Purdy, M A; Rose, N; Thiry, E; de Oliveira-Filho, E F

2017-02-01

Hepatitis E is an acute human liver disease in healthy individuals which may eventually become chronic. It is caused by the hepatitis E virus (HEV) and can have a zoonotic origin. Nearly 57,000 people die yearly from hepatitis E-related conditions. The disease is endemic in both developing and developed countries with distinct epidemiologic profiles. In developing countries, the disease is associated with inadequate water treatment, while in developed countries, transmission is associated with animal contact and the ingestion of raw or uncooked meat, especially liver. All human HEV are grouped into at least four genotypes, while HEV or HEV-related viruses have been identified in an increasing number of domestic and wild animal species. Despite a high genetic diversity, only one single HEV serotype has been described to date for HEV genotypes 1-4. The discovery of new HEV or HEV-related viruses leads to a continuing increase in the number of genotypes. In addition, the genome organization of all these viruses is variable with overlapping open reading frames (ORF) and differences in the location of ORF3. In spite of the role of some domestic and wild animals as reservoir, the origin of HEV and HEV-related viruses in humans and animals is still unclear. This review discusses aspects of the detection, molecular virology, zoonotic transmission and origin of HEV and HEV-related viruses in the context of 'One Health' and establishes a link between the previous and the new taxonomy of this growing virus family. © 2015 Blackwell Verlag GmbH.

"The evil virus cell": Students' knowledge and beliefs about viruses.

Science.gov (United States)

Simon, Uwe K; Enzinger, Sonja M; Fink, Andreas

2017-01-01

Education about virus biology at school is of pivotal interest to raise public awareness concerning means of disease transmission and, thus, methods to prevent infection, and to reduce unnecessary antibiotic treatment due to patient pressure on physicians in case of viral diseases such as influenza. This study aimed at making visible the knowledge of Austrian high school and university students with respect to virus biology, virus structure and health-education issues. The data presented here stem from comprehensive questionnaire analyses, including the task to draw a virus, from a cross-sectional study with 133 grade 7 and 199 grade 10 high school students, and 133 first-year biology and 181 first-year non-biology university students. Analyses were performed both quantitatively and qualitatively. ANOVA revealed a highly significant group effect for total knowledge relating to virus biology and health issues (F(3, 642) = 44.17, p students and grade 10 high school students. Students enrolled in university-level biology outperformed all other groups, even though they had not yet encountered this topic at their courses; part of this phenomenon might be due to their affinity for learning about biological topics. However, even many first-year biology students had a high number of severe misconceptions, e.g., defining a virus as a pro- or eukaryotic cell, or falsely naming malaria as a viral disease. Since there was no significant difference in virus-related knowledge between high schools, virus biology seems to have been taught similarly among the tested schools. However, the majority of participants stated that the virus-related knowledge they had acquired at school was not sufficient. Based on the results presented here we urgently suggest improving and intensifying teaching this topic at school, since virus-related knowledge was by far too fragmentary among many participants. Such lack of health-relevant knowledge may contribute to pressure on physicians by patients

Herpes viruses and human papilloma virus in nasal polyposis and controls.

Science.gov (United States)

Ioannidis, Dimitrios; Lachanas, Vasileios A; Florou, Zoe; Bizakis, John G; Petinaki, Efthymia; Skoulakis, Charalampos E

2015-01-01

Chronic rhinosinusitis with nasal polyps is a multifactorial disease entity with an unclear pathogenesis. Contradictory data exist in the literature on the potential implication of viral elements in adult patients with chronic rhinosinusitis. To compare the prevalence of human herpes viruses (1-6) and Human Papilloma Virus in adult patients with chronic rhinosinusitis with nasal polyps and healthy controls. Viral DNA presence was evaluated by real-time polymerase chain reaction application to nasal polyps specimens from 91 chronic rhinosinusitis with nasal polyps patients and nasal turbinate mucosa from 38 healthy controls. Epstein-Barr virus positivity was higher in nasal polyps (24/91; 26.4%) versus controls (4/38; 10.5%), but the difference did not reach significance (p=0.06). Human herpes virus-6 positivity was lower in nasal polyps (13/91; 14.29%) versus controls (10/38; 26.32%, p=0.13). In chronic rhinosinusitis with nasal polyps group, 1 sample was herpes simplex virus-1-positive (1/91; 1.1%), and another was cytomegalovirus-positive (1/91; 1.1%), versus none in controls. No sample was positive for herpes simplex virus-2, varicella-zoster virus, high-risk-human papilloma viruses (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59) and low-risk-human papilloma viruses (6, 11). Differences in Epstein-Barr virus and human herpes virus-6 positivity among patients with chronic rhinosinusitis with nasal polyps and healthy controls are not statistically significant, weakening the likelihood of their implication in chronic rhinosinusitis with nasal polyps pathogenesis. Copyright © 2015 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

Production of polyclonal antisera using recombinant coat proteins of Grapevine leafroll-associated virus 2 and Grapevine virus B Produção de anti-soros policlonais a partir de proteínas capsidiais recombinantes de Grapevine leafroll-associated virus 2 e Grapevine virus B

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Paula Radaelli

2008-10-01

Full Text Available The objective of this work was to produce and characterize specific antisera against Brazilian isolates of Grapevine leafroll-associated virus 2 (GLRaV-2 and Grapevine virus B (GVB, developed from expressed coat proteins (CPs in Escherichia coli, and to test their possible use for the detection of these two viruses in diseased grapevines. The coat protein (CP genes were RT-PCR-amplified, cloned and sequenced. The CP genes were subsequently subcloned, and the recombinant plasmids were used to transform E. coli cells and express the coat proteins. The recombinant coat proteins were purified, and their identities were confirmed by SDS-PAGE and Western blot and used for rabbit immunizations. Antisera raised against these proteins were able to recognize the corresponding recombinant proteins in Western blots and to detect GLRaV-2 and GVB in infected grapevine tissues, by indirect ELISA, discriminating healthy and infected grapevines with absorbances (A405 of 0.08/1.15 and 0.12/1.30, respectively. Expressing CP genes can yield high amount of viral protein with high antigenicity, and GLRaV-2 and GVB antisera obtained in this study can allow reliable virus disease diagnosis.O objetivo deste trabalho foi produzir e caracterizar anti-soros específicos contra isolados brasileiros do Vírus do enrolamento-da-folha da videira 2 (GLRaV-2 e do Vírus B da videira (GVB, desenvolvidos a partir das proteínas capsidiais expressas em Escherichia coli, e testar seu possível uso para a detecção destes dois vírus em videiras infectadas. Os genes da proteína capsidial (CP foram amplificados via RT-PCR, clonados e seqüenciados. Foram, subseqüentemente, subclonados, e os plasmídeos recombinantes foram empregados na transformação das células de E. coli e na expressão das proteínas capsidiais. As proteínas capsidiais recombinantes foram purificadas, e suas identidades foram confirmadas em SDS-PAGE e "Western blot" e utilizadas para imunizar coelhos. Os anti

Computer Virus and Trends

OpenAIRE

Tutut Handayani; Soenarto Usna,Drs.MMSI

2004-01-01

Since its appearance the first time in the mid-1980s, computer virus has invited various controversies that still lasts to this day. Along with the development of computer systems technology, viruses komputerpun find new ways to spread itself through a variety of existing communications media. This paper discusses about some things related to computer viruses, namely: the definition and history of computer viruses; the basics of computer viruses; state of computer viruses at this time; and ...

Viruses in reptiles

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Ariel Ellen

2011-09-01

Full Text Available Abstract The etiology of reptilian viral diseases can be attributed to a wide range of viruses occurring across different genera and families. Thirty to forty years ago, studies of viruses in reptiles focused mainly on the zoonotic potential of arboviruses in reptiles and much effort went into surveys and challenge trials of a range of reptiles with eastern and western equine encephalitis as well as Japanese encephalitis viruses. In the past decade, outbreaks of infection with West Nile virus in human populations and in farmed alligators in the USA has seen the research emphasis placed on the issue of reptiles, particularly crocodiles and alligators, being susceptible to, and reservoirs for, this serious zoonotic disease. Although there are many recognised reptilian viruses, the evidence for those being primary pathogens is relatively limited. Transmission studies establishing pathogenicity and cofactors are likewise scarce, possibly due to the relatively low commercial importance of reptiles, difficulties with the availability of animals and permits for statistically sound experiments, difficulties with housing of reptiles in an experimental setting or the inability to propagate some viruses in cell culture to sufficient titres for transmission studies. Viruses as causes of direct loss of threatened species, such as the chelonid fibropapilloma associated herpesvirus and ranaviruses in farmed and wild tortoises and turtles, have re-focused attention back to the characterisation of the viruses as well as diagnosis and pathogenesis in the host itself. 1. Introduction 2. Methods for working with reptilian viruses 3. Reptilian viruses described by virus families 3.1. Herpesviridae 3.2. Iridoviridae 3.2.1 Ranavirus 3.2.2 Erythrocytic virus 3.2.3 Iridovirus 3.3. Poxviridae 3.4. Adenoviridae 3.5. Papillomaviridae 3.6. Parvoviridae 3.7. Reoviridae 3.8. Retroviridae and inclusion body disease of Boid snakes 3.9. Arboviruses 3.9.1. Flaviviridae 3

Genomic characterisation of Almpiwar virus, Harrison Dam virus and Walkabout Creek virus; three novel rhabdoviruses from northern Australia

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Jane McAllister

2014-09-01

Full Text Available Rhabdoviridae represent a diverse group of viruses with the potential to cause disease in humans, animals and plants. Currently there are nine genera in the family; however a large number of rhabdoviruses remain unassigned. Here we characterise three novel rhabdoviruses genomes. Almpiwar virus (ALMV, isolated from skinks in northern Queensland, is the first completely sequenced rhabdovirus from squamates, with serological studies indicating multiple animal host species. Harrison Dam virus (HARDV and Walkabout Creek virus (WACV were isolated from mosquitoes in the Northern Territory and biting midges in southern Queensland respectively and their vertebrate hosts remain unknown. Serological cross-neutralisation tests with other Australian rhabdoviruses indicate that ALMV, WACV and HARDV are distinct viruses with little antigenic cross-reactivity. Next-generation sequencing revealed that all viruses encode the core proteins common to rhabdoviruses (N, P, M, G and L, plus additional ORFs between the M and G genes. HARDV also contains a small ORF between the G and L genes. Phylogenetic analysis of N and L proteins suggests that HARDV and WACV share a common lineage with the tupaviruses and Sandjimba group, whereas ALMV is a distinct and divergent virus showing no clear relationship to any rhabdovirus except the recently characterised Niahka virus (NIAV.

Evidence for a role for interleukin-17, Th17 cells and iron homeostasis in protective immunity against tuberculosis in cynomolgus macaques.

Science.gov (United States)

Wareham, Alice S; Tree, Julia A; Marsh, Philip D; Butcher, Philip D; Dennis, Mike; Sharpe, Sally A

2014-01-01

Tuberculosis (TB) remains a major global public health problem. The only vaccine, BCG, gives variable protection, especially in adults, so several new vaccines are in clinical trials. There are no correlates of protective immunity to TB; therefore vaccines progress through lengthy and expensive pre-clinical assessments and human trials. Correlates of protection could act as early end-points during clinical trials, accelerating vaccine development and reducing costs. A genome-wide microarray was utilised to identify potential correlates of protection and biomarkers of disease induced post-BCG vaccination and post-Mycobacterium tuberculosis challenge in PPD-stimulated peripheral blood mononuclear cells from cynomolgus macaques where the outcome of infection was known. Gene expression post BCG-vaccination and post challenge was compared with gene expression when the animals were naïve. Differentially expressed genes were identified using a moderated T test with Benjamini Hochberg multiple testing correction. After BCG vaccination and six weeks post-M. tuberculosis challenge, up-regulation of genes related to a Th1 and Th17 response was observed in disease controllers. At post-mortem, RT-PCR revealed an up-regulation of iron regulatory genes in animals that developed TB and down-regulation of these genes in disease controllers, indicating the ability to successfully withhold iron may be important in the control of TB disease. The induction of a balanced Th1 and Th17 response, together with expression of effector cytokines, such as IFNG, IL2, IL17, IL21 and IL22, could be used as correlates of a protective host response.

Evidence for a role for interleukin-17, Th17 cells and iron homeostasis in protective immunity against tuberculosis in cynomolgus macaques.

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Alice S Wareham

Full Text Available Tuberculosis (TB remains a major global public health problem. The only vaccine, BCG, gives variable protection, especially in adults, so several new vaccines are in clinical trials. There are no correlates of protective immunity to TB; therefore vaccines progress through lengthy and expensive pre-clinical assessments and human trials. Correlates of protection could act as early end-points during clinical trials, accelerating vaccine development and reducing costs. A genome-wide microarray was utilised to identify potential correlates of protection and biomarkers of disease induced post-BCG vaccination and post-Mycobacterium tuberculosis challenge in PPD-stimulated peripheral blood mononuclear cells from cynomolgus macaques where the outcome of infection was known. Gene expression post BCG-vaccination and post challenge was compared with gene expression when the animals were naïve. Differentially expressed genes were identified using a moderated T test with Benjamini Hochberg multiple testing correction. After BCG vaccination and six weeks post-M. tuberculosis challenge, up-regulation of genes related to a Th1 and Th17 response was observed in disease controllers. At post-mortem, RT-PCR revealed an up-regulation of iron regulatory genes in animals that developed TB and down-regulation of these genes in disease controllers, indicating the ability to successfully withhold iron may be important in the control of TB disease. The induction of a balanced Th1 and Th17 response, together with expression of effector cytokines, such as IFNG, IL2, IL17, IL21 and IL22, could be used as correlates of a protective host response.

Powassan (POW) Virus Basics

Science.gov (United States)

... Health Professionals Related Topics For International Travelers Powassan Virus Disease Basics Download this fact sheet formatted for ... Virus Disease Fact Sheet (PDF) What is Powassan virus? Powassan virus is a tickborne flavivirus that is ...

O impacto de um projeto de educação pelo esporte no desenvolvimento infantil

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Paula Xavier Machado

Full Text Available Este artigo trata de um estudo com pré-teste (T1 e pós-teste (T2 que avaliou o impacto de um projeto esportivo no desenvolvimento infantil. Participaram 39 estudantes de 6 a 11 anos, matriculados da 1a a 4a séries do Ensino Fundamental de escola pública. Eles foram distribuídos em dois grupos: G1 (24 integrantes do projeto esportivo e G2 (15 crianças do grupo comparativo e os professores dos estudantes também participaram. O impacto foi avaliado pelas diferenças em desempenho escolar, stress, qualidade de vida e avaliação de atitudes acadêmicas e sociais do aluno pelo professor. De T1 para T2, houve aumento significativo no desempenho escolar em G1 e G2. O stress diminuiu para todas as crianças, de T1 para T2, embora seja significativo apenas para G1. A percepção da qualidade de vida diminuiu, entre T1 e T2, para G1 e G2, sendo significativo apenas para G2. Não houve diferença significativa na avaliação dos alunos de G1 e G2, em T1 e T2, pelos professores.

Mulheres em situação de violência pelo parceiro íntimo: tomada de decisão por apoio institucional especializado

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Leônidas de Albuquerque Netto

Full Text Available RESUMO Objetivo Propõe-se analisar fatores envolvidos na tomada de decisão de mulheres em situação de violência interpessoal, praticada pelo parceiro íntimo, na busca por apoio institucional de referência. Métodos Pesquisa qualitativa, descritiva e exploratória. Dezesseis mulheres foram entrevistadas, entre junho e setembro de 2012, em um Centro de Referência à Mulher de Duque de Caxias, Rio de Janeiro, Brasil, por meio de instrumento semiestruturado e individual. Os relatos foram analisados pelo método do Discurso do Sujeito Coletivo. Resultados As mulheres buscaram suporte psicossocial quando a violência interpessoal alcançou o limite da tolerância. Este suporte possibilitou o resgate da autoestima e da confiança, além da tomada de consciência para a necessidade de mudança de vida e de autonomia econômica. Conclusões As mulheres alcançaram sua autoconfiança com a superação da violência, o que possibilitou o resgate da autoestima e a tomada de decisão para a saída da situação de violência interpessoal praticada pelo parceiro íntimo.

Abordagem pedagógica e diversificação dos cenários de ensino médico: projetos selecionados pelo PROMED

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Lucia Maria Horta Figueiredo Goulart

Full Text Available Este trabalho analisa as principais propostas de abordagem pedagógica e diversificação de cenários do processo de ensino apresentadas pelas escolas selecionadas pelo Programa de Incentivo a Mudanças Curriculares nas Escolas de Medicina (Promed, instituído em 2002 pelos ministérios da Saúde e da Educação. Foi realizada pesquisa documental, utilizando-se roteiro com base no termo de referência do programa para a leitura dos projetos. Verificou-se que todas as escolas selecionadas já se encontravam em processo de mudança curricular por ocasião do edital Promed. Embora buscassem alcançar os objetivos apresentados pelo programa, os projetos selecionados apontaram diferentes caminhos para sua realização. Conhecer essas propostas e a maneira como se articularam entre si e com o objetivo final do Promed é de capital importância para os educadores da área de saúde envolvidos com mudanças curriculares em suas instituições, bem como para os gestores dessa área que vêm apresentando suas demandas em consonância com as necessidades de saúde da população

Initial characterization of Vaccinia Virus B4 suggests a role in virus spread

Energy Technology Data Exchange (ETDEWEB)

Burles, Kristin; Irwin, Chad R.; Burton, Robyn-Lee [Li Ka Shing Institute of Virology, Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada T6G 2S2 (Canada); Schriewer, Jill [Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, MO (United States); Evans, David H. [Li Ka Shing Institute of Virology, Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada T6G 2S2 (Canada); Buller, R. Mark [Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, MO (United States); Barry, Michele, E-mail: michele.barry@ualberta.ca [Li Ka Shing Institute of Virology, Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada T6G 2S2 (Canada)

2014-05-15

Currently, little is known about the ankyrin/F-box protein B4. Here, we report that B4R-null viruses exhibited reduced plaque size in tissue culture, and decreased ability to spread, as assessed by multiple-step growth analysis. Electron microscopy indicated that B4R-null viruses still formed mature and extracellular virions; however, there was a slight decrease of virions released into the media following deletion of B4R. Deletion of B4R did not affect the ability of the virus to rearrange actin; however, VACV811, a large vaccinia virus deletion mutant missing 55 open reading frames, had decreased ability to produce actin tails. Using ectromelia virus, a natural mouse pathogen, we demonstrated that virus devoid of EVM154, the B4R homolog, showed decreased spread to organs and was attenuated during infection. This initial characterization suggests that B4 may play a role in virus spread, and that other unidentified mediators of actin tail formation may exist in vaccinia virus. - Highlights: • B4R-null viruses show reduced plaque size, and decreased ability to spread. • B4R-null viruses formed mature and extracellular virions; and rearranged actin. • Virus devoid of EVM154, the B4R homolog, was attenuated during infection. • Initial characterization suggests that B4 may play a role in virus spread. • Unidentified mediators of actin tail formation may exist in vaccinia virus.

