Epidemiological aspects of scorpionic accidents in a municipality in Brazil's northeastern / Aspectos epidemiológicos dos acidentes escorpiônicos em um munícipio do nordeste brasileiro

Scorpionic accidents are a major public health problem due to the high occurrence with potential seriousness. In this manner, the research aimed to analyze the occurrence of scorpionic accidents in a municipality in the northeastern of Brazil. An exploratory, descriptive study was made, with a quantitative approach, using secondary data which was gotten from the Notifiable Diseases Information System (SINAN), from 2008 to 2018. Data such as neighborhood, presence of street markets were also used, and the existence of sanitation and climatic data such as temperature and season. Geoprocessing was used to identify possible changes in the environment. In the analyzed period, 9,330 cases of scorpion accidents were recorded, with an average of 848 annual notifications. Scorpionic accidents occurred more frequently in women (5,686; 60.94%). Individuals aged 20 to 29 years (1.727; 18.51%) were more frequent to scorpion stings. Regarding the body parts where the stings were made, the highlights were on the foot (3.515; 37.67%) followed by the hand (2.818; 30.20%). No statistically significant relation was observed between climatic factors and scorpionic accidents. However, the high number of cases of scorpionic accidents was observed in the last 11 years studied. It was evident that during the study period there was no statistical relationship when climatic factors were correlated to scorpionic accidents. On its turn, when it was verified the results of the geoprocessing analysis, it was seen that anthropic factors have been motivating the potentiation of the occurrence of these accidents.

Os acidentes escorpiônicos apresentam-se como um grande problema de saúde pública em virtude da grande ocorrência com potencial gravidade. Nesse sentido, o trabalho teve como objetivo analisar a ocorrência de acidentes escorpiônicos em um município do nordeste brasileiro. Foi realizado um estudo descritivo, de caráter exploratório, com abordagem quantitativa em que foram utilizados dados secundários obtidos no Sistema de Informação de Agravos de Notificação (SINAN), no período de 2008 a 2018. Também foram utilizados dados como bairro, presença de feiras livres e a existência de saneamento básico e dados climáticos como temperatura e estação do ano. O geoprocessamento foi utilizado para identificar as possíveis alterações no ambiente. No período analisado, foram registrados 9,330 casos de acidentes com escorpião, com média de 848 notificações anuais. Os acidentes escorpiônicos ocorreram com mais frequência em mulheres (5,686; 60,94%). Em indivíduos na faixa etária de 20 a 29 anos (1,727; 18,51%) foram mais frequentes a picada de escorpião. Com relação ao local das picadas destacaram-se o pé (3,515; 37,67%), seguido da mão (2,818; 30,20%). Não foi observada relação estatisticamente significativa entre os fatores clímáticos e os acidentes escorpiônicos. Foi observado elevado número de casos de acidentes escorpiônicos nos últimos 11 anos estudados. Ficou evidente que durante o período de estudo não existiu relação estatística quando se correlacionou fatores climáticos aos acidentes escorpiônicos. Por sua vez, ao verificar os resultados da análise de geoprocessamento foi visto que fatores antrópicos têm sido motivadores da potencialização da ocorrência desses acidentes.

Epidemiological aspects of scorpionic accidents in a municipality in Brazils northeastern

Abstract Scorpionic accidents are a major public health problem due to the high occurrence with potential seriousness. In this manner, the research aimed to analyze the occurrence of scorpionic accidents in a municipality in the northeastern of Brazil. An exploratory, descriptive study was made, with a quantitative approach, using secondary data which was gotten from the Notifiable Diseases Information System (SINAN), from 2008 to 2018. Data such as neighborhood, presence of street markets were also used, and the existence of sanitation and climatic data such as temperature and season. Geoprocessing was used to identify possible changes in the environment. In the analyzed period, 9,330 cases of scorpion accidents were recorded, with an average of 848 annual notifications. Scorpionic accidents occurred more frequently in women (5,686; 60.94%). Individuals aged 20 to 29 years (1.727; 18.51%) were more frequent to scorpion stings. Regarding the body parts where the stings were made, the highlights were on the foot (3.515; 37.67%) followed by the hand (2.818; 30.20%). No statistically significant relation was observed between climatic factors and scorpionic accidents. However, the high number of cases of scorpionic accidents was observed in the last 11 years studied. It was evident that during the study period there was no statistical relationship when climatic factors were correlated to scorpionic accidents. On its turn, when it was verified the results of the geoprocessing analysis, it was seen that anthropic factors have been motivating the potentiation of the occurrence of these accidents.

