Search

This work was funded in part by PROPESP-UFPA. Federal University of Par?. Jo?o de Barros Barreto University Hospital. Laboratory of Experimental Neuropathology. Bel?m, PA, Brazil. Federal University of Par?. Jo?o de Barros Barreto University Hospital. Laboratory of Experimental Neuropathology. Bel?m, PA, Brazil. Federal University of Par?. Institute Biological Science. Laboratory of Pharmacology and Toxicology of Natural Products. Bel?m, PA, Brazil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Federal University of Par?. Jo?o de Barros Barreto University Hospital. Laboratory of Experimental Neuropathology. Bel?m, PA, Brazil. Federal University of Par?. Jo?o de Barros Barreto University Hospital. Laboratory of Experimental Neuropathology. Bel?m, PA, Brazil. Federal University of Par?. Institute Biological Science. Laboratory of Pharmacology and Toxicology of Natural Products. Bel?m, PA, Brazil. Federal University of Par?. Jo?o de Barros Barreto University Hospital. Laboratory of Experimental Neuropathology. Bel?m, PA, Brazil. The present study describes the electroencephalographic changes that occur during cerebral ischemia and reperfusion in animals submitted to transient focal cerebral ischemia by middle cerebral artery occlusion (MCAO) for 30 min. For this, male Wistar rats were divided into two groups (n = 6 animals/group): (1) sham (control) group, and (2) ischemic/reperfusion group. The quantitative electroencephalography (qEEG) was recorded during the ischemic and immediate reperfusion (acute) phases, and then once a day for 7 days after the MCAO (subacute phase). The acute phase was characterized by a marked increase in the relative delta wave band power (p < 0.001), with a smaller, but significant increase in the relative alpha wave bandpower in the ischemic stroke phase, in comparison with the control group (p = 0.0054). In the immediate reperfusion phase, however, there was an increase in the theta, alpha, and beta waves bandpower (p < 0.001), but no alteration in the delta waves (p = 0.9984), in comparison with the control group. We also observed high values in the delta/theta ratio (DTR), the delta/alpha ratio (DAR), and the (delta+theta)/(alpha+beta) ratio (DTABR) indices during the ischemia (p < 0.05), with a major reduction in the reperfusion phase. In the subacute phase, the activity of all the waves was lower than that of the control group (p < 0.05), although the DTR, DAR, and DTABR indices remained relatively high. In conclusion, early and accurate identification of decreased delta wave bandpower, DTR, DAR, and DTABR indices, and an increase in the activity of other waves in the immediate reperfusion phase may represent an important advance for the recognition of the effectiveness of reperfusion therapy.

Acetaminophen is a widely used over-the-counter analgesic and antipyretic drug, but in large doses can produce hepatic and/or renal injury. Based on its human toxicity by N-acetyl-p- benzoquinone imine formation as reactive toxic intermediate, an acetaminophen regioisomer substituted on 5-position, named chloraminophen, was proposed. The electron and hydrogen transfers were related to the ionization potential and bond dissociation energies on phenol and acetamide moieties. These calculations were performed by using quantum chemical calculations at the density functional theory (DFT/B3LYP) with the 6-311 + + G(d,p) basis set. For acute toxicity study was performed using a single dose test of 300 or 2000 mg/kg. No differences were found in the biochemical parameters except for aspartate aminotransferase levels, probably due to corn oil used as dilution solvent. The second energy of hydrogen abstraction may have great impact on amino-phenols toxicity. The regioisomerism can be a useful strategy in drug design for safer acetaminophen derivatives.

Chronic low back pain (CLBP) is associated with postural control impairments and is highly prevalent in elderly people. The objective of this study is to verify whether anticipatory postural adjustments (APAs) and compensatory postural adjustments (CPAs) are affected by CLBP in elderly people by assessing their postural control during a self-initiated perturbation paradigm induced by rapid upper arm movement when pointing to a target. The participants’ lower limb muscle onset and center of pressure (COP) displacements were assessed prior to perturbation and throughout the entire movement. T0 moment (i.e., the beginning of the movement) was defined as the anterior deltoid (DEL) onset, and all parameters were calculated with respect to it. The rectus femoris (RT), semitendinosus (ST), and soleous (SOL) showed delayed onset in the CLBP group compared with the control group: RF (control: − 0.094 ± 0.017 s; CLBP: − 0.026 ± 0.012 s, t = 12, p APA [control: 0.444 cm (0.187; 0.648); CLBP: 0.228 cm (0.096; 0.310), U = 53, p = 0.012]. The CLBP group required a longer time to reach the maximum displacement after the perturbation (control: 0.211 ± 0.047 s; CLBP 0.296 ± 0.078 s, t = 3.582, p = 0.0013). This indicates that CLBP elderly patients have impairments to recover their postural control and less efficient anticipatory adjustments. Our results suggest that people with CLBP have altered feedforward hip and ankle muscle control, as shown from the SOL, ST, and RT muscle onset. This study is the first study in the field of aging that investigates the postural adjustments of an elderly population with CLBP. Clinical assessment of this population should consider postural stability as part of a rehabilitation program.