Initial characterization of Vaccinia Virus B4 suggests a role in virus spread

International Nuclear Information System (INIS)

Burles, Kristin; Irwin, Chad R.; Burton, Robyn-Lee; Schriewer, Jill; Evans, David H.; Buller, R. Mark; Barry, Michele

2014-01-01

Currently, little is known about the ankyrin/F-box protein B4. Here, we report that B4R-null viruses exhibited reduced plaque size in tissue culture, and decreased ability to spread, as assessed by multiple-step growth analysis. Electron microscopy indicated that B4R-null viruses still formed mature and extracellular virions; however, there was a slight decrease of virions released into the media following deletion of B4R. Deletion of B4R did not affect the ability of the virus to rearrange actin; however, VACV811, a large vaccinia virus deletion mutant missing 55 open reading frames, had decreased ability to produce actin tails. Using ectromelia virus, a natural mouse pathogen, we demonstrated that virus devoid of EVM154, the B4R homolog, showed decreased spread to organs and was attenuated during infection. This initial characterization suggests that B4 may play a role in virus spread, and that other unidentified mediators of actin tail formation may exist in vaccinia virus. - Highlights: • B4R-null viruses show reduced plaque size, and decreased ability to spread. • B4R-null viruses formed mature and extracellular virions; and rearranged actin. • Virus devoid of EVM154, the B4R homolog, was attenuated during infection. • Initial characterization suggests that B4 may play a role in virus spread. • Unidentified mediators of actin tail formation may exist in vaccinia virus

How Hepatitis D Virus Can Hinder the Control of Hepatitis B Virus

NARCIS (Netherlands)

Xiridiou, M.; Borkent-Raven, B.; Hulshof, J.; Wallinga, J.

2009-01-01

Background: Hepatitis D (or hepatitis delta) virus is a defective virus that relies on hepatitis B virus (HBV) for transmission; infection with hepatitis D can occur only as coinfection with HBV or superinfection of an existing HBV infection. Because of the bond between the two viruses, control

9 CFR 113.215 - Bovine Virus Diarrhea Vaccine, Killed Virus.

Science.gov (United States)

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Bovine Virus Diarrhea Vaccine, Killed Virus. 113.215 Section 113.215 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS STANDARD...

Influenza (Flu) Viruses

Science.gov (United States)

... Types Seasonal Avian Swine Variant Pandemic Other Influenza (Flu) Viruses Language: English (US) Español Recommend on Facebook ... influenza circulate and cause illness. More Information about Flu Viruses Types of Influenza Viruses Influenza A and ...

[The growth of attenuated strains of canine parvovirus, mink enteritis virus, feline panleukopenia virus, and rabies virus on various types of cell cultures].

Science.gov (United States)

Zuffa, T

1987-10-01

The growth characteristics were studied in the attenuated strains of canine parvovirus CPVA-BN 80/82, mink enteritis virus MEVA-BN 63/82 and feline panleucopenia virus FPVA-BN 110/83 on the stable feline kidney cell line FE, and in the attenuated canine distemper virus CDV-F-BN 10/83 on chicken embryo cell cultures (KEB) and cultures of the stable cell line VERO. When the FE cultures were infected with different parvoviruses in cell suspension at MOI 2-4 TKID50 per cell, the first multiplication of the intracellular virus was recorded 20 hours p. i. In the canine parvovirus, the content of intracellular and extracellular virus continued increasing parallelly until the fourth day; then, from the fourth to the sixth day, the content of extracellular virus still increased whereas that of intracellular virus fell rapidly. In the case of the mink enteritis virus the release of the virus into the culture medium continued parallelly with the production of the cellular virus until the sixth day. In the case of the feline panleucopenia virus the values concerning free virus and virus bound to cells were lower, starting from the second day p. i. When KEB or VERO cultures were infected in cell suspension with the canine distemper virus at MOI about 0.004 per 1 cell, the replicated intracellular virus was first recorded in the KEB cultures five hours after infection but in the VERO cultures only 20 hours after infection, with a timely release of the virus into the culture medium in both kinds of tissue. In the KEB and VERO cultures the highest values of infection titres were recorded on the fourth day p. i., the course of virus multiplication on the cells being parallel with its release into the culture medium.

Psicodiagnostico : a busca de novas abordagens e a maneira como vem sendo desenvolvido pelos psicologos da região do Vale do Paraiba-SP

OpenAIRE

Ana Cristina Araujo do Nascimento

1998-01-01

Resumo: O trabalho investiga a prática psicodiagnóstica realizada pelos psicólogos do Vale do Paraíba, no Estado de São Paulo. Objetivamos caracterizar a fonna como esse recurso é desenvolvido na região, no que diz respeito ao modelo utilizado, aos objetivos para sua realização, ao referencial teórico que o fundamenta, aos locais de desenvolvimento e à preparação oferecida pelos cursos de graduação que atendem a região. Da mesma fonna, procuramos saber o nível de conhecimento e engajamento do...

Efeito do tratamento clínico de um corredor de longa distância com broncoespasmo induzido pelo exercício: relato de caso

OpenAIRE

Teixeira,Renata Nakata; Gonçalves,Raquel Calvo; Costa,Luiz Augusto Riani; Silva,Leonardo Borges de Barros e; Martins,Milton de Arruda; Teixeira,Luzimar Raimundo; Carvalho,Celso Ricardo Fernandes

2009-01-01

O broncoespasmo induzido pelo exercício (BIE) é uma condição que se caracteriza pelo estreitamento transitório das vias aéreas durante ou após o esforço físico e afeta principalmente portadores de asma. Em atletas profissionais que praticam esportes de alta intensidade, a prevalência também é alta; no entanto, seu diagnóstico permanece subestimado. O presente estudo descreve o caso de um atleta do sexo masculino, 23 anos, corredor de longa distância sem histórico de asma, que após um teste gr...

An Enhanced Pre- and Postnatal Development Study in Cynomolgus Monkeys with Tabalumab: A Human IgG4 Monoclonal Antibody.

Science.gov (United States)

Breslin, William J; Hilbish, Kim G; Martin, Jennifer A; Halstead, Carolyn A; Newcomb, Deanna L; Chellman, Gary J

2015-06-01

Tabalumab, a human IgG4 monoclonal antibody (mAb) with neutralizing activity against both soluble and membrane B-cell activating factor (BAFF), has been under development for the treatment of autoimmune diseases. The purpose of this study was to determine the potential adverse effects of maternal tabalumab exposure on pregnancy, parturition, and lactation of the mothers and on the growth, viability, and development of the offspring through postnatal day (PND) 204. Tabalumab was administered by subcutaneous injection to presumed pregnant cynomolgus monkeys (16-19 per group) every 2 weeks from gestation day (GD) 20 to 22 until parturition at doses of 0, 0.3, or 30 mg/kg. Evaluations in mothers and infants included clinical signs, body weight, toxicokinetics, blood lymphocyte phenotyping, T-cell-dependent antibody response (infants only), antitherapeutic antibody (ATA), organ weights (infants only), and gross and microscopic histopathology. Infants were also examined for external and visceral morphologic and neurobehavioral development. There were no adverse tabalumab-related effects on maternal or infant endpoints. An expected pharmacological decrease in peripheral blood B-lymphocytes occurred in adults and infants; however, B-cell recovery was evident by PND154 in adults and infants at 0.3 mg/kg and by PND204 in infants at 30 mg/kg. At 30 mg/kg, a reduced IgM antibody response to T-cell-dependent antigen keyhole limpet hemocyanin (KLH) was observed following primary immunization. Following secondary KLH immunization, all infants in both dose groups mounted anti-KLH IgM and IgG antibody responses similar to control. Placental and mammary transfer of tabalumab was demonstrated. In conclusion, the no-observed-adverse-effect level for maternal and developmental toxicity was 30 mg/kg, the highest dose tested. Exposures at 30 mg/kg provide a margin of safety of 16× the anticipated clinical exposure. © 2015 Wiley Periodicals, Inc.

Viruses of asparagus.

Science.gov (United States)

Tomassoli, Laura; Tiberini, Antonio; Vetten, Heinrich-Josef

2012-01-01

The current knowledge on viruses infecting asparagus (Asparagus officinalis) is reviewed. Over half a century, nine virus species belonging to the genera Ilarvirus, Cucumovirus, Nepovirus, Tobamovirus, Potexvirus, and Potyvirus have been found in this crop. The potyvirus Asparagus virus 1 (AV1) and the ilarvirus Asparagus virus 2 (AV2) are widespread and negatively affect the economic life of asparagus crops reducing yield and increasing the susceptibility to biotic and abiotic stress. The main properties and epidemiology of AV1 and AV2 as well as diagnostic techniques for their detection and identification are described. Minor viruses and control are briefly outlined. Copyright © 2012 Elsevier Inc. All rights reserved.

Facilitação da memória olfativa pelo etanol em ratos

OpenAIRE

Prediger, Rui Daniel Schröder

2002-01-01

Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciências Biológicas. Programa de Pós-Graduação em Farmacologia. Um crescente número de estudos em humanos, e em outros animais, têm revelado uma facilitação dos processos de memória pelo etanol quando este é administrado imediatamente após o treino e os indivíduos são posteriormente testados sem a ação da droga. O objetivo do presente trabalho foi avaliar os efeitos de uma única dose de etanol (0,5; 1,0 e 2,0 g/Kg),...

Conhecendo as estrategias de acao e interacao utilizadas pelos clientes para o enfrentamento da dialise peritoneal

Directory of Open Access Journals (Sweden)

Felipe Kaezer dos Santos

2013-09-01

Full Text Available Este artigo teve por objetivo apresentar as principais estratégias de ação e interação utilizadas pelos clientes portadores de doença renal crônica para o enfrentamento da diálise peritoneal. O referencial teórico utilizado foi o Interacionismo Simbólico, por ser um arcabouço que valoriza o significado da interação como determinante do comportamento humano. A Teoria Fundamentada nos Dados foi utilizada como referencial metodológico. Após a sua obtenção, realizada por meio de um roteiro de entrevista semi-estruturado, os dados foram gravados, transcritos, codificados e organizados para compor a teoria explicativa sobre o fenômeno estudado. Durante a análise foram identificados vários recursos utilizados pelos clientes, como a necessidade de obter informações sobre a diálise peritoneal, o refúgio na espiritualidade e a falsa ilusão da cura. Destaca-se também a importância da rede de apoio, em que o enfermeiro poderá atuar como facilitador do processo de enfrentamento, em prol da adaptação dos clientes à nova realidade.

Viruses and Breast Cancer

Science.gov (United States)

Lawson, James S.; Heng, Benjamin

2010-01-01

Viruses are the accepted cause of many important cancers including cancers of the cervix and anogenital area, the liver, some lymphomas, head and neck cancers and indirectly human immunodeficiency virus associated cancers. For over 50 years, there have been serious attempts to identify viruses which may have a role in breast cancer. Despite these efforts, the establishment of conclusive evidence for such a role has been elusive. However, the development of extremely sophisticated new experimental techniques has allowed the recent development of evidence that human papilloma virus, Epstein-Barr virus, mouse mammary tumor virus and bovine leukemia virus may each have a role in the causation of human breast cancers. This is potentially good news as effective vaccines are already available to prevent infections from carcinogenic strains of human papilloma virus, which causes cancer of the uterine cervix. PMID:24281093

Viruses and Breast Cancer

International Nuclear Information System (INIS)

Lawson, James S.; Heng, Benjamin

2010-01-01

Viruses are the accepted cause of many important cancers including cancers of the cervix and anogenital area, the liver, some lymphomas, head and neck cancers and indirectly human immunodeficiency virus associated cancers. For over 50 years, there have been serious attempts to identify viruses which may have a role in breast cancer. Despite these efforts, the establishment of conclusive evidence for such a role has been elusive. However, the development of extremely sophisticated new experimental techniques has allowed the recent development of evidence that human papilloma virus, Epstein-Barr virus, mouse mammary tumor virus and bovine leukemia virus may each have a role in the causation of human breast cancers. This is potentially good news as effective vaccines are already available to prevent infections from carcinogenic strains of human papilloma virus, which causes cancer of the uterine cervix

Viruses and Breast Cancer

Energy Technology Data Exchange (ETDEWEB)

Lawson, James S., E-mail: james.lawson@unsw.edu.au; Heng, Benjamin [School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney (Australia)

2010-04-30

Viruses are the accepted cause of many important cancers including cancers of the cervix and anogenital area, the liver, some lymphomas, head and neck cancers and indirectly human immunodeficiency virus associated cancers. For over 50 years, there have been serious attempts to identify viruses which may have a role in breast cancer. Despite these efforts, the establishment of conclusive evidence for such a role has been elusive. However, the development of extremely sophisticated new experimental techniques has allowed the recent development of evidence that human papilloma virus, Epstein-Barr virus, mouse mammary tumor virus and bovine leukemia virus may each have a role in the causation of human breast cancers. This is potentially good news as effective vaccines are already available to prevent infections from carcinogenic strains of human papilloma virus, which causes cancer of the uterine cervix.

"The evil virus cell": Students‘ knowledge and beliefs about viruses

Science.gov (United States)

Enzinger, Sonja M.; Fink, Andreas

2017-01-01

Education about virus biology at school is of pivotal interest to raise public awareness concerning means of disease transmission and, thus, methods to prevent infection, and to reduce unnecessary antibiotic treatment due to patient pressure on physicians in case of viral diseases such as influenza. This study aimed at making visible the knowledge of Austrian high school and university students with respect to virus biology, virus structure and health-education issues. The data presented here stem from comprehensive questionnaire analyses, including the task to draw a virus, from a cross-sectional study with 133 grade 7 and 199 grade 10 high school students, and 133 first-year biology and 181 first-year non-biology university students. Analyses were performed both quantitatively and qualitatively. ANOVA revealed a highly significant group effect for total knowledge relating to virus biology and health issues (F(3, 642) = 44.17, p students and grade 10 high school students. Students enrolled in university-level biology outperformed all other groups, even though they had not yet encountered this topic at their courses; part of this phenomenon might be due to their affinity for learning about biological topics. However, even many first-year biology students had a high number of severe misconceptions, e.g., defining a virus as a pro- or eukaryotic cell, or falsely naming malaria as a viral disease. Since there was no significant difference in virus-related knowledge between high schools, virus biology seems to have been taught similarly among the tested schools. However, the majority of participants stated that the virus-related knowledge they had acquired at school was not sufficient. Based on the results presented here we urgently suggest improving and intensifying teaching this topic at school, since virus-related knowledge was by far too fragmentary among many participants. Such lack of health-relevant knowledge may contribute to pressure on physicians by patients

Influenza virus inactivated by artificial ribonucleases as a prospective killed virus vaccine.

Science.gov (United States)

Fedorova, Antonina A; Goncharova, Elena P; Kovpak, Mikhail P; Vlassov, Valentin V; Zenkova, Marina A

2012-04-19

The inactivation of viral particles with agents causing minimal damage to the structure of surface epitopes is a well-established approach for the production of killed virus vaccines. Here, we describe new agents for the inactivation of influenza virus, artificial ribonucleases (aRNases), which are chemical compounds capable of cleaving RNA molecules. Several aRNases were identified, exhibiting significant virucidal activity against the influenza A virus and causing a minimal effect on the affinity of monoclonal antibodies for the inactivated virus. Using a murine model of the influenza virus infection, a high protective activity of the aRNase-inactivated virus as a vaccine was demonstrated. The results of the experiments demonstrate the efficacy of novel chemical agents in the preparation of vaccines against influenza and, perhaps, against other infections caused by RNA viruses. Copyright © 2012 Elsevier Ltd. All rights reserved.

[The great virus comeback].

