Exploring the ability of strength and dexterity tests to detect hand function impairment in individuals with Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) can affect hand function since the beginning of the motor symptoms. OBJECTIVE: To compare the ability of different hand function tests to: 1) distinguish individuals with PD from healthy controls; 2) differentiate stages of the disease; and 3) indicate changes over time due to disease progression. METHODS: Twenty-four individuals with PD (Hoehn and Yahr: I-III) and 24 age- and sex-matched controls performed the Jebsen-Taylor Hand Function Test (JTHFT), the Nine-Hole Peg Test (9HPT), and the maximum grip and the maximum pinch strength tests using their right and left hands. Eight individuals with PD (six females and two males) were reassessed after 18 months. The ROC analyses and Mann-Whitney U tests (for disease progression) using the average performance of the hands were done. RESULTS: Individuals with PD presented worse test performances than controls, except for the writing subtest of the JTHFT and the grip strength test. The JTHFT without the writing subtest (JTHFTnoW) was the most accurate to discriminate PD from controls (AUC = 0.899; sensitivity 75% and specificity 95.8%). The 9HPT and the simulated feeding and moving large, light objects JTHFT subtests were sensitive to distinguish stages, while the 9HPT, the moving small, common objects JTHFT subtest, and the grip strength were sensitive to changes with disease progression. CONCLUSION: The JTHFTnoW was highly discriminative of the hand function impairments in PD. TwoJTHFT subtests were the most sensitives to distinguish PD stages (i.e. simulated feeding JTHFT subtest) and disease progression (i.e. moving small, common objects JTHFT subtest).

Reproductive and relational trajectories leading to pregnancy: Differences between adolescents and adult women who had an abortion.

OBJECTIVES: The literature has been conceptualizing pregnancy occurrence as a multiphase event. However, the different combinations of decisions and behaviors leading to pregnancy that end in abortion remain unexplored in the literature. The aims of the study were to describe the reproductive and relational trajectories leading to pregnancy in women who decide to abort and to explore the differences in this process according to women's age [adolescents (<20 years old) vs. adults]. STUDY DESIGN: In this cross-sectional study, 426 women [246 adolescents (58.4%), 177 adults (41.6%)] who chose abortion were recruited. Data on reproductive and relational characteristics were collected through a self-report questionnaire at 16 healthcare services that provide abortion. The variables were introduced in trajectories according to the criterion of temporal sequence between them: age at first sexual intercourse, relationship type, pregnancy planning, use of contraception, identification of contraceptive failure, and occurrence of pregnancy. RESULTS: Seven trajectories leading to pregnancy were identified. The most frequent trajectory (30.8%) included women who 1) were involved in a long-term romantic relationship, 2) did not plan the pregnancy, 3) were using contraception, and 4) did not identify the contraceptive failure that led to pregnancy. Although this was the most frequent trajectory for both age groups, the remaining trajectories showed a different distribution. Compared to adolescents, adult women's trajectories more frequently included casual relationships with non-use of contraception, or contraceptive use with no contraceptive failure identification. CONCLUSION: Our study highlights the need to recognize the multiplicity of reproductive and relational trajectories leading to pregnancies that end in abortion and their specificities according to women's age. These findings have important implications for abortion counselling and for the development of age-appropriate guidelines for preventive interventions, by drawing attention to prioritization of different contexts of intervention according women's age.

Distinct neuroplasticity processes are induced by different periods of acrobatic exercise training.