Federal University of Par?. Institute of Exact and Natural Sciences. Bel?m, PA, Brazil. Federal University of Par?. Institute of Exact and Natural Sciences. Bel?m, PA, Brazil. Federal University of Par?. Institute of Biological Sciences. Bel?m, PA, Brazil. Federal University of Par?. Institute of Biological Sciences. Bel?m, PA, Brazil. Federal University of Par?. Institute of Biological Sciences. Bel?m, PA, Brazil. Federal University of Par?. Institute of Biological Sciences. Bel?m, PA, Brazil. Federal University of Par?. Institute of Biological Sciences. Bel?m, PA, Brazil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Federal University of Par?. Institute of Biological Sciences. Bel?m, PA, Brazil. Federal University of Par?. Institute of Exact and Natural Sciences. Bel?m, PA, Brazil. Universit? de Limoges. Centre Europ?en de la C?ramique. Laboratoire IRCER. Limoges, France Universit? de Limoges. Centre Europ?en de la C?ramique. Laboratoire IRCER. Limoges, France Universit? de Limoges. Centre Europ?en de la C?ramique. Laboratoire IRCER. Limoges, France Federal University of Par?. Institute of Biological Sciences. Bel?m, PA, Brazil. Federal University of Par?. Institute of Exact and Natural Sciences. Bel?m, PA, Brazil. Indomethacin (INDO) demonstrates therapeutic efficacy in the treatment of neuroinflammatory diseases. Despite its importance as a drug, INDO causes gastrointestinal problems and adverse reactions in the central nervous system (CNS). In this study, we prepared nanoparticles of layered double hydroxide (LDH) loaded with INDO. The structure of the nanohybrid (LDH-INDO) was synthesized via a coprecipitation method, and the nanohybrid was characterized using X-ray powder diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy, thermogravimetric analysis?differential scanning colorimetry (TGA?DSC), field-emission scanning electron microscopy (FE-SEM), and ultraviolet (UV)?vis spectroscopy. Moreover, the drug release profiles of the nanohybrid were investigated using kinetic models. INDO was incorporated within the LDH interlayer space with 50% intercalation. The release of INDO anions from LDH-INDO after 10?h was 90% at pH 4.8???0.02 and 51% at pH 7.4???0.02. The results show that the release profiles follow a pseudo-second-order model. In addition, lipopolysaccharide (LPS)-induced sickness behavior in animals and treatment with INDO and LDH-INDO suggest recovery of the variables (weight and food intake) used in this study. LDH-INDO did not alter hepatic and renal biomarkers. Moreover, LPS increased the number of Iba1+ cells (microgliosis) and caused morphological alterations in these cells in the hippocampus and somatosensory cortex. However, the LPS effect was attenuated after treatment with INDO, both free and LDH-intercalated, in both regions of the brain.

Background: Recent studies suggest that glycemic variability could influence the risk of complications in type 1 diabetes mellitus (T1DM). There are no data about the action of vitamin D (VD) on glycemic variability. Our pilot study aims to evaluate glycemic variability and insulin needs in patients with T1DM supplemented with VD. Methods: 22 patients received doses of 4000 and 10000 IU/day of cholecalciferol for 12 weeks, according to the patient’s baseline VD levels and underwent continuous glucose monitoring system. Results: Correlations were found between percentage variation (∆) of glycemia standard deviation (∆SDG), calculated using continuous glucose monitoring, with ∆ of basal (r= 0.6; p

The goals of this study were to describe the morphology, neurotransmitter content and synaptic connections of neurons in primate retinas that contain the neuropeptide secretoneurin. Amacrine cells were labeled with antibodies to secretoneurin in macaque and baboon retinas. Their processes formed three distinct plexuses in the inner plexiform layer: one in the outermost stratum, one in the center and one in the innermost stratum. In light microscopic double immunolabeling experiments, GABA was colocalized with secretoneurin in these cells, but glycine transporter 1 and Substance P were not. ON bipolar cell axon terminals labeled with antibody to the cholecystokinin precursor, G6-gly, have ON responses to stimulation of short wavelength sensitive (S) cones. Axons of these bipolar cells made contacts with amacrine cell dendrites containing secretoneurin. Secretoneurin-IR amacrine cells also made contacts with retinal ganglion cell dendrites labeled with antibody to the photopigment melanopsin, which have OFF responses to stimulation of S cones. Using electron microscopic immunolabeling, 436 synapses from macaque retina were analyzed. Axons from bipolar cells were identified by their characteristic synaptic ribbons; their synaptic densities were asymmetric like those of excitatory synapses in the brain. Amacrine cells made and received conventional synapses with symmetric synaptic densities, like those of inhibitory synapses in the brain. Ganglion cell dendrites were identified by their absence of presynaptic specializations; they received inputs from both amacrine cells and bipolar cells. The majority of inputs to the secretoneurin-IR amacrine cells were from other amacrine cells, but they also received 21% of their input from bipolar cells. They directed most of their output, 54%, to amacrine cells, but there were many synapses onto bipolar cell axons and ganglion cell dendrites, as well. The synaptic connections were very similar in the three plexuses with one notable exception; output synapses to bipolar cells were significantly less common in the innermost one, where the S-ON bipolar cells terminate. Taken together, these findings suggest that the secretoneurin-IR amacrine cells in primates receive excitatory input from S-ON bipolar cells and, in turn, inhibit intrinsically photosensitive retinal ganglion cells.

Mutações no gene GBA têm sido reportadas em pacientes com doença de Parkinson (DP) em diferentes países, incluindo o Brasil. Com o objetivo de confirmar esse padrão em uma amostra de pacientes com DP provenientes do Norte brasileiro, foi conduzindo esse estudo caso-controle investigando a frequência das duas mutações mais comuns do gene GBA (c.1226A>G; p.N370S e c.1448T>C; p.L444P) em um grupo de 81 pacientes com DP e 81 controles, usando PCR-RFLP e confirmado pelo sequenciamento direto de produtos de PCR. No grupo experimental, três pacientes (3,7%) foram heterozigotos para a mutação c.1226A>G; p.N370S e três (3,7%), para a mutação c.1448T>C; p.L444P Nenhuma das duas mutações foi detectada no grupo controle (p =0,0284). Pacientes com a mutação c.1448T>C; p.L444P demonstraram uma tendência a apresentar os sintomas mais precocemente, porém um número amostrai maior é necessário para confirmar essa observação. Nossos resultados sugerem uma associação entre essas duas mutações no gene GBA e o desenvolvimento de DP na população de pacientes do norte Brasileiro. Mutations of the GBA gene have been reported in patients with Parkinson's disease (PD) from a number of different countries, including Brazil. In order to confirm this pattern in a sample of PD patients from northern Brazil, we conducted a case-control study of the occurrence of the two most common mutations of the GBA gene (c.1226A>G; p.N370S and c.1448T>C; p.L444P) in a group of 81 PD patients and 81 control individuals, using PCR-RFLP, confirmed by the direct sequencing of the PCR products. In the patient group, three patients (3.7%) were heterozygous for the GBA c.1226A>G; p.N370S mutation, and three (3.7%) for GBA c.1448T>C; p.L444P Neither mutation was detected in the control group (p =0.0284). Patients with the c.1448T>C; p.L444P mutation showed a tendency to have an earlier disease onset, but a larger sample number is required to confirm this observation. Our results suggest an association between the GBA c.1226A>G; p.N370S and c.1448T>C; p.L444P mutations and the development of PD in the population of patients from the Northern Brazil. CAVALCANTE, Fernando Otávio Quaresma. Universidade Federal do Pará, Hospital Universitário João de Barros Barreto (HUJBB)