Science.gov (United States)

Forterre, Patrick

2013-01-01

Viruses have been considered for a long time as by-products of biological evolution. This view is changing now as a result of several recent discoveries. Viral ecologists have shown that viral particles are the most abundant biological entities on our planet, whereas metagenomic analyses have revealed an unexpected abundance and diversity of viral genes in the biosphere. Comparative genomics have highlighted the uniqueness of viral sequences, in contradiction with the traditional view of viruses as pickpockets of cellular genes. On the contrary, cellular genomes, especially eukaryotic ones, turned out to be full of genes derived from viruses or related elements (plasmids, transposons, retroelements and so on). The discovery of unusual viruses infecting archaea has shown that the viral world is much more diverse than previously thought, ruining the traditional dichotomy between bacteriophages and viruses. Finally, the discovery of giant viruses has blurred the traditional image of viruses as small entities. Furthermore, essential clues on virus history have been obtained in the last ten years. In particular, structural analyses of capsid proteins have uncovered deeply rooted homologies between viruses infecting different cellular domains, suggesting that viruses originated before the last universal common ancestor (LUCA). These studies have shown that several lineages of viruses originated independently, i.e., viruses are polyphyletic. From the time of LUCA, viruses have coevolved with their hosts, and viral lineages can be viewed as lianas wrapping around the trunk, branches and leaves of the tree of life. Although viruses are very diverse, with genomes encoding from one to more than one thousand proteins, they can all be simply defined as organisms producing virions. Virions themselves can be defined as infectious particles made of at least one protein associated with the viral nucleic acid, endowed with the capability to protect the viral genome and ensure its

Lesões histológicas no sistema nervoso central de cães com encefalite e diagnóstico molecular da infecção pelo vírus da cinomose canina Histopathological lesions in the central nervous system of dogs with encephalitis and molecular diagnosis of canine distemper virus infection

Directory of Open Access Journals (Sweden)

C.M.S. Gebara

2004-04-01

Full Text Available Dez amostras de urina de cães que apresentavam sinais clínicos sistêmicos e neurológicos indicativos da infecção pelo vírus da cinomose canina (CDV foram analisadas pela técnica da reação em cadeia pela polimerase precedida de transcrição reversa (RT-PCR para a detecção do RNA do CDV. O exame histopatológico foi realizado em fragmentos de cérebro, cerebelo e bexiga. Como controle negativo foram colhidos fragmentos de órgãos e urina de quatro cães sem sinais clínicos de doença infecciosa e que morreram por outras causas. Todos os cães (9/10 positivos em RT-PCR apresentaram alterações histológicas no cérebro e cerebelo, características de encefalite aguda (5/9 ou crônica (4/9 compatíveis com as causadas pelo CDV. Um dos cães com alterações clínicas neurológicas semelhantes às observadas em cinomose foi negativo na RT-PCR e apresentou alterações histopatológicas inespecíficas. Nas amostras de bexiga não foram observadas lesões histológicas. Todas as amostras biológicas provenientes dos cães-controle foram negativas na RT-PCR (urina e não apresentaram alterações histológicas (fragmentos de órgãos. O trabalho evidenciou a especificidade da RT-PCR no diagnóstico precoce e ante mortem na infecção pelo CDV.The reverse transcription-polymerase chain reaction (RT-PCR was used to detect canine distemper virus (CDV RNA in 10 urine samples from dogs that had died with clinical systemic and neurological signs indicative of CDV infection. Brain, cerebellum and urinary bladder fragments were collected for histopathological examination. For the negative control, urine and organ fragments were collected at necropsy from four dogs without clinical symptoms of infectious diseases that had died from other causes. The dogs positives in RT-PCR (9/10 presented histological lesions in the brain and cerebellum characteristic of acute (5/9 or chronic (4/9 encephalitis compatible with those caused by CDV. One of the dogs

Protoplasts and plant viruses

International Nuclear Information System (INIS)

Murakishi, H.; Lesney, M.S.; Carlson, P.

1984-01-01

The use of protoplasts in the study of plant viruses has attracted considerable attention since its inception in the late 1960s. This article is an attempt to assess the current status of protoplasts (primarily) and all cell cultures (in some instances) in studies of virus infection, virus replication, cytopathology, cross-protection, virus resistance, and the use of in vitro methods and genetic engineering to recover virus-resistant plants. These areas of study proved difficult to do entirely with whole plants or plant parts. However, because protoplasts could be synchronously infected with virus, they provided a valuable alternative means of following biochemical and cytological events in relation to the virus growth cycle in a more precise manner than previously possible

Hepatitis A Virus and Hepatitis E Virus: Emerging and Re-Emerging Enterically Transmitted Hepatitis Viruses.

Science.gov (United States)

Lemon, Stanley M; Walker, Christopher M

2018-05-07

Over the past two decades, progress in understanding human infections with hepatitis A virus (HAV) and hepatitis E virus (HEV) has been eclipsed by the priority of combating persistent hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. During that time, the global burden of liver disease caused by enteric hepatitis viruses has not abated. Because of vaccines, hepatitis A has become increasingly a disease of adults instead of early childhood in many regions of the world, resulting in an age-related shift toward more severe disease. HEV has remained endemic in many developing countries, and in well-developed, economically advanced countries it is now recognized as a cause of chronic, progressive liver disease in individuals with compromised immunity. The goal of this collection of articles is to review recent progress and to shine a bright light on gaps in our understanding of how these viruses replicate, cause disease, interact with the liver and host immune system, and are transmitted, along with prospects for improved control in human populations. Renewed efforts to study and compare HAV and HEV biology in humans and animal models have high potential to enhance our understanding of host-pathogen balance in the liver, and may contribute ultimately to the control of other infectious diseases of the liver. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

Evolutionary ecology of virus emergence.

Science.gov (United States)

Dennehy, John J

2017-02-01

The cross-species transmission of viruses into new host populations, termed virus emergence, is a significant issue in public health, agriculture, wildlife management, and related fields. Virus emergence requires overlap between host populations, alterations in virus genetics to permit infection of new hosts, and adaptation to novel hosts such that between-host transmission is sustainable, all of which are the purview of the fields of ecology and evolution. A firm understanding of the ecology of viruses and how they evolve is required for understanding how and why viruses emerge. In this paper, I address the evolutionary mechanisms of virus emergence and how they relate to virus ecology. I argue that, while virus acquisition of the ability to infect new hosts is not difficult, limited evolutionary trajectories to sustained virus between-host transmission and the combined effects of mutational meltdown, bottlenecking, demographic stochasticity, density dependence, and genetic erosion in ecological sinks limit most emergence events to dead-end spillover infections. Despite the relative rarity of pandemic emerging viruses, the potential of viruses to search evolutionary space and find means to spread epidemically and the consequences of pandemic viruses that do emerge necessitate sustained attention to virus research, surveillance, prophylaxis, and treatment. © 2016 New York Academy of Sciences.

A virus of hyperthermophilic archaea with a unique architecture among DNA viruses.

Science.gov (United States)

Rensen, Elena Ilka; Mochizuki, Tomohiro; Quemin, Emmanuelle; Schouten, Stefan; Krupovic, Mart; Prangishvili, David

2016-03-01

Viruses package their genetic material in diverse ways. Most known strategies include encapsulation of nucleic acids into spherical or filamentous virions with icosahedral or helical symmetry, respectively. Filamentous viruses with dsDNA genomes are currently associated exclusively with Archaea. Here, we describe a filamentous hyperthermophilic archaeal virus, Pyrobaculum filamentous virus 1 (PFV1), with a type of virion organization not previously observed in DNA viruses. The PFV1 virion, 400 ± 20 × 32 ± 3 nm, contains an envelope and an inner core consisting of two structural units: a rod-shaped helical nucleocapsid formed of two 14-kDa major virion proteins and a nucleocapsid-encompassing protein sheath composed of a single major virion protein of 18 kDa. The virion organization of PFV1 is superficially similar to that of negative-sense RNA viruses of the family Filoviridae, including Ebola virus and Marburg virus. The linear dsDNA of PFV1 carries 17,714 bp, including 60-bp-long terminal inverted repeats, and contains 39 predicted ORFs, most of which do not show similarities to sequences in public databases. PFV1 is a lytic virus that completely disrupts the host cell membrane at the end of the infection cycle.

DIAGNOSTICS OF VIRUS PHYTOPATHOGENS FRUIT TREE PLUM POX VIRUS, PRUNUS NECROTIC RINGSPOT VIRUS AND PRUNUS DWARF VIRUS BY BIOLOGICAL AND MOLECULAR DIAGNOSTICS

OpenAIRE

Július Rozák; Zdenka Gálová

2013-01-01

The aim of this study was to determine the incidence of viral phytopathogen Plum pox virus, Prunus necrotic ringspot virus and Prunus dwarf virus in selected localities of Slovakia and diagnose them using a molecular and biological methods. Forty samples of fruit trees of the genus Prunus, twenty samples from intensive plantings and twenty samples from wild subject were analysed. Biological diagnostic by using biological indicators Prunus persica cv. GF 305, Prunus serrulata cv. Schirofugen a...

Functional properties of Virus-Encoded and Virus-Regulated 7TM Receptors

DEFF Research Database (Denmark)

Spiess, Katja; Rosenkilde, Mette Marie

2014-01-01

During co-evolution with their hosts, viruses have developed several survival strategies that involve exploitation of 7TM receptors. These include virus-encoded 7TM receptors and ligands and viral regulation of endogenous receptors. Many functional properties have been ascribed to virus-exploited...

Biological Characterization of a Stable Effector Functionless (SEFL) Monoclonal Antibody Scaffold in Vitro*

Science.gov (United States)

Liu, Ling; Jacobsen, Frederick W.; Everds, Nancy; Zhuang, Yao; Yu, Yan Bin; Li, Nianyu; Clark, Darcey; Nguyen, Mai Phuong; Fort, Madeline; Narayanan, Padma; Kim, Kei; Stevenson, Riki; Narhi, Linda; Gunasekaran, Kannan; Bussiere, Jeanine L.

2017-01-01

The stable effector functionLess (SEFL) antibody was designed as an IgG1 antibody with a constant region that lacks the ability to interact with Fcγ receptors. The engineering and stability and pharmacokinetic assessments of the SEFL scaffold is described in the accompanying article (Jacobsen, F. W., Stevenson, R., Li, C., Salimi-Moosavi, H., Liu, L., Wen, J., Luo, Q., Daris, K., Buck, L., Miller, S., Ho, S-Y., Wang, W., Chen, Q., Walker, K., Wypych, J., Narhi, L., and Gunasekaran, K. (2017) J. Biol. Chem. 292). The biological properties of these SEFL antibodies were assessed in a variety of human and cynomolgus monkey in vitro assays. Binding of parent molecules and their SEFL variants to human and cynomolgus monkey FcγRs were evaluated using flow cytometry-based binding assays. The SEFL variants tested showed decreased binding affinity to human and cynomolgus FcγRs compared with the wild-type IgG1 antibody. In addition, SEFL variants demonstrated no antibody-dependent cell-mediated cytotoxicity in vitro against Daudi cells with cynomolgus monkey peripheral blood mononuclear cells, and had minimal complement-dependent cytotoxicity activity similar to that of the negative control IgG2 in a CD20+ human Raji lymphoma cell line. SEFL mutations eliminated off-target antibody-dependent monocyte phagocytosis of cynomolgus monkey platelets, and cynomolgus platelet activation in vitro. These experiments demonstrate that the SEFL modifications successfully eliminated Fc-associated effector binding and functions. PMID:27994063

Electron microscopic identification of Zinga virus as a strain of Rift Valley fever virus.

Science.gov (United States)

Olaleye, O D; Baigent, C L; Mueller, G; Tomori, O; Schmitz, H

1992-01-01

Electron microscopic examination of a negatively stained suspension of Zinga virus showed particles 90-100 nm in diameter, enveloped with spikes 12-20 nm in length and 5 nm in diameter. Further identification of the virus by immune electron microscopy showed the reactivity of human Rift Valley fever virus-positive serum with Zinga virus. Results of this study are in agreement with earlier reports that Zinga virus is a strain of Rift Valley fever virus.

O conhecimento pré-colombiano do Brasil pelos portugueses

Directory of Open Access Journals (Sweden)

Thomaz Oscar Marcondes de Souza

1961-09-01

Full Text Available A brilhante emprêsa marítima realizada pelo infante D. Henrique ao longo da costa ocidental da África; a passagem do cabo da Boa Esperança em 1488 por Bartolomeu Dias; o desco-brimento do caminho marítimo para a índia por Vasco da Ga-ma em 1498; as guerras e conquistas na Ásia com a figura ím-par de Afonso de Albuquerque; o ter Portugal mantido por mais de três séculos a integridade territorial do Brasil, vencendo fran-ceses, holandeses e espanhóis, não satisfazem a vaidade nacio-nal de certos historiadores portuguêses . Querem mais . Que-rem que tudo que possa constituir prioridade, em se tratando de descobrimento marítimos, pertença a Portugal. Navegado-res do quilate de Colombo, Caboto, Vespucci, Pinzon, Verraz-zano, Cartier e outros, não passam de medíocres, de embustei-ros e de falsos descobridores que se apropriaram de glórias alheias, sendo que o Genovês, o pouco que sabia de navegação, aprendeu em Portugal.

Perda auditiva induzida pelo ruído em trabalhadores de metalúrgica Noise induced hearing loss in metallurgical workers

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Simone Adad Araújo

Full Text Available Introdução: A perda auditiva induzida pelo ruído é uma patologia insidiosa cumulativa, que cresce ao longo dos anos de exposição ao ruído associado ao ambiente de trabalho. Objetivos: Identificar e quantificar a ocorrência de alterações auditivas sugestivas de Perda Auditiva Induzida pelo Ruído e os principais sintomas otorrinolaringológicos referidos pelos trabalhadores. Forma de estudo: prospectivo clínico randomizado. Casuística e métodos: Pesquisa realizada no período de janeiro a março de 2000 com 187 trabalhadores de indústria metalúrgica no município de Goiânia, avaliados por médicos otorrinolaringologistas através de roteiro de entrevista e audiometria ocupacional. Resultados: Foram obtidas audiometrias ocupacionais sendo: 21% sugestivas de PAIR, 72%, normais e 7%, sugestivas de outras doenças auditivas. Os sintomas auditivos mais freqüentes foram: dificuldade de compreensão da fala, 12%; hipoacusia, 7%; tinitus, 13%; sensação de plenitude auricular, 4%; otorreia, 6%; tonturas, 12%. Conclusão: Concluímos que em metalúrgica há ocorrência de alterações auditivas sugestivas de Perda Auditiva Induzida pelo Ruído e queixa de sintomas otorrinolaringológicos significativos.Introduction: Noise induced hearing loss is a cumulative pathological disease that increases over the years with exposure to noise associated with the work atmosphere. Objectives: To identify and quantify the occurrence of hearing loss suggestive of Noise Induced Hearing Loss (NIHL and the principle otolaryngological symptoms referred to by workers. Study design: prospective clinical randomized. Material and method: Research was carried out from January to March of 2000 with 187 metallurgical workers in the city of Goiânia, who were evaluated by otolaryngologists by means of a combination of interviews and occupational hearing exams. Results: Occupational hearing tests results were: 21% suggestive of NIHL, 72% normal, and 7% suggestive of

Infestaçao humana pelo Dipylidium caninum

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Carlos Henrique Lemos

1985-12-01

Full Text Available Os autores descrevem um caso de infestação pelo Dipylidium caninum numa criança residente em Araguari, Minas Gerais, que apresentou lesões cutâneas, insônia, irritabilidade, vômitos eperda do apetite. Relatam a eliminação abundante deproglotes quando a paciente foi tratada com medicamentos caseiros e a remissão dos sintomas, após dois tratamentos com mebendazol. Contudo não puderam concluir sobre a eficiência das drogas, devido à medicação empírica e ã administração de 200 mg/dia de mebendazol, contrariando a dosagem recomendada para Cestodas, que é de 400 mg/dia. Relatam, ainda, que exames das fezes do cão de propriedade da família revelaram apenas a presença de ancilostomídeos.The authors describe a case of Dipylidium caninum infestation in a child living in Araguari, state of Minas Gerais, Brazil, who has presented skin lesions, insomnia, irritability, vomitingand lossof appetite. When the patient was treated with folk medicine they noticed excessive elimination of proglotids and the elimination of symptoms after being treated twice with mebendazol. However it was not possible to conclude anything about the drugs, due to the empiric medication and the administration of mebendazol in a dose of200 mg daily, which is not the quantity recommended for Cestodes (400 mg daily. The fecal examination of the dog that belongs to the family showed only ancylostomides.

O vírus do Nilo Ocidental West Nile virus

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Eduardo Furtado Flores

2009-04-01

árias brasileiras da área humana e animal temem que a infecção seja introduzida no país, onde provavelmente encontraria condições ecológicas para a sua disseminação e manutenção. Este artigo apresenta uma breve revisão dos principais aspectos epidemiológicos e clínico-patológicos da infecção pelo WNV, com ênfase na infecção de humanos, aves e eqüinos.West Nile virus (WNV is a Flavivirus maintained in nature through alternate cycles of infection in wild birds and haematophagus mosquitoes, mainly Culex sp. Natural infection by WNV has been demonstrated in more than 200 bird species, which present variable susceptibility to infection and disease. Corvids and passeriformes are particularly susceptible and develop high levels of viremia and mortality. Occasionally, the virus may be transmitted to mammals by mosquitoes feeding previously on viremic birds. Human and horses are highly susceptible to WNV infection and often develop fever, which may be followed by neurological infection and fatal meningoencephalitis. Originally identified in Uganda (1937, WNV infection remained for decades restricted to North Africa, East Asia, Middle East and Mediterranean Europe. In these areas, isolated cases of human and horse disease, or small outbreaks were occasionally reported. In 1999, the virus was introduced in New York, USA, where it caused mortality in thousands of wild and captive birds and infected hundreds of people, killing 21. Thereafter, the infection rapidly spread out over the US territory, causing thousands of human infections (more than 27.000 - around 1100 deaths and equine infections (more than 25.000 cases. WNV infection has also been detected in wild and domestic birds, horses and other mammals across Mexico, Central America and the Caribbean, and northern South America, indicating its dissemination southwards. In 2006, WNV was first identified as the agent of fatal neurological disease in three horses in Argentina, where it has been shown to be circulating in

Nonhuman Primate Models of Hepatitis A Virus and Hepatitis E Virus Infections.

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Lanford, Robert E; Walker, Christopher M; Lemon, Stanley M

2018-04-23

Although phylogenetically unrelated, human hepatitis viruses share an exclusive or near exclusive tropism for replication in differentiated hepatocytes. This narrow tissue tropism may contribute to the restriction of the host ranges of these viruses to relatively few host species, mostly nonhuman primates. Nonhuman primate models thus figure prominently in our current understanding of the replication and pathogenesis of these viruses, including the enterically transmitted hepatitis A virus (HAV) and hepatitis E virus (HEV), and have also played major roles in vaccine development. This review draws comparisons of HAV and HEV infection from studies conducted in nonhuman primates, and describes how such studies have contributed to our current understanding of the biology of these viruses. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

Zika Virus

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... Funding CDC Activities For Healthcare Providers Clinical Evaluation & Disease Sexual Transmission HIV Infection & Zika Virus Testing for Zika Test Specimens – At Time of Birth Diagnostic Tests Understanding Zika Virus Test Results ...