Resumo Os acidentes escorpiônicos apresentam-se como um grande problema de saúde pública em virtude da grande ocorrência com potencial gravidade. Nesse sentido, o trabalho teve como objetivo analisar a ocorrência de acidentes escorpiônicos em um município do nordeste brasileiro. Foi realizado um estudo descritivo, de caráter exploratório, com abordagem quantitativa em que foram utilizados dados secundários obtidos no Sistema de Informação de Agravos de Notificação (SINAN), no período de 2008 a 2018. Também foram utilizados dados como bairro, presença de feiras livres e a existência de saneamento básico e dados climáticos como temperatura e estação do ano. O geoprocessamento foi utilizado para identificar as possíveis alterações no ambiente. No período analisado, foram registrados 9,330 casos de acidentes com escorpião, com média de 848 notificações anuais. Os acidentes escorpiônicos ocorreram com mais frequência em mulheres (5,686; 60,94%). Em indivíduos na faixa etária de 20 a 29 anos (1,727; 18,51%) foram mais frequentes a picada de escorpião. Com relação ao local das picadas destacaram-se o pé (3,515; 37,67%), seguido da mão (2,818; 30,20%). Não foi observada relação estatisticamente significativa entre os fatores clímáticos e os acidentes escorpiônicos. Foi observado elevado número de casos de acidentes escorpiônicos nos últimos 11 anos estudados. Ficou evidente que durante o período de estudo não existiu relação estatística quando se correlacionou fatores climáticos aos acidentes escorpiônicos. Por sua vez, ao verificar os resultados da análise de geoprocessamento foi visto que fatores antrópicos têm sido motivadores da potencialização da ocorrência desses acidentes.

Epidemiological aspects of scorpionic accidents in a municipality in Brazil's northeastern / Aspectos epidemiológicos dos acidentes escorpiônicos em um munícipio do nordeste brasileiro

Scorpionic accidents are a major public health problem due to the high occurrence with potential seriousness. In this manner, the research aimed to analyze the occurrence of scorpionic accidents in a municipality in the northeastern of Brazil. An exploratory, descriptive study was made, with a quantitative approach, using secondary data which was gotten from the Notifiable Diseases Information System (SINAN), from 2008 to 2018. Data such as neighborhood, presence of street markets were also used, and the existence of sanitation and climatic data such as temperature and season. Geoprocessing was used to identify possible changes in the environment. In the analyzed period, 9,330 cases of scorpion accidents were recorded, with an average of 848 annual notifications. Scorpionic accidents occurred more frequently in women (5,686; 60.94%). Individuals aged 20 to 29 years (1.727; 18.51%) were more frequent to scorpion stings. Regarding the body parts where the stings were made, the highlights were on the foot (3.515; 37.67%) followed by the hand (2.818; 30.20%). No statistically significant relation was observed between climatic factors and scorpionic accidents. However, the high number of cases of scorpionic accidents was observed in the last 11 years studied. It was evident that during the study period there was no statistical relationship when climatic factors were correlated to scorpionic accidents. On its turn, when it was verified the results of the geoprocessing analysis, it was seen that anthropic factors have been motivating the potentiation of the occurrence of these accidents.

Os acidentes escorpiônicos apresentam-se como um grande problema de saúde pública em virtude da grande ocorrência com potencial gravidade. Nesse sentido, o trabalho teve como objetivo analisar a ocorrência de acidentes escorpiônicos em um município do nordeste brasileiro. Foi realizado um estudo descritivo, de caráter exploratório, com abordagem quantitativa em que foram utilizados dados secundários obtidos no Sistema de Informação de Agravos de Notificação (SINAN), no período de 2008 a 2018. Também foram utilizados dados como bairro, presença de feiras livres e a existência de saneamento básico e dados climáticos como temperatura e estação do ano. O geoprocessamento foi utilizado para identificar as possíveis alterações no ambiente. No período analisado, foram registrados 9,330 casos de acidentes com escorpião, com média de 848 notificações anuais. Os acidentes escorpiônicos ocorreram com mais frequência em mulheres (5,686; 60,94%). Em indivíduos na faixa etária de 20 a 29 anos (1,727; 18,51%) foram mais frequentes a picada de escorpião. Com relação ao local das picadas destacaram-se o pé (3,515; 37,67%), seguido da mão (2,818; 30,20%). Não foi observada relação estatisticamente significativa entre os fatores climáticos e os acidentes escorpiônicos. Foi observado elevado número de casos de acidentes escorpiônicos nos últimos 11 anos estudados. Ficou evidente que durante o período de estudo não existiu relação estatística quando se correlacionou fatores climáticos aos acidentes escorpiônicos. Por sua vez, ao verificar os resultados da análise de geoprocessamento foi visto que fatores antrópicos têm sido motivadores da potencialização da ocorrência desses acidentes.

Epidemiological aspects of scorpionic accidents in a municipality in Brazil's northeastern.

