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1.
Behav Brain Res ; 459: 114793, 2024 02 29.
Artigo em Inglês | MEDLINE | ID: mdl-38048909

RESUMO

This study investigated the antinociceptive potential of cannabidiol (CBD) in male and female Wistar rats. The assessment and analysis included tail withdrawal to thermal stimulation (tail flick test) and mechanical allodynia induced by plantar incision injury (von Frey test). CBD reduced acute thermal sensitivity in uninjured animals and post-operative mechanical allodynia in males and females. In the tail flick test, CBD 30 mg/kg i.p. was required to induce antinociception in males. During the proestrus phase, females did not show a statistically significant antinociceptive response to CBD treatment despite a noticeable trend. In contrast, in a separate group of rats tested during the late diestrus phase, antinociception varied with CBD dosage and time. In the post-operative pain model, CBD at 3 mg/kg decreased mechanical allodynia in males. Similarly, this dose reduced allodynia in females during proestrus. However, in females during late diestrus, the lower dose of CBD (0.3 mg/kg) reduced mechanical allodynia, although the latency to onset of the effect was slower (90 min). The effectiveness of a 10-fold lower dose of CBD during the late diestrus stage in females suggests that ovarian hormones can influence the action of CBD. While CBD has potential for alleviating pain in humans, personalized dosing regimens may need to be developed to treat pain in women.


Assuntos
Canabidiol , Ratos , Feminino , Masculino , Humanos , Animais , Canabidiol/farmacologia , Hiperalgesia/tratamento farmacológico , Ratos Wistar , Dor Pós-Operatória/tratamento farmacológico , Analgésicos/farmacologia , Analgésicos/uso terapêutico
2.
Int J Biol Macromol ; 257(Pt 1): 128362, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38029898

RESUMO

N-glycosylation at the antibody variable domain has emerged as an important modification influencing antibody function. Despite its significance, information regarding its role and regulation remains limited. To address this gap, we comprehensively explored antibody structures housing N-glycosylation within the Protein Data Bank, yielding fresh insights into this intricate landscape. Our findings revealed that among 208 structures, N-glycosylation was more prevalent in human and mouse antibodies containing IGHV1-8 and IGHV2-2 germline genes, respectively. Moreover, our research highlights the potential for somatic hypermutation to introduce N-glycosylation sites by substituting polar residues (Ser or Thr) in germline variable genes with asparagine. Notably, our study underscores the prevalence of N-glycosylation in antiviral antibodies, especially anti-HIV. Besides antigen-antibody interaction, our findings suggest that N-glycosylation may impact antibody specificity, affinity, and avidity by influencing Fab dimer formation and complementary-determining region orientation. We also identified different glycan structures in HIV and SARS-CoV-2 antibody proteomic datasets, highlighting disparities from the N-glycan structures between PDB antibodies and biological repertoires further highlighting the complexity of N-glycosylation patterns. Our findings significantly enrich our understanding of the N-glycosylation's multifaceted characteristics within the antibody variable domain. Additionally, they underscore the pressing imperative for a more comprehensive characterization of its impact on antibody function.


Assuntos
Anticorpos Antivirais , Proteômica , Humanos , Camundongos , Animais , Glicosilação , Anticorpos Antivirais/metabolismo , Polissacarídeos/metabolismo
3.
Plants (Basel) ; 12(23)2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38068664

RESUMO

The adaptive potential of plants is commonly used as an indicator of genotypes with higher breeding program potential. However, the complexity and interaction of plant metabolic parameters pose a challenge to selection strategies. In this context, this study aimed to explore phenotypic plasticity within the germplasm of Hybrid Timor coffee. Additionally, we assessed the utility of the multivariate phenotypic plasticity index (MVPi) as a promising tool to predict genotype performance across diverse climatic conditions. To achieve this, we evaluated the performance of seven accessions from the Hybrid Timor germplasm in comparison to the Rubi and IPR 100 cultivars, known for their susceptibility and resistance to drought, respectively. The experiment took place in a greenhouse under two conditions: one with normal soil moisture levels near maximum capacity, and the other with a water deficit scenario involving a period of no irrigation followed by rehydration. Data on physiological and biochemical factors were collected at three stages: before applying the water deficit, during its imposition, and after rehydration. Growth data were obtained by the difference between the beginning and end of the experimental period Furthermore, field evaluations of the productivity of the same genotypes were carried out over two consecutive seasons. Based on physiological and biochemical assessments, the MVPi was computed, employing Euclidean distance between principal component multivariate analysis scores. Subsequently, this index was correlated with growth and productivity data through linear regressions. Our findings reveal that the plastic genotypes that are capable of significantly altering physiological and biochemical parameters in response to environmental stimuli exhibited reduced biomass loss in both aerial and root parts. As a result, this positively influenced their productivity. Enhanced plasticity was particularly prominent in accessions from the MG Germplasm Collection: MG 311-Hybrid Timor UFV 428-02, MG 270-Hybrid Timor UFV 377-21, and MG 279-Hybrid Timor UFV 376-31, alongside the Rubi MG 1192 cultivar. The MVPi emerged as a valuable instrument to assess genotype adaptability and predict their performance under varying climatic scenarios.