The pathogenesis of diabetic cardiomyopathy (DCM) is partially understood and is likely to be multifactorial, involving metabolic disturbances, hypertension and cardiovascular autonomic neuropathy (CAN). Therefore, an important need remains to further delineate the basic mechanisms of diabetic cardiomyopathy and to apply them to daily clinical practice. We attempt to detail some of these underlying mechanisms, focusing in the clinical features and management. The novelty of this review is the role of CAN and reduction of blood pressure descent during sleep in the development of DCM. Evidence has suggested that CAN might precede left ventricular hypertrophy and diastolic dysfunction in normotensive patients with type 2 diabetes, serving as an early marker for the evaluation of preclinical cardiac abnormalities. Additionally, a prospective study demonstrated that an elevation of nocturnal systolic blood pressure and a loss of nocturnal blood pressure fall might precede the onset of abnormal albuminuria and cardiovascular events in hypertensive normoalbuminuric patients with type 2 diabetes. Therefore, existing microalbuminuria could imply the presence of myocardium abnormalities. Considering that DCM could be asymptomatic for a long period and progress to irreversible cardiac damage, early recognition and treatment of the preclinical cardiac abnormalities are essential to avoid severe cardiovascular outcomes. In this sense, we recommend that all type 2 diabetic patients, especially those with microalbuminuria, should be regularly submitted to CAN tests, Ambulatory Blood Pressure Monitoring and echocardiography, and treated for any abnormalities in these tests in the attempt of reducing cardiovascular morbidity and mortality.

The molecular mechanisms behind aneurysmal subarachnoid haemorrhage (aSAH) are still poorly understood. Expression patterns of miRNAs may help elucidate the post-transcriptional gene expression in aSAH. Here, we evaluate the global miRNAs expression profile (miRnome) of patients with aSAH to identify potential biomarkers. We collected 33 peripheral blood samples (27 patients with cerebral aneurysm, collected 7 to 10 days after the haemorrhage, when usually is the cerebral vasospasm risk peak, and six controls). Then, were performed small RNA sequencing using an Illumina Next Generation Sequencing (NGS) platform. Differential expression analysis identified eight differentially expressed miRNAs. Among them, three were identified being up-regulated, and five down-regulated. miR-486-5p was the most abundant expressed and is associated with poor neurological admission status. In silico miRNA gene target prediction showed 148 genes associated with at least two differentially expressed miRNAs. Among these, THBS1 and VEGFA, known to be related to thrombospondin and vascular endothelial growth factor. Moreover, MYC gene was found to be regulated by four miRNAs, suggesting an important role in aneurysmal subarachnoid haemorrhage. Additionally, 15 novel miRNAs were predicted being expressed only in aSAH, suggesting possible involvement in aneurysm pathogenesis. These findings may help the identification of novel biomarkers of clinical interest.

Swietenia macrophylla (mahogany) is a highly valued timber species, whereas the leaves are considered to be waste product. A total of 27 phenolic compounds were identified in aqueous extracts from mahogany leaves by comparing retention times and mass spectra data with those of authentic standards using LC-ESI-MS/MS. Polyphenols play an important role in plants as defense mechanisms against pests and pathogens and have potent antioxidant properties. In terms of health applications, interest has increased considerably in naturally occurring antioxidant sources, since they can retard the progress of many important neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. The antioxidant capacities of two aqueous extracts, M1 (decoction) and M2 (infusion), were measured using TEAC and Folin-Ciocalteau methods. Additionally, M1 was used in order to investigate its potential cytoprotective effects on an in vitro model of neurodegeneration, by using primary cerebellar cultures exposed to methyl mercury (MeHg). Under experimental sub-chronic conditions (72 h), concomitant exposure of the same cultures to MeHg and M1 extract resulted in a statistically significant increase in cell viability in all three concentrations tested (10, 50 and 100 μg/mL), strongly suggesting that due to its high content of antioxidant compounds, the M1 extract provides significant cytoprotection against the MeHg-induced in vitro neurotoxicity.

International audience; Both genetic and environmental factors likely contribute to the neuropathology of tauopathies, but it remains unclear how specific genetic backgrounds affect the susceptibility towards environmental toxins. Mutations in the tau gene have been associated with familial tauopathies, while annonacin, a plant-derived mitochondrial inhibitor, has been implicated in an environmental form of tauopathy. We therefore determined whether there was a pathogenic synergy between annonacin exposure and the expression of the R406W-tau mutation in transgenic mice. We found that annonacin exposure caused an increase in the number of neurons with phosphorylated tau in the somatodendritic compartment in several brain areas in R406W(+/+) mice as opposed to mice that had only the endogenous mouse tau (R406W(-/-)). Western blot analysis demonstrated a concomitant increase in total tau protein without increase in tau mRNA, but reduced proteasomal proteolytic activity in R406W(+/+), but not R406W(-/-) mice, upon annonacin-treatment. Phosphorylated tau levels exceeded the increase in total tau protein, along with increased levels of different tau kinases, foremost a striking increase in the p25/p35 ratio, known to activate the tau kinase Cdk5. In summary, we observed a synergistic interaction between annonacin exposure and the presence of the R406W-tau mutation, which resulted in reduced degradation, increased phosphorylation and redistribution of neuronal tau.