Hepatitis C virus infection in the human immunodeficiency virus infected patient

DEFF Research Database (Denmark)

Clausen, Louise Nygaard; Lundbo, Lene Fogt; Benfield, Thomas

2014-01-01

Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) share the same transmission routes; therefore, coinfection is frequent. An estimated 5-10 million individuals alone in the western world are infected with both viruses. The majority of people acquire HCV by injection drug use and...

Immunological responses against human papilloma virus and human papilloma virus induced laryngeal cancer.

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Chitose, Shun-ichi; Sakazaki, T; Ono, T; Kurita, T; Mihashi, H; Nakashima, T

2010-06-01

This study aimed to clarify the local immune status in the larynx in the presence of infection or carcinogenesis associated with human papilloma virus. Cytological samples (for human papilloma virus detection) and laryngeal secretions (for immunoglobulin assessment) were obtained from 31 patients with laryngeal disease, during microscopic laryngeal surgery. On histological examination, 12 patients had squamous cell carcinoma, four had laryngeal papilloma and 15 had other benign laryngeal disease. Cytological samples were tested for human papilloma virus DNA using the Hybrid Capture 2 assay. High risk human papilloma virus DNA was detected in 25 per cent of patients (three of 12) with laryngeal cancer. Low risk human papilloma virus DNA was detected only in three laryngeal papilloma patients. The mean laryngeal secretion concentrations of immunoglobulins M, G and A and secretory immunoglobulin A in human papilloma virus DNA positive patients were more than twice those in human papilloma virus DNA negative patients. A statistically significant difference was observed between the secretory immunoglobulin A concentrations in the two groups. Patients with laryngeal cancer had higher laryngeal secretion concentrations of each immunoglobulin type, compared with patients with benign laryngeal disease. The study assessed the mean laryngeal secretion concentrations of each immunoglobulin type in the 12 laryngeal cancer patients, comparing human papilloma virus DNA positive patients (n = 3) and human papilloma virus DNA negative patients (n = 9); the mean concentrations of immunoglobulins M, G and A and secretory immunoglobulin A tended to be greater in human papilloma virus DNA positive cancer patients, compared with human papilloma virus DNA negative cancer patients. These results suggest that the local laryngeal immune response is activated by infection or carcinogenesis due to human papilloma virus. The findings strongly suggest that secretory IgA has inhibitory activity

IMPROPRIEDADE DOS PRINCÍPIOS DA VERDADE MATERIAL E DA VERDADE FORMAL: UMA ANÁLISE FILOSÓFICA SOBRE A VERDADE ALCANÇÁVEL PELO DIREITO

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Patrícia de Almeida Cardoso

2010-08-01

Full Text Available A doutrina relaciona à atividade probatória os princípios da verdade material e da verdade formal. Entretanto, o presente trabalho tem por escopo demonstrar a impropriedade desta divisão principiológica. Transportando-se para o Direito o conceito de verdade para a Filosofia, em destaque à Escola do Pragmatismo e do Neopragmatismo, bem como, apresentando-se o conjunto de limitações intrínsecas à natureza humana e criadas pelo ordenamento jurídico, busca-se evidenciar a intangibilidade da verdade pelo sistema jusprocessual e individualizar o que, de fato, é retratado pelas sentenças penal e civil.

Deep-Sea Hydrothermal Vent Viruses Compensate for Microbial Metabolism in Virus-Host Interactions.

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He, Tianliang; Li, Hongyun; Zhang, Xiaobo

2017-07-11

Viruses are believed to be responsible for the mortality of host organisms. However, some recent investigations reveal that viruses may be essential for host survival. To date, it remains unclear whether viruses are beneficial or harmful to their hosts. To reveal the roles of viruses in the virus-host interactions, viromes and microbiomes of sediment samples from three deep-sea hydrothermal vents were explored in this study. To exclude the influence of exogenous DNAs on viromes, the virus particles were purified with nuclease (DNase I and RNase A) treatments and cesium chloride density gradient centrifugation. The metagenomic analysis of viromes without exogenous DNA contamination and microbiomes of vent samples indicated that viruses had compensation effects on the metabolisms of their host microorganisms. Viral genes not only participated in most of the microbial metabolic pathways but also formed branched pathways in microbial metabolisms, including pyrimidine metabolism; alanine, aspartate, and glutamate metabolism; nitrogen metabolism and assimilation pathways of the two-component system; selenocompound metabolism; aminoacyl-tRNA biosynthesis; and amino sugar and nucleotide sugar metabolism. As is well known, deep-sea hydrothermal vent ecosystems exist in relatively isolated environments which are barely influenced by other ecosystems. The metabolic compensation of hosts mediated by viruses might represent a very important aspect of virus-host interactions. IMPORTANCE Viruses are the most abundant biological entities in the oceans and have very important roles in regulating microbial community structure and biogeochemical cycles. The relationship between virus and host microbes is broadly thought to be that of predator and prey. Viruses can lyse host cells to control microbial population sizes and affect community structures of hosts by killing specific microbes. However, viruses also influence their hosts through manipulation of bacterial metabolism. We found

Acesso aos medicamentos para tratamento da doença de Alzheimer fornecidos pelo Sistema Único de Saúde em Minas Gerais, Brasil

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Celline Cardoso Almeida-Brasil

Full Text Available Resumo: Avaliou-se as barreiras de acesso ao tratamento da doença de Alzheimer com base nos processos administrativos de medicamentos inibidores da colinesterase (IChE, enviados à Secretaria de Estado de Saúde de Minas Gerais, Brasil, entre 2012 e 2013. Utilizando-se informações de 165 processos selecionados aleatoriamente, abordaram-se as dimensões de acesso: acessibilidade geográfica, acomodação, aceitabilidade, disponibilidade e capacidade aquisitiva. O trâmite administrativo para o fornecimento dos IChE levou em média 39 dias e foi influenciado por características do trajeto percorrido pelo usuário. A maioria dos prescritores cumpriu menos de 80% dos critérios exigidos pelo Protocolo Clínico e Diretrizes Terapêuticas (PCDT da doença de Alzheimer. Como resultado, 38% dos processos não foram deferidos. A capacidade aquisitiva para o tratamento privado mensal com IChE foi de cerca de 21 dias de salário mínimo. Conclui-se que a burocracia do trâmite administrativo e a dificuldade de seguimento do PCDT pelos prescritores prejudicam o acesso ao tratamento da doença de Alzheimer e constituem uma grande carga para o orçamento dos pacientes.

Viruses in reptiles.

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Ariel, Ellen

2011-09-21

The etiology of reptilian viral diseases can be attributed to a wide range of viruses occurring across different genera and families. Thirty to forty years ago, studies of viruses in reptiles focused mainly on the zoonotic potential of arboviruses in reptiles and much effort went into surveys and challenge trials of a range of reptiles with eastern and western equine encephalitis as well as Japanese encephalitis viruses. In the past decade, outbreaks of infection with West Nile virus in human populations and in farmed alligators in the USA has seen the research emphasis placed on the issue of reptiles, particularly crocodiles and alligators, being susceptible to, and reservoirs for, this serious zoonotic disease. Although there are many recognised reptilian viruses, the evidence for those being primary pathogens is relatively limited. Transmission studies establishing pathogenicity and cofactors are likewise scarce, possibly due to the relatively low commercial importance of reptiles, difficulties with the availability of animals and permits for statistically sound experiments, difficulties with housing of reptiles in an experimental setting or the inability to propagate some viruses in cell culture to sufficient titres for transmission studies. Viruses as causes of direct loss of threatened species, such as the chelonid fibropapilloma associated herpesvirus and ranaviruses in farmed and wild tortoises and turtles, have re-focused attention back to the characterisation of the viruses as well as diagnosis and pathogenesis in the host itself.

Canine distemper virus detection in asymptomatic and non vaccinated dogs

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Helen L. Del Puerto

2010-02-01

Full Text Available A quantitative real time polymerase chain reaction (PCR revealed canine distemper virus presence in peripheral blood samples from asymptomatic and non vaccinated dogs. Samples from eleven domestic dogs with no signs of canine distemper and not vaccinated at the month of collection were used. Canine distemper virus vaccine samples in VERO cells were used as positive controls. RNA was isolated with Trizol®, and treated with a TURBO DNA-free kit. Primers were designed for canine distemper virus nucleocapsid protein coding region fragment amplification (84 bp. Canine b-actin (93 bp was utilized as the endogenous control for normalization. Quantitative results of real time PCR generated by ABI Prism 7000 SDS Software showed that 54.5% of dogs with asymptomatic canine distemper were positive for canine distemper virus. Dissociation curves confirmed the specificity of the real time PCR fragments. This technique could detect even a few copies of viral RNA and identificate subclinically infected dogs providing accurate diagnosis of this disease at an early stage.A reação em cadeia da polimerase (PCR em tempo real revelou a presença do vírus da cinomose canina em amostra de sangue de cães assintomáticos e não vacinados. Amostra de onze cães domésticos sem nenhum sinal clínico de cinomose e que não foram vacinados no mês da coleta de sangue foram utilizados para análise. Amostra vacinal do vírus da cinomose canina em células VERO foi utilizada como controle positivo. O RNA total foi isolado utilizando-se Trizol®, e tratadas com o Kit TURBO DNA-free. Os iniciadores foram desenhados para amplificar a região do nucleocapsídeo viral com 319pb e 84pb para a PCR convencional e PCR em tempo real, respectivamente. O fragmento alvo da b-actina canina com 93pb foi utilizado como controle endógeno e normalizador. Resultados quantitativos da PCR em tempo real gerados pelo programa ABI Prism 7000 SDS demonstraram que 54,5% dos cães assintom

A REVIEW ON ZIKA VIRUS (ZIKV) -A DREADFUL MEMBER OF THE VIRUS FAMILY FLAVIVIRIDAE

OpenAIRE

1Rafiya Begum, 2 Raafia Aseena, 3Nuha Rasheed and 4 Abdul Saleem Mohammad

2017-01-01

Research on zika virus examine the virus that is spread to humans through a mosquito bite, with symptoms that include fever, rash, joint pain, and conjuctivities. For most people zika virus is not necessarily anything to worry, as it is not fatal and symptoms are generally mild for period up to a week. Hospitalization because of zika virus is almost always not necessary. However, the zika virus can be extremely dangerous to pregnant womes. Key Words: Zika, virus, transmission, fatal, flavivir...

Type C virus activation in nontransformed mouse cells by uv-irradiated herpes simplex virus

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Hampar, B. (National Institutes of Health, Bethesda, MD); Hatanaka, M.; Aulakh, G.; Derge, J.G.; Lee, L.; Showalter, S.

1977-02-01

Infection of nontransformed mouse cells with uv-irradiated herpes simplex virus (uv-HSV) resulted in the activation of an endogenous xenotropic (x-tropic) type C virus. Synthesis of type C virus persisted for only a few days, with most of the virus remaining cell associated. The levels of type C virus activated by uv-HSV varied depending on the multiplicity of infection (m.o.i.) and the uv dose. At low uv doses, where cell killing occurred, little or no type C virus synthesis was observed. Maximum levels of type C virus synthesis were observed with the minimum uv dose which eliminated cell killing by HSV. Synthesis of type C virus, albeit at lower levels, was still observed at uv doses beyond those required to prevent cell killing.

Type C virus activation in nontransformed mouse cells by uv-irradiated herpes simplex virus

International Nuclear Information System (INIS)

Hampar, B.; Hatanaka, M.; Aulakh, G.; Derge, J.G.; Lee, L.; Showalter, S.

1977-01-01

Infection of nontransformed mouse cells with uv-irradiated herpes simplex virus (uv-HSV) resulted in the activation of an endogenous xenotropic (x-tropic) type C virus. Synthesis of type C virus persisted for only a few days, with most of the virus remaining cell associated. The levels of type C virus activated by uv-HSV varied depending on the multiplicity of infection (m.o.i.) and the uv dose. At low uv doses, where cell killing occurred, little or no type C virus synthesis was observed. Maximum levels of type C virus synthesis were observed with the minimum uv dose which eliminated cell killing by HSV. Synthesis of type C virus, albeit at lower levels, was still observed at uv doses beyond those required to prevent cell killing

Chikungunya virus

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Chikungunya virus infection; Chikungunya ... Where Chikungunya is Found Before 2013, the virus was found in Africa, Asia, Europe, and the Indian and Pacific oceans. In late 2013, outbreaks occurred for the first time in the ...

Perinatal hepatitis B virus detection by hepatitis B virus-DNA analysis.

OpenAIRE

De Virgiliis, S; Frau, F; Sanna, G; Turco, M P; Figus, A L; Cornacchia, G; Cao, A

1985-01-01

Maternal transmission of hepatitis B virus infection in relation to the hepatitis B e antigen/antibody system and serum hepatitis B virus-DNA were evaluated. Results indicate that hepatitis B virus-DNA analysis can identify hepatitis B serum antigen positive mothers who may transmit infection to their offspring.

Virus like particle-based vaccines against emerging infectious disease viruses.

Science.gov (United States)

Liu, Jinliang; Dai, Shiyu; Wang, Manli; Hu, Zhihong; Wang, Hualin; Deng, Fei

2016-08-01

Emerging infectious diseases are major threats to human health. Most severe viral disease outbreaks occur in developing regions where health conditions are poor. With increased international travel and business, the possibility of eventually transmitting infectious viruses between different countries is increasing. The most effective approach in preventing viral diseases is vaccination. However, vaccines are not currently available for numerous viral diseases. Virus-like particles (VLPs) are engineered vaccine candidates that have been studied for decades. VLPs are constructed by viral protein expression in various expression systems that promote the selfassembly of proteins into structures resembling virus particles. VLPs have antigenicity similar to that of the native virus, but are non-infectious as they lack key viral genetic material. VLP vaccines have attracted considerable research interest because they offer several advantages over traditional vaccines. Studies have shown that VLP vaccines can stimulate both humoral and cellular immune responses, which may offer effective antiviral protection. Here we review recent developments with VLP-based vaccines for several highly virulent emerging or re-emerging infectious diseases. The infectious agents discussed include RNA viruses from different virus families, such as the Arenaviridae, Bunyaviridae, Caliciviridae, Coronaviridae, Filoviridae, Flaviviridae, Orthomyxoviridae, Paramyxoviridae, and Togaviridae families.

Immunogenicity of a modified-live virus vaccine against bovine viral diarrhea virus types 1 and 2, infectious bovine rhinotracheitis virus, bovine parainfluenza-3 virus, and bovine respiratory syncytial virus when administered intranasally in young calves.

Science.gov (United States)

Xue, Wenzhi; Ellis, John; Mattick, Debra; Smith, Linda; Brady, Ryan; Trigo, Emilio

2010-05-14

The immunogenicity of an intranasally-administered modified-live virus (MLV) vaccine in 3-8 day old calves was evaluated against bovine viral diarrhea virus (BVDV) types 1 and 2, infectious bovine rhinotracheitis (IBR) virus, parainfluenza-3 (PI-3) virus and bovine respiratory syncytial virus (BRSV). Calves were intranasally vaccinated with a single dose of a multivalent MLV vaccine and were challenged with one of the respective viruses three to four weeks post-vaccination in five separate studies. There was significant sparing of diseases in calves intranasally vaccinated with the MLV vaccine, as indicated by significantly fewer clinical signs, lower rectal temperatures, reduced viral shedding, greater white blood cell and platelet counts, and less severe pulmonary lesions than control animals. This was the first MLV combination vaccine to demonstrate efficacy against BVDV types 1 and 2, IBR, PI-3 and BRSV in calves 3-8 days of age. Copyright 2010 Elsevier Ltd. All rights reserved.

Ocular Tropism of Respiratory Viruses

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Rota, Paul A.; Tumpey, Terrence M.

2013-01-01

SUMMARY Respiratory viruses (including adenovirus, influenza virus, respiratory syncytial virus, coronavirus, and rhinovirus) cause a broad spectrum of disease in humans, ranging from mild influenza-like symptoms to acute respiratory failure. While species D adenoviruses and subtype H7 influenza viruses are known to possess an ocular tropism, documented human ocular disease has been reported following infection with all principal respiratory viruses. In this review, we describe the anatomical proximity and cellular receptor distribution between ocular and respiratory tissues. All major respiratory viruses and their association with human ocular disease are discussed. Research utilizing in vitro and in vivo models to study the ability of respiratory viruses to use the eye as a portal of entry as well as a primary site of virus replication is highlighted. Identification of shared receptor-binding preferences, host responses, and laboratory modeling protocols among these viruses provides a needed bridge between clinical and laboratory studies of virus tropism. PMID:23471620

Understanding Ebola Virus Transmission

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Seth Judson

2015-02-01

Full Text Available An unprecedented number of Ebola virus infections among healthcare workers and patients have raised questions about our understanding of Ebola virus transmission. Here, we explore different routes of Ebola virus transmission between people, summarizing the known epidemiological and experimental data. From this data, we expose important gaps in Ebola virus research pertinent to outbreak situations. We further propose experiments and methods of data collection that will enable scientists to fill these voids in our knowledge about the transmission of Ebola virus.