4.
J Psychopharmacol ; 36(11): 1257-1272, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36239034

RESUMO

BACKGROUND: Panic-like reactions elicited by electrical stimulation of the dorsal periaqueductal grey matter (ES-dPAG) seem to be regulated by dopamine (DA). We showed that DA applied intranasally (IN) increased escape-behaviour thresholds induced by ES-dPAG of rats, indicating a panicolytic-like effect. AIMS: We investigated whether IN-DA increases escape-response thresholds induced by ES-dPAG by acting on D2-like receptors, and whether IN-DA affects escape responses elicited by the presence of a potential predator and by open space and height of the elevated T-maze (ETM) as well as motor performance in the open field (OF) test. METHODS: Wistar rats exposed to ES-dPAG were treated with Sulpiride (SUL, 40 mg/kg, D2-like receptor antagonist) previously IN-DA (2 mg/kg). Independent groups of rats treated with IN-DA were submitted to prey versus snake paradigm (PSP), ETM and OF. RESULTS: Anti-aversive effects of the IN-DA were reduced by SUL pretreatment in the ES-dPAG test. IN-DA did not affect the escape number in the PSP nor the escape latencies in the ETM as well as motor performance in the OF. CONCLUSIONS/INTERPRETATION: The IN-DA effects in reducing unconditioned fear responses elicited by ES-dPAG seem to be mediated by D2-like receptors. The lack of effects on panic-related responses in the ETM and PSP may be related to the possibility of avoiding the danger inherent to these models, a defence strategy not available during ES-dPAG. These findings cannot be attributed to motor performance. The decision-making responses to avoid dangerous situations can be orchestrated by supra-mesencephalic structures connected by non-dopaminergic inputs.


Assuntos
Crotalinae , Substância Cinzenta Periaquedutal , Ratos , Animais , Dopamina/farmacologia , Ratos Wistar , Medo , Estimulação Elétrica , Reação de Fuga
5.
J Psychopharmacol ; 36(12): 1371-1383, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36239039

RESUMO

RATIONALE: Cannabidiol (CBD), the major non-psychoactive constituent of cannabis, has therapeutic potential for the treatment of anxiety. Most preclinical studies investigate only acute effects of CBD and only in males, yet the drug is most likely to be used over a sustained period in clinical practice. OBJECTIVES: The objectives of this study were to investigate the anxiolytic-like effect of CBD in female rats compared to males and to determine whether the responsiveness of females was influenced by the stage of the estrous cycle. METHODS: We carried out experiments to compare the effect of CBD in male and female rats in the elevated plus maze (EPM) in response to acute and short-term (4 days) administration through a complete cycle in females. RESULTS: Male and female rats behaved in a similar manner in the EPM, but females in the late diestrus (LD) phase exhibited more anxiety-like behavior than at other stages, the difference reaching statistical significance compared to proestrus stages. CBD produced anxiolytic-like effects in both sexes, but female rats were responsive only in LD and 10-fold lower dose than males. After sub-chronic (4 days) treatment, responsiveness to CBD was maintained in females in LD, but females in proestrus remained unresponsive to CBD treatment. CONCLUSIONS: We suggest that there are sex differences in the anxiolytic-like effects of CBD in rats that reflect different underlying mechanisms: based on literature data, gonadal hormone status linked to GABAA receptor expression in females, and 5-HT1A receptor activation in males.