Context: Genetic and environmental factors are involved in the pathogenesis of type 1 diabetes mellitus (T1DM), and vitamin D deficiency appears as a candidate to risk factor for developing diabetic kidney disease (DKD). Objective: The purpose of study was to evaluate the existence of an association between low levels of vitamin D and the presence and degree of DKD in T1DM. Patients and methods: We performed a cross-sectional study, between November 2014 and December 2015. Levels of 25(OH)D and albuminuria were analyzed in 37 patients with T1DM and normal glomerular filtration rate. Thirty- six subjects were evaluated as a control group. Results: Patients with T1DM and hypovitaminosis D had higher levels of albuminuria compared to those with normal vitamin D levels (albuminuria (log10) = 1.92 vs 1.44; p

The aneurysmal subarachnoid hemorrhage is a major public health problem described as a sudden drastic event with no warning symptoms and high morbidity and mortality rates. The role of the endothelial isoform of nitric oxide synthase gene polymorphism in intracranial aneurysms (IAs) is still a matter of controversy with divergent findings among European, American, and Asian populations. Our study purposed to test the association between intracranial aneurysms formation and nitric oxide gene polymorphisms through a systematic review and meta-analysis. Systematic search on Medline, Lilacs, and EMBASE was performed. The primary search resulted in 139 papers, out of which 9 met our inclusion criteria after a full text analysis. The dominant T786C model found a significant association with IA (OR 1.22, 95 % CI 1.04-1.44, p = 0.01), so did studies of the recessive T786C model (OR 0.37, 95 % CI 0.30-0.45, p

Background Type 1 Diabetes Mellitus (Type 1 DM) affects the psychological and emotional well-being of patients and their families. This study aims to evaluate the health- related quality of life (HRQoL) of people with Type 1 DM in Brazil, a country of continental proportions, using the EuroQol questionnaires. Methods This was a retrospective, cross-sectional, multicenter study performed by the Brazilian Type 1 Diabetes Study Group, by analyzing EuroQol scores from 3,005 participants with Type 1 DM, in 28 public clinics in Brazil. Data on demography, economical status, chronic complications, glycemic control and lipid profile were also collected. Results The assessment of HRQoL by the EuroQol showed that the average score assigned to general health in Brazil is markedly lower than those found in two other Type 1 DM population-based studies conducted in Europe (EQ–VAS from the Netherlands, the United Kingdom and Brazil were 80.8 ± 15.2, 75.1 ± 18.4 and 72.5 ± 22, respectively). Additionally, our data suggest that a better glycemic control could positively impact the HRQoL of people with Type 1 DM, implying that each 1 % reduction in glycated haemoglobin might lead to an increase of 1.5 points in general health status assessed by the EuroQol. Conclusions This is a population-based study evaluating the HRQoL of people with Type 1 DM in Brazil. Our data indicate a worse quality of health of people with Type 1 DM in Brazil in comparison to Europe, and suggest that a better glycemic control could positively impact the HRQoL of these individuals. However, this study points to the existence of additional factors not yet evaluated that could be determinant in the HRQoL of these people.

A neurodegenerative tauopathy endemic to the Caribbean island of Guadeloupe has been associated with the consumption of anonaceous plants that contain acetogenins, potent lipophilic inhibitors of complex I of the mitochondrial respiratory chain. To test the hypothesis that annonacin, a prototypical acetogenin, contributes to the etiology of the disease, we investigated whether annonacin affects the cellular distribution of the protein tau. In primary cultures of rat striatal neurons treated for 48 h with annonacin, there was a concentration-dependent decrease in ATP levels, a redistribution of tau from the axons to the cell body, and cell death. Annonacin induced the retrograde transport of mitochondria, some of which had tau attached to their outer membrane. Taxol, a drug that displaces tau from microtubules, prevented the somatic redistribution of both mitochondria and tau but not cell death. Antioxidants, which scavenged the reactive oxygen species produced by complex I inhibition, did not affect either the redistribution of tau or cell death. Both were prevented, however, by forced expression of the NDI1 nicotinamide adenine dinucleotide (NADH)-quinone-oxidoreductase ofSaccharomyces cerevisiae, which can restore NADH oxidation in complex I-deficient mammalian cells and stimulation of energy production via anaerobic glycolysis. Consistently, other ATP-depleting neurotoxins (1-methyl-4-phenylpyridinium, 3-nitropropionic, and carbonyl cyanidem-chlorophenylhydrazone) reproduced the somatic redistribution of tau, whereas toxins that did not decrease ATP levels did not cause the redistribution of tau. Therefore, the annonacin-induced ATP depletion causes the retrograde transport of mitochondria to the cell soma and induces changes in the intracellular distribution of tau in a way that shares characteristics with some neurodegenerative diseases.

Background: In type 1 diabetes mellitus (T1DM) management, enhancing health-related quality of life (HRQoL) is as important as good metabolic control and prevention of secondary complications. This study aims to evaluate possible regional differences in HRQoL, demographic features and clinical characteristics of patients with T1DM in Brazil, a country of continental proportions, as well as investigate which variables could influence the HRQoL of these individuals and contribute to these regional disparities. Methods: This was a retrospective, cross-sectional, multicenter study performed by the Brazilian Type 1 Diabetes Study Group (BrazDiab1SG), by analyzing EuroQol scores from 3005 participants with T1DM, in 28 public clinics, among all geographical regions of Brazil. Data on demography, economic status, chronic complications, glycemic control and lipid profile were also collected. Results: We have found that the North-Northeast region presents a higher index in the assessment of the overall health status (EQ-VAS) compared to the Southeast (74.6 ± 30 and 70.4 ± 19, respectively; p < 0.05). In addition, North- Northeast presented a lower frequency of self-reported anxiety-depression compared to all regions of the country (North-Northeast: 1.53 ± 0.6; Southeast: 1.65 ± 0.7; South: 1.72 ± 0.7; Midwest: 1.67 ± 0.7; p < 0.05). These findings could not be entirely explained by the HbA1c levels or the other variables examined. Conclusions: Our study points to the existence of additional factors not yet evaluated that could be determinant in the HRQoL of people with T1DM and contribute to these regional disparities.

Fish of the genusAnableps(Anablepidae, Cyprinodontiformes) have eyes that are adapted for simultaneous aerial and aquatic vision. In this study we investigate some of the corresponding retinal specializations of the adultAnableps anablepseye using retinal transverse sections and wholemounts. The linear dimensions of the retina were found to be asymmetric with a greater representation of the dorsal compared to the ventral visual field. The total number of neurons in the ganglion cell layer of the ventral hemiretina was on average 3.6 times greater than the values obtained in the dorsal hemiretina. Isodensity contour maps revealed a prominent horizontal visual streak in the ventral hemiretina with an average peak cell density of 18,286 cells/mm2. A second less-well-developed horizontal visual streak was also observed in the dorsal hemiretina. A sub-population of large cells with soma areas between 74 and 188 μm2was identified and found to be distributed evenly across both hemiretinas. Together, these results show that the sampling gain of the ventral retina is significantly greater than the dorsal segment, that retinal specializations important for mediating acute vision are present in the parts of the visual field immediately above and below the surface of the water, and that visual functions related with the large ganglion cells require more even sampling across the visual field. The relevance of these retinal specializations to the feeding and other behavioral strategies adopted byAnablepsis discussed.