Short and long-term physical exercise induce physiological and structural changes in brain motor areas. The relationship between changes of structural and synaptic proteins in brain motor areas and acrobatic exercise is less understood. Our aim was to evaluate the expression of synapsin I (SYS), synaptophysin (SYP), microtubule-associated protein 2 (MAP2), neurofilament (NF), and a marker for recent neuronal activity (Egr-1) in the motor cortex, striatum and cerebellum of adult rats subjected to acrobatic exercise (AE, for 1-4 weeks). We used adult Wistar rats, divided into 4 groups based on duration of acrobatic training, namely 1 week (AE1, n=15), 2 weeks (AE2, n=15), 4 weeks (AE4, n=15), and sedentary (SED, n=15). In AE groups, the rats covered 5 times a circuit that was composed of obstacles, three times a week. The protein levels were analyzed by immunoblotting and immunohistochemistry. The results revealed that short-term AE (AE1 and AE2) induced MAP2 decreases and NF, SYP and Egr-1 increases in the motor cortex; an increase of MAP2, SYS and SYP in the dorsolateral striatum, whereas the dorsomedial striatum showed increased NF, SYS, SYP and Egr-1. Granular cerebellar layer showed increased NF and Egr-1, with increased NF and SYP in the molecular layer. Long-term AE (AE4) promoted an increase of MAP2, SYP and Egr-1 in motor cortex; MAP2, SYS and SYP in the dorsomedial striatum; and NF and Egr-1 in the cerebellar granular layer. In conclusion, our data suggest that different durations of AE induce distinct plastic responses among distinct cortical and subcortical circuits.

Age-related changes in neurochemical components and retinal projections of rat intergeniculate leaflet.

Aging leads to several anatomical and functional deficits in circadian timing system. In previous works, we observed morphological alterations with age in hypothalamic suprachiasmatic nuclei, one central component of this system. However, there are few data regarding aging effects on other central components of this system, such as thalamic intergeniculate leaflet (IGL). In this context, we studied possible age-related alterations in neurochemical components and retinal projections of rat IGL. For this goal, young (3 months), adult (13 months), and aged (23 months) Wistar rats were submitted to an intraocular injection of neural tracer, cholera toxin subunit b (CTb), 5 days before a tissue fixation process by paraformaldehyde perfusion. Optical density measurements and cell count were performed at digital pictures of brain tissue slices processed by immunostaining for glutamic acid decarboxylase (GAD), enkephalin (ENK), neuropeptide Y (NPY) and CTb, characteristic markers of IGL and its retinal terminals. We found a significant age-related loss in NPY immunoreactive neurons, but not in immunoreactivity to GAD and ENK. We also found a decline of retinal projections to IGL with age. We conclude aging impairs both a photic environmental clue afferent to IGL and a neurochemical expression which has an important modulatory circadian function, providing strong anatomical correlates to functional deficits of the aged biological clock.

Different protocols of treadmill exercise induce distinct neuroplastic effects in rat brain motor areas.

A variety of exercise protocols have been used to promote experimental neuroplasticity. However, the plastic brain responses generated by several aspects of training (types, frequency, regimens, duration) remain undetermined. The aim of this study was to compare the plastic changes in the glutamatergic system and synaptic proteins in motor cortex, striatum and cerebellum promoted by two different treadmill exercise regimens. The present study analyzed by immunohistochemistry and Western blotting the expression of the subunits of AMPA receptors (GluA1 and GluA2/3) and synaptic proteins (synapsin I and synaptophysin) in adult male Wistar rat brains. The animals were divided into animals subjected to two different frequencies of aerobic exercise groups and sedentary animals. The exercise groups were: intermittent treadmill exercise (ITE) - animals that exercised 3 times a week (every other day) during four weeks, and continuous treadmill exercise (CTE) - animals that exercised every day during four weeks. Our results reveal that different protocols of treadmill exercise were able to promote distinct synaptic reorganization processes among the exercised groups. In general, the intermittent exercise regimen induced a higher expression of presynaptic proteins, whereas the continuous exercise regimen increased postsynaptic GluA1 and GluA2/3 receptors.

Analysis of reporting of systematic reviews in physical therapy published in Portuguese.