Scorpionic accidents are a major public health problem due to the high occurrence with potential seriousness. In this manner, the research aimed to analyze the occurrence of scorpionic accidents in a municipality in the northeastern of Brazil. An exploratory, descriptive study was made, with a quantitative approach, using secondary data which was gotten from the Notifiable Diseases Information System (SINAN), from 2008 to 2018. Data such as neighborhood, presence of street markets were also used, and the existence of sanitation and climatic data such as temperature and season. Geoprocessing was used to identify possible changes in the environment. In the analyzed period, 9,330 cases of scorpion accidents were recorded, with an average of 848 annual notifications. Scorpionic accidents occurred more frequently in women (5,686; 60.94%). Individuals aged 20 to 29 years (1.727; 18.51%) were more frequent to scorpion stings. Regarding the body parts where the stings were made, the highlights were on the foot (3.515; 37.67%) followed by the hand (2.818; 30.20%). No statistically significant relation was observed between climatic factors and scorpionic accidents. However, the high number of cases of scorpionic accidents was observed in the last 11 years studied. It was evident that during the study period there was no statistical relationship when climatic factors were correlated to scorpionic accidents. On its turn, when it was verified the results of the geoprocessing analysis, it was seen that anthropic factors have been motivating the potentiation of the occurrence of these accidents.

Entomopathogenic Viruses in the Neotropics: Current Status and Recently Discovered Species.

The market for biological control of insect pests in the world and in Brazil has grown in recent years due to the unwanted ecological and human health impacts of chemical insecticides. Therefore, research on biological control agents for pest management has also increased. For instance, insect viruses have been used to protect crops and forests around the world for decades. Among insect viruses, the baculoviruses are the most studied and used viral biocontrol agent. More than 700 species of insects have been found to be naturally infected by baculoviruses, with 90% isolated from lepidopteran insects. In this review, some basic aspects of baculovirus infection in vivo and in vitro infection, gene content, viral replication will be discussed. Furthermore, we provide examples of the use of insect viruses for biological pest control and recently characterized baculoviruses in Brazil.

Genome-wide diversity in temporal and regional populations of the betabaculovirus Erinnyis ello granulovirus (ErelGV).

BACKGROUND: Erinnyis ello granulovirus (ErelGV) is a betabaculovirus infecting caterpillars of the sphingid moth E. ello ello (cassava hornworm), an important pest of cassava crops (Manihot esculenta). In this study, the genome of seven field isolates of the virus ErelGV were deep sequenced and their inter- and intrapopulational sequence diversity were analyzed. RESULTS: No events of gene gain/loss or translocations were observed, and indels were mainly found within highly repetitive regions (direct repeats, drs). A naturally occurring isolate from Northern Brazil (Acre State, an Amazonian region) has shown to be the most diverse population, with a unique pattern of polymorphisms. Overall, non-synonymous substitutions were found all over the seven genomes, with no specific gathering of mutations on hotspot regions. Independently of their sizes, some ORFs have shown higher levels of non-synonymous changes than others. Non-core genes of known functions and structural genes were among the most diverse ones; and as expected, core genes were the least variable genes. We observed remarkable differences on diversity of paralogous genes, as in multiple copies of p10, fgf, and pep. Another important contrast on sequence diversity was found on genes encoding complex subunits and/or involved in the same biological processes, as late expression factors (lefs) and per os infectivity factors (pifs). Interestingly, several polymorphisms in coding regions lie on sequences encoding specific protein domains. CONCLUSIONS: By comparing and integrating information about inter- and intrapopulational diversity of viral isolates, we provide a detailed description on how evolution operates on field isolates of a betabaculovirus. Our results revealed that 35-41% of the SNPs of ErelGV lead to amino acid changes (non-synonymous substitutions). Some genes, especially non-core genes of unknown functions, tend to accumulate more mutations, while core genes evolve slowly and are more conserved. Additional studies would be necessary to understand the actual effects of such gene variations on viral infection and fitness.

The complete genome of a baculovirus isolated from an insect of medical interest: Lonomia obliqua (Lepidoptera: Saturniidae).

Lonomia obliqua (Lepidoptera: Saturniidae) is a species of medical importance due to the severity of reactions caused by accidental contact with the caterpillar bristles. Several natural pathogens have been identified in L. obliqua, and among them the baculovirus Lonomia obliqua multiple nucleopolyhedrovirus (LoobMNPV). The complete genome of LoobMNPV was sequenced and shown to have 120,022 bp long with 134 putative open reading frames (ORFs). Phylogenetic analysis of the LoobMNPV genome showed that it belongs to Alphabaculovirus group I (lepidopteran-infective NPV). A total of 12 unique ORFs were identified with no homologs in other sequenced baculovirus genomes. One of these, the predicted protein encoded by loob035, showed significant identity to an eukaryotic transcription terminator factor (TTF2) from the Lepidoptera Danaus plexippus, suggesting an independent acquisition through horizontal gene transfer. Homologs of cathepsin and chitinase genes, which are involved in host integument liquefaction and viral spread, were not found in this genome. As L. obliqua presents a gregarious behavior during the larvae stage the impact of this deletion might be neglectable.

Investigation of ground- and excited-state photophysical properties of 5,10,15,20-tetra(4-pyridyl)-21H,23H-porphyrin with ruthenium outlying complexes.