Assuntos
Ansiolíticos , Canabidiol , Feminino , Masculino , Ratos , Animais , Ansiolíticos/farmacologia , Canabidiol/farmacologia , Canabidiol/uso terapêutico , Teste de Labirinto em Cruz Elevado , Caracteres Sexuais , Ratos Wistar , Ansiedade/tratamento farmacológico , Ansiedade/metabolismo , Receptores de GABA-A
6.
Neurosci Lett ; 772: 136477, 2022 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-35090949

RESUMO

Treating depression associated with type-1 diabetesmellitus(T1DM) is a major clinical challenge. Fish oil (FO), composed mostly of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), has been pointed out as quite promising for the treatment of depression given its neuroprotective property. Although DHA and EPA exert several physiological actions, DHA is known to play a critical role in postnatal brain development. This study aimed to investigate the effect of preventive treatment with FO (with more DHA in the composition) alone or associated with antidepressant drugs on depression-like behaviors and brain monoamines levels of juvenile induced-T1DM rats. Thus, prepubescent rats were submitted to a prolonged treatment with vehicle (VEH) or FO (50% of DHA and 20% EPA) starting 4 weeks before the induction of experimental T1DM (on day 28) by streptozotocin. When combined, the treatment with vehicle, fluoxetine (FLX, a selective serotonin reuptake inhibitor) or imipramine (IMI, a tricyclic antidepressant) started at week 6 (day 42) and lasted for 2 weeks (until day 56). The behavioral tests were conducted on days 55 and 56, followed by hippocampal and prefrontal cortex dissection for neurochemical analyses. Our results showed that induced-T1DM rats pretreated with FO showed a significant increase of EPA and DHA in plasma, indicative of an increase in the systemic availability of these acids. As previously observed, induced-T1DM rats presented increased immobility and decreased swimming and climbing frequencies in the modified forced swimming test, indicative of depressive-like behavior. Only the combined treatment - FO plus antidepressants (FLX or IMI - both in the highest dose) - was able to induce a significant improvement of depressive-like behaviors. Here, it is noteworthy that swimming behavior has been associated with an increase in serotonergic neurotransmission. Interestingly, our data showed that the combined treatment (FO + antidepressants - including the ineffective dose of FLX) was able to increase the swimming of animals more significantly compared to animals not pretreated with FO. In addition, confirming these assumptions, the decreased 5-HT levels in the hippocampus from induced-T1DM rats were increased after treatment with FLX (highest dose) or IMI (both doses), being this increase more pronounced in animal pretreated with FO. Intriguingly, in these animals pretreated with FO, the ineffective dose of FLX in association with FO was able to increase the levels of 5-HT. The decreased hippocampal levels of noradrenaline were increased only after IMI treatment, not being influenced by FO pretreatment. In conclusion, ours results pointed out that the choice of the DHA/EPA ratio may be an important factor to be considered for the FO antidepressant-like effectper se,but the FO treatment in this composition associated with the antidepressant drugs - especially that ones that increase preferentially the availability of 5-HT -, may represent a better alternative of treatment to individuals with T1DM-associated depression.


Assuntos
Depressão/tratamento farmacológico , Diabetes Mellitus Tipo 1/prevenção & controle , Óleos de Peixe/uso terapêutico , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Serotonina/metabolismo , Animais , Depressão/etiologia , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/psicologia , Sinergismo Farmacológico , Óleos de Peixe/farmacologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Ratos , Ratos Wistar , Inibidores Seletivos de Recaptação de Serotonina/farmacologia
7.
Behav Brain Res ; 417: 113611, 2022 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-34592376

RESUMO

Fear extinction (FExt) is used to treat patients with posttraumatic stress disorder (PTSD). However, fear related to traumatic events can be persistent and return even after successful extinction. The neurochemical control of extinction seems to be performed by several neurotransmitters, including dopamine (DA), through D1 and D2 receptors. Recently, we showed that intranasally applied DA (IN-DA) facilitated the FExt, but the mechanisms by which it promoted this effect are still unknown. This study focused on investigating whether these effects are mediated by the action of DA on D2-like receptors since these receptors seem to be related to neurochemical and molecular changes underlying extinction. Also, we investigated whether IN-DA treatment would affect conditioned fear-induced antinociception (Fear-IA). Rats treated with IN-DA (1 mg/kg) twenty-five minutes after sulpiride (SUL; 40 mg/kg, i.p., D2-antagonist) were subjected to the extinction of contextual fear. IN-DA applied before the extinction session induced the FExt and prevented Fear-IA. These effects were impaired by pre-treatment with SUL, suggesting that the IN-DA effects are mediated by DA on D2-like receptors. SUL per se also facilitated the FExt but did not affect Fear-IA. These data suggest IN-DA as a promising pharmacological tool to supplement the psychotherapy of patients suffering from PTSD.