A Neurobiotin-injected OFF parasol cell from midperipheral macaque retina was studied by reconstruction of serial ultrathin sections and compared with ON parasol cells studied previously. In most respects, the synaptic inputs to the two subtypes were similar. Only a few of the amacrine cell processes that provided input to the labeled OFF parasol ganglion cell dendrites made or received inputs within the series, and none of these interactions were with the bipolar cells or other amacrine cells presynaptic to the OFF parasol cell. These findings suggest that the direct inhibitory input to OFF parasol cells originates from other areas of the retina. OFF parasol cells were known to receive inputs from two types of diffuse bipolar cells. To identify candidates for the presynaptic amacrine cells, OFF parasol cells were labeled with Lucifer yellow by using a juxtacellular labeling technique, and amacrine cells known to costratify with them were labeled via immunofluorescent methods. Appositions were observed with amacrine cells containing immunoreactive calretinin, parvalbumin, choline acetylatransferase, and G6-Gly, a cholecystokinin precursor. These findings suggest that the inhibitory input to parasol cells conveys information about several different attributes of visual stimuli and, particularly, about their global properties.

Tyrant flycatchers comprise the largest group of passerine birds of the Neotropical region but their retinal organization is unknown. The great kiskadee, Pitangus sulphuratus, is categorized as a supreme generalist and utilizes a variety of foraging strategies. The rusty margined flycatcher, Myiozetetes cayanensis, is partially frugivorous and captures insects in the air. Using retinal wholemounts, we described the topographic distribution of density and size of neurons lying in the retinal ganglion cell layer in those two species of tyrant flycatchers. Maps of neuron distribution showing isodensity contours revealed the presence of a pronounced central fovea and a temporal area in both species. Both retinal specializations were circumscribed by an inconspicuous horizontal visual streak. The highest foveal densities ranged from 48,000 to 55,000 cells/mm2 for Pitangus sulphuratus and between 62,000 and 65,000 cells/mm2 for Myiozetetes cayanensis. The peak density in the temporal area was around 40,000 cells/mm2 for Pitangus sulphuratus and 46,000 cells/mm2 for Myiozetetes cayanensis. At central, mid-peripheral and peripheral eccentricities, perikaryon size varied quite similarly in both species. A cohort of giant retinal ganglion cells with perikaryon size > 300 µm2 was observed at the temporal periphery and defines an ‘area giganto cellularis’ described previously in procellariiform seabirds. This specialization is thought to be involved in movement detection and could aid the tyrant flycatchers to capture moving prey. Functionally, the presence of a fovea associated with a temporal area would allow high spatial resolution for capturing insects by the tyrant flycatchers. Nonetheless, even though both species exhibit different foraging strategies, they shared a similar topographic arrangement of neuronal density in the ganglion cell layer. This suggests that the retinal topography did not accompany changes in the foraging ecology throughout evolutionary history for these species of tyrant flycatchers.

To describe the wide-field ganglion cells, they were injected intracellularly with Neurobiotin using an in vitro preparation of macaque retina and labeled with streptavidin-Cy3. The retinas were then labeled with antibodies to choline acetyltransferase and other markers to indicate the depth of the dendrites within the inner plexiform layer (IPL) and analyzed by confocal microscopy. There were eight different subtypes of narrowly unistratified cells that ramified in each of the 5 strata, S1–5, including narrow thorny, large sparse, large moderate, large dense, large radiate, narrow wavy, large very sparse, and fine very sparse. There were four types of broadly stratified cells with dendritic trees extending from S4 to S2. One type resembled the parvocellular giant cell and another the broad thorny type described previously in primates. Another broadly stratified cell was called multi-tufted based on its distinctive dendritic branching pattern. The fourth type had been described previously, but not named; we called it broad wavy. There was a bistratified type with its major arbor in S5, the same level as the blue cone bipolar cell; it resembled the large, bistratified cell with blue ON-yellow OFF responses described recently. Two wide-field ganglion cell types were classified as diffuse because they had dendrites throughout the IPL. One had many small branches and was named thorny diffuse. The second was named smooth diffuse because it had straighter dendrites that lacked these processes. Dendrites of the large moderate and multi-tufted cells cofasciculated with ON-starburst cell dendrites and were, therefore, candidates to be ON- and ON–OFF direction-selective ganglion cells, respectively. We concluded that there are at least 15 morphoplogical types of wide-field ganglion cells in macaque retinas.

Starburst amacrine cells in the macaque retina were studied by electron microscopic immunohistochemistry. We found that these amacrine cells make a type of synapse not described previously; they are presynaptic to axon terminals of bipolar cells. We also confirmed that starburst amacrine cells are presynaptic to ganglion cell dendrites and amacrine cell processes. In order to determine the functions of these synapses, we localized acetylcholine receptors using a monoclonal antibody (mAb210) that recognizes human alpha3- and alpha5-containing nicotinic receptors and also antisera against the five known subtypes of muscarinic receptors. The majority of the mAb210-immunoreactive perikarya were amacrine cells and ganglion cells, but a subpopulation of bipolar cells was also labeled. A subset of bipolar cells and a subset of horizontal cells were labeled with antibodies to M3 muscarinic receptors. A subset of amacrine cells, including those that contain cholecystokinin, were labeled with antibodies to M2 receptors. Taken together, these results suggest that acetylcholine can modulate the activity of retinal ganglion cells by multiple pathways.