A relação entre o preço pago pelo consumidor de carne bovina em Santa Maria e o recebido pelo produtor de gado de corte no Rio Grande do Sul, Brasil Relationship between price paid by consumers in Santa Maria and prices paid to beef cattle farmers in Rio Grande do Sul, Brazil

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João Garibaldi Almeida Viana

2007-08-01

Full Text Available Este estudo analisa em que medida os preços pagos pelos consumidores de carne bovina - ponto final da cadeia - são repassados ao produtor. Os preços dos diferentes cortes de carne foram coletados através de pesquisa mensal de preços, em quatro supermercados de Santa Maria, RS, Brasil. Depois de obtidos os valores percentuais dos diferentes cortes na composição da carcaça, estes valores foram multiplicados pelo preço pago pelo consumidor, obtendo-se assim os preços e as proporções dos cortes referentes ao valor ajustado de um quilo de carcaça pago pelo consumidor. Para a obtenção do preço médio do kg do boi vivo recebido pelos produtores, foram considerados os preços coletados pela EMATER-RS. Verificou-se uma baixa variação ao longo do ano das partes componentes da carcaça, na contribuição do preço total. Na média, o dianteiro contribui com 26,10%, o costilhar com 13,40% e o traseiro com 60,50% do preço total da carcaça. O setor a jusante na cadeia bovina tem função reguladora do preço final ao consumidor, com uma margem de operação de 7,61 pontos ao longo do ano. Nos três quadrimestres ao longo do ano, a associação entre o preço recebido pelo produtor (PRP e o pago pelo consumidor (PPC teve um comportamento diferenciado. As associações verificadas foram fraca, negativamente forte e positivamente muito forte para o primeiro, segundo e terceiro quadrimestres, respectivamente.This study analyses how much of prices paid by the consumers of beef meat are passed on to the farmer. The prices of different types of beef cuts were collected monthly in four supermarkets in Santa Maria-RS, Brazil. The percentage values of different cuts were obtained and multiplied by the price paid by consumers. Thus, it was calculated the adjusted price of kilogram of carcass commercialized at supermarket. The average price per kilogram of live steers received by the farmer was collected by EMATER-RS. There was a low price variation

Ganjam virus/Nairobi sheep disease virus induces a pro-inflammatory response in infected sheep

OpenAIRE

bin Tarif, Abid; Lasecka, Lidia; Holzer, Barbara; Baron, Michael D

2012-01-01

Abstract Partly due to climate change, and partly due to changes of human habitat occupation, the impact of tick-borne viruses is increasing. Nairobi sheep disease virus (NSDV) and Ganjam virus (GV) are two names for the same virus, which causes disease in sheep and goats and is currently known to be circulating in India and East Africa. The virus is transmitted by ixodid ticks and causes a severe hemorrhagic disease. We have developed a real-time PCR assay for the virus genome and validated ...

Zika Virus

Science.gov (United States)

... through blood transfusions. There have been outbreaks of Zika virus in the United States, Africa, Southeast Asia, the ... not travel to areas where there is a Zika virus outbreak. If you do decide to travel, first ...

Ganjam virus/Nairobi sheep disease virus induces a pro-inflammatory response in infected sheep

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bin Tarif Abid

2012-10-01

Full Text Available Abstract Partly due to climate change, and partly due to changes of human habitat occupation, the impact of tick-borne viruses is increasing. Nairobi sheep disease virus (NSDV and Ganjam virus (GV are two names for the same virus, which causes disease in sheep and goats and is currently known to be circulating in India and East Africa. The virus is transmitted by ixodid ticks and causes a severe hemorrhagic disease. We have developed a real-time PCR assay for the virus genome and validated it in a pilot study of the pathogenicity induced by two different isolates of NSDV/GV. One isolate was highly adapted to tissue culture, grew in most cell lines tested, and was essentially apathogenic in sheep. The second isolate appeared to be poorly adapted to cell culture and retained pathogenicity in sheep. The real-time PCR assay for virus easily detected 4 copies or less of the viral genome, and allowed a quantitative measure of the virus in whole blood. Measurement of the changes in cytokine mRNAs showed similar changes to those observed in humans infected by the closely related virus Crimean Congo hemorrhagic fever virus.

Ganjam virus/Nairobi sheep disease virus induces a pro-inflammatory response in infected sheep.

Science.gov (United States)

Bin Tarif, Abid; Lasecka, Lidia; Holzer, Barbara; Baron, Michael D

2012-10-19

Partly due to climate change, and partly due to changes of human habitat occupation, the impact of tick-borne viruses is increasing. Nairobi sheep disease virus (NSDV) and Ganjam virus (GV) are two names for the same virus, which causes disease in sheep and goats and is currently known to be circulating in India and East Africa. The virus is transmitted by ixodid ticks and causes a severe hemorrhagic disease. We have developed a real-time PCR assay for the virus genome and validated it in a pilot study of the pathogenicity induced by two different isolates of NSDV/GV. One isolate was highly adapted to tissue culture, grew in most cell lines tested, and was essentially apathogenic in sheep. The second isolate appeared to be poorly adapted to cell culture and retained pathogenicity in sheep. The real-time PCR assay for virus easily detected 4 copies or less of the viral genome, and allowed a quantitative measure of the virus in whole blood. Measurement of the changes in cytokine mRNAs showed similar changes to those observed in humans infected by the closely related virus Crimean Congo hemorrhagic fever virus.

Transmission of Influenza A Viruses

Science.gov (United States)

Neumann, Gabriele; Kawaoka, Yoshihiro

2015-01-01

Influenza A viruses cause respiratory infections that range from asymptomatic to deadly in humans. Widespread outbreaks (pandemics) are attributable to ‘novel’ viruses that possess a viral hemagglutinin (HA) gene to which humans lack immunity. After a pandemic, these novel viruses form stable virus lineages in humans and circulate until they are replaced by other novel viruses. The factors and mechanisms that facilitate virus transmission among hosts and the establishment of novel lineages are not completely understood, but the HA and basic polymerase 2 (PB2) proteins are thought to play essential roles in these processes by enabling avian influenza viruses to infect mammals and replicate efficiently in their new host. Here, we summarize our current knowledge of the contributions of HA, PB2, and other viral components to virus transmission and the formation of new virus lineages. PMID:25812763

New frontiers in oncolytic viruses: optimizing and selecting for virus strains with improved efficacy

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Lundstrom K

2018-02-01

Full Text Available Kenneth Lundstrom PanTherapeutics, Lutry, Switzerland Abstract: Oncolytic viruses have demonstrated selective replication and killing of tumor cells. Different types of oncolytic viruses – adenoviruses, alphaviruses, herpes simplex viruses, Newcastle disease viruses, rhabdoviruses, Coxsackie viruses, and vaccinia viruses – have been applied as either naturally occurring or engineered vectors. Numerous studies in animal-tumor models have demonstrated substantial tumor regression and prolonged survival rates. Moreover, clinical trials have confirmed good safety profiles and therapeutic efficacy for oncolytic viruses. Most encouragingly, the first cancer gene-therapy drug – Gendicine, based on oncolytic adenovirus type 5 – was approved in China. Likewise, a second-generation oncolytic herpes simplex virus-based drug for the treatment of melanoma has been registered in the US and Europe as talimogene laherparepvec. Keywords: immunotherapy, viral vectors, clinical trials, drug approval

Developmental milestones of vertically HIV infected and seroreverters children: follow up of 83 children Desenvolvimento psicomotor de crianças verticalmente infectadas pelo HIV e sororevertidas: seguimento de 83 crianças

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Isac Bruck

2001-09-01

Full Text Available The aim of the study was to detect neurological abnormalities in human immunodeficiency virus (HIV infected children. This was achieved by a prospective evaluation, from November/1995 to April/2000, of 43 HIV infected children (group I and 40 HIV seroreverters children (group II through neurological exam and neurodevelopmental tests: Denver Developmental Screening Test (DDST and Clinical Adaptive Test / Clinical Linguistic and Auditory Milestone Scale (CAT/CLAMS. A control group (III, of 67 children, were evaluated by CAT/CLAMS. Hyperactivity, irritability and hypotonia were the findings on neurological examination, without statistical differences between group I and II. On CAT/CLAMS, the group I developmental quotient (DQ was significantly lower than the other groups. The same occurred in DDST, with group I presenting significantly more failures than group II. Nineteen HIV children of group I had brain computed tomographic scan, with abnormalities in three of them (basal ganglia calcification, white matter hypodensity and asymmetry of lateral ventricles. We conclude that in HIV infected children a neurodevelopment delay occur early in the disease, and it can be detected by screening tests.Objetivou-se com o presente estudo detectar anormalidades neurológicas em crianças infectadas pelo vírus da imunodeficiência humana (HIV. Avaliou-se prospectivamente, de novembro de 1995 a abril de 2000, 43 crianças infectadas pelo HIV (grupo I e 40 crianças sororevertidas (grupo II, por meio de exame neurológico, testes de screening de neurodesenvolvimento: Teste Denver de Triagem de Desenvolvimento (DDST e Teste de Adaptação Clínica / Escala Linguística e Desenvolvimento Auditivo (CAT/CLAMS. Como grupo controle (III, foram avaliadas 67 crianças pelo CAT/CLAMS. Hiperatividade, irritabilidade e hipotonia foram as alterações encontradas ao exame neurológico, não ocorrendo diferenças estatísticas entre as crianças infectadas ou sororevertidas

Acessibilidade de indivíduos infectados pelo HIV aos serviços de saúde: uma revisão de literatura Accessibility to health services by HIV-infected patients: a literature review

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Francisco de Assis Acurcio

1996-06-01

Full Text Available Este trabalho tem por objetivo apresentar uma revisão de estudos que enfocam o tema da acessibilidade a ações e serviços de saúde. Tem-se demonstrado que indivíduos infectados pelo vírus da imunodeficiência humana (HIV podem apresentar uma melhor sobrevida dependendo do tipo de acesso que tenham às ações e serviços de saúde, como, por exemplo, acesso a medicamentos profiláticos (por exemplo, zidovudina, pentamidina. Desta forma, o presente trabalho enfatiza e utiliza dados da epidemia do HIV como forma de abordar o tema proposto. O artigo inicia-se com uma exposição do marco teórico sobre acessibilidade, seguida de uma revisão bibliográfica estruturada em quatro tópicos, a saber: 1 aspectos epidemiológicos da AIDS; 2 avaliação de qualidade dos serviços de saúde; 3 acessibilidade às ações e serviços de saúde e 4 estudos de acessibilidade em pacientes infectados pelo HIV. Considerações finais sobre o tema enfocado apontam para a necessidade de se compreender as implicações das diversas barreiras de acesso aos serviços, levando-se em conta os custos sociais e humanos da infecção pelo HIV, as necessidades e demandas dos indivíduos infectados e as conseqüências que o não-atendimento em tempo hábil pode ter para estes indivíduos.The aim of this paper is to provide a review of studies on accessibility to health care. It has been shown that patients infected by the human immunodeficiency virus (HIV may present better survival estimates depending upon their access to adequate health care, such as the availability of prophylactic therapy (e.g. zidovudine, pentamidine. The present review has emphasized access to health care in light of data from the current HIV epidemic. Theorical aspects pertaining to accessibility are presented, followed by a brief literature review on four main topics: 1. epidemiological aspects of HIV; 2. evaluation of health service quality; 3. accessibility to health care; and 4

Postmortem stability of Ebola virus.

Science.gov (United States)

Prescott, Joseph; Bushmaker, Trenton; Fischer, Robert; Miazgowicz, Kerri; Judson, Seth; Munster, Vincent J

2015-05-01

The ongoing Ebola virus outbreak in West Africa has highlighted questions regarding stability of the virus and detection of RNA from corpses. We used Ebola virus-infected macaques to model humans who died of Ebola virus disease. Viable virus was isolated <7 days posteuthanasia; viral RNA was detectable for 10 weeks.

A Foxtail mosaic virus Vector for Virus-Induced Gene Silencing in Maize.

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Mei, Yu; Zhang, Chunquan; Kernodle, Bliss M; Hill, John H; Whitham, Steven A

2016-06-01

Plant viruses have been widely used as vectors for foreign gene expression and virus-induced gene silencing (VIGS). A limited number of viruses have been developed into viral vectors for the purposes of gene expression or VIGS in monocotyledonous plants, and among these, the tripartite viruses Brome mosaic virus and Cucumber mosaic virus have been shown to induce VIGS in maize (Zea mays). We describe here a new DNA-based VIGS system derived from Foxtail mosaic virus (FoMV), a monopartite virus that is able to establish systemic infection and silencing of endogenous maize genes homologous to gene fragments inserted into the FoMV genome. To demonstrate VIGS applications of this FoMV vector system, four genes, phytoene desaturase (functions in carotenoid biosynthesis), lesion mimic22 (encodes a key enzyme of the porphyrin pathway), iojap (functions in plastid development), and brown midrib3 (caffeic acid O-methyltransferase), were silenced and characterized in the sweet corn line Golden × Bantam. Furthermore, we demonstrate that the FoMV infectious clone establishes systemic infection in maize inbred lines, sorghum (Sorghum bicolor), and green foxtail (Setaria viridis), indicating the potential wide applications of this viral vector system for functional genomics studies in maize and other monocots. © 2016 American Society of Plant Biologists. All Rights Reserved.

Effects of social reorganization on dopamine D2/D3 receptor availability and cocaine self-administration in male cynomolgus monkeys.

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Czoty, P W; Gould, R W; Gage, H D; Nader, M A

2017-09-01

Studies have demonstrated that brain dopamine D2/D3 receptors (D2/D3R) and the reinforcing effects of cocaine can be influenced by a monkey's position in the social dominance hierarchy. In this study, we manipulated the social ranks of monkeys by reorganizing social groups and assessed effects on D2/D3R availability and cocaine self-administration. Male cynomolgus monkeys (N = 12) had been trained to self-administer cocaine under a concurrent cocaine-food reinforcement schedule. Previously, PET measures of D2/D3R availability in the caudate nucleus and putamen had been obtained with [ 18 F]fluoroclebopride during cocaine abstinence, while monkeys lived in stable social groups of four monkeys/pen. For this study, monkeys were reorganized into groups that consisted of (1) four previously dominant, (2) four previously subordinate, and (3) a mix of previously dominant and subordinate monkeys. After 3 months, D2/D3R availability was redetermined and cocaine self-administration was reexamined. D2/D3R availability significantly increased after reorganization in monkeys who were formerly subordinate, with the greatest increases observed in those that became dominant. No consistent changes in D2/D3R availability were observed in formerly dominant monkeys. Cocaine self-administration did not vary according to rank after reorganization of social groups. However, when compared to their previous cocaine self-administration data, the potency of cocaine as a reinforcer decreased in 9 of 11 monkeys. These results indicate that changing the social conditions can alter D2/D3R availability in subordinate monkeys in a manner suggestive of environmental enrichment. In most monkeys, social reorganization shifted the cocaine dose-response curve to the right, also consistent with environmental enrichment.

Aplicabilidade das ações preconizadas pelo método canguru Share applicability recommended by kangaroo method

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Alessandra Patricia Stelmak

2017-07-01

Full Text Available Objetivo:Identificar a prevalência das ações preconizadas pelo MC, na prática de cuidados ao recém-nascido pré-termo e/ou baixo peso, pela equipe de enfermagem de uma unidade de terapia intensiva neonatal que é referência estadual para o MC. Método: Pesquisa descritiva quantitativa, realizada através da aplicação de um questionário estruturado com 37 profissionais de enfermagem de nível médio, em Unidade de Terapia Intensiva Neonatal, de fevereiro a abril de 2014. Resultados: o acolhimento, o incentivo ao toque, o aleitamento materno e o controle ambiental são as ações mais executadas pela equipe, apresentando cada uma 97% de aplicabilidade prática, e como ações menos executadas, a troca de fralda em decúbito lateral (83%, e o banho envolto em cueiros (58%. Conclusão: Esta equipe realiza as ações humanizadas de cuidado conforme preconizados pelo MC, e compreende a importância desses cuidados para o desenvolvimento infantil dos recém-nascidos. Existe necessidade de processo de educação permanente em serviço.

Perfis de consumo alcoolico entre pacientes da atencao primaria a saude e seu reconhecimento pelos profissionais de saude

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Maira Lemos de Castro Taufick

2014-02-01

Full Text Available Neste estudo transversal verificaram-se os perfis de consumo alcoólico entre pacientes das Equipes de Saúde da Família (ESF em uma cidade do sudeste brasileiro, e o reconhecimento deste consumo pelos profissionais das ESF. Avaliaram-se 932 pacientes adultos entre novembro de 2010 e novembro de 2011. Entre todos, 17,5% faziam consumo de risco (AUDIT ≥ 8, que foi mais frequente em homens, entre as pessoas mais jovens e aqueles sem doenças crônicas. O questionário CAGE foi positivo em 98 (10,5% pacientes, sendo mais frequente em homens. Homens, pessoas com idades ≥ 55 anos, com doenças crônicas ou com consumo alcoólico mais grave foram mais frequentemente questionadas sobre o uso do álcool (438/932; 47,8%. Homens, pessoas de 35 a 54 anos ou com consumo alcoólico mais grave foram mais frequentemente reconhecidos como alcoolistas (22/175; 12,6%. Conclui-se que o consumo do álcool é frequente entre os pacientes atendidos pelas ESF, é pouco reconhecido pelos profissionais e a minoria dos alcoolistas é orientada quanto aos seus riscos.

Efficient production of infectious viruses requires enzymatic activity of Epstein-Barr virus protein kinase.

Science.gov (United States)

Murata, Takayuki; Isomura, Hiroki; Yamashita, Yoriko; Toyama, Shigenori; Sato, Yoshitaka; Nakayama, Sanae; Kudoh, Ayumi; Iwahori, Satoko; Kanda, Teru; Tsurumi, Tatsuya

2009-06-20

The Epstein-Barr virus (EBV) BGLF4 gene product is the only protein kinase encoded by the virus genome. In order to elucidate its physiological roles in viral productive replication, we here established a BGLF4-knockout mutant and a revertant virus. While the levels of viral DNA replication of the deficient mutant were equivalent to those of the wild-type and the revertant, virus production was significantly impaired. Expression of the BGLF4 protein in trans fully complemented the low yield of the mutant virus, while expression of a kinase-dead (K102I) form of the protein failed to restore the virus titer. These results demonstrate that BGLF4 plays a significant role in production of infectious viruses and that the kinase activity is crucial.

Propagation Effect of a Virus Outbreak on a Network with Limited Anti-Virus Ability.

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Yonghong Xu

Full Text Available This paper describes a new computer virus spreading model which takes into account the possibility of a virus outbreak on a network with limited anti-virus ability. Then, the model is investigated for the existence of equilibria and their stabilities are proved and illustrated. Moreover, it is found that these two factors are not only relative to the threshold value determining whether the virus becomes extinct or not, but that they are also relative to the virus epidemic levels. Theoretical and experimental results indicate that, in some ways, it would be practically possible to eradicate the virus or suppress its prevalence below a suitable level. Consequently, some suggestions are proposed that may help eradicate or suppress virus propagation over a real computer network.

