RESUMO
Influenza constitutes a challenge to animal and human health. It is a highly contagious disease with wildlife reservoirs and considered as endemic among swine populations. Pigs are crucial in the disease dynamics due to their capacity to generate new reassortant viruses. The risk of informal animal trade in the spread of zoonotic diseases is well recognized worldwide. Nevertheless, the contribution of the backyard pig trade network in the transmission of influenza in a wildlife/livestock interface area is unknown. This study provides the first simulation of influenza transmission based on backyard farm connections in Mexico. A susceptible-infectious-recovered (SIR) model was implemented using the Epimodel software package in R, and 260 backyard farms were considered as nodes. Three different scenarios of connectivity (low, medium, and high) mediated by trade were generated and compared. Our results suggest that half of the pig population were infected within 5 days in the high connectivity scenario and the number of infected farms was approximately 65-fold higher compared to the low connected one. The consequence of connectivity variations directly influenced both time and duration of influenza virus transmission. Therefore, high connectivity driven by informal trade constitutes a significant risk to animal health. Trade patterns of animal movements are complex. This approach emphasizes the importance of pig movements and spatial dynamics among backyard production, live animal markets, and wildlife.
Assuntos
Criação de Animais Domésticos , Vírus da Influenza A/fisiologia , Infecções por Orthomyxoviridae/veterinária , Doenças dos Suínos/transmissão , Animais , Animais Selvagens , Gado , México , Modelos Teóricos , Infecções por Orthomyxoviridae/transmissão , Sus scrofa , SuínosRESUMO
Although there are over 1,150 bat species worldwide, the diversity of viruses harbored by bats has only recently come into focus as a result of expanded wildlife surveillance. Such surveys are of importance in determining the potential for novel viruses to emerge in humans, and for optimal management of bats and their habitats. To enhance our knowledge of the viral diversity present in bats, we initially surveyed 415 sera from African and Central American bats. Unbiased high-throughput sequencing revealed the presence of a highly diverse group of bat-derived viruses related to hepaciviruses and pegiviruses within the family Flaviridae. Subsequent PCR screening of 1,258 bat specimens collected worldwide indicated the presence of these viruses also in North America and Asia. A total of 83 bat-derived viruses were identified, representing an infection rate of nearly 5%. Evolutionary analyses revealed that all known hepaciviruses and pegiviruses, including those previously documented in humans and other primates, fall within the phylogenetic diversity of the bat-derived viruses described here. The prevalence, unprecedented viral biodiversity, phylogenetic divergence, and worldwide distribution of the bat-derived viruses suggest that bats are a major and ancient natural reservoir for both hepaciviruses and pegiviruses and provide insights into the evolutionary history of hepatitis C virus and the human GB viruses.
Assuntos
Quirópteros/virologia , Reservatórios de Doenças/veterinária , Flaviviridae/genética , Hepacivirus/genética , Viroses/virologia , Sequência de Aminoácidos , Animais , Teorema de Bayes , Códon , Reservatórios de Doenças/virologia , Variação Genética , Genoma Viral , Geografia , Dados de Sequência Molecular , Filogenia , Reação em Cadeia da Polimerase , Análise de Sequência de DNA , Homologia de Sequência de Aminoácidos , Viroses/veterináriaRESUMO
Aquatic habitats provide a bridge for influenza transmission among wild and domestic species. However, water sources pose highly variable physicochemical and ecological characteristics that affect avian influenza virus (AIV) stability. Therefore, the risk of survival or transmissibility of AIV in the environment is quite variable and has been understudied. In this study, we determine the risk of waterborne transmission and environmental persistence of AIV in a wild/domestic bird interface in the Central Mexico plateau (North America) during the winter season using a multi-criteria decision analysis (MCDA). A total of 13 eco-epidemiological factors were selected from public-access databases to develop the risk assessment. The MCDA showed that the Atarasquillo wetland presents a higher persistence risk in January. Likewise, most of the backyard poultry farms at this wild-domestic interface present a high persistence risk (50%). Our results suggest that drinking water may represent a more enabling environment for AIV persistence in contrast with wastewater. Moreover, almost all backyard poultry farms evidence a moderate or high risk of waterborne transmission especially farms close to water bodies. The wildlife/domestic bird interface on the Atarasquillo wetland holds eco-epidemiological factors such as the presence of farms in flood-prone areas, the poultry access to outdoor water, and the use of drinking-water troughs among multiple animal species that may enhance waterborne transmission of AIV. These findings highlight the relevance of understanding the influence of multiple factors on AIV ecology for early intervention and long-term control strategies.