BACKGROUND: Systematic reviews are considered the best design to synthesize all existing information of a given research topic. To date, there is no study that investigated the quality of reporting of systematic reviews relevant to physical therapy published in Portuguese. OBJECTIVE: To analyse the quality of reporting of systematic reviews in the field of physical therapy published in Portuguese by using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) checklist. METHOD: All systematic reviews published in Portuguese that were indexed on PEDro database up to August 2011 were included. The quality of reporting of the eligible papers was analysed by using the PRISMA checklist. Each quality assessment was performed by two independent reviewers with arbitration of a third reviewer if necessary. RESULTS: A total of 37 systematic reviews were identified. These studies were published between 2003 and 2010. Less than 30% of the PRISMA checklist items were satisfied, being most of the items related to the introduction and discussion sections. No improvements over time were observed. CONCLUSIONS: Most of the studies did not satisfy the items from the PRISMA Checklist. It seems that most of authors did not know the existence of this checklist. The implementation of reporting statements such as the PRISMA statement by Portuguese-written journals is likely to help authors to write their systematic reviews in a more transparent and clear way.

Analysis of reporting of systematic reviews in physical therapy published in Portuguese / Análise da apresentação textual de revisões sistemáticas em fisioterapia publicadas no idioma português

BACKGROUND: Systematic reviews are considered the best design to synthesize all existing information of a given research topic. To date, there is no study that investigated the quality of reporting of systematic reviews relevant to physical therapy published in Portuguese. Objective: To analyse the quality of reporting of systematic reviews in the field of physical therapy published in Portuguese by using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) checklist. METHOD: All systematic reviews published in Portuguese that were indexed on PEDro database up to August 2011 were included. The quality of reporting of the eligible papers was analysed by using the PRISMA checklist. Each quality assessment was performed by two independent reviewers with arbitration of a third reviewer if necessary. RESULTS: A total of 37 systematic reviews were identified. These studies were published between 2003 and 2010. Less than 30% of the PRISMA checklist items were satisfied, being most of the items related to the introduction and discussion sections. No improvements over time were observed. CONCLUSIONS: Most of the studies did not satisfy the items from the PRISMA Checklist. It seems that most of authors did not know the existence of this checklist. The implementation of reporting statements such as the PRISMA statement by Portuguese-written journals is likely to help authors to write their systematic reviews in a more transparent and clear way.

CONTEXTUALIZAÇÃO: As revisões sistemáticas são consideradas a melhor forma de sintetizar toda a informação existente sobre um determinado tópico, porém não se conhece, até o momento, a qualidade da apresentação textual das revisões sistemáticas em fisioterapia publicadas no idioma português. Objetivo: Analisar a apresentação textual de revisões sistemáticas em fisioterapia publicadas no idioma português utilizando as recomendações PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). MÉTODO: Foram analisadas todas as revisões sistemáticas apresentadas na base de dados PEDro até o mês de agosto de 2011. Para a análise da descrição textual foi utilizada a lista de verificação PRISMA. Cada revisão foi avaliada por pares de revisores independentes e, em caso de discordância entre os pares, um terceiro avaliador fez a arbitragem final. RESULTADOS: Foram identificadas 37 revisões sistemáticas que foram publicadas entre os anos de 2003 e 2010. Menos de 30% dos itens da lista de verificação PRISMA foram descritos pelos autores, sendo que a maioria dos itens satisfeitos se refere às seções de introdução e discussão. Observou-se que não houve um aumento na adesão aos itens recomendados para a apresentação textual com o passar do tempo. CONCLUSÕES: A adesão aos critérios preconizados pela lista de verificação da PRISMA é baixa para revisões sistemáticas publicadas no idioma português, o que pode ser reflexo do desconhecimento da existência de tais recomendações. A implementação de recomendações aos autores pelos periódicos nacionais poderá auxiliar os autores na redação de seus artigos, melhorando a clareza com que reportam seus estudos.

Different protocols of physical exercise produce different effects on synaptic and structural proteins in motor areas of the rat brain.