1. The genetic basis of colour vision in New-World primates differs from that in humans and other Old-World primates. Most New-World primate species show a polymorphism; all males are dichromats and most females trichromats. 2. In the retina of Old-World primates such as the macaque, the physiological correlates of trichromacy are well established. Comparison of the retinae in New- and Old-World species may help constrain hypotheses as to the evolution of colour vision and the pathways associated with it. 3. Ganglion cell behaviour was recorded from trichromatic and dichromatic members of a New-World species (the capuchin monkey, Cebus apella) and compared with macaque data. Despite some differences in quantitative detail (such as a temporal response extended to higher frequencies), results from trichromatic animals strongly resembled those from the macaque. 4. In particular, cells of the parvocellular (PC) pathway showed characteristic frequency-dependent changes in responsivity to luminance and chromatic modulation, cells of the magnocellular (MC) pathway showed frequency-doubled responses to chromatic modulation, and the surround of MC cells received a chromatic input revealed on changing the phase of heterochromatically modulated lights. 5. Ganglion cells of dichromats were colour-blind versions of those of trichromats. 6. This strong physiological homology is consistent with a common origin of trichromacy in New- and Old-World monkeys; in the New-World primate the presence of two pigments in the middle-to-long wavelength range permits full expression of the retinal mechanisms of trichromatic vision.

The foveal specializations of five New World monkeys, the marmoset, Callithrix jacchus; the golden-handed tamarin, Saguinus midas niger; the squirrel monkey, Saimiri ustius; the capuchin monkey, Cebus apella; and the howler monkey, Alouatta caraya were compared. Although retinal area varies by over a factor of two in these monkeys, the area of the fovea does not covary with retinal area and remains approximately the same absolute size, as measured by the dimensions of the high density region of cones, or the rod-free region. This constancy in foveal size also holds for rhesus monkeys and humans, bringing the variation in retinal area to a factor of five. Alouatta caraya is unusual, distinguished by a very high central cone density and a small rod-free zone. Physiological constraints that might limit foveal area over a wide range of eye sizes are considered.

The anatomy of the owl monkey (Aotus) retina is reviewed and compared with that of one of its diurnal relatives, the capuchin monkey (Cebus). A mechanism is suggested by which the owl monkey has biased its retinal organization towards a conformation most advantageous for scotopic vision. © 2000 John Wiley & Sons, Inc. Col Res Appl, 26, S118–S122, 2001

P:midget ganglion cells mediate red-green color opponency in anthropoids. It has been proposed that these cells evolved as a specialization to subserve color vision in primates. If that is correct, they must have evolved about the same time as the long-wavelength (‘red’) and medium-wavelength (‘green’) pigment genes diverged, thirty million years ago. Strepsirhines are another group of primates that diverged from the ancestor of the anthropoids at least 55 million years ago. If P:midget ganglion cells evolved to subserve color vision, they should be absent in strepsirhines. We tested this hypothesis in a nocturnal strepsirhine, the greater bush baby Otolemur. The retinal ganglion cells were labeled with the lipophilic tracer DiI and the results show that bush babies have P:midget and M:parasol cells similar to those found in the peripheral retinas of anthropoids. A number of studies have shown that the P and M pathways of bush babies share many similarities with those of anthropoids, and our results show that the same is true for their retinal ganglion cells. These results support the hypothesis that the P system evolved prior to the emergence of red‐green color opponency. © 1998 Elsevier Science Ltd. All rights reserved.

Male Cebus monkeys are all dichromats, but about two thirds of the females are trichromats. M and P retinal ganglion cells were studied in the male Cebus monkey to investigate the relationship of their morphology to retinal eccentricity. Retinal ganglion cells were retrogradely labeled after optic nerve deposits of biocytin to reveal their entire dendritic tree. Cebus M and P ganglion cell morphology revealed by biocytin retrograde filling is similar to that described for macaque and human M and P ganglion cells obtained by in vitro intracellular injection of HRP and neurobiotin. We measured 264 and 441 M and P ganglion cells, respectively. M ganglion cells have larger dendritic field and cell body size than P ganglion cells at any comparable temporal or nasal eccentricity. Dendritic trees of both M and P ganglion cells are smaller in the nasal than in the temporal region at eccentricities greater than 5 mm and 2 mm for M and P ganglion cells, respectively. The depth of terminal dendrites allows identification of both inner and outer subclasses of M and P ganglion cells. The difference in dendritic tree size between inner and outer cells is small or absent. Comparison between Cebus and Macaca shows that M and P ganglion cells have similar sizes in the central retinal region. The results support the view that M and P pathways are similarly organized in diurnal dichromat and trichromat primates.

Using a reduced-silver neurofibrillar method, we stained a population of bipolar cells in the capybara retina. These cells are distributed throughout the retina following the same topography of other retinal cell classes as the A-type horizontal cells and ganglion cells. The level of axonal stratification, mosaic regularity, and dendritic coverage factor suggest that these neurofibrillar bipolar cells comprise a population of sublamina a cone bipolar cells.