RESUMO
The current COVID-19 pandemic highlights the need for zoonotic infectious disease surveillance. Avian influenza virus (AIV) poses a significant threat to animal and public health due to its pandemic potential. Virus-contaminated water has been suggested as an important AIV spread mechanism among multiple species. Nevertheless, few studies have characterized the global AIV subtype diversity and distribution in environmental water. Therefore, this study aims to provide an updated descriptive and phylogenetic analysis of AIVs isolated in water samples from high risk-sites for influenza outbreaks (i.e. live bird markets, poultry farms, and wild bird habitats) on a global scale. The descriptive analysis evidenced that 21 subtypes were reported from nine countries between 2003 and 2020. Fourteen AIV subtypes were solely reported from Asian countries. Most of the viral sequences were obtained in China and Bangladesh with 47.44% and 23.93%, respectively. Likewise, the greatest global AIV subtype diversity was observed in China with 12 subtypes. Live bird markets represented the main sampling site for AIV detection in water samples (64.1%), mostly from poultry cage water. Nevertheless, the highest subtype diversity was observed in water samples from wild bird habitats, especially from the Izumi plain and the Dongting Lake located in Japan and China, respectively. Water from drinking poultry troughs evidenced the greatest subtype diversity in live bird markets; meanwhile, environmental water used by ducks had the highest number of different subtypes in poultry farms. Maximum-likelihood phylogenetic trees of hemagglutinin (HA) and neuraminidase (NA) genes showed that some sequences were closely related among different poultry/wild bird-related environments from different geographic origins. Therefore, the results suggest that even though the availability of gene sequences in public-access databases varies greatly among countries, environmental AIV surveillance represents a useful tool to elucidate potential viral diversity in wild and domestic bird populations.
Assuntos
COVID-19 , Vírus da Influenza A , Influenza Aviária , Animais , Animais Selvagens , COVID-19/veterinária , Influenza Aviária/epidemiologia , Pandemias , Filogenia , Aves Domésticas , ÁguaRESUMO
Tick-borne rickettsioses are caused at least by 15 species of Rickettsia of the Spotted fever group, which represent a major emerging and re-emerging public health problem worldwide. Some of these microorganisms have complex cycles involving the interaction of multiple species of ticks and wild and domestic mammals. Rickettsia infection was investigated in ticks collected from wild pigs at six localities in southeastern Mexico. We collected and tested 196 ticks belonging to four species, including Amblyomma maculatum, Amblyomma mixtum, Amblyomma ovale and Riphicephalus microplus, from 13 of 20 (65%) wild pigs sampled. Overall, Rickettsia DNA was detected in 13.8% of ticks tested (10 â and 17 â). Of the 27 Rickettsia-positive ticks, six were A. maculatum, and 21 A. mixtum. Sequencing and phylogenetic analysis of the gltA and ompB genes revealed the presence of Rickettsia parkeri sensu stricto in one female A. maculatum and Rickettsia amblyommatis in five A. maculatum (2 â, 3 â) and 21 A. mixtum ticks (8 â, 13 â). The finding of two rickettsial agents in ticks collected from a wild pig population that is regularly captured and kept in captivity or hunted as a source of food raises concern about potential disease transmission to humans and domestic animals. However, more investigations are needed to further understand the ecology of Rickettsia species in free-ranging animals and their implications for human health.
Assuntos
Ixodidae , Rickettsia , Carrapatos , Animais , Feminino , Ixodidae/microbiologia , Mamíferos , México/epidemiologia , Filogenia , Rickettsia/genética , Suínos , Carrapatos/microbiologiaRESUMO
Global change and ecosystem transformation at regional and local scales during recent decades have facilitated the exponential increase of outbreaks of mosquito-borne diseases. Mosquito-borne pathogens are responsible for millions of infections, mainly in tropical regions where marginalized human populations are located, and where in recent years processes of landscape anthropization have occurred. Anthropogenic landscape transformation is known to change species assemblages. However, the magnitude of these effects is largely unknown, and the effects of anthropogenic landscape transformation on sylvatic mosquito assemblages are poorly known in Mexican ecosystems. We evaluate how mosquito abundance, richness, and diversity change along a gradient of three human-modified landscapes-one highly anthropized, one moderately anthropized, and one slightly anthropized-within a tropical forest matrix in a Protected Natural Area in Chiapas. A total of 4 538 mosquitoes belonging to 23 species were captured and identified at the three sites. We found differences in the structure and abundance of the three mosquito assemblages. The species assemblage of the highly anthropized site was significantly different from the other sites, and the relative abundance of the assemblages increased with landscape anthropization. Our results suggest that landscape anthropization alters the composition and structure of mosquito assemblages, modifying the abundance and species richness of mosquitoes associated with sylvatic ecosystems. This could support the hypothesis of intermediate disturbance that suggests the diversity is maximized when late and early successional species coexist in these ecosystems. This information is essential to understand the ecology of potential sylvatic vectors and the environmental factors that are involved in the emergence and re-emergence of mosquito-borne diseases.