The present work employs a set of complementary techniques to investigate the influence of outlying Ru(II) groups on the ground- and excited-state photophysical properties of free-base tetrapyridyl porphyrin (H(2)TPyP). Single pulse and pulse train Z-scan techniques used in association with laser flash photolysis, absorbance and fluorescence spectroscopy, and fluorescence decay measurements, allowed us to conclude that the presence of outlying Ru(II) groups causes significant changes on both electronic structure and vibrational properties of porphyrin. Such modifications take place mainly due to the activation of nonradiative decay channels responsible for the emission quenching, as well as by favoring some vibrational modes in the light absorption process. It is also observed that, differently from what happens when the Ru(II) is placed at the center of the macrocycle, the peripheral groups cause an increase of the intersystem crossing processes, probably due to the structural distortion of the ring that implies a worse spin-orbit coupling, responsible for the intersystem crossing mechanism.

Survival of patients with multiple primary malignancies: a study of 783 patients with gastrointestinal stromal tumor.

BACKGROUND: We sought to investigate the characteristics and survival rate of patients with gastrointestinal stromal tumor (GIST) associated with other primary malignancies. PATIENTS AND METHODS: A total of 783 patients with GIST were identified from 1995 to 2007. Additional primaries included tumors not considered metastasis, invasion, or recurrence of GIST, nor non-melanoma skin cancer. Data on gender, age at diagnosis, follow-up time after diagnosis, and death were collected. RESULTS: Of the 783 patients with GIST, 153(20%) were identified with at least one additional primary. Patients with additional primaries were more often men (M : F 1.5 versus 1.3) and older (66 versus 53 years). More patients had another cancer diagnosed before (134) than after (52) GIST. Primaries observed before GIST were cancers of the prostate (25), breast (12), esophagus (9), and kidney (7) and melanoma (6). Lung (5) and kidney (5) primaries were the most frequent after GIST. The 5-year survival was 68% for patients with primaries before GIST, 61% for patients with primaries after GIST, 58% for patients with GIST only, and 49% for patients with two or more primaries in addition to GIST (P = 0.002). CONCLUSIONS: Approximately 20% of patients with GIST develop other cancers. Inferior median 5-year survival was observed in patients with GIST with two or more other cancers. The etiology and clinical implications of other malignancies in patients with GIST should be investigated.

Reducing bleeding complications after thrombolytic therapy for stroke: clinical potential of metalloproteinase inhibitors and spin trap agents.

Thrombolysis with alteplase (recombinant tissue plasminogen activator; rtPA) has proven to be beneficial for acute stroke management, despite the narrow window of opportunity for treatment and the increased risk of haemorrhage. Because of the latter, recent studies have attempted to identify compounds that may be given concomitantly with alteplase to reduce the haemorrhage rate Matrix metalloproteinase (MMP) inhibitors have been proposed as potential combination therapy candidates because they prevent MMP-induced production of the cytokine tumour necrosis factor-alpha (TNFalpha), as well as membrane and vessel remodelling following ischaemia. Spin trap agents also have been put forward due to their free radical scavenging capabilities. In the rabbit large clot embolism model, alteplase effectively lysed blood clots, whether or not other drugs were used in combination. However, haemorrhage rate also was increased compared with that in control animals. The alteplase-induced haemorrhage rate was reduced significantly by administration of the MMP inhibitor batimastat (BB-94) or the spin trap agent alpha-phenyl-N-t-butylnitrone (PBN). Other rodent studies have also demonstrated that PBN is effective in decreasing the haemorrhage rate following alteplase administration. Overall, preclinical studies indicate that MMP inhibition or free radical scavenging in combination with alteplase may circumvent the high risk of haemorrhaging with alteplase.

Preclinical development of neurosteroids as neuroprotective agents for the treatment of neurodegenerative diseases.

Recent literature has emphasized the unique role that the neurosteroid subclass of steroids, which includes dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS), play in the developing and adult central nervous system (CNS). Both DHEA and DHEAS are found in abundance in the CNS (Majewska, 1995), and both can be synthesized and metabolized in the brain of many species (Baulieu, 1981, 1998; Corpéchot et al., 1981, 1983; Zwain and Yen, 1999). DHEA and DHEAS have been implicated as potential signaling molecules for neocortical organization during neuronal development, suggesting that they have trophic factor-like activity (neurotrophic or neurotropic) or can interact with various neurotransmitter systems to promote neuronal remodeling (Compagnone and Mellon, 1998; Mao and Barger, 1998). Consistent with a neurotrophic role for these steroids, studies have shown that DHEAS protects certain neuronal populations against neurotoxic insults inflicted by the excitatory amino acid glutamate (Kimonides et al., 1998; Mao and Barger, 1998). This finding suggests that DHEAS may be useful in treating neurodegenerative diseases in which excitotoxicity is believed to be the underlying cause or a major contributor to cell death. Moreover, because DHEA and DHEAS are multifunctional and exhibit a variety of properties in the CNS, including memory consolidation, neuroprotection, and reduction of neurodegeneration (Majewska, 1992, 1995; Lapchak et al., 2000), their potential therapeutic benefits may be extended to include the treatment of other neurodegenerative diseases not directly linked to excitotoxicity.