The plastic brain responses generated by the training with acrobatic exercise (AE) and with treadmill exercise (TE) may be different. We evaluated the protein expression of synapsin I (SYS), synaptophysin (SYP), microtubule-associated protein 2 (MAP2) and neurofilaments (NF) by immunohistochemistry and Western blotting in the motor cortex, striatum and cerebellum of rats subjected to TE and AE. Young adult male Wistar rats were divided into 3 groups: sedentary (Sed) (n=15), TE (n=20) and AE (n=20). The rats were trained 3 days/week for 4 weeks on a treadmill at 0.6 km/h, 40 min/day (TE), or moved through a circuit of obstacles 5 times/day (AE). The rats from the TE group exhibited a significant increase of SYS and SYP in the motor cortex, of NF68, SYS and SYP in the striatum, and of MAP2, NF and SYS in the cerebellum, whereas NF was decreased in the motor cortex and the molecular layer of the cerebellar cortex. On the other hand, the rats from the AE group showed a significant increase of MAP2 and SYP in the motor cortex, of all four proteins in the striatum, and of SYS in the cerebellum. In conclusion, AE induced changes in the expression of synaptic and structural proteins mainly in the motor cortex and striatum, which may underlie part of the learning of complex motor tasks. TE, on the other hand, promoted more robust changes of structural proteins in all three regions, especially in the cerebellum, which is involved in learned and automatic tasks.

Fall-related factors among less and more active older outpatients / Fatores associados a quedas em pacientes idosos ambulatoriais menos ativos e mais ativos

BACKGROUND: Fall-related factors in older adults with different levels of physical activity, within a multidimensional approach, have not been widely investigated. OBJECTIVE: To explore fall-related factors among older adults with different physical activity levels. METHODS: A cross-sectional, exploratory study with 118 older adult outpatients. Participants who reported at least one fall in the previous 12 months were considered fallers. The activity level was assessed through the Human Activity Profile. A cutoff of 54 points was used to define the less active group and the more active group. A multidimensional questionnaire and a set of physical functioning tests were applied. RESULTS: Fall prevalence was lower among the more active older adults (47.4%) when compared with the less active older adults (71.4%) (p<0.013). Logistic regression analysis showed that, among the more active group, falls were associated with: depressive symptoms (OR=0.747, 95%CI=0.575-0.970; p=0.029), concern about falling (OR=1.17, 95%CI=1.072-1.290; p=0.001), and self-selected walking speed (OR=0.030, 95%CI=0.004-0.244; p=0.001). For the less active group, the model was composed of age (OR=1.197, 95%CI=1.032-1.387; p=0.017) and functional disability (OR=14.447, 95%CI=1.435-145.45; p=0.023). CONCLUSION: For the more active older adults, reduced self-efficacy suggests that falling can trigger some protective behavior, such as slower gait and depressive symptoms, but the casual link between falls and these outcomes should be further investigated. These data emphasize that physical therapists should be aware that there are differences in fall-related factors depending on the older patients' physical activity level, and this must be considered when planning interventions for this population.

CONTEXTUALIZAÇÃO: Fatores relacionados a quedas em idosos com diferentes níveis de atividade física, por meio de uma abordagem multidimensional, não têm sido amplamente investigados. OBJETIVO: Explorar os fatores relacionados a quedas em idosos com diferentes níveis de atividade física. MÉTODOS: Estudo transversal exploratório com 118 pacientes idosos ambulatoriais. Participantes que relataram ao menos uma queda nos últimos 12 meses foram considerados caidores. O nível de atividade física foi avaliado por meio do Perfil de Atividade Humana (PAH). O ponto de corte de 54 pontos foi usado para definir o grupo menos ativo e o grupo mais ativo. Um questionário multidimensional e uma bateria de testes físico-funcionais foram utilizados. RESULTADOS: A prevalência de quedas foi menor no grupo de idosos mais ativos (47,4%) quando comparada à dos idosos menos ativos (71,4%) (p<0,013). A análise de regressão logística multivariada identificou que, no grupo mais ativo, ter caído estava associado a sintomas depressivos (OR=0,747, IC95%=0,575-0,970; p=0,029), preocupação em cair (OR=1,17, IC95%=1,072-1,290; p=0,001) e velocidade de marcha autosselecionada (OR=0,030, IC95%=0,004-0,244; p=0,001). Para o grupo menos ativo, o modelo foi composto de idade (OR=1,197, IC95%=1,032-1,387; p=0,017) e incapacidade funcional (OR=14,447, IC95%=1,435-145,45; p=0,023). CONCLUSÃO: Para os idosos mais ativos, a redução na autoeficácia pode sugerir que cair desencadeia alguns comportamentos protetores, tais como lentidão na marcha e sintomas depressivos, mas a relação causal entre quedas e esses desfechos devem ser mais investigados. Esses dados enfatizam que os fisioterapeutas devem ficar atentos ao fato de que há diferenças nos fatores relacionados a quedas, dependendo do nível de atividade física dos pacientes idosos, e isso deve ser considerado ao se planejarem intervenções para tal população.