Assuntos
Ecossistema , Mosquitos Vetores , Floresta Úmida , Animais , Humanos , MéxicoRESUMO
Influenza A virus (IAV) outbreaks constitute a constant threat to public health and pose a remarkable impact on socio-economic systems worldwide. Interactions between wild and domestic birds, humans and swine can lead to spillover events. Backyard livestock systems in proximity to wetlands represent high-risk areas for viral spread. However, some gaps remain in our knowledge of IAV transmission at the wildlife-livestock interface in Mexico. Hence, the study aimed at molecular identification and phylogenetic characterization of IAV in the wild duck-backyard livestock interface at a wetland of Mexico. A total of 875 animals were tested by real-time RT-PCR (qRT-PCR). We detected IAV in 3.68% of the wild ducks sampled during the winter season 2016-2017. Nonetheless, the samples obtained from backyard poultry and swine tested negative. The highest IAV frequency (11.10%) was found in the Mexican duck (Anas diazi). Subtypes H1N1, H3N2 and H5N2 were detected. Phylogenetic analyses revealed that IAV detected in wild birds from the Lerma wetlands was mostly related to swine and poultry IAV strains previously isolated in the United States and Mexico. Except, the UIFMVZ377/H5N2 related to North American waterbirds. In conclusion, the co-circulation of three IAV subtypes in wild ducks close to backyard farms in Mexico, as well as the local identification of influenza viruses genetically related to Mexican and North American IAV strains, highlights the importance of the Lerma marshes for influenza surveillance given the close interaction among wild birds, poultry, pigs and humans.
Assuntos
Vírus da Influenza A Subtipo H1N1 , Vírus da Influenza A Subtipo H5N2 , Vírus da Influenza A , Influenza Aviária , Doenças dos Suínos , Animais , Animais Selvagens , Vírus da Influenza A Subtipo H3N2 , Vírus da Influenza A/genética , Influenza Aviária/epidemiologia , Gado , México/epidemiologia , Filogenia , Suínos , Doenças dos Suínos/epidemiologia , Estados UnidosRESUMO
Congregation of different migratory and resident bird species on aquatic ecosystems during winter migration increases contact rates and enhances influenza A virus (IAV) transmission. However, scarce research has been focused on the resident bird's contribution to the viral ecology at a local scale. The Mexican duck (Anas diazi) is an endemic endangered anatid from Mexico. This resident species shares aquatic habitats with migratory birds in the wetlands of Central Mexico. Therefore, here we describe the phylogenetic analysis of an IAV (A/Mexican duck/EstadodeMexico; Lerma/UIFMVZ377/2016(H5N2)) isolated in this species, during spatiotemporal concurrence with migratory anatids in the winter season. All eight gene sequences were obtained by nextgeneration sequencing. Maximum Likelihood trees were constructed using MEGA-X, with General Time Reversible + Invariant (GTR+I), Subtree Pruning and Regrafting (SPR) heuristic method, and 1000 bootstrap replicates. Similarities with six different IAV subtypes were observed through a BLAST search: H6N5, H7N7, H5N2, H4N6, H9N2, and H11N9, detected in wild ducks during 2015 in the Pacific, Central and Mississippi flyways stop sites across the United States of America and Canada. The molecular identification of this reassortant H5N2 IAV highlights the importance of resident species as a reservoir host and its potential participation in the maintenance and transmission of IAV in wetlands surrounded by rural areas.