An introduction to computer viruses

Energy Technology Data Exchange (ETDEWEB)

Brown, D.R.

1992-03-01

This report on computer viruses is based upon a thesis written for the Master of Science degree in Computer Science from the University of Tennessee in December 1989 by David R. Brown. This thesis is entitled An Analysis of Computer Virus Construction, Proliferation, and Control and is available through the University of Tennessee Library. This paper contains an overview of the computer virus arena that can help the reader to evaluate the threat that computer viruses pose. The extent of this threat can only be determined by evaluating many different factors. These factors include the relative ease with which a computer virus can be written, the motivation involved in writing a computer virus, the damage and overhead incurred by infected systems, and the legal implications of computer viruses, among others. Based upon the research, the development of a computer virus seems to require more persistence than technical expertise. This is a frightening proclamation to the computing community. The education of computer professionals to the dangers that viruses pose to the welfare of the computing industry as a whole is stressed as a means of inhibiting the current proliferation of computer virus programs. Recommendations are made to assist computer users in preventing infection by computer viruses. These recommendations support solid general computer security practices as a means of combating computer viruses.

Viruses infecting marine molluscs.

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Arzul, Isabelle; Corbeil, Serge; Morga, Benjamin; Renault, Tristan

2017-07-01

Although a wide range of viruses have been reported in marine molluscs, most of these reports rely on ultrastructural examination and few of these viruses have been fully characterized. The lack of marine mollusc cell lines restricts virus isolation capacities and subsequent characterization works. Our current knowledge is mostly restricted to viruses affecting farmed species such as oysters Crassostrea gigas, abalone Haliotis diversicolor supertexta or the scallop Chlamys farreri. Molecular approaches which are needed to identify virus affiliation have been carried out for a small number of viruses, most of them belonging to the Herpesviridae and birnaviridae families. These last years, the use of New Generation Sequencing approach has allowed increasing the number of sequenced viral genomes and has improved our capacity to investigate the diversity of viruses infecting marine molluscs. This new information has in turn allowed designing more efficient diagnostic tools. Moreover, the development of experimental infection protocols has answered some questions regarding the pathogenesis of these viruses and their interactions with their hosts. Control and management of viral diseases in molluscs mostly involve active surveillance, implementation of effective bio security measures and development of breeding programs. However factors triggering pathogen development and the life cycle and status of the viruses outside their mollusc hosts still need further investigations. Copyright © 2017 Elsevier Inc. All rights reserved.

Coinfection with Epstein–Barr Virus (EBV), Human Papilloma Virus (HPV) and Polyoma BK Virus (BKPyV) in Laryngeal, Oropharyngeal and Oral Cavity Cancer

OpenAIRE

Drop, Bartłomiej; Strycharz-Dudziak, Małgorzata; Kliszczewska, Ewa; Polz-Dacewicz, Małgorzata

2017-01-01

Most research providing evidence for the role of oncogenic viruses in head and neck squamous cell carcinoma (SCC) development is focused on one type of virus without analyzing possible interactions between two or more types of viruses. The aim of this study was to analyse the prevalence of co-infection with human papillomavirus (HPV), Epstein–Barr virus (EBV) and polyoma BK virus (BKPyV) in oral, oropharyngeal and laryngeal squamous cell carcinomas in Polish patients. The correlations between...

RNA viruses in the sea.

Science.gov (United States)

Lang, Andrew S; Rise, Matthew L; Culley, Alexander I; Steward, Grieg F

2009-03-01

Viruses are ubiquitous in the sea and appear to outnumber all other forms of marine life by at least an order of magnitude. Through selective infection, viruses influence nutrient cycling, community structure, and evolution in the ocean. Over the past 20 years we have learned a great deal about the diversity and ecology of the viruses that constitute the marine virioplankton, but until recently the emphasis has been on DNA viruses. Along with expanding knowledge about RNA viruses that infect important marine animals, recent isolations of RNA viruses that infect single-celled eukaryotes and molecular analyses of the RNA virioplankton have revealed that marine RNA viruses are novel, widespread, and genetically diverse. Discoveries in marine RNA virology are broadening our understanding of the biology, ecology, and evolution of viruses, and the epidemiology of viral diseases, but there is still much that we need to learn about the ecology and diversity of RNA viruses before we can fully appreciate their contributions to the dynamics of marine ecosystems. As a step toward making sense of how RNA viruses contribute to the extraordinary viral diversity in the sea, we summarize in this review what is currently known about RNA viruses that infect marine organisms.

Reverse genetics of measles virus and resulting multivalent recombinant vaccines: applications of recombinant measles viruses.

Science.gov (United States)

Billeter, M A; Naim, H Y; Udem, S A

2009-01-01

An overview is given on the development of technologies to allow reverse genetics of RNA viruses, i.e., the rescue of viruses from cDNA, with emphasis on nonsegmented negative-strand RNA viruses (Mononegavirales), as exemplified for measles virus (MV). Primarily, these technologies allowed site-directed mutagenesis, enabling important insights into a variety of aspects of the biology of these viruses. Concomitantly, foreign coding sequences were inserted to (a) allow localization of virus replication in vivo through marker gene expression, (b) develop candidate multivalent vaccines against measles and other pathogens, and (c) create candidate oncolytic viruses. The vector use of these viruses was experimentally encouraged by the pronounced genetic stability of the recombinants unexpected for RNA viruses, and by the high load of insertable genetic material, in excess of 6 kb. The known assets, such as the small genome size of the vector in comparison to DNA viruses proposed as vectors, the extensive clinical experience of attenuated MV as vaccine with a proven record of high safety and efficacy, and the low production cost per vaccination dose are thus favorably complemented.

Schmallenberg Virus

Indian Academy of Sciences (India)

IAS Admin

explore the potential of this infection crossing the species barrier and thereby .... The virus targets mainly the brain of the unborn animal resulting in neurological ... The virus is located in the blood of the adult infected animal or in the central ...

A combination in-ovo vaccine for avian influenza virus and Newcastle disease virus.

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Steel, John; Burmakina, Svetlana V; Thomas, Colleen; Spackman, Erica; García-Sastre, Adolfo; Swayne, David E; Palese, Peter

2008-01-24

The protection of poultry from H5N1 highly pathogenic avian influenza A (HPAI) and Newcastle disease virus (NDV) can be achieved through vaccination, as part of a broader disease control strategy. We have previously generated a recombinant influenza virus expressing, (i) an H5 hemagglutinin protein, modified by the removal of the polybasic cleavage peptide and (ii) the ectodomain of the NDV hemagglutinin-neuraminidase (HN) protein in the place of the ectodomain of influenza neuraminidase (Park MS, et al. Proc Natl Acad Sci USA 2006;103(21):8203-8). Here we show this virus is attenuated in primary normal human bronchial epithelial (NHBE) cell culture, and demonstrate protection of C57BL/6 mice from lethal challenge with an H5 HA-containing influenza virus through immunisation with the recombinant virus. In addition, in-ovo vaccination of 18-day-old embryonated chicken eggs provided 90% and 80% protection against highly stringent lethal challenge by NDV and H5N1 virus, respectively. We propose that this virus has potential as a safe in-ovo live, attenuated, bivalent avian influenza and Newcastle disease virus vaccine.

Evaluation of the suitability of a plant virus, pepper mild mottle virus, as a surrogate of human enteric viruses for assessment of the efficacy of coagulation-rapid sand filtration to remove those viruses.

Science.gov (United States)

Shirasaki, N; Matsushita, T; Matsui, Y; Yamashita, R

2018-02-01

Here, we evaluated the removal of three representative human enteric viruses - adenovirus (AdV) type 40, coxsackievirus (CV) B5, and hepatitis A virus (HAV) IB - and one surrogate of human caliciviruses - murine norovirus (MNV) type 1 - by coagulation-rapid sand filtration, using water samples from eight water sources for drinking water treatment plants in Japan. The removal ratios of a plant virus (pepper mild mottle virus; PMMoV) and two bacteriophages (MS2 and φX174) were compared with the removal ratios of human enteric viruses to assess the suitability of PMMoV, MS2, and φX174 as surrogates for human enteric viruses. The removal ratios of AdV, CV, HAV, and MNV, evaluated via the real-time polymerase chain reaction (PCR) method, were 0.8-2.5-log 10 when commercially available polyaluminum chloride (PACl, basicity 1.5) and virgin silica sand were used as the coagulant and filter medium, respectively. The type of coagulant affected the virus removal efficiency, but the age of silica sand used in the rapid sand filtration did not. Coagulation-rapid sand filtration with non-sulfated, high-basicity PACls (basicity 2.1 or 2.5) removed viruses more efficiently than the other aluminum-based coagulants. The removal ratios of MS2 were sometimes higher than those of the three human enteric viruses and MNV, whereas the removal ratios of φX174 tended to be smaller than those of the three human enteric viruses and MNV. In contrast, the removal ratios of PMMoV were similar to and strongly correlated with those of the three human enteric viruses and MNV. Thus, PMMoV appears to be a suitable surrogate for human enteric viruses for the assessment of the efficacy of coagulation-rapid sand filtration to remove viruses. Copyright © 2017 Elsevier Ltd. All rights reserved.

An inactivated whole-virus porcine parvovirus vaccine protects pigs against disease but does not prevent virus shedding even after homologous virus challenge.

Science.gov (United States)

Foerster, Tessa; Streck, André Felipe; Speck, Stephanie; Selbitz, Hans-Joachim; Lindner, Thomas; Truyen, Uwe

2016-06-01

Inactivated whole-virus vaccines against porcine parvovirus (PPV) can prevent disease but not infection and virus shedding after heterologous virus challenge. Here, we showed that the same is true for a homologous challenge. Pregnant sows were vaccinated with an experimental inactivated vaccine based on PPV strain 27a. They were challenged on day 40 of gestation with the virulent porcine parvovirus PPV-27a from which the vaccine was prepared (homologous challenge). On day 90 of gestation, the fetuses from vaccinated sows were protected against disease, while the fetuses of the non-vaccinated sows (control group) exhibited signs of parvovirus disease. All gilts, whether vaccinated or not vaccinated, showed a boost of PPV-specific antibodies indicative of virus infection and replication. Low DNA copy numbers, but not infectious virus, could be demonstrated in nasal or rectal swabs of immunized sows, but high copy numbers of challenge virus DNA as well as infectious virus could both be demonstrated in non-vaccinated sows.

Dinucleotide Composition in Animal RNA Viruses Is Shaped More by Virus Family than by Host Species.

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Di Giallonardo, Francesca; Schlub, Timothy E; Shi, Mang; Holmes, Edward C

2017-04-15

Viruses use the cellular machinery of their hosts for replication. It has therefore been proposed that the nucleotide and dinucleotide compositions of viruses should match those of their host species. If this is upheld, it may then be possible to use dinucleotide composition to predict the true host species of viruses sampled in metagenomic surveys. However, it is also clear that different taxonomic groups of viruses tend to have distinctive patterns of dinucleotide composition that may be independent of host species. To determine the relative strength of the effect of host versus virus family in shaping dinucleotide composition, we performed a comparative analysis of 20 RNA virus families from 15 host groupings, spanning two animal phyla and more than 900 virus species. In particular, we determined the odds ratios for the 16 possible dinucleotides and performed a discriminant analysis to evaluate the capability of virus dinucleotide composition to predict the correct virus family or host taxon from which it was isolated. Notably, while 81% of the data analyzed here were predicted to the correct virus family, only 62% of these data were predicted to their correct subphylum/class host and a mere 32% to their correct mammalian order. Similarly, dinucleotide composition has a weak predictive power for different hosts within individual virus families. We therefore conclude that dinucleotide composition is generally uniform within a virus family but less well reflects that of its host species. This has obvious implications for attempts to accurately predict host species from virus genome sequences alone. IMPORTANCE Determining the processes that shape virus genomes is central to understanding virus evolution and emergence. One question of particular importance is why nucleotide and dinucleotide frequencies differ so markedly between viruses. In particular, it is currently unclear whether host species or virus family has the biggest impact on dinucleotide frequencies and

Monoclonal antibodies against plant viruses

International Nuclear Information System (INIS)

Sandler, E.; Dietzgen, R.G.

1984-01-01

Ever since antigenic properties of plant viruses were discovered antisera have been raised and used for plant virus diagnosis and for the analysis of virus structure as well. From the early qualitative diagnosis method of precipitating the virus in clarified sap of an infected plant and the first quantitative application of the precipitin test vast progress has been made with regard to the development of highly sensitive and highly quantitative methods for virus detection. Of equal importance was the improvement of methods for separating virus from host cell components since the specificity of antisera raised against a virus could be increased by using an antigen for immunization highly concentrated and largely freed from contaminating host substances. The introduction of the enzyme-linked immunosorbent assay (ELISA) into plant virology allows detection of virus in nanogram quantities. Still, the conventionally raised antisera, no matter how pure an antigen was used for immunization, are polyclonal. They contain products of thousands of different antibody-secreting plasma cell clones which can be directed against all antigenic determinants (epitopes) of the virus, but also against antigens of the host plant that may not have been entirely separated from the immunizing virus during the purification procedure. Even after cross adsorption of polyclonal antisera some residual heterogeneity can be expected to remain. Within these boundaries the information gained with polyclonal antisera on virus structure and on virus diagnosis has to be interpreted

Técnicas de análise multivariada na avaliação de injúrias pelo frio em mangas cv. Tommy Atkins

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Ana Carolina Almeida Miguel

2011-10-01

Full Text Available Este trabalho objetivou identificar as variáveis que se associam às injúrias pelo frio e determinar as diferenças nos parâmetros de qualidade que melhor caracterizam mangas 'Tommy Atkins' submetidas à condição de injúria pelo frio, utilizando-se da análise de fatores em componentes principais e a análise de agrupamentos. Frutos colhidos no estádio "de vez" foram cuidadosamente transportados, selecionados, padronizados quanto a coloração, tamanho e ausência de injúrias, e tratados com fungicida antes de serem armazenados a 2 ºC (74,8% UR, 5 °C (75,4% UR e 12 °C (76,4% UR, por até 28 dias. Os frutos foram avaliados semanalmente quanto à ocorrência de danos pelo frio, coloração da casca e da polpa, firmeza da polpa, teores de sólidos solúveis, acidez titulável, açúcares solúveis e redutores, ácido ascórbico e atividade das enzimas peroxidase, polifenoloxidase e fenilalanina amônia-liase. A análise estatística multivariada dos fatores em componentes principais e agrupamentos permitiram melhor compreensão do efeito do armazenamento, sob condição de chilling, no metabolismo de mangas 'Tommy Atkins' e indicaram que o dano está intimamente relacionado com a casca e que a resposta da polpa ao estresse ocorre de forma tardia.

Zika Virus and Pregnancy

Science.gov (United States)

... Management Education & Events Advocacy For Patients About ACOG Zika Virus and Pregnancy Home For Patients Zika Virus and ... Patient Education Pamphlets - Spanish Share: PEV002, September 2016 Zika Virus and Pregnancy There are risks to your fetus ...

Zika Virus

Science.gov (United States)

... with facebook share with twitter share with linkedin Zika Virus Credit: NIAID A female Aedes mosquito. This type of mosquito can transmit Zika, ... transmitted to humans through the bite of infected Aedes aegypti mosquitoes. Zika virus can be transmitted from an infected pregnant woman ...

CHANDIPURA VIRUS

Indian Academy of Sciences (India)

First page Back Continue Last page Overview Graphics. CHANDIPURA VIRUS. First isolated from a village called Chandipura near Nagpur in 1965 in India. Belongs to rhabdoviridae family. Used as a Model System to study RNA virus multiplication in the infected cell at molecular level. Notes:

Clinical and biological differences between recurrent herpes simplex virus and varicella-zoster virus infections

International Nuclear Information System (INIS)

Straus, S.E.

1989-01-01

The major features that distinguish recurrent herpes simplex virus infections from zoster are illustrated in this article by two case histories. The clinical and epidemiologic features that characterize recurrent herpes simplex virus and varicella-zoster virus infections are reviewed. It is noted that herpesvirus infections are more common and severe in patients with cellular immune deficiency. Each virus evokes both humoral and cellular immune response in the course of primary infection. DNA hybridization studies with RNA probes labelled with sulfur-35 indicate that herpes simplex viruses persist within neurons, and that varicella-zoster virus is found in the satellite cells that encircle the neurons

Movement disorders in 28 HIV-infected patients Distúrbios do movimento em 28 pacientes infectados pelo HIV

Directory of Open Access Journals (Sweden)

James Pitágoras de Mattos

2002-09-01

. Todos com hemicoréia/hemiballismo eram homens e estavam relacionados com toxoplasmose nos gânglios da base. Nos quatro pacientes com mioclonia, em dois era generalizada, relacionada, em um, com toxoplasmose e, em outro, com a encefalopatia pelo HIV; nos outros dois era de origem medular. Nos dois pacientes com painful legs and moving toes, ficou demonstrada a neuropatia axonal pela biópsia do nervo periférico. Toxoplasmose da gânglia basal estava relacionada com hemidistonia contralateral. No paciente com tremor de Holmes havia lesões no mesencéfalo e no cerebelo, secundárias à co-infecção pelo bacilo da tuberculose e pelo Toxoplasma gondii. Concluímos que diversos distúrbios do movimento podem ocorrer em pacientes infectados pelo HIV. Costumam estar relacionados às infecções oportunísticas, ao uso de certos medicamentos, às lesões com efeito de massa e, possivelmente, à ação direta ou indireta do HIV.

Zika Virus and Pregnancy

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Full Text Available ... Management Education & Events Advocacy For Patients About ACOG Zika Virus and Pregnancy Home For Patients Zika Virus ... Patient Education Pamphlets - Spanish Share: PEV002, September 2016 Zika Virus and Pregnancy There are risks to your ...

Zika Virus and Pregnancy

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Full Text Available ... Education & Events Advocacy For Patients About ACOG Zika Virus and Pregnancy Home For Patients Zika Virus and ... Education Pamphlets - Spanish Share: PEV002, September 2016 Zika Virus and Pregnancy There are risks to your fetus ...

What's West Nile Virus?