Das folhas de Deguelia utilis foram isolados cinco flavonoides: 5,3'-di-hidróxi-4'-metóxi2'',2''-dimetilcromeno-(5'',6'':6,7)-di-hidroflavonol (1), 5,3'-di-hidróxi-7,4'-dimetóxi-6,8dimetilalil-di-hidroflavonol (2), 5,3'-di-hidróxi-4'-metóxi-8-prenil-2'',2''-dimetilcromeno(5'',6'':6,7)-flavanona (3), 5,3'-di-hidróxi-7,4'-dimetóxi-6,8-dimetilalil-flavanona (4), 3,5,3'-tri-hidróxi-7,4'-dimetóxi-6,8-dimetilalil-flavanol (5), juntamente com os estilbenos: 4-metoxilonchocarpeno (6) e lonchocarpeno (7). Suas estruturas químicas foram elucidadas com base nos seus dados de NMR (ressonância magnética nuclear) e HRESITOF-MS (espectrometria de massas de alta resolução por tempo de vôo, com ionização por eletrospray). Além disso, a fim de investigar o potencial efeito citoprotetor desses flavonoides, foi utilizada uma fração eluída com hexano:AcOEt contendo os sete flavonoides, em um modelo in vitro de neurodegeneração, utilizando culturas primárias do hipocampo de ratos neonatal (PND2-P3) expostos à rotenona, um inibidor mitocondrial do complexo I. Houve uma redução significativa da viabilidade celular (19,4 ± 1,6%), quando as culturas foram expostas à rotenona 30 nmol L-1 por 72 h. A exposição concomitante das culturas a FR3 (5 µg mL-1) e rotenona 30 nmol L-1 resultou em valores de viabilidade celular semelhante ao grupo controle (99,6 ± 4,8%), sugerindo um efeito citoprotetor para essa fração. Five new flavonoids, 5,3'-dihydroxy-4'-methoxy-2'',2''-dimethylchromene-(5'',6'':6,7)dihydroflavonol (1), 5,3'-dihydroxy-7,4'-dimethoxy-6,8-dimethylallyl-dihydroflavonol (2), 5,3'-dihydroxy-4'-methoxy-8-allyl-2'',2''-dimethylchromene-(5'',6'':6,7) flavanone (3), 5,3'-dihydroxy-7,4'-dimethoxy-6,8-dimethylallyl-flavanone (4), 3,5,3'-trihydroxy-7,4'-dimethoxy6,8-dimethylallyl-flavanol (5), together with the stilbenes 4-methoxylonchocarpene (6) and lonchocarpene (7) were isolated from the leaves of Deguelia utilis. Their chemical structures were established on the basis of NMR (nuclear magnetic resonance) spectral data and HRESITOF-MS (electrospray ionization-high resolution time-of-flight mass spectrometry). Also, in order to investigate potential cytoprotective effects of these flavonoids, we used a fraction eluted with hexane:EtOAc containing all seven flavonoids, in an in vitro model of neurodegeneration, using hippocampal primary cultures from neonatal (PND2-P3) rats exposed to rotenone, a mitochondrial complex I inhibitor. There was a significant reduction in cell viability (19.4 ± 1.6%) when the cultures were exposed to 30 nmol L-1 rotenone for 72 h. Concomitant exposure of the cultures to the FR3 (5 µg mL-1) and 30 nmol L-1 rotenone resulted in values of cell viability similar to control groups (99.6 ± 4.8%), strongly suggesting a cytoprotective effect for this flavonoid-rich fraction.

M and P retinal ganglion cell morphology revealed by biocytin retrograde labelling was compared in two closely related New-World monkeys, Cebus and Aotus, to investigate whether nocturnal and diurnal species of primates have similar cell classes. Monkey and cat ganglion cells from regions of matching cell class densities were also compared. Cat alpha, cat beta, Aotus M, and Cebus M cells were similar in many aspects, but Cebus M cells had higher branching density. Cebus and Aotus P cells formed a distinct group and represent a primate specialization common to diurnal and nocturnal simians.

The distribution of ganglion cells and displaced amacrine cells was determined in whole-mounted Aotus retinae. In contrast to diurnal simians, Aotus has only a rudimentary fovea. Ganglion cell density decreases towards the periphery at approximately the same rate along all meridians, but is 1.2–1.8 times higher in the nasal periphery when compared to temporal region at the same eccentricities. The total number of ganglion cells varied from 421,500 to 508,700. Ganglion cell density peaked at 15,000/mm2 at 0.25 mm dorsal to the fovea. The displaced amacrine cells have a shallow density gradient, their peak density in the central region is about 1500–2000/mm2 and their total number varied from 315,900 to 482,800. Comparison between ganglion cell density and areal cortical magnification factor for the primary visual cortex, area 17, shows that there is not a simple proportional representation of the ganglion cell distribution. There is an overrepresentation of the central 10 deg of the visual field in the visual cortex. The present results for Aotus and the results of a similar analysis of data from other primates indicate that the overrepresentation of the central visual field is a general feature of the visual system of primates.

The tyrant flycatchers represent a monophyletic radiation of predominantly insectivorous passerine birds that exhibit a plethora of stereotyped prey capture techniques. However, little is known about their retinal organization. Using retinal wholemounts, we estimated the total number and topography of neurons in the ganglion cell layer in the generalist yellow-bellied elaenia (Elaenia flavogaster) and the uphover-gleaner mouse-colored tyrannulet (Phaeomyias murina) with the optical fractionator method. The mean estimated total number of neurons in the ganglion cell layer was 4,152,416 189,310 in E. flavogaster and 2,965,132 354,359 in P. murina. Topographic maps of isocounting lines revealed a similar distribution for both species: a central fovea and a temporal area surrounded by a poorly defined horizontal streak. In addition, both species had increased numbers of giant ganglion cells in the dorsotemporal retina forming an area giganto cellularis. In E. flavogaster, these giant ganglion cells were also distributed across the nasal and ventral retinal peripheries, which is in agreement with the generalist habits of this species. However, in P. murina these cells were rarely seen along the nasal and ventral peripheries, possibly reflecting a lesser need to perceive movement because this species captures stationary insects resting on foliage. Thus, we suggest that the retinas of the tyrant flycatchers in the present study show a general common pattern of neuron distribution in the ganglion cell layer irrespective of their foraging habits. We also suggest that the distribution of giant ganglion cells is indicative of the visual requirements of the species. J. Comp. Neurol. 514

The clinical motor dysfunction in Parkinson's disease is primarily the consequence of a progressive degeneration of dopaminergic neurons in the substantia nigra of the nigrostriatal pathway. The degeneration of this tract provokes a depletion of dopamine in the striatum, where it is required as a permissive factor for normal motor function. Despite intense investigations, no effective therapy is available to prevent the onset or to halt the progression of the neuronal cell loss. Therefore, recent years have seen research into the mechanisms of endogenous repair processes occurring in the adult brain, particularly in the substantia nigra. Neurogenesis occurs in the adult brain in a constitutive manner under physiological circumstances within two regions: the dentate gyrus of the hippocampus and the subventricular zone of the lateral ventricles. In contrast to these two so-called neurogenic areas, the remainder of the brain is considered to be primarily nonneurogenic in nature, implying that no new neurons are produced there under normal conditions. The occurrence of adult neurogenesis in the substantia nigra under the pathological conditions of Parkinson's disease, however, remains controversial. Here, we review the published evidence of whether adult neurogenesis exists or not within the substantia nigra, where dopaminergic neurons are lost in Parkinson's disease.