Assuntos
Patos/virologia , Vírus da Influenza A Subtipo H5N2/genética , Influenza Aviária/virologia , Filogenia , Animais , Influenza Aviária/epidemiologia , México/epidemiologiaRESUMO
Most mosquito species are active during a certain part of the day, but climatic factors such as light intensity and relative humidity play an important role in the control of their activity. We selected three types of land use that were sampled in state of Campeche in 2018 (low semi-evergreen forest, secondary low semi-evergreen forest, and mango plantation), using ten CDC light traps baited with CO2 , that were active during nine hours of three activity periods (dawn, noon, and nightfall). A GLM was used to investigate changes in the assembly of mosquitoes between different types of land use and temporal variations. Rank abundance curves were used to detect changes in the spatial and activity period of the mosquitoes and we then calculated the Exponential Shannon Index. A total of 6,110 mosquitoes belonging to 23 species were captured. The greatest richness and abundance were found in the secondary low semi-evergreen forest, with greater richness and lower abundance than the mango plantation which showed more abundance. Of the activity periods, dusk had the greatest abundance and richness followed by dawn and finally noon.
Assuntos
Ciclos de Atividade , Distribuição Animal , Culicidae , Agricultura , Animais , Biodiversidade , México , Floresta ÚmidaRESUMO
Influenza, a zoonosis caused by various influenza A virus subtypes, affects a wide range of species, including humans. Pig cells express both sialyl-α-2,3-Gal and sialyl-α-2,6-Gal receptors, which make them susceptible to infection by avian and human viruses, respectively. To date, it is not known whether wild pigs in Mexico are affected by influenza virus subtypes, nor whether this would make them a potential risk of influenza transmission to humans. In this work, 61 hogs from two municipalities in Campeche, Mexico, were sampled. Hemagglutination inhibition assays were performed in 61 serum samples, and positive results were found for human H1N1 (11.47%), swine H1N1 (8.19%), and avian H5N2 (1.63%) virus variants. qRT-PCR assays were performed on the nasal swab, tracheal, and lung samples, and 19.67% of all hogs were positive to these assays. An avian H5N2 virus, first reported in 1994, was identified by sequencing. Our results demonstrate that wild pigs are participating in the exposure, transmission, maintenance, and possible diversification of influenza viruses in fragmented habitats, highlighting the synanthropic behavior of this species, which has been poorly studied in Mexico.
Assuntos
Vírus da Influenza A/isolamento & purificação , Influenza Humana/transmissão , Influenza Humana/virologia , Infecções por Orthomyxoviridae/veterinária , Doenças dos Suínos/virologia , Animais , Animais Selvagens/virologia , Testes de Inibição da Hemaglutinação , Humanos , Vírus da Influenza A Subtipo H1N1/classificação , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Vírus da Influenza A Subtipo H5N2/classificação , Vírus da Influenza A Subtipo H5N2/genética , Vírus da Influenza A Subtipo H5N2/isolamento & purificação , Vírus da Influenza A/classificação , Vírus da Influenza A/genética , Influenza Humana/epidemiologia , Pulmão/patologia , Pulmão/virologia , México/epidemiologia , Infecções por Orthomyxoviridae/epidemiologia , Infecções por Orthomyxoviridae/patologia , Infecções por Orthomyxoviridae/virologia , Suínos , Doenças dos Suínos/epidemiologia , Doenças dos Suínos/patologia , Doenças dos Suínos/transmissão , Traqueia/patologia , Traqueia/virologia , Zoonoses/epidemiologia , Zoonoses/transmissão , Zoonoses/virologiaRESUMO
Parkinson's disease (PD) is a progressive neurodegenerative disorder. An experimental model of this disease is produced in nonhuman primates by the administration of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In this work, we put forward a new quantitative evaluation method that uses video recordings to measure the displacement, gate, gross and fine motor performance of freely moving subjects. Four Vervet monkeys (Cercopithecus aethiops) were trained in a behavioral observation hallway while being recorded with digital video cameras from four different angles. After MPTP intoxication the animals were tested without any drug and after 30 and 90 min of Levodopa/Carbidopa administration. Using a personal computer the following behaviors were measured and evaluated from the video recordings: displacement time across the hallway, reaching time towards rewards, ingestion time, number of attempts to obtain rewards, number of rewards obtained, and level of the highest shelf reached for rewards. Our results show that there was an overall behavioral deterioration after MPTP administration and an overall improvement after Levodopa/Carbidopa treatment. This demonstrates that the HALLWAY task is a sensitive and objective method that allows detailed behavioral evaluation of freely moving monkeys in the MPTP Parkinson's disease model.