Science.gov (United States)

... for Educators Search English Español What's West Nile Virus? KidsHealth / For Kids / What's West Nile Virus? Print en español ¿Qué es el Virus del Nilo Occidental? What exactly is the West ...

Zika Virus and Pregnancy

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Full Text Available ... Advocacy For Patients About ACOG Zika Virus and Pregnancy Home For Patients Zika Virus and Pregnancy Page ... Spanish Share: PEV002, September 2016 Zika Virus and Pregnancy There are risks to your fetus if you ...

Human Immunodeficiency Virus and Hepatitis C Virus Co-infection ...

African Journals Online (AJOL)

Human Immunodeficiency Virus and Hepatitis C Virus Co-infection in Cameroon: Investigation of the Genetic Diversity and Virulent ... AFRICAN JOURNALS ONLINE (AJOL) · Journals · Advanced Search · USING AJOL · RESOURCES ... DNA sequencing, and bioinformatics tools for sequence management and analysis.

Toxicidade ocular causada pelo tamoxifeno: relato de caso Ocular toxicity caused by tamoxifen: case report

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Eliane Terumi Inada

2005-08-01

Full Text Available O objetivo desse trabalho é relatar um caso de toxicidade ocular pelo tamoxifeno. Para isso, aferiu-se a melhor acuidade visual corrigida de ambos os olhos em tabela de Snellen. Foram realizados biomicroscopia do segmento anterior, refração, oftalmoscopia, angiofluoresceinografia e retinografia numa paciente de 63 anos, sexo feminino, cor branca, em uso de tamoxifeno 20 mg/dia há 4 anos, com acuidade visual corrigida de 20/70 e 20/40. A biomicroscopia do segmento anterior apresentava ceratopatia verticilata e catarata nuclear e cortical posterior de 1+/4 em ambos os olhos. À oftalmoscopia, foi verificado alteração do brilho macular de ambos os olhos. E a angiofluoresceinografia mostrou hiperfluorescência na área macular em fase precoce (defeito em janela. Relata-se um caso de ceratopatia e maculopatia causadas pelo tamoxifeno.To report tamoxifen ocular toxicity. The best visual acuity was measured in both eyes with Snellen chart, slit-lamp examination of anterior segment, refraction, dilated fundus examination, fluorescein angiography and retinography in a 63-year-old patient, female, white, using tamoxifen 20 mg/day for 4 years, with 20/70 and 20/40 corrected visual acuity. The anterior segment examination showed corneal linear subepithelial opacity inferior to the visual axis and nuclear and posterior cortical cataract (1+/4 in both eyes. Fundus examination showed alteration of macular color in both eyes. Fluorescein angiography presented hyperfluorescence in the macular area at an early phase (window defect. Report of keratopathy and maculopathy caused by tamoxifen.

Virus world as an evolutionary network of viruses and capsidless selfish elements.

Science.gov (United States)

Koonin, Eugene V; Dolja, Valerian V

2014-06-01

Viruses were defined as one of the two principal types of organisms in the biosphere, namely, as capsid-encoding organisms in contrast to ribosome-encoding organisms, i.e., all cellular life forms. Structurally similar, apparently homologous capsids are present in a huge variety of icosahedral viruses that infect bacteria, archaea, and eukaryotes. These findings prompted the concept of the capsid as the virus "self" that defines the identity of deep, ancient viral lineages. However, several other widespread viral "hallmark genes" encode key components of the viral replication apparatus (such as polymerases and helicases) and combine with different capsid proteins, given the inherently modular character of viral evolution. Furthermore, diverse, widespread, capsidless selfish genetic elements, such as plasmids and various types of transposons, share hallmark genes with viruses. Viruses appear to have evolved from capsidless selfish elements, and vice versa, on multiple occasions during evolution. At the earliest, precellular stage of life's evolution, capsidless genetic parasites most likely emerged first and subsequently gave rise to different classes of viruses. In this review, we develop the concept of a greater virus world which forms an evolutionary network that is held together by shared conserved genes and includes both bona fide capsid-encoding viruses and different classes of capsidless replicons. Theoretical studies indicate that selfish replicons (genetic parasites) inevitably emerge in any sufficiently complex evolving ensemble of replicators. Therefore, the key signature of the greater virus world is not the presence of a capsid but rather genetic, informational parasitism itself, i.e., various degrees of reliance on the information processing systems of the host. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Replacement of Murine Leukemia Virus Readthrough Mechanism by Human Immunodeficiency Virus Frameshift Allows Synthesis of Viral Proteins and Virus Replication

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Brunelle, Marie-Noëlle; Brakier-Gingras, Léa; Lemay, Guy

2003-01-01

Retroviruses use unusual recoding strategies to synthesize the Gag-Pol polyprotein precursor of viral enzymes. In human immunodeficiency virus, ribosomes translating full-length viral RNA can shift back by 1 nucleotide at a specific site defined by the presence of both a slippery sequence and a downstream stimulatory element made of an extensive secondary structure. This so-called frameshift mechanism could become a target for the development of novel antiviral strategies. A different recoding strategy is used by other retroviruses, such as murine leukemia viruses, to synthesize the Gag-Pol precursor; in this case, a stop codon is suppressed in a readthrough process, again due to the presence of a specific structure adopted by the mRNA. Development of antiframeshift agents will greatly benefit from the availability of a simple animal and virus model. For this purpose, the murine leukemia virus readthrough region was rendered inactive by mutagenesis and the frameshift region of human immunodeficiency virus was inserted to generate a chimeric provirus. This substitution of readthrough by frameshift allows the synthesis of viral proteins, and the chimeric provirus sequence was found to generate infectious viruses. This system could be a most interesting alternative to study ribosomal frameshift in the context of a virus amenable to the use of a simple animal model. PMID:12584361

[Mumps vaccine virus transmission].

Science.gov (United States)

Otrashevskaia, E V; Kulak, M V; Otrashevskaia, A V; Karpov, I A; Fisenko, E G; Ignat'ev, G M

2013-01-01

In this work we report the mumps vaccine virus shedding based on the laboratory confirmed cases of the mumps virus (MuV) infection. The likely epidemiological sources of the transmitted mumps virus were children who were recently vaccinated with the mumps vaccine containing Leningrad-Zagreb or Leningrad-3 MuV. The etiology of the described cases of the horizontal transmission of both mumps vaccine viruses was confirmed by PCR with the sequential restriction analysis.

Reconstitution of the myeloid and lymphoid compartments after the transplantation of autologous and genetically modified CD34+ bone marrow cells, following gamma irradiation in cynomolgus macaques

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Auregan Gwenaelle

2008-06-01

Full Text Available Abstract Background Prolonged, altered hematopoietic reconstitution is commonly observed in patients undergoing myeloablative conditioning and bone marrow and/or mobilized peripheral blood-derived stem cell transplantation. We studied the reconstitution of myeloid and lymphoid compartments after the transplantation of autologous CD34+ bone marrow cells following gamma irradiation in cynomolgus macaques. Results The bone marrow cells were first transduced ex vivo with a lentiviral vector encoding eGFP, with a mean efficiency of 72% ± 4%. The vector used was derived from the simian immunodeficiency lentivirus SIVmac251, VSV-g pseudotyped and encoded eGFP under the control of the phosphoglycerate kinase promoter. After myeloid differentiation, GFP was detected in colony-forming cells (37% ± 10%. A previous study showed that transduction rates did not differ significantly between colony-forming cells and immature cells capable of initiating long-term cultures, indicating that progenitor cells and highly immature hematopoietic cells were transduced with similar efficiency. Blood cells producingeGFP were detected as early as three days after transplantation, and eGFP-producing granulocyte and mononuclear cells persisted for more than one year in the periphery. Conclusion The transplantation of CD34+ bone marrow cells had beneficial effects for the ex vivo proliferation and differentiation of hematopoietic progenitors, favoring reconstitution of the T- and B-lymphocyte, thrombocyte and red blood cell compartments.

Zika Virus and Pregnancy

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Full Text Available ... Management Education & Events Advocacy For Patients About ACOG Zika Virus and Pregnancy Home For Patients Zika Virus and ... Patient Education Pamphlets - Spanish Share: PEV002, September 2016 Zika Virus and Pregnancy There are risks to your fetus ...

Zika Virus Fact Sheet

Science.gov (United States)

... is caused by a virus transmitted primarily by Aedes mosquitoes. People with Zika virus disease can have symptoms including mild fever, skin ... framework. Q&A: Zika virus and complication ... mosquito from the Aedes genus, mainly Aedes aegypti in tropical regions. Aedes ...

Computer Viruses: An Overview.

Science.gov (United States)

Marmion, Dan

1990-01-01

Discusses the early history and current proliferation of computer viruses that occur on Macintosh and DOS personal computers, mentions virus detection programs, and offers suggestions for how libraries can protect themselves and their users from damage by computer viruses. (LRW)

An infectious bat-derived chimeric influenza virus harbouring the entry machinery of an influenza A virus.

Science.gov (United States)

Juozapaitis, Mindaugas; Aguiar Moreira, Étori; Mena, Ignacio; Giese, Sebastian; Riegger, David; Pohlmann, Anne; Höper, Dirk; Zimmer, Gert; Beer, Martin; García-Sastre, Adolfo; Schwemmle, Martin

2014-07-23

In 2012, the complete genomic sequence of a new and potentially harmful influenza A-like virus from bats (H17N10) was identified. However, infectious influenza virus was neither isolated from infected bats nor reconstituted, impeding further characterization of this virus. Here we show the generation of an infectious chimeric virus containing six out of the eight bat virus genes, with the remaining two genes encoding the haemagglutinin and neuraminidase proteins of a prototypic influenza A virus. This engineered virus replicates well in a broad range of mammalian cell cultures, human primary airway epithelial cells and mice, but poorly in avian cells and chicken embryos without further adaptation. Importantly, the bat chimeric virus is unable to reassort with other influenza A viruses. Although our data do not exclude the possibility of zoonotic transmission of bat influenza viruses into the human population, they indicate that multiple barriers exist that makes this an unlikely event.

Zika virus infection.

Science.gov (United States)

Pougnet, Laurence; Thill, Chloé; Pougnet, Richard; Auvinet, Henri; Giacardi, Christophe; Drouillard, Isabelle

2016-12-01

A 21-year old woman from New-Caledonia had 40 ̊C fever with vomiting, arthralgia, myalgia, and measles-like rash. Etiological analyses showed primary infection with Zika virus. Because of severe clinical presentation, she was hospitalized in the intensive care unit of the Brest military Hospital. Zika virus is mainly transmitted by Aedes mosquitoes. If they settle in Metropolitan France, Zika virus might also spread there.

Comparative analysis of rabbit hemorrhagic disease virus (RHDV) and new RHDV2 virus antigenicity, using specific virus-like particles.

Science.gov (United States)

Bárcena, Juan; Guerra, Beatriz; Angulo, Iván; González, Julia; Valcárcel, Félix; Mata, Carlos P; Castón, José R; Blanco, Esther; Alejo, Alí

2015-09-24

In 2010 a new Lagovirus related to rabbit haemorrhagic disease virus (RHDV) emerged in France and has since rapidly spread throughout domestic and wild rabbit populations of several European countries. The new virus, termed RHDV2, exhibits distinctive genetic, antigenic and pathogenic features. Notably, RHDV2 kills rabbits previously vaccinated with RHDV vaccines. Here we report for the first time the generation and characterization of RHDV2-specific virus-like particles (VLPs). Our results further confirmed the differential antigenic properties exhibited by RHDV and RHDV2, highlighting the need of using RHDV2-specific diagnostic assays to monitor the spread of this new virus.

Structural and Functional Studies on the Fusion and Attachment Envelope Glycoproteins of Nipah Virus and Hendra Virus

Science.gov (United States)

2003-01-01

including measles virus (MeV), mumps virus, Sendai virus (SeV), Newcastle disease virus (NDV), rinderpest virus, canine distemper virus (CDV), human...Institute of Health, Bethesda, MD. Hut 102, MT2, MT4, and CEM human T cell lines were provided by Chou-Zen Giam, USUHS, Bethesda, MD. The human osteosarcoma

Single Assay Detection of Acute Bee Paralysis Virus, Kashmir Bee Virus and Israeli Acute Paralysis Virus

DEFF Research Database (Denmark)

Francis, Roy Mathew; Kryger, Per

2012-01-01

A new RT-PCR primer pair designed to identify Acute Bee Paralysis Virus (ABPV), Kashmir Bee Virus (KBV) or Israeli Acute Bee Paralysis Virus (IAPV) of honey bees (Apis mellifera L.) in a single assay is described. These primers are used to screen samples for ABPV, KBV, or IAPV in a single RT-PCR ......-PCR reaction saving time and money. The primers are located in the predicted overlapping gene (pog/ORFX) which is highly conserved across ABPV, KBV, IAPV and other dicistroviruses of social insects. This study has also identified the first case of IAPV in Denmark....

Structure of viruses: a short history.

Science.gov (United States)

Rossmann, Michael G

2013-05-01

This review is a partially personal account of the discovery of virus structure and its implication for virus function. Although I have endeavored to cover all aspects of structural virology and to acknowledge relevant individuals, I know that I have favored taking examples from my own experience in telling this story. I am anxious to apologize to all those who I might have unintentionally offended by omitting their work. The first knowledge of virus structure was a result of Stanley's studies of tobacco mosaic virus (TMV) and the subsequent X-ray fiber diffraction analysis by Bernal and Fankuchen in the 1930s. At about the same time it became apparent that crystals of small RNA plant and animal viruses could diffract X-rays, demonstrating that viruses must have distinct and unique structures. More advances were made in the 1950s with the realization by Watson and Crick that viruses might have icosahedral symmetry. With the improvement of experimental and computational techniques in the 1970s, it became possible to determine the three-dimensional, near-atomic resolution structures of some small icosahedral plant and animal RNA viruses. It was a great surprise that the protecting capsids of the first virus structures to be determined had the same architecture. The capsid proteins of these viruses all had a 'jelly-roll' fold and, furthermore, the organization of the capsid protein in the virus were similar, suggesting a common ancestral virus from which many of today's viruses have evolved. By this time a more detailed structure of TMV had also been established, but both the architecture and capsid protein fold were quite different to that of the icosahedral viruses. The small icosahedral RNA virus structures were also informative of how and where cellular receptors, anti-viral compounds, and neutralizing antibodies bound to these viruses. However, larger lipid membrane enveloped viruses did not form sufficiently ordered crystals to obtain good X-ray diffraction

Computer Viruses: Pathology and Detection.

Science.gov (United States)

Maxwell, John R.; Lamon, William E.

1992-01-01

Explains how computer viruses were originally created, how a computer can become infected by a virus, how viruses operate, symptoms that indicate a computer is infected, how to detect and remove viruses, and how to prevent a reinfection. A sidebar lists eight antivirus resources. (four references) (LRW)

Yeast for virus research

Science.gov (United States)

Zhao, Richard Yuqi

2017-01-01

Budding yeast (Saccharomyces cerevisiae) and fission yeast (Schizosaccharomyces pombe) are two popular model organisms for virus research. They are natural hosts for viruses as they carry their own indigenous viruses. Both yeasts have been used for studies of plant, animal and human viruses. Many positive sense (+) RNA viruses and some DNA viruses replicate with various levels in yeasts, thus allowing study of those viral activities during viral life cycle. Yeasts are single cell eukaryotic organisms. Hence, many of the fundamental cellular functions such as cell cycle regulation or programed cell death are highly conserved from yeasts to higher eukaryotes. Therefore, they are particularly suited to study the impact of those viral activities on related cellular activities during virus-host interactions. Yeasts present many unique advantages in virus research over high eukaryotes. Yeast cells are easy to maintain in the laboratory with relative short doubling time. They are non-biohazardous, genetically amendable with small genomes that permit genome-wide analysis of virologic and cellular functions. In this review, similarities and differences of these two yeasts are described. Studies of virologic activities such as viral translation, viral replication and genome-wide study of virus-cell interactions in yeasts are highlighted. Impacts of viral proteins on basic cellular functions such as cell cycle regulation and programed cell death are discussed. Potential applications of using yeasts as hosts to carry out functional analysis of small viral genome and to develop high throughput drug screening platform for the discovery of antiviral drugs are presented. PMID:29082230

Special Issue: Honey Bee Viruses

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Sebastian Gisder

2015-10-01

Full Text Available Pollination of flowering plants is an important ecosystem service provided by wild insect pollinators and managed honey bees. Hence, losses and declines of pollinating insect species threaten human food security and are of major concern not only for apiculture or agriculture but for human society in general. Honey bee colony losses and bumblebee declines have attracted intensive research interest over the last decade and although the problem is far from being solved we now know that viruses are among the key players of many of these bee losses and bumblebee declines. With this special issue on bee viruses we, therefore, aimed to collect high quality original papers reflecting the current state of bee virus research. To this end, we focused on newly discovered viruses (Lake Sinai viruses, bee macula-like virus, or a so far neglected virus species (Apis mellifera filamentous virus, and cutting edge technologies (mass spectrometry, RNAi approach applied in the field.

Special Issue: Honey Bee Viruses

Science.gov (United States)

Gisder, Sebastian; Genersch, Elke

2015-01-01

Pollination of flowering plants is an important ecosystem service provided by wild insect pollinators and managed honey bees. Hence, losses and declines of pollinating insect species threaten human food security and are of major concern not only for apiculture or agriculture but for human society in general. Honey bee colony losses and bumblebee declines have attracted intensive research interest over the last decade and although the problem is far from being solved we now know that viruses are among the key players of many of these bee losses and bumblebee declines. With this special issue on bee viruses we, therefore, aimed to collect high quality original papers reflecting the current state of bee virus research. To this end, we focused on newly discovered viruses (Lake Sinai viruses, bee macula-like virus), or a so far neglected virus species (Apis mellifera filamentous virus), and cutting edge technologies (mass spectrometry, RNAi approach) applied in the field. PMID:26702462

Diversity of viruses in Ixodes ricinus, and characterization of a neurotropic strain of Eyach virus.