Neuroprotection by the selective cyclooxygenase-2 inhibitor SC-236 results in improvements in behavioral deficits induced by reversible spinal cord ischemia.

BACKGROUND AND PURPOSE: Cyclooxygenase-2 (COX-2), an enzyme that is induced in the central nervous system after various insults, has been localized to neurons and in cells associated with the cerebral vasculature, where it may be involved in the inflammatory component of the ischemic cascade. COX-2 is part of the initial reaction that involves the arachidonic acid cascade, which produces molecules that support an inflammatory response. The present study evaluated the pharmacological effects of a specific long-acting COX-2 inhibitor, SC-236, in a reversible rabbit spinal cord ischemia model using clinical rating scores (behavioral analysis) as the primary end point. METHODS: SC-236 was administered (10 to 100 mg/kg SC) 5 minutes after the start of occlusion to groups of rabbits exposed to ischemia induced by temporary (10 to 40 minutes) occlusion of the infrarenal aorta. Behavioral analysis, which allowed for the calculation of an ET(50) value representing the duration of ischemia (minutes) associated with a 50% probability of resultant permanent paraplegia, was conducted 18 and 48 hours later. A drug was determined to be neuroprotective if it prolonged the ET(50) significantly compared with the appropriate control group. RESULTS: Since SC-236 is not readily soluble in aqueous solutions, it was dissolved in 100% dimethyl sulfoxide (DMSO) for subcutaneous administration. Therefore, the vehicle-treated control group consisted of rabbits given an equal volume of DMSO without drug. In the DMSO-treated control group, the ET(50) assessed 18 hours after initiation of aortal occlusion was 18.84+/-3.19 minutes. In contrast, treatment with 100 mg/kg of SC-236 given 5 minutes after the start of occlusion prolonged the ET(50) of the group significantly to 30.04+/-3.55, an effect that was still evident 48 hours later. In addition, lower doses of the drug (10 and 50 mg/kg) also showed a trend for an increase in ET(50). SC-236 (100 mg/kg) did not significantly alter body temperature after a subcutaneous injection. CONCLUSIONS: The present study suggests that COX-2 plays an important role in the ischemic cascade of events that translate into ischemia-induced behavioral deficits and furthermore that selective COX-2 inhibitors may be useful in the treatment of ischemic stroke to improve behavioral functions.

Prosaptide exacerbates ischemia-induced behavioral deficits in vivo; an effect that does not involve mitogen-activated protein kinase activation.

Prosaposin is a 517 amino acid membrane component and secreted protein(5,7,9) that is proteolytically cleaved to generate the four small glycoproteins; saposins A, B, C and D.(9,13,19) Prosaposin's ability to promote neurite outgrowth(31) and to protect neurons from programmed cell death(28) in vitro, as well as to rescue neurons from ischemia and other damage in vivo(11,12,15,25) implied that prosaposin was neurotrophic/neuroprotectant.(1,7,24,31) The neurotrophic sequence of prosaposin was isolated to smaller peptide fragments termed prosaptides(15,31) within the amino terminal portion of saposin C.(1,6,8,10,17,20,21,28) The proposed use of synthetic prosaptides as peripherally administered neuroprotective and/or neurotrophic therapeutic agents has stemmed from their ability to cross the blood-brain barrier,(27) as well as their reported neurotrophic activity in vitro.(15,23,31) Few studies, however, have attempted to characterize these peptides, presumably due to their reported instability following peripheral administration.(27) With the recent design of a stable 11-mer retro-inverso prosaptide,(15,31) it has become feasible to investigate the pharmacological effects of a stable version of these peptides in the validated rabbit spinal cord ischemia model that has been used extensively in the development of therapeutics to treat ischemic stroke.(4,14,16,18) Our results show not only that prosaptide was not neurotrophic/neuroprotectant in vivo, but rather it worsened ischemia-induced behavioral deficits.

Deficits in striatal dopamine D(2) receptors and energy metabolism detected by in vivo microPET imaging in a rat model of Huntington's disease.