Assuntos
Ciências do Comportamento/métodos , Fenômenos Biomecânicos/fisiologia , Avaliação da Deficiência , Estudos de Avaliação como Assunto , Transtornos Parkinsonianos/diagnóstico , Gravação em Vídeo/métodos , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/farmacologia , Animais , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/fisiologia , Ciências do Comportamento/instrumentação , Chlorocebus aethiops , Modelos Animais de Doenças , Agonistas de Dopamina/farmacologia , Feminino , Coxeadura Animal/induzido quimicamente , Coxeadura Animal/diagnóstico , Coxeadura Animal/fisiopatologia , Masculino , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , Exame Neurológico/instrumentação , Exame Neurológico/métodos , Neurotoxinas/farmacologia , Transtornos Parkinsonianos/tratamento farmacológico , Transtornos Parkinsonianos/fisiopatologia , Gravação em Vídeo/instrumentaçãoRESUMO
Arboviruses are important zoonotic agents with complex transmission cycles and are not well understood because they may involve many vectors and hosts. We studied sympatric wild mammals and hematophagous mosquitoes having the potential to act as hosts and vectors in two areas of southern Mexico. Mosquitoes, bats, and rodents were captured in Calakmul (Campeche) and Montes Azules (Chiapas), between November 2010 and August 2011. Spleen samples from 146 bats and 14 rodents were tested for molecular evidence of Venezuelan equine encephalitis virus (VEEV), eastern equine encephalitis virus (EEEV), western equine encephalitis virus (WEEV), and West Nile virus (WNV) using PCR protocols. Bat ( Artibeus lituratus , Carollia sowelli , Glossophaga soricina , and Sturnira parvidens) and rodent ( Sigmodon hispidus and Oryzomys alfaroi ) species were positive for VEEV. No individuals were positive for WNV, EEEV, or WEEV. A total of 1,298 mosquitoes were collected at the same sites, and five of the mosquito species collected were known VEEV vectors (Aedes fulvus, Mansonia indubitans, Psorophora ferox, Psorophora cilipes, and Psorophora confinnis). This survey simultaneously presents the first molecular evidence, to our knowledge, of VEEV in bats and rodents from southern Mexico and the identification of potential sympatric vectors. Studies investigating sympatric nonhuman hosts, vectors, and arboviruses must be expanded to determine arboviral dynamics in complex systems in which outbreaks of emerging and reemerging zoonoses are continuously occurring.
Assuntos
Vírus da Encefalite Equina do Leste , Vírus da Encefalite Equina Venezuelana/isolamento & purificação , Mamíferos/virologia , Animais , Arbovírus , Culicidae , Vetores de Doenças , Vírus da Encefalite Equina Venezuelana/patogenicidade , Cavalos , Humanos , Insetos Vetores , México , ZoonosesRESUMO
It is currently unclear whether changes in viral communities will ever be predictable. Here we investigate whether viral communities in wildlife are inherently structured (inferring predictability) by looking at whether communities are assembled through deterministic (often predictable) or stochastic (not predictable) processes. We sample macaque faeces across nine sites in Bangladesh and use consensus PCR and sequencing to discover 184 viruses from 14 viral families. We then use network modelling and statistical null-hypothesis testing to show the presence of non-random deterministic patterns at different scales, between sites and within individuals. We show that the effects of determinism are not absolute however, as stochastic patterns are also observed. In showing that determinism is an important process in viral community assembly we conclude that it should be possible to forecast changes to some portion of a viral community, however there will always be some portion for which prediction will be unlikely.
Assuntos
Fezes/virologia , Variação Genética , Macaca mulatta , Doenças dos Macacos/virologia , Viroses/veterinária , Vírus/genética , Animais , Animais Selvagens , Bangladesh/epidemiologia , Dados de Sequência Molecular , Doenças dos Macacos/epidemiologia , Viroses/epidemiologia , Viroses/virologiaRESUMO
To identify the relationship between landscape use and dengue virus (DENV) occurrence in bats, we investigated the presence of DENV from anthropogenically changed and unaltered landscapes in two Biosphere Reserves: Calakmul (Campeche) and Montes Azules (Chiapas) in southern Mexico. Spleen samples of 146 bats, belonging to 16 species, were tested for four DENV serotypes with standard reverse transcriptase polymerase chain reaction (RT-PCR) protocols. Six bats (4.1%) tested positive for DENV-2: four bats in Calakmul (two Glossophaga soricina, one Artibeus jamaicensis, and one A. lituratus) and two bats in Montes Azules (both A. lituratus). No effect of anthropogenic disturbance on the occurrence of DENV was detected; however, all three RT-PCR-positive bat species are considered abundant species in the Neotropics and well-adapted to disturbed habitats. To our knowledge, this study is the first study conducted in southeastern Mexico to identify DENV-2 in bats by a widely accepted RT-PCR protocol. The role that bats play on DENV's ecology remains undetermined.