Science.gov (United States)

Moutailler, S; Popovici, I; Devillers, E; Vayssier-Taussat, M; Eloit, M

2016-05-01

Ticks transmit more pathogens-including bacteria, parasites and viruses-than any other arthropod vector. Although the epidemiological status of many tick-borne bacteria is very well characterized, tick-borne viruses are still relatively under-studied. Recently, several novel tick-borne viruses have been isolated from human febrile illnesses following tick bites, indicating the existence of other potential new and unknown tick-borne viruses. We used high-throughput sequencing to analyse the virome of Ixodes ricinus, the main vector of tick-borne pathogens in Europe. The majority of collected viral sequences were assigned to two potentially novel Nairovirus and Phlebovirus viruses, with prevalence rates ranging from 3.95% to 23.88% in adults and estimated to be between 0.14% and 72.16% in nymphs. These viruses could not be isolated from the brains of inoculated immunocompromised mice, perhaps indicating that they are unable to infect vertebrates. Within the I. ricinus virome, we also identified contigs with >90% identity to the known Eyach virus. Initially isolated in the 1980s, this virus was indirectly associated with human disease, but had never been extensively studied. Eyach virus prevalence varied between 0.07% and 5.26% in ticks from the French Ardennes and Alsace regions. Eyach virus was successfully isolated following intracerebral inoculation of immunocompromised mice with Eyach virus-positive tick extracts. This virus was also able to multiply and persist in the blood of immunocompetent mice inoculated by intraperitoneal injection, and caused brain infections in three of nine juveniles, without any obvious deleterious effects.

Zika Virus: An Emerging Worldwide Threat

OpenAIRE

Irfan A. Rather; Jameel B. Lone; Vivek K. Bajpai; Woon K. Paek; Jeongheui Lim

2017-01-01

ZIKA virus (ZIKV) poses a severe threat to the world. Recent outbreaks of ZIKV after 2007 along with its quick transmission have made this virus a matter of international concern. The virus shows symptoms that are similar to those caused in the wake of dengue virus (DENV) and other flaviviruses, which makes it difficult to discern the viral infection. Diagnosis is further complicated as the virus cross-reacts with antibodies of other viruses. Currently, molecular diagnosis of the virus is bei...

How hepatitis D virus can hinder the control of hepatitis B virus.

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Maria Xiridou

Full Text Available BACKGROUND: Hepatitis D (or hepatitis delta virus is a defective virus that relies on hepatitis B virus (HBV for transmission; infection with hepatitis D can occur only as coinfection with HBV or superinfection of an existing HBV infection. Because of the bond between the two viruses, control measures for HBV may have also affected the spread of hepatitis D, as evidenced by the decline of hepatitis D in recent years. Since the presence of hepatitis D is associated with suppressed HBV replication and possibly infectivity, it is reasonable to speculate that hepatitis D may facilitate the control of HBV. METHODOLOGY AND PRINCIPAL FINDINGS: We introduced a mathematical model for the transmission of HBV and hepatitis D, where individuals with dual HBV and hepatitis D infection transmit both viruses. We calculated the reproduction numbers of single HBV infections and dual HBV and hepatitis D infections and examined the endemic prevalences of the two viruses. The results show that hepatitis D virus modulates not only the severity of the HBV epidemic, but also the impact of interventions for HBV. Surprisingly we find that the presence of hepatitis D virus may hamper the eradication of HBV. Interventions that aim to reduce the basic reproduction number of HBV below one may not be sufficient to eradicate the virus, as control of HBV depends also on the reproduction numbers of dual infections. CONCLUSIONS AND SIGNIFICANCE: For populations where hepatitis D is endemic, plans for control programs ignoring the presence of hepatitis D may underestimate the HBV epidemic and produce overoptimistic results. The current HBV surveillance should be augmented with monitoring of hepatitis D, in order to improve accuracy of the monitoring and the efficacy of control measures.

Archaeal viruses of the sulfolobales

DEFF Research Database (Denmark)

Erdmann, Susanne; Garrett, Roger Antony

2015-01-01

in CRISPR loci of Sulfolobus species from a second coinfecting conjugative plasmid or virus (Erdmann and Garrett, Mol Microbiol 85:1044-1056, 2012; Erdmann et al. Mol Microbiol 91:900-917, 2014). Here we describe, firstly, the isolation of archaeal virus mixtures from terrestrial hot springs...... with an environmental virus mixture isolated from Yellowstone National Park (Erdmann and Garrett, Mol Microbiol 85:1044-1056, 2012). Experimental studies of isolated genetic elements from this mixture revealed that SMV1 (S ulfolobus Monocauda Virus 1), a tailed spindle-shaped virus, can induce spacer acquisition...... and the techniques used both to infect laboratory strains with these virus mixtures and to obtain purified virus particles. Secondly, we present the experimental conditions required for activating SMV1-induced spacer acquisition in two different Sulfolobus species....

Seasonal and pandemic human influenza viruses attach better to human upper respiratory tract epithelium than avian influenza viruses.

Science.gov (United States)

van Riel, Debby; den Bakker, Michael A; Leijten, Lonneke M E; Chutinimitkul, Salin; Munster, Vincent J; de Wit, Emmie; Rimmelzwaan, Guus F; Fouchier, Ron A M; Osterhaus, Albert D M E; Kuiken, Thijs

2010-04-01

Influenza viruses vary markedly in their efficiency of human-to-human transmission. This variation has been speculated to be determined in part by the tropism of influenza virus for the human upper respiratory tract. To study this tropism, we determined the pattern of virus attachment by virus histochemistry of three human and three avian influenza viruses in human nasal septum, conchae, nasopharynx, paranasal sinuses, and larynx. We found that the human influenza viruses-two seasonal influenza viruses and pandemic H1N1 virus-attached abundantly to ciliated epithelial cells and goblet cells throughout the upper respiratory tract. In contrast, the avian influenza viruses, including the highly pathogenic H5N1 virus, attached only rarely to epithelial cells or goblet cells. Both human and avian viruses attached occasionally to cells of the submucosal glands. The pattern of virus attachment was similar among the different sites of the human upper respiratory tract for each virus tested. We conclude that influenza viruses that are transmitted efficiently among humans attach abundantly to human upper respiratory tract, whereas inefficiently transmitted influenza viruses attach rarely. These results suggest that the ability of an influenza virus to attach to human upper respiratory tract is a critical factor for efficient transmission in the human population.

MiniCD4 microbicide prevents HIV infection of human mucosal explants and vaginal transmission of SHIV(162P3 in cynomolgus macaques.

Directory of Open Access Journals (Sweden)

Nathalie Dereuddre-Bosquet

Full Text Available In complement to an effective vaccine, development of potent anti-HIV microbicides remains an important priority. We have previously shown that the miniCD4 M48U1, a functional mimetic of sCD4 presented on a 27 amino-acid stable scaffold, inhibits a broad range of HIV-1 isolates at sub-nanomolar concentrations in cellular models. Here, we report that M48U1 inhibits efficiently HIV-1(Ba-L in human mucosal explants of cervical and colorectal tissues. In vivo efficacy of M48U1 was evaluated in nonhuman primate (NHP model of mucosal challenge with SHIV(162P3 after assessing pharmacokinetics and pharmacodynamics of a miniCD4 gel formulation in sexually matured female cynomolgus macaques. Among 12 females, half were treated with hydroxyethylcellulose-based gel (control, the other half received the same gel containing 3 mg/g of M48U1, one hour before vaginal route challenge with 10 AID(50 of SHIV(162P3. All control animals were infected with a peak plasma viral load of 10(5-10(6 viral RNA (vRNA copies per mL. In animals treated with miniCD4, 5 out of 6 were fully protected from acquisition of infection, as assessed by qRT-PCR for vRNA detection in plasma, qPCR for viral DNA detection in PBMC and lymph node cells. The only infected animal in this group had a delayed peak of viremia of one week. These results demonstrate that M48U1 miniCD4 acts in vivo as a potent entry inhibitor, which may be considered in microbicide developments.

Prevalence of intestinal microsporidiosis in Human Immunodeficiency Virus-infected patients with diarrhea in major United States cities Prevalência de microsporidiose intestinal em pacientes infectados pelo HIV com diarréia nas principais cidades dos Estados Unidos da América do Norte

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Mark S. Dworkin

2007-12-01

Full Text Available To determine the prevalence of intestinal microsporidiosis in HIV-infected patients, we performed a prospective study of HIV-infected patients with diarrheal illnesses in three US hospitals and examined an observational database of HIV-infected patients in 10 US cities. Among 737 specimens from the three hospitals, results were positive for 11 (prevalence 1.5%; seven (64% acquired HIV through male-to-male sexual contact, two (18% through male-to-male sexual contact and injection drug use, and one (9% through heterosexual contact; one (9% had an undetermined mode of transmission. Median CD4 count within six months of diagnosis of microsporidiosis was 33 cells/µL (range 3 to 319 cells/µL. For the national observational database (n = 24,098, the overall prevalence of microsporidiosis was 0.16%. Prevalence of microsporidiosis among HIV-infected patients with diarrheal disease is low, and microsporidiosis is most often diagnosed in patients with very low CD4+ cell counts. Testing for microsporidia appears to be indicated, especially for patients with very low CD4+ cell counts.Para determinar a prevalência de microsporidiose intestinal em pacientes infectados pelo HIV foi realizado um estudo prospectivo em três hospitais dos Estados Unidos da América do Norte (EUA e analizada uma base de dados nacional composta de dados coletados de pacientes infectados pelo HIV em 10 cidades dos EUA. De um total de 737 amostras de fezes de pacientes infectados pelo HIV que apresentavam diarréia, amostras de 11 pacientes (prevalência de 1,5% foram positivas para microsporídios. Todos os positivos eram do sexo masculino e, entre eles, sete (64% pacientes adquiriram a infecção pelo HIV através de relação homossexual, dois (18% através de relação sexual e drogas injetáveis e um (9% através de contato heterosexual, enquanto que em um paciente o modo de transmissão do HIV não foi determinado. A contagem média de linfócitos CD4 realizada até seis

Mutagenesis-mediated virus extinction: virus-dependent effect of viral load on sensitivity to lethal defection.

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Héctor Moreno

Full Text Available BACKGROUND: Lethal mutagenesis is a transition towards virus extinction mediated by enhanced mutation rates during viral genome replication, and it is currently under investigation as a potential new antiviral strategy. Viral load and virus fitness are known to influence virus extinction. Here we examine the effect or the multiplicity of infection (MOI on progeny production of several RNA viruses under enhanced mutagenesis. RESULTS: The effect of the mutagenic base analogue 5-fluorouracil (FU on the replication of the arenavirus lymphocytic choriomeningitis virus (LCMV can result either in inhibition of progeny production and virus extinction in infections carried out at low multiplicity of infection (MOI, or in a moderate titer decrease without extinction at high MOI. The effect of the MOI is similar for LCMV and vesicular stomatitis virus (VSV, but minimal or absent for the picornaviruses foot-and-mouth disease virus (FMDV and encephalomyocarditis virus (EMCV. The increase in mutation frequency and Shannon entropy (mutant spectrum complexity as a result of virus passage in the presence of FU was more accentuated at low MOI for LCMV and VSV, and at high MOI for FMDV and EMCV. We present an extension of the lethal defection model that agrees with the experimental results. CONCLUSIONS: (i Low infecting load favoured the extinction of negative strand viruses, LCMV or VSV, with an increase of mutant spectrum complexity. (ii This behaviour is not observed in RNA positive strand viruses, FMDV or EMCV. (iii The accumulation of defector genomes may underlie the MOI-dependent behaviour. (iv LCMV coinfections are allowed but superinfection is strongly restricted in BHK-21 cells. (v The dissimilar effects of the MOI on the efficiency of mutagenic-based extinction of different RNA viruses can have implications for the design of antiviral protocols based on lethal mutagenesis, presently under development.

Coinfection of hepatitis E virus and other hepatitis virus in Colombia and its genotypic characterization.

Science.gov (United States)

Peláez, Dioselina; Martínez-Vargas, Daniel; Escalante-Mora, Martha; Palacios-Vivero, Mariel; Contreras-Gómez, Lady

2015-12-04

Hepatitis E virus has emerged as a public health problem, particularly in developing countries. The four genotypes identified in mammals include the G3 found in indigenous hepatitis in countries and regions with high porcine population, and the G1, associated with maternal deaths.  To determine coinfection by hepatitis E virus and the circulating genotypes in Colombia in 1,097 samples using serological markers for hepatitis A, B and C.  Serum samples of 1,097 patients from different regions of Colombia stored at the Laboratorio de Virología of the Instituto Nacional de Salud were selected to detect IgG and IgM anti-hepatitis E virus antibodies. The viral genomes of positive samples were amplified by RT-PCR, and the products were sequenced and phylogenetically analyzed by comparing ORF2 sequences deposited in the GenBank.  IgG anti-hepatitis E virus antibodies were found in 278 samples, IgM in 62, and both markers in 64. Hepatitis E virus and hepatitis A virus coinfection determined by IgG anti-hepatitis E virus was 33.6% and 16.1% by IgM; hepatitis E virus and hepatitis B virus coinfection was 23.4% and 8.1%, and hepatitis E virus and hepatitis C virus coinfection was 35.4% and 5.83%, respectively. Among the 52 positive samples by PCR nine were sequenced and grouped within genotype 3A of the American porcine strain.  The highest seropositivity was observed for hepatitis A and E. The incidence of hepatitis E virus coinfection with other hepatotropic viruses indicated that this pathogen is more frequent than expected. The circulation of genotype 3A implies that this disease may occur in outbreaks and as zoonosis in Colombia.

Comparative Pathology of Hepatitis A Virus and Hepatitis E Virus Infection.

Science.gov (United States)

Cullen, John M; Lemon, Stanley M

2018-04-30

Hepatitis A virus (HAV) and hepatitis E virus (HEV) cause acute, self-limiting hepatic infections that are usually spread by the fecal-oral route in humans. Naturally occurring and experimental infections are possible in a variety of nonhuman primates and, in the case of HEV, a number of other species. Many advances in understanding the pathogenesis of these viruses have come from studies in experimental animals. In general, animals infected with these viruses recapitulate the histologic lesions seen in infected humans, but typically with less severe clinical and histopathological manifestations. This review describes the histopathologic changes associated with HAV and HEV infection in humans and experimental animals. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

[Zika virus infection during pregnancy].

Science.gov (United States)

Picone, O; Vauloup-Fellous, C; D'Ortenzio, E; Huissoud, C; Carles, G; Benachi, A; Faye, A; Luton, D; Paty, M-C; Ayoubi, J-M; Yazdanpanah, Y; Mandelbrot, L; Matheron, S

2016-05-01

A Zika virus epidemic is currently ongoing in the Americas. This virus is linked to congenital infections with potential severe neurodevelopmental dysfunction. However, incidence of fetal infection and whether this virus is responsible of other fetal complications are still unknown. National and international public health authorities recommend caution and several prevention measures. Declaration of Zika virus infection is now mandatory in France. Given the available knowledge on Zika virus, we suggest here a review of the current recommendations for management of pregnancy in case of suspicious or infection by Zika virus in a pregnant woman. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Computer virus information update CIAC-2301

Energy Technology Data Exchange (ETDEWEB)

Orvis, W.J.

1994-01-15

While CIAC periodically issues bulletins about specific computer viruses, these bulletins do not cover all the computer viruses that affect desktop computers. The purpose of this document is to identify most of the known viruses for the MS-DOS and Macintosh platforms and give an overview of the effects of each virus. The authors also include information on some windows, Atari, and Amiga viruses. This document is revised periodically as new virus information becomes available. This document replaces all earlier versions of the CIAC Computer virus Information Update. The date on the front cover indicates date on which the information in this document was extracted from CIAC`s Virus database.

Human immunodeficiency virus and hepatitus B virus co-infection ...

African Journals Online (AJOL)

Human immunodeficiency virus and hepatitus B virus co-infection amog patients in Kano Nigeria. EE Nwokedi, MA Emokpae, AI Dutse. Abstract. No Abstract. Nigerian Journal of Medicine Vol. 15(3) July-September 2006: 227-229. Full Text: EMAIL FULL TEXT EMAIL FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD ...

Vaccination with Recombinant Parainfluenza Virus 5 Expressing Neuraminidase Protects against Homologous and Heterologous Influenza Virus Challenge.

Science.gov (United States)

Mooney, Alaina J; Gabbard, Jon D; Li, Zhuo; Dlugolenski, Daniel A; Johnson, Scott K; Tripp, Ralph A; He, Biao; Tompkins, S Mark

2017-12-01

Seasonal human influenza virus continues to cause morbidity and mortality annually, and highly pathogenic avian influenza (HPAI) viruses along with other emerging influenza viruses continue to pose pandemic threats. Vaccination is considered the most effective measure for controlling influenza; however, current strategies rely on a precise vaccine match with currently circulating virus strains for efficacy, requiring constant surveillance and regular development of matched vaccines. Current vaccines focus on eliciting specific antibody responses against the hemagglutinin (HA) surface glycoprotein; however, the diversity of HAs across species and antigenic drift of circulating strains enable the evasion of virus-inhibiting antibody responses, resulting in vaccine failure. The neuraminidase (NA) surface glycoprotein, while diverse, has a conserved enzymatic site and presents an appealing target for priming broadly effective antibody responses. Here we show that vaccination with parainfluenza virus 5 (PIV5), a promising live viral vector expressing NA from avian (H5N1) or pandemic (H1N1) influenza virus, elicited NA-specific antibody and T cell responses, which conferred protection against homologous and heterologous influenza virus challenges. Vaccination with PIV5-N1 NA provided cross-protection against challenge with a heterosubtypic (H3N2) virus. Experiments using antibody transfer indicate that antibodies to NA have an important role in protection. These findings indicate that PIV5 expressing NA may be effective as a broadly protective vaccine against seasonal influenza and emerging pandemic threats. IMPORTANCE Seasonal influenza viruses cause considerable morbidity and mortality annually, while emerging viruses pose potential pandemic threats. Currently licensed influenza virus vaccines rely on the antigenic match of hemagglutinin (HA) for vaccine strain selection, and most vaccines rely on HA inhibition titers to determine efficacy, despite the growing