Fall-related factors among less and more active older outpatients.

BACKGROUND: Fall-related factors in older adults with different levels of physical activity, within a multidimensional approach, have not been widely investigated. OBJECTIVE: To explore fall-related factors among older adults with different physical activity levels. METHODS: A cross-sectional, exploratory study with 118 older adult outpatients. Participants who reported at least one fall in the previous 12 months were considered fallers. The activity level was assessed through the Human Activity Profile. A cutoff of 54 points was used to define the less active group and the more active group. A multidimensional questionnaire and a set of physical functioning tests were applied. RESULTS: Fall prevalence was lower among the more active older adults (47.4%) when compared with the less active older adults (71.4%) (p<0.013). Logistic regression analysis showed that, among the more active group, falls were associated with: depressive symptoms (OR=0.747, 95%CI=0.575-0.970; p=0.029), concern about falling (OR=1.17, 95%CI=1.072-1.290; p=0.001), and self-selected walking speed (OR=0.030, 95%CI=0.004-0.244; p=0.001). For the less active group, the model was composed of age (OR=1.197, 95%CI=1.032-1.387; p=0.017) and functional disability (OR=14.447, 95%CI=1.435-145.45; p=0.023). CONCLUSION: For the more active older adults, reduced self-efficacy suggests that falling can trigger some protective behavior, such as slower gait and depressive symptoms, but the casual link between falls and these outcomes should be further investigated. These data emphasize that physical therapists should be aware that there are differences in fall-related factors depending on the older patients' physical activity level, and this must be considered when planning interventions for this population.

Exercise-induced plasticity of AMPA-type glutamate receptor subunits in the rat brain.

The aim of this study was to analyze the plastic effects of moderate exercise upon the motor cortex (M1 and M2 areas), cerebellum (Cb), and striatum (CPu) of the rat brain. This assessment was made by verifying the expression of AMPA-type glutamate receptor subunits (GluR1 and GluR2/3). We used adult Wistar rats, divided into 5 groups based on duration of exercise training, namely 3 days (EX3), 7 days (EX7), 15 days (EX15), 30 days (EX30), and sedentary (S). The exercised animals were subjected to a treadmill exercise protocol at the speed of the 10 meters/min for 40 min. After exercise, the brains were subjected to immunohistochemistry and immunoblotting to analyze changes of GluR1 and GluR2/3, and plasma corticosterone was measured by ELISA in order to verify potential stress induced by physical training. Overall, the results of immunohistochemistry and immunoblotting were similar and revealed that GluR subunits show distinct responses over the exercise periods and for the different structures analyzed. In general, there was increased expression of GluR subunits after longer exercise periods (such as EX30), although some opposite effects were seen after short periods of exercise (EX3). In a few cases, biphasic patterns with decreases and subsequent increases of GluR expression were seen and may represent the outcome of exercise-dependent, complex regulatory processes. The data show that the protocol used was able to promote plastic GluR changes during exercise, suggesting a specific involvement of these receptors in exercise-induced plasticity processes in the brain areas tested.

Differential response of AMPA and NMDA glutamate receptors of Purkinje cells to aging of the chicken cerebellum.