Assuntos
Vírus da Dengue/genética , Dengue/veterinária , Animais , Quirópteros , Dengue/epidemiologia , Dengue/virologia , Vírus da Dengue/classificação , México/epidemiologia , Tipagem Molecular , Reação em Cadeia da Polimerase/veterinária , Baço/virologia , Reforma UrbanaRESUMO
UNLABELLED: The majority of emerging zoonoses originate in wildlife, and many are caused by viruses. However, there are no rigorous estimates of total viral diversity (here termed "virodiversity") for any wildlife species, despite the utility of this to future surveillance and control of emerging zoonoses. In this case study, we repeatedly sampled a mammalian wildlife host known to harbor emerging zoonotic pathogens (the Indian Flying Fox, Pteropus giganteus) and used PCR with degenerate viral family-level primers to discover and analyze the occurrence patterns of 55 viruses from nine viral families. We then adapted statistical techniques used to estimate biodiversity in vertebrates and plants and estimated the total viral richness of these nine families in P. giganteus to be 58 viruses. Our analyses demonstrate proof-of-concept of a strategy for estimating viral richness and provide the first statistically supported estimate of the number of undiscovered viruses in a mammalian host. We used a simple extrapolation to estimate that there are a minimum of 320,000 mammalian viruses awaiting discovery within these nine families, assuming all species harbor a similar number of viruses, with minimal turnover between host species. We estimate the cost of discovering these viruses to be ~$6.3 billion (or ~$1.4 billion for 85% of the total diversity), which if annualized over a 10-year study time frame would represent a small fraction of the cost of many pandemic zoonoses. IMPORTANCE: Recent years have seen a dramatic increase in viral discovery efforts. However, most lack rigorous systematic design, which limits our ability to understand viral diversity and its ecological drivers and reduces their value to public health intervention. Here, we present a new framework for the discovery of novel viruses in wildlife and use it to make the first-ever estimate of the number of viruses that exist in a mammalian host. As pathogens continue to emerge from wildlife, this estimate allows us to put preliminary bounds around the potential size of the total zoonotic pool and facilitates a better understanding of where best to allocate resources for the subsequent discovery of global viral diversity.
Assuntos
Biodiversidade , Quirópteros/virologia , Vírus/classificação , Vírus/isolamento & purificação , Animais , Animais Selvagens/virologia , Dados de Sequência Molecular , Filogenia , Reação em Cadeia da Polimerase/economia , Reação em Cadeia da Polimerase/métodos , Vírus/genética , Zoonoses/virologiaRESUMO
Parkinson's disease is a neurodegenerative disease, resulting from deterioration of the substantia nigra which in turn leads to a decrease of dopamine levels in the striatum. Clinically the syndrome is characterized by motor alterations that are treated by the oral administration of levodopa. However, this treatment typically loses efficacy over time and therefore new treatments that procure a steady long term supplement of dopamine are needed. Here we tested the expression of a tyrosine hydroxilase (TH) transgene in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treated primates own astrocytes. The transgene, whose expression of TH cDNA was controlled by a glial fibrillary acidic protein (GFAP) promoter, was injected into MPTP treated primate's brains using liposomes as a delivery system. Monkeys were tested before and after MPTP administration, and after gene therapy treatment on the HALLWAY behavioral task. Results showed both transgene expression and significant behavioral improvements in the hallway task after the TH cDNA transfer. The behavioral recovery observed in the primates whose astrocytes expressed rat TH, is a first step that warrant further studies using primate's astrocytes as a good cell lineage to express therapeutic molecules.