Functional imaging by repeated noninvasive scans of specific (18)F tracer distribution using a high-resolution small-animal PET scanner, the microPET, assessed the time course of alterations in energy utilization and dopamine receptors in rats with unilateral striatal quinolinic acid lesions. Energy utilization ipsilateral to the lesion, determined using scans of 2-deoxy-2-[(18)F]fluoro-d-glucose uptake, was compromised severely 1 week after intrastriatal excitotoxin injections. When the same rats were imaged 5 and 7 weeks postlesion, decrements in energy metabolism were even more prominent. In contrast, lesion-induced effects on dopamine D(2) receptor binding were more progressive, with an initial upregulation of [3-(2'-(18)F]fluoroethyl)spiperone binding apparent 1 week postlesion followed by a decline 5 and 7 weeks thereafter. Additional experiments revealed that marked upregulation of dopamine D(2) receptors consequent to quinolinic acid injections could be detected as early as 3 days after the initial insult. Postmortem markers of striatal GABAergic neurons were assessed in the same rats 7 weeks after the lesion: expression of glutamic acid decarboxylase and dopamine D(1) receptor mRNA, as well as [(3)H]SCH-23,390 and [(3)H]spiperone binding to dopamine D(1) and D(2) receptors, respectively, detected prominent decrements consequent to the lesion. In contrast, by 7 weeks postlesion [(3)H]WIN-35,428 binding to dopamine transport sites within the striatum appeared to be enhanced proximal to the quinolinic acid injection sites. The results demonstrate that functional imaging using the microPET is a useful technique to explore not only the progressive neurodegeneration that occurs in response to excitotoxic insults, but also to examine more closely the intricacies of neurotransmitter activity in a small animal model of HD.

Relationship of mercury with aluminum, iron and manganese oxy-hydroxides in sediments from the Alto Pantanal, Brazil.

Sediments from nine floodplain lakes in Pantanal were analyzed for a large-scale (300 km) survey of mercury (Hg) load in sediments and soils of the Alto Pantanal and to study the relationship between Hg and reactive aluminum, iron, and manganese oxy-hydroxides. The results were compared with the Hg content in river and stream sediments from the Poconé gold mining area, where Hg has been extensively used and still is in use. The results indicate that the Hg concentrations were elevated in river sediment close to the mining area in Bento Gomes river basin (average in the < 74-microm fraction 88.9 ng Hg g(-1) dry wt.; interquartile range 50.3-119.5), but there was no clear indication that the local Hg emissions have contaminated the remote floodplain lakes, where concentrations were surprisingly low (average in the < 74-microm fraction 33.2 ng Hg g(-1) dry wt. sediment; interquartile range 18.4-46.8), in particular when considering geochemical characteristics of the sediment. The sediment from the floodplain lakes contained less Hg-tot and more reactive iron oxy-hydroxides than soils from the Tapajós area in the Amazon basin. This resulted in a mass ratio between Hg and amorphous oxy-hydroxides of only 5 x 10(-6) for Hg-tot/Fe-oxa (interquartile range 3-7 x 10(-6).

In vivo imaging of neuronal activation and plasticity in the rat brain by high resolution positron emission tomography (microPET).

The study of neural repair and neuroplasticity in rodents would be enhanced by the ability to assess neuronal function in vivo. Positron emission tomography (PET) is used to study brain plasticity in humans, but the limited resolution and sensitivity of conventional scanners have generally precluded the use of PET to study neuroplasticity in rodents. We now demonstrate that microPET, a PET scanner developed for use with small animals, can be used to assess metabolic activity in different regions of the conscious rodent brain using [18F]fluorodeoxyglucose (FDG) as the tracer, and to monitor changes in neuronal activity. Limbic seizures result in dramatically elevated metabolic activity in the hippocampus, whereas vibrissal stimulation results in more modest increases in FDG uptake in the contralateral neocortex. We also show that microPET can be used to study lesion-induced plasticity of the brain. Cerebral hemidecortication resulted in diminished relative glucose metabolism in the neostriatum and thalamus ipsilateral to the lesion, with subsequent, significant recovery of metabolic function. These studies demonstrate that microPET can be used for serial assessment of metabolic function of individual, awake rats with a minimal degree of invasiveness, and therefore, has the potential for use in the study of brain disorders and repair.

Topographical distribution of [125I]-glial cell line-derived neurotrophic factor in unlesioned and MPTP-lesioned rhesus monkey brain following a bolus intraventricular injection.