Aging can lead to cognitive, affective, learning, memory and motor deficits. Since the cerebellum and glutamatergic neurotransmission are involved in several of those functions, the present work aimed at studying the expression of AMPA and NMDA glutamate receptor subunits in the chick cerebellum during aging. Young (30 days old) and aged (ca. 4 years old) chickens (Gallus gallus) were used in order to evaluate the expression of GluR1, GluR2/3 and NR1 subunits. The cerebella of young and aged chickens were subjected to immunohistochemical and immunoblotting techniques. Numbers of GluR1, GluR2/3 and NR1-positive cells and optical density of the immunoblotting data were analyzed and submitted to statistical analysis using ANOVA and the Bonferroni post hoc test. Mean density of Purkinje cells stained for Giemsa, GluR1, GluR2/3 and NR1 in the cerebellum all showed a statistically significant decrease in aged animals when compared to the young animals (Giemsa, P<0.01; GluRs and NR1, P<0.03). However, the ratio of GluR1 and GluR2/3-positive Purkinje cells in relation the total number of Purkinje cells found in each time point decreased with aging (ca. 10%), whereas the ratio of NR1-positive cells increased (ca. 9%). The immunoblotting data showed a significant decrease of GluR1 (ca. 66%) and GluR2/3 (ca. 55%) protein expression with aging, but did not reveal changes for NR1. Our data suggest that aging can lead to differential changes in the pattern of expression of glutamate receptor subunits, which can underlie at least part of the cognitive and motor disorders found in aged animals.

Ontogeny of subunits 2 and 3 of the AMPA-type glutamate receptors in Purkinje cells of the developing chick cerebellum.

Several molecules, involved in cellular communication in the mature nervous system, appear to play important roles during neural development. These roles include neuronal growth, morphological changes of neurites, and neuronal survival. Such plasticity processes seem to be in part the result of activation of different receptor subtypes, which could cause Ca(2+) influx, a major candidate to be an outgrowth promoter. In this context, we performed immunohistochemical and in situ hybridization experiments to examine the following aspects of the development of chick cerebellum Purkinje cells: (i) expression of AMPA-type glutamate receptor GluR2/3 proteins; (ii) the levels of mRNAs coding for the GluR2 and GluR3 flip/flop isoforms; and (iii) expression of calbindin (CB) and parvalbumin (PV). Expression of GluR2/3 proteins, CB, PV, and the mRNAs coding for GluR2 and GluR3 splice variants all revealed a differential expression during development in chick Purkinje cells. GluR2/3 proteins and the GluR3 flop variant start to be expressed at E10, while the expression of CB, PV, the GluR3 flip isoform and the splice variants of GluR2 all started around E12-E14. All proteins showed an increasing expression from embryonic stages into the posthatching period. These results reveal a developmentally regulated expression of GluR2/3 proteins, including their splice variants, and of CB and PV in Purkinje cells. These findings may suggest a relationship between these proteins and specific cerebellar developmental processes.

Neurotransmitter receptor regulation after deafferentation in the visual system

The present study aimed at understanding the regulation of AMPA-type glutamate receptors (GluRs) and nicotinic acetylcholine receptors (nAChRs) during experimentally-induced neurodegeneration in the chick visual system. Immunohistochemistry, in situ hybridization, and RNAse protection techniques were used to verify the expression of GluR and nAChR subunits at several periods after deafferentation, ranging from 1 to 30 days. The results indicate that GluR1 and 2 expression changes in a biphasic way after deafferentation, decreasing after the shortest survival periods (1-4 days) and increasing afterwards. These effects clearly involve regulation of gene expression, as verified by in situ hybridization and RNAse protection. The regulation of the α2, α4, α5, and β2 nAChR subunits after deafferentation, on the other hand, exhibited a pattern that was exactly the opposite, with an early increase followed by a consistent decrease of expression until 30 days postlesion. Furthermore, nAChR changes were not apparently due to gene expression regulation, but instead by up-regulation/ down-regulation at a protein level. These results suggest that neurotransmitter receptors undergo differential plastic changes after deafferentation in the nervous system and contribute data to their possible role in neurodegeneration and neuroprotection processes.

The C-type natriuretic peptide precursor of snake brain contains highly specific inhibitors of the angiotensin-converting enzyme.