Assuntos
Astrócitos/fisiologia , Comportamento Animal/efeitos dos fármacos , DNA Complementar/fisiologia , Intoxicação por MPTP/tratamento farmacológico , Intoxicação por MPTP/psicologia , Desempenho Psicomotor/efeitos dos fármacos , Tirosina 3-Mono-Oxigenase/fisiologia , Animais , Astrócitos/efeitos dos fármacos , Chlorocebus aethiops , DNA Complementar/genética , Dopaminérgicos/farmacologia , Técnicas de Transferência de Genes , Vetores Genéticos , Proteína Glial Fibrilar Ácida/metabolismo , Humanos , Levodopa/farmacologia , Imageamento por Ressonância Magnética , Masculino , Neostriado/fisiologia , Tirosina 3-Mono-Oxigenase/genéticaRESUMO
OBJECTIVE: To standardize an acquisition protocol for the study of myocardial glucolitic and oxidative metabolism and perfusion in a rat model. METHODS: Studies were carried out with the three main radiopharmaceuticals used to assess heart function:[18F]-FDG for glucolitic metabolism; [1-11C]-acetate for oxidative metabolism and [13N]-NH3for myocardial perfusion.[18F]-FDG -Five Wistar adult male rats were studied in three different protocols: non-fasting group, fasting group,8 h before the study with water provided ad libitum, and a fasting group by the same time receiving an oral 50%-glucose solution. Thirty-minute scans were performed with a microPET Focus 120, 30 and 60 min after the administration of 370 - 555 MBq 18F-FDG. [1-11C]-Acetate -Eight rats were studied. Four static and four dynamic 30 min acquisitions after a 370 - 555 MBq of [1-11C]-acetate caudal vein administration.[13N]-NH3-Ten static studies were acquired 15 min post-administration of 370- 555 MBq of 13NH3 isofluorane anesthesia. Comparative and visual analyses wy performer by two experts in the field. A semi-quantitative analysis was performa using 3D reconstructions and ROI selections with AMIDE software. RESULTS: The best images were those obtained from the non-fasting group, especially those taken at 60 min after the [18F]-FDG administration. High quality myocardial, static images were obtained with [1-11C]-acetate, and the dynamic adquisitions allowed the identification of myocardial perfusion. The 13NH3images showed a homogeneous distribution of the radiotracer in different segments of the short, long and horizontal axes in the left ventricle. CONCLUSIONS: It is possible to standardize the microPET acquisition protocols for the three main radiopharmaceuticals to evaluate the heart function in a rat model. It is feasible to establish a valid protocol for measuring glucolitic and oxidative myocardial metabolism and perfusion for gene, drug or surgical therapy assessment.
Assuntos
Acetatos , Carbono , Circulação Coronária , Fluordesoxiglucose F18 , Miocárdio/metabolismo , Radioisótopos de Nitrogênio , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Amônia , Animais , Masculino , Modelos Animais , Tomografia por Emissão de Pósitrons/métodos , Ratos , Ratos WistarRESUMO
Objetivos: Estandarizar un protocolo de adquisición para el estudio del metabolismo glucolítico, oxidativo y de perfusión miocárdicos en un modelo de rata. Métodos: Se realizaron estudios con los tres principales radiotrazadores usados para evaluar la función cardiaca: 18F-FDG para evaluar el metabolismo glucolítico en tres protocolos distintos; 1-11C-acetato para el metabolismo oxidativo y 13NH3 para la perfusión cardiaca. (18F-FDG)- cinco ratas Wistar macho en tres diferentes protocolos: con acceso a libre demanda de comida y agua; con ayuno de ocho horas y con ayuno de ocho horas más carga oral de glucosa al 50%. Se adquirieron imágenes del área torácica durante 30 minutos mediante microPET; 30 y 60 minutos post-administración de 370 - 555 MBq de 18F-FDG vía IP. (1-11C-acetato)- Se estudiaron ocho ratas. Cuatro estudios estáticos de 30 minutos y cuatro adquisiciones dinámicas de 30 minutos tras administración de 370 - 555 MBq de1-11C-acetato por vena caudal.(13NH3)- 10 estudios estáticos de 15 minutos después de una dosis IV de 370 - 555 MBq de 13NH3, bajo anestesia inhalada con isofluorano a 1.5% a 2%. Se realizó análisis comparativo y cualitativo de todas las imágenes obtenidas por dos médicos especialistas en el área y un análisis semi-cuantitativo mediante reconstrucciones 3D y selección de ROIs con el programa AMIDE en el caso de 18F-FDG. Resultados: Se determinó que las mejores imágenes para fines de evaluación metabólica del miocardio fueron las correspondientes a los 60 minutos post-administración de la 18F-FDG del protocolo sin ayuno. Se visualizó sin problemas el miocardio de rata de las imágenes estáticas con 1-11C-acetato, y mediante adquisición dinámica, se pudo apreciar la perfusión miocárdica. Las imágenes con 13NH3 permitieron observar una distribución homogénea del radiotrazador en los diferentes segmentos del ventrículo izquierdo en el eje corto, eje largo vertical y eje largo horizontal. Conclusiones: Se logró la estandarización de protocolos de adquisición de imágenes de los tres principales radiotrazadores utilizados para el estudio del metabolismo y perfusión cardiacos, en un modelo animal. Es factible establecer un protocolo válido para la valoración de perfusión, metabolismo glucolítico y oxidativo miocárdicos, con el fin de utilizarlo como punto de referencia para la evaluación de terapias génica, farmacológica o quirúrgica a nivel experimental.