The present study determined the topographical distribution profile for [125I]-glial cell line-derived neurotrophic factor in unlesioned and MPTP-lesioned (unilateral intracarotid injection) rhesus monkeys following an intraventricular injection. Autoradiographic analysis showed that following a bolus intraventricular injection, there was widespread distribution of [125I]-glial cell line-derived neurotrophic factor throughout the ventricular system (walls of lateral, third, and fourth ventricles and aqueduct), with some accumulation at the lateral ventricle injection site, possibly associated with the ependymal cell layer. In both unlesioned and MPTP-lesioned monkeys, there was labelling of the cerebral cortex, substantia nigra/ventral tegmental area and sequestration of [125I]-glial cell line-derived neurotrophic factor adjacent to the hippocampal formation, globus pallidus, ventral to and in the substantia nigra. However, [125I]-glial cell line-derived neurotrophic factor did not appear to diffuse readily or accumulate in the caudate-putamen even though there was some penetration away from the ventricular walls. Throughout the brain, there was also substantial non-parenchymal labelling of [125I]-glial cell line-derived neurotrophic factor, possibly associated with extracellular matrix components, meninges and vasculature due to the heparin binding properties of glial cell line-derived neurotrophic factor. In addition to the extensive loss of tyrosine hydroxylase immunoreactivity within the substantia nigra, there was also decreased accumulation of [125I]-glial cell line-derived neurotrophic factor and reduced glial cell line-derived neurotrophic factor immunoreactivity ipsilateral to the lesion. Microscopic analysis showed that glial cell line-derived neurotrophic factor immunoreactivity was associated with upper cortical layers including a high density of immunoreactivity at the surface of the cortex (meningeal, pial layer, vasculature) and around the ventricular walls (with some cellular labelling and labelling of vasculature). Moderate staining was observed in nigral cells contralateral to the MPTP-lesion, whereas only minimal levels of that glial cell line-derived neurotrophic factor immunoreactivity were detected ipsilateral to the lesion. This study shows that intraventricularly injected glial cell line-derived neurotrophic factor accumulates not only around the ventricular walls, but also in specific brain regions in which sub-populations of cells are more readily accessible than others. The presence of cells labelled with [125I] and immunopositive for glial cell line-derived neurotrophic factor in the substantia nigra indicates that these cells are a target for the trophic factor following intraventricular administration. Thus, the behavioral improvement observed in MPTP-lesioned monkeys following an intraventricular injection of glial cell line-derived neurotrophic factor is likely the result of activation of nigral cells.

Glial cell line-derived neurotrophic factor attenuates the locomotor hypofunction and striatonigral neurochemical deficits induced by chronic systemic administration of the mitochondrial toxin 3-nitropropionic acid.

The present study investigated whether glial cell line-derived neurotrophic factor prevents the progressive striatal degeneration induced by chronic systemic administration of the mitochondrial toxin, 3-nitropropionic acid. In addition, the effects of delayed treatment with glial cell line-derived neurotrophic factor on toxin-induced behavioural and neurochemical deficits were determined. Locomotor activity in rats infused with 3-nitropropionic acid (15 mg/kg/day, for four weeks) via subcutaneous osmotic minipumps was considerably reduced compared to control rats. However, in rats given a single intracerebroventricular injection of 100 micrograms of glial cell line-derived neurotrophic factor, locomotor activity was significantly higher than in rats injected with the vehicle, an effect that was most pronounced at the onset of toxin infusion. Consistent with a protective or restorative effect in this model of striatal neurodegeneration, toxin-induced deficits in markers of neurotransmitter function were attenuated by glial cell line-derived neurotrophic factor. Thus, [3H]GABA uptake and [3H]tiagabine/GABA uptake sites in striatal target tissues (globus pallidus and substantia nigra), as well as [3H]choline uptake, choline acetyltransferase activity and dopamine receptor binding in the striatum were decreased by the toxin and restored to varying degrees by glial cell line-derived neurotrophic factor administration. As with locomotor abnormalities, effects on neurochemical deficits were most prominent when glial cell line-derived neurotrophic factor was given at the start of toxin infusion, but remained significantly higher than in the vehicle-injected rats when given up to two weeks after. Substance P, dynorphin A and [Met]enkephalin levels in the striatal target tissues also were reduced by 3-nitropropionic acid. The results show that glial cell line-derived neurotrophic factor protects striatal neurons from slow excitotoxic cell death resulting from energy deprivation, secondary to mitochondrial dysfunction. Moreover, they suggest that glial cell line-derived neurotrophic factor may be a viable therapeutic agent for slowly progressive central nervous system disorders, like Huntington's disease, that may be caused by secondary excitotoxicity resulting from abnormal energy utilization.

Glial cell line-derived neurotrophic factor attenuates the excitotoxin-induced behavioral and neurochemical deficits in a rodent model of Huntington's disease.