Assuntos
Condicionamento Psicológico/fisiologia , Antagonistas dos Receptores de Dopamina D2/farmacologia , Dopamina/farmacologia , Extinção Psicológica/fisiologia , Medo/fisiologia , Receptores de Dopamina D2/fisiologia , Sulpirida/farmacologia , Administração Intranasal , Animais , Condicionamento Psicológico/efeitos dos fármacos , Dopaminérgicos/farmacologia , Extinção Psicológica/efeitos dos fármacos , Masculino , Ratos , Sulpirida/antagonistas & inibidores
8.
Physiol Behav ; 234: 113372, 2021 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-33647267

RESUMO

It is unclear whether all animal models of anxiety-like states developed using males are appropriate for use in females. In females, tests involving a learning component might be influenced not only by estrous cycle stage on the test day but also by the stage during the conditioning process. We used two tests - conditioned freezing (CF) and fear potentiated startle (FPS) to compare responsiveness of male rats and females conditioned and/or tested in proestrus (P) or late diestrus (LD). For CF all rats displayed a similar freezing response regardless of sex or estrous cycle stage. In terms of FPS, males and females conditioned in P and tested in P or LD, and females conditioned in LD and tested in LD all showed potentiated startle. The response waned during the test session in males and in females conditioned in P, but not in those conditioned in LD. In contrast, FPS was not apparent in the first half of the test session in females conditioned in LD and tested in P but developed in the second half. We suggest that fear learning during P and LD is robust but may be initially be obscured in rats tested in P because of generalization to the CS due to high estrogen. Estrous cycle stage is an important consideration which must be taken into account in designing behavioural tests in females.


Assuntos
Ciclo Estral , Reflexo de Sobressalto , Animais , Medo , Feminino , Masculino , Proestro , Ratos , Ratos Sprague-Dawley
9.
Neurobiol Stress ; 12: 100219, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32435668

RESUMO

Avoidance behavior is a hallmark in pathological anxiety disorders and results in impairment of daily activities. Individual differences in avoidance responses are critical in determining vulnerability or resistance to anxiety disorders. Dopaminergic activation is implicated in the processing of avoidance responses; however, the mechanisms underlying these responses are unknown. In this sense, we used a preclinical model of avoidance behavior to investigate the possibility of an intrinsic differential dopaminergic pattern between good and poor performers. The specific goal was to assess the participation of dopamine (DA) through pharmacological manipulation, and we further evaluated the effects of systemic injections of the dopaminergic receptor type 1 (D1 antagonist - SCH23390) and dopaminergic receptor type 2 (D2 antagonist - sulpiride) antagonists in the good performers. Additionally, we evaluated the effects of intra-amygdala microinjection of a D1 antagonist (SCH23390) and a D2 antagonist (sulpiride) in good performers as well as intra-amygdala microinjection of a D1 agonist (SKF38393) and D2 agonist (quinpirole) in poor performers. Furthermore, we quantified the contents of dopamine and metabolites (3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA)) in the amygdala, evaluated the basal levels of tyrosine hydroxylase expression (catecholamine synthesis enzyme) and measured the volume of the substantia nigra, ventral tegmental area and locus coeruleus. Our results showed that it could be possible to convert animals from good to poor performers, and vice versa, by intra-amygdala (basolateral and central nucleus) injections of D1 receptor antagonists in good performers or D2 receptor agonists in poor performers. Additionally, the good performers had lower levels of DOPAC and HVA in the amygdala, an increase in the total volume of the amygdala (AMG), substantia nigra (SN), ventral tegmental area (VTA) and locus coeruleus (LC), and an increase in the number of tyrosine hydroxylase-positive cells in SN, VTA and LC, which positively correlates with the avoidance behavior. Taken together, our data show evidence for a dopaminergic signature of avoidance performers, emphasizing the role of distinct dopaminergic receptors in individual differences in avoidance behavior based on pharmacological, immunohistochemical, neurochemical and volumetric analyses. Our findings provide a better understanding of the role of the dopaminergic system in the execution of avoidance behavior.