Objective: To standardize an acquisition protocol for the study of myocardial glucolitic and oxidative metabolism and perfusion in a rat model. Methods: Studies were carried out with the three main radiopharmaceuticals used to assess heart function:[18F]-FDG for glucolitic metabolism; [1-11C]-acetate for oxidative metabolism and [13N]-NH3for myocardial perfusion.[18F]-FDG -Five Wistar adult male rats were studied in three different protocols: non-fasting group, fasting group,8 h before the study with water provided ad libitum, and a fasting group by the same time receiving an oral 50%-glucose solution. Thirty-minute scans were performed with a microPET Focus 120, 30 and 60 min after the administration of 370-555 MBq 18F-FDG. [1-11C]-Acetate -Eight rats were studied. Four static and four dynamic 30 min acquisitions after a 370-555 MBq of [1-11C]-acetate caudal vein administration.[13N]-NH3-Ten static studies were acquired 15 min post-administration of 370555 MBqof13NH3, under 1.5-2% isofluorane anesthesia. Comparative and visual analyses were performed by two experts in the field. A semi-quantitative analysis was performed using 3D reconstructions and ROI selections with AMIDE software. Results: The best images were those obtained from the non-fasting group, especially those taken at 60 min after the [18F]-FDG administration. High quality myocardial, static images were obtained with [1-11C]-acetate, and the dynamic acquisitions allowed the identification of myocardial perfusion. The 13NH3images showed a homogeneous distribution of the radiotracer in different segments of the short, long and horizontal axes in the left ventricle. Conclusions: It is possible to standardize the microPET acquisition protocols for the three main radiopharmaceuticals to evaluate the heart function in a rat model. It is feasible to establish a valid protocol for measuring glucolitic and oxidative myocardial metabolism and perfusion for gene, drug or surgical therapy assessment.
Assuntos
Animais , Masculino , Ratos , Acetatos , Circulação Coronária , Carbono , Miocárdio/metabolismo , Radioisótopos de Nitrogênio , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Amônia , Modelos Animais , Tomografia por Emissão de Pósitrons/métodos , Ratos WistarRESUMO
The objective of the present qualitative study was to analyze the morphological aspects of the inner cerebral anatomy of two species of primates, using magnetic resonance images (MRI): spider monkey (A. geoffroyi) and human (H. sapiens), on the basis of a comparative study of the cerebral structures of the two species, focusing upon the brain of the spider monkey and, primarily, its limbic system. In spite of being an endemic Western hemisphere species, a fact which is by its own right interesting for research due to this animal’s social organization and motor functions, the spider monkey (A. geoffroyi) has hardly been studied in regard to its neuroanatomy. MRI was carried out, in one spider monkey, employing a General Electric Signa 1.5 T scanner. This investigation was carried in accordance to international regulations for the protection of animals in captivity, taking into account all protective means utilized in experimental handling, and not leaving behind any residual effects, either physiological or behavioral. From a qualitative point of view, the brains of the spider monkey and the human were found to have similar structures. In reference to shape, the most similar structures were found in the limbic system; proportionally, however, cervi cal curvature, amygdala, hippocampus, anterior commissure and the colliculi, were larger in the spider monkey than in the human.
El objetivo del presente estudio cualitativo fue analizar los aspectos morfológicos de la anatomía cerebral interna utilizando imágenes de resonancia magnética (IRM) en dos especies de primates, El mono Araña (A. geoffroyi) y el humano (H. sapiens), tomando como base un estudio comparativo de las estructuras cerebrales de las dos especies, concentrándose primordialmente en el sistema límbico del cerebro del mono araña. Aunque es una especie común en el hemisferio occidental, es interesante para estudiar dada su organización social y funciones motoras, el mono araña (A. geoffroyi) ha sido poco estudiado en cuanto a su neuroanatomía. Las IRM fueron hechas a un mono araña utilizando un resonador General Electrics Signa 1.5 T. Esta investigación se llevo a cabo conforme a las leyes internacionales para la protección de animales en cautiverio y teniendo en cuenta todas las medidas de protección para el manejo experimental para evitar cualquier efecto residual de índole comportamental o fisiológico. Desde un punto de vista cualitativo, los cerebros del mono araña y el humano tenían estructuras similares. Con respecto a la forma, las estructuras más parecidas fueron encontradas en el sistema límbico, sin embargo la curvatura cervical, la amígdala, el hipocampo, la comisura anterior y el colículo fueron más grandes proporcionalmente en el mono araña que en el humano.