The present study determined the effects of intraventricularly administered glial cell line-derived neurotrophic factor on the behavioral and neurochemical sequelae of unilateral excitotoxic lesions of the striatum. Distinct asymmetrical rotational behavior in response to peripheral administration of amphetamine (5 mg/kg) was noted one and two weeks following injections of quinolinic acid (200 nmol) into two sites in the left striatum. In rats given a single intraventricular injection of glial cell line-derived neurotrophic factor (10-1000 micrograms) 30 min before the toxin, amphetamine-induced rotational behavior was significantly attenuated. Analysis of Nissl-stained coronal sections showed marked neuronal loss in the striatum ipsilateral to the quinolinic acid injections, which was at least partially prevented by glial cell line-derived neurotrophic factor D1 and D2 dopamine binding sites in the striatum, the majority of which are localized to subpopulations of GABAergic neurons, were decreased to a similar extent by quinolinic acid. Moreover, the reduction was attenuated by glial cell line-derived neurotrophic factor treatment to a similar degree, suggesting that the two subpopulations of GABAergic striatal output neurons are equally vulnerable to excitotoxic damage. Concomitant changes in neurotransmitter function as a result of the lesion were also observed: [3H]GABA uptake into striatal target tissues (globus pallidus and substantia nigra) was considerably reduced in the lesioned compared to the contralateral unlesioned tissues, as were [3H]choline and [3H]dopamine uptake into striatal synaptosomes. Similarly, striatal choline acetyltransferase activity was decreased by the lesion. Decrements in neuropeptide levels of similar magnitude were evident ipsilateral to the lesion; substance P, met-enkephalin and dynorphin A contents in the globus pallidus and substantia nigra were significantly reduced. Striatal somatostatin and neuropeptide Y levels were not altered. All of the neurochemical deficits induced by striatal quinolinic acid lesions were attenuated by intraventricular delivery of glial cell line-derived neurotrophic factor. Continuous intraventricular infusion of this trophic factor (10 micrograms/day) over a two-week period did not afford notable improvement compared to the single injection of 10 micrograms. In contrast, continuous infusion of brain-derived neurotrophic factor (10 micrograms/day) directly into the striatum did not affect any of the neurochemical parameters studied. However, neurotrophin-3 (10 micrograms/day) delivery into the striatum significantly increased [3H]GABA uptake, but only modestly affected [3H]choline uptake. The results indicate that glial cell line-derived neurotrophic factor counteracts neuronal damage induced by a striatal excitotoxic insult and support its potential use as a treatment for central nervous system disorders that may be a consequence of excitotoxic processes, such as Huntington's disease.

ret receptor tyrosine kinase immunoreactivity is altered in glial cell line-derived neurotrophic factor-responsive neurons following lesions of the nigrostriatal and septohippocampal pathways.

Glial cell line-derived neurotrophic factor was initially identified as a survival factor for developing midbrain dopamine neurons (for reviews, see Refs 17 and 19). Subsequent studies have demonstrated a more wide-spread role for glial cell line-derived neurotrophic factor in the developing and adult CNS. In the adult rat brain, for instance, prior administration of glial cell line-derived neurotrophic factor protects nigrostriatal dopamine neurons from 6-hydroxydopamine-induced damage. When given several weeks after 6-hydroxydopamine injection, glial cell line-derived neurotrophic factor also restores the function of these neurons. Glial cell line-derived neurotrophic factor attenuates excitotoxin-induced cell death in the striatum and hippocampal formation and protective effects of glial cell line-derived neurotrophic factor following axotomy have been reported for spinal motor neurons and basal forebrain cholinergic neurons. These findings suggest that glial cell line-derived neurotrophic factor may be a protective/restorative agent for a diverse population of neurons and imply that it may be a useful therapeutic tool for a variety of neurodegenerative diseases including Parkinson's, Huntington's and Alzheimer's diseases. The potential receptor mediating the pleiotropic effects of glial cell line-derived neurotrophic factor has been characterized only recently as a novel glycosyl-phosphatidylinositol-linked protein, GDNFR-alpha. Because GDNFR-alpha is a cell surface receptor, an additional protein(s) was thought to be involved in the glial cell line-derived neurotrophic factor signalling cascade. The identity of the likely candidate, ret, was inferred initially from indirect evidence. Not only were there remarkable similarities in the distribution of glial cell line-derived neurotrophic factor and the proto-oncogene ret in the developing rat and mouse brain, but also in the phenotype of glial cell line-derived neurotrophic factor knockout mice and mice with ret mutations. Mice with either mutation exhibited pronounced renal and enteric abnormalities, implicating the receptor tyrosine kinase protein product of the ret proto-oncogene as the glial cell line-derived neurotrophic factor signalling protein. More conclusive evidence showing that activation of GDNFR-alpha by glial cell line-derived neurotrophic factor induces phosphorylation of ret has confirmed ret as a signalling protein for glial cell line-derived neurotrophic factor. Preliminary results showing that 6-hydroxydopamine lesions of the substantia nigra markedly reduced ret messenger RNA expression, established its localization to presumably glial cell line-derived neurotrophic factor-responsive dopamine neurons in the nigrostriatal pathway. In contrast, it is not clear whether other glial cell line-derived neurotrophic factor-responsive neurons in the CNS, such as the basal forebrain cholinergic neurons and striatal neurons, also express ret, nor is it evident whether levels of the protein are regulated by disruption of the respective pathways. The present study shows that dense networks of ret immunoreactivity are distributed throughout the nigrostriatal pathway, with lower densities of staining in other brain regions, including the septohippocampal pathway. Following extensive unilateral 6-hydroxydopamine lesions of the medial forebrain bundle, ret immunoreactivity in the substantia nigra and striatum was reduced significantly, to a similar extent as tyrosine hydroxylase immunoreactivity. In contrast, excitotoxic lesions of the striatum, achieved by intrastriatal quinolinic acid injections, resulted in increased ret staining in this brain region. In addition, marked decrements in septal ret immunoreactivity were consequent to complete transections of the fimbria-fornix.