10.
Front Plant Sci ; 11: 309, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32265962

RESUMO

Epidemics of coffee leaf rust (CLR) leads to great yield losses and huge depreciation of coffee marketing values, if no control measures are applied. Societal expectations of a more sustainable coffee production are increasingly imposing the replacement of fungicide treatments by alternative solutions. A protection strategy is to take advantage of the plant immune system by eliciting constitutive defenses. Based on such concept, plant resistance inducers (PRIs) have been developed. The Greenforce CuCa formulation, similarly to acibenzolar-S-methyl (ASM), shows promising results in the control of CLR (Hemileia vastatrix) in Coffea arabica cv. Mundo Novo. The molecular mechanisms of PRIs action are poorly understood. In order to contribute to its elucidation a proteomic, physiological (leaf gas-exchange) and biochemical (enzymatic) analyses were performed. Coffee leaves treated with Greenforce CuCa and ASM and inoculation with H. vastatrix were considered. Proteomics revealed that both PRIs lead to metabolic adjustments but, inducing distinct proteins. These proteins were related with photosynthesis, protein metabolism and stress responses. Greenforce CuCa increased photosynthesis and stomatal conductance, while ASM caused a decrease in these parameters. It was further observed that Greenforce CuCa reinforces the redox homeostasis of the leaf, while ASM seems to affect preferentially the secondary metabolism and the stress-related proteins. So, the PRIs prepare the plant to resist CLR but, inducing different defense mechanisms upon pathogen infection. The existence of a link between the primary metabolism and defense responses was evidenced. The identification of components of the plant primary metabolism, essential for plant growth and development that, simultaneously, participate in the plant defense responses can open new perspectives for plant breeding programs.

11.
J Psychopharmacol ; 33(12): 1524-1532, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31328620

RESUMO

PURPOSE: Intranasally applied dopamine (IN-DA), which likely reaches the brain via nasal-brain pathways and bypasses the blood-brain barrier, has been found to increase extracellular DA and bind to the DA2 transporter in the striatum. Recent studies suggest that DA plays a significant role in the processing of signaled and unconditioned aversive stimulation, including evidence that may attenuate responses to painful input. The purpose of this study was to examine the effects of IN-DA on fear-related behaviors induced by electric shock to the foot or by electrical stimulation of the dorsal periaqueductal gray matter (dPAG). METHODS: DA hydrochloride suspended in a viscous castor oil gel (1 or 2 mg/kg) was applied (IN-DA) in a volume of 5 µL into the nostrils of adult Wistar male rats in order to evaluate its effects on (a) freezing induced by electric shock to the foot and (b) thresholds of freezing and escape and duration of post-stimulation freezing induced by electrical stimulation of the dPAG. RESULTS: IN-DA attenuated freezing induced by electric shock to the foot in the three test trials, indicating that it reduced long-term fear responses. IN-DA also increased the threshold of dPAG stimulation-induced escape responses and reduced post-stimulation freezing. CONCLUSIONS: IN-DA, which has previously been shown to facilitate learning and to have antidepressive-like effects, attenuated unconditioned fear responses elicited by peripheral and intramesencephalic (dPAG) stimulation and reduced long-term conditioned fear responses.


Assuntos
Dopamina/farmacologia , Estimulação Elétrica , Medo/efeitos dos fármacos , Substância Cinzenta Periaquedutal/metabolismo , Administração Intranasal , Animais , Comportamento Animal/efeitos dos fármacos , Dopamina/administração & dosagem , Eletrochoque , Reação de Fuga/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar , Fatores de Tempo
12.
J Pathol ; 249(1): 102-113, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31038736