The bradykinin-potentiating peptides from Bothrops jararaca venom are the most potent natural inhibitors of the angiotensin-converting enzyme. The biochemical and biological features of these peptides were crucial to demonstrate the pivotal role of the angiotensin-converting enzyme in blood pressure regulation. In the present study, seven bradykinin-potentiating peptides were identified within the C-type natriuretic peptide precursor cloned from snake brain. The bradykinin-potentiating peptides deduced from the B. jararaca brain precursor are strong in vitro inhibitors of the angiotensin-converting enzyme (nanomolar range), and also potentiate the bradykinin effects in ex vivo and in vivo experiments. Two of these peptides are novel bradykinin-potentiating peptides, one of which displays high specificity toward the N-domain active site of the somatic angiotensin-converting enzyme. In situ hybridization studies revealed the presence of the bradykinin-potentiating peptides precursor mRNAs in distinct regions of the B. jararaca brain, such as the ventromedial hypothalamus, the paraventricular nuclei, the paraventricular organ, and the subcommissural organ. The biochemical and pharmacological properties of the brain bradykinin-potentiating peptides, their presence within the neuroendocrine regulator C-type natriuretic peptide precursor, and their expression in regions of the snake brain correlated to neuroendocrine functions, strongly suggest that these peptides belong to a novel class of endogenous vasoactive peptides.

The C-type natriuretic peptide precursor of snake brain contains highly specific inhibitors of the angiotensin-converting enzyme

The bradykinin-potentiating peptides from Bothrops jararaca venom are the most potent natural inhibitors of the angiotensin-converting enzyme. The biochemical and biological features of these peptides were crucial to demonstrate the pivotal role of the angiotensin-converting enzyme in blood pressure regulation. In the present study, seven bradykinin-potentiating peptides were identified within the C-type natriuretic peptide precursor cloned from snake brain. The bradykinin-potentiating peptides deduced from the B. jararaca brain precursor are strong in vitro inhibitors of the angiotensin-converting enzyme (nanomolar range), and also potentiate the bradykinin effects in ex vivo and in vivo experiments. Two of these peptides are novel bradykinin-potentiating peptides, one of which displays high specificity toward the N-domain active site of the somatic angiotensin-converting enzyme. In situ hybridization studies revealed the presence of the bradykinin-potentiating peptides precursor mRNAs in distinct regions of the B. jararaca brain, such as the ventromedial hypothalamus, the paraventricular nuclei, the paraventricular organ, and the subcommissural organ. The biochemical and pharmacological properties of the brain bradykinin-potentiating peptides, their presence within the neuroendocrine regulator C-type natriuretic peptide precursor, and their expression in regions of the snake brain correlated to neuroendocrine functions, strongly suggest that these peptides belong to a novel class of endogenous vasoactive peptides.

Interspecific differences in the expression of the AMPA-type glutamate receptors and parvalbumin in the nucleus of Edinger-Westphal of chicks and pigeons.

The distribution of AMPA-type glutamate receptor (GluR) subunits was studied in the Edinger-Westphal nucleus (EW) of chicks and pigeons. GluR1, GluR2, GluR3 and GluR4 subunits appeared to be present in EW neurons of both species, but interspecific differences were observed in the abundance of the different types of subunits found in EW neurons. Of particular note, GluR2 immunoreactivity was present in the vast majority (ca. 80%) of neurons of pigeon EW but was found in only a small fraction (ca. 15%) of chick EW neurons. Scarcity of the GluR2 subunit in chick EW was confirmed by in situ hybridization. Because of the tendency for parvalbumin to be localized to neurons that are selectively deficient in GluR2, we also studied the localization of parvalbumin, as well as other calcium-binding proteins, in EW of chick and pigeon. Parvalbumin was found in more than 50% of chick EW neurons but was not detected in pigeon EW neurons. Our results suggest that there are major glutamatergic inputs to EW neurons in both pigeons and chicks. Furthermore, there are likely to be more AMPA-type calcium-permeable glutamate receptors in EW neurons of chick than in pigeon, since it is known that the subtype containing the edited GluR2 subunit is not calcium permeable.