To better understand the evolution of spatial and color vision, the number and spatial distributions of cones, rods, and optic nerve axon numbers were assessed in seven New World primates (Cebus apella, Saimiri ustius, Saguinus midas niger, Alouatta caraya, Aotus azarae, Calllithrix jacchus, and Callicebus moloch). The spatial distribution and number of rods and cones was determined from counts of retinal whole mounts. Optic axon number was determined from optic nerve sections by electron microscopy. These data were amassed with existing data on retinal cell number and distribution in Old World primates, and the scaling of relative densities and numbers with respect to retinal area, eye and brain sizes, and foveal specializations were evaluated. Regular scaling of all cell types was observed, with the exceptionally large, rod-enriched retina of the nocturnal owl monkey Aotus azarae, and the unusually high cone density of the fovea of the trichromatic howler monkey Alouatta caraya presenting interesting variations on this basic plan. Over all species, the lawful scaling of rods, cones, and retinal ganglion cell number is hypothesized to result from a conserved sequence of cell generation that defends retinal acuity and sensitivity over a large range of eye sizes.

Rotenone is a heterocyclic compound widely used as an insecticide, acaricide and piscicide. Its toxicity is mainly caused by the inhibition of mitochondrial respiratory processes and ATP production, resulting in the generation of reactive oxygen species. Reactive oxygen species can interact with DNA, RNA and proteins, leading to cell damage, followed by death. We used the Comet assay, and we analyzed chromosome aberrations, in order to evaluate the genotoxic and clastogenic effects of rotenone on the different phases of the cell cycle. Cultured human lymphocytes were treated with 1.0, 1.5 and 2.0 microg/mL rotenone during the G1, G1/S, S (pulses of 1 and 6 h), and G2 phases of the cell cycle. Rotenone induced DNA damage and was clastogenic, but the clastogenicity was detected only with treatments conducted during the G1/S and S phases of the cell cycle. Rotenone also induced endoreduplication and polyploidy in treatments made during G1, while it significantly reduced the mitotic index in all phases of the cell cycle.

Neural systems are necessarily the adaptive products of natural selection, but a neural system, dedicated to any particular function in a complex brain, may be composed of components that covary with functionally unrelated systems, owing to constraints beyond immediate functional requirements. Some studies support a modular or mosaic organization of the brain, whereas others emphasize coordination and covariation. To contrast these views, we have analysed the retina, striate cortex (V1) and extrastriate cortex (V2, V3, MT, etc.) in 30 mammals, examining the area of the neocortex and individual neocortical areas and the relative numbers of rods and cones. Controlling for brain size and species relatedness, the sizes of visual cortical areas (striate, extrastriate) within the brains of nocturnal and diurnal mammals are not statistically different from one another. The relative sizes of all cortical areas, visual, somatosensory and auditory, are best predicted by the total size of the neocortex. In the sensory periphery, the retina is clearly specialized for niche. New data on rod and cone numbers in various New World primates confirm that rod and cone complements of the retina vary substantially between nocturnal and diurnal species. Although peripheral specializations or receptor surfaces may be highly susceptible to niche-specific selection pressures, the areal divisions of the cerebral cortex are considerably more conservative.

Tyrant flycatchers comprise the largest group of passerine birds of the Neotropical region but their retinal organization is unknown. The great kiskadee, Pitangus sulphuratus, is categorized as a supreme generalist and utilizes a variety of foraging strategies. The rusty margined flycatcher, Myiozetetes cayanensis, is partially frugivorous and captures insects in the air. Using retinal wholemounts, we described the topographic distribution of density and size of neurons lying in the retinal ganglion cell layer in those two species of tyrant flycatchers. Maps of neuron distribution showing isodensity contours revealed the presence of a pronounced central fovea and a temporal area in both species. Both retinal specializations were circumscribed by an inconspicuous horizontal visual streak. The highest foveal densities ranged from 48,000 to 55,000 cells/mm(2) for Pitangus sulphuratus and between 62,000 and 65,000 cells/mm(2) for Myiozetetes cayanensis. The peak density in the temporal area was around 40,000 cells/mm(2) for Pitangus sulphuratus and 46,000 cells/mm(2) for Myiozetetes cayanensis. At central, mid-peripheral and peripheral eccentricities, perikaryon size varied quite similarly in both species. A cohort of giant retinal ganglion cells with perikaryon size300 microm(2) was observed at the temporal periphery and defines an 'area giganto cellularis' described previously in procellariiform seabirds. This specialization is thought to be involved in movement detection and could aid the tyrant flycatchers to capture moving prey. Functionally, the presence of a fovea associated with a temporal area would allow high spatial resolution for capturing insects by the tyrant flycatchers. Nonetheless, even though both species exhibit different foraging strategies, they shared a similar topographic arrangement of neuronal density in the ganglion cell layer. This suggests that the retinal topography did not accompany changes in the foraging ecology throughout evolutionary history for these species of tyrant flycatchers.

Catarrhines and platyrrhines, the so-called Old- and New-World anthropoids, have different cone photopigments. Postreceptoral mechanisms must have coevolved with the receptors to provide trichromatic color vision, and so it is important to compare postreceptoral processes in these two primate groups, both from anatomical and physiological perspectives. The morphology of ganglion cells has been studied in the retina of catarrhines such as the diurnal and trichromatic Macaca , as well as platyrrhines such as the diurnal, di- or trichromatic Cebus , and the nocturnal, monochromatic Aotus . Diurnal platyrrhines, both di- and trichromats, have ganglion cell classes very similar to those found in catarrhines: M (parasol), P (midget), small-field bistratified, and several classes of wide-field ganglion cells. In the fovea of all diurnal anthropoids, P-cell dendritic trees contact single midget bipolars, which contact single cones. The Aotus retina has far fewer cones than diurnal species, but M- and P-cells are similar to those in diurnal primates although of larger size. As in diurnal anthropoids, in the Aotus , the majority of midget bipolar cells, found in the central 2 mm of eccentricity, receive input from a single cone and the sizes of their axon terminals match the sizes of P-cell dendritic fields in the same region. The visual responses of retinal ganglion cells of these species have been studied using single-unit electrophysiological recordings. Recordings from retinal ganglion cells in Cebus and Aotus showed that they have very similar properties as those in the macaque, except that P-cells of mono- and dichromatic animals lack cone opponency. Whatever the original role of the M- and P-cells was, they are likely to have evolved prior to the divergence of catarrhines and platyrrhines. M- and P-cell systems thus appear to be strongly conserved in the various primate species. The reasons for this may lie in the roles of these systems for both achromatic and chromatic vision.