RESUMO

Serotonin (5-HT) signaling pathways are thought to be involved in colorectal tumorigenesis (CRT), but the role of 5-HT synthesis in the early steps of this process is presently unknown. In this study, we used carcinogen treatment in the tryptophan hydroxylase 1 knockout (Tph1KO) and transgenic (Tph1fl/fl VillinCre ) mouse models defective in 5-HT synthesis to investigate the early mutagenic events associated with CRT. Our observations of the colonic crypt post-treatment followed a timeline designed to understand how disruption of 5-HT synthesis affects the initial steps leading to CRT. We found Tph1KO mice had decreased development of both allograft tumors and colitis-related CRT. Interestingly, carcinogenic exposure alone induced multiple colon tumors and increased cyclooxygenase-2 (Ptgs2) expression in Tph1KO mice. Deletion of interleukin 6 (Il6) in Tph1KO mice confirmed that inflammation was a part of the process. 5-HT deficiency increased colonic DNA damage but inhibited genetic repair of specific carcinogen-related damage, leading to CRT-related inflammatory reactions and dysplasia. To validate a secondary effect of 5-HT deficiency on another DNA repair pathway, we exposed Tph1KO mice to ionizing radiation and found an increase in DNA damage associated with reduced levels of ataxia telangiectasia and Rad3 related (Atr) gene expression in colonocytes. Restoring 5-HT levels with 5-hydroxytryptophan treatment decreased levels of DNA damage and increased Atr expression. Analysis of Tph1fl/fl VillinCre mice with intestine-specific loss of 5-HT synthesis confirmed that DNA repair was tissue specific. In this study, we report a novel protective role for 5-HT synthesis that promotes DNA repair activity during the early stages of colorectal carcinogenesis. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Assuntos
Transformação Celular Neoplásica/metabolismo , Colo/metabolismo , Neoplasias Colorretais/prevenção & controle , Dano ao DNA , Reparo do DNA , Lesões Pré-Cancerosas/prevenção & controle , Serotonina/biossíntese , Animais , Proteínas Mutadas de Ataxia Telangiectasia/genética , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Fator de Transcrição CDX2/genética , Fator de Transcrição CDX2/metabolismo , Linhagem Celular Tumoral , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/patologia , Colo/patologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Interleucina-6/deficiência , Interleucina-6/genética , Camundongos Knockout , Proteínas dos Microfilamentos/genética , Proteínas dos Microfilamentos/metabolismo , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/metabolismo , Lesões Pré-Cancerosas/patologia , Transdução de Sinais , Fatores de Tempo , Triptofano Hidroxilase/deficiência , Triptofano Hidroxilase/genética
13.
Nucleic Acids Res ; 47(W1): W490-W495, 2019 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-31106372

RESUMO

As antibodies are a very important tool for diagnosis, therapy, and experimental biology, a large number of antibody structures and sequences have become available in recent years. Therefore, tools that allow the analysis, comparison, and visualization of this large amount of antibody data are crucially needed. We developed the antibody high-density alignment visualization and analysis (Yvis) platform to provide an innovative, robust and high-density data visualization of antibody sequence alignments, called Collier de Diamants. The Yvis platform also provides an integrated structural database, which is updated weekly, and many different search and filter options. This platform can help to formulate hypotheses concerning the key residues in antibody structures or interactions to improve the understanding of antibody properties. The Yvis platform is available at http://bioinfo.icb.ufmg.br/yvis/.


Assuntos
Anticorpos/química , Alinhamento de Sequência , Software , Gráficos por Computador , Bases de Dados de Proteínas , Anticorpos Anti-HIV/química , Humanos , Região Variável de Imunoglobulina/química , Análise de Sequência de Proteína
14.
J Psychopharmacol ; 33(5): 548-557, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31012390

RESUMO

BACKGROUND AND AIMS: We sought a robust behavioural test that evoked increased anxiety-like behaviour during the late dioestrus phase of the oestrous cycle (similar to the premenstrual period in women) and tested whether this could be prevented by acute low-dose fluoxetine (FLX). METHODS: Female Wistar rats in different stages of their cycle were exposed to four different tests of anxiety-like behaviour. RESULTS: No oestrous cycle differences were detected in fear potentiated startle or conditioned freezing to an aversive context. In a light switch-off test where rats move from one compartment of a shuttle-box to the other to turn off an aversive light, females displayed enhanced responding in late dioestrus. During isolation restraint stress females in late dioestrus emitted three times more 22 kHz ultrasound vocalisations (USV) than at other cycle stages. Using the USV test, short-term administration of low-dose FLX (1.75 mg kg-1, i.p.) designed to blunt the sharp fall in brain allopregnanolone concentration during late dioestrus but without affecting 5-HT systems, prevented the increase in isolation stress-evoked USVs. CONCLUSIONS: The light switch-off and isolation restraint-induced USV tests evoke unconditioned adverse emotional responses that are ethologically relevant and sensitive to oestrous cycle stage. The USV test fulfils many criteria required of a model for premenstrual syndrome in women. Using the USV test, short-term administration of FLX to increase brain allopregnanolone concentration without affecting 5-HT systems prevented the increased USV responding in late dioestrus. Short-term low-dose FLX treatment may have potential to alleviate development of adverse premenstrual symptoms in women.


Assuntos
Ansiedade/metabolismo , Ansiedade/prevenção & controle , Comportamento Animal/efeitos dos fármacos , Ciclo Estral/metabolismo , Fluoxetina/farmacologia , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Animais , Modelos Animais de Doenças , Medo/efeitos dos fármacos , Feminino , Fluoxetina/administração & dosagem , Ratos , Ratos Wistar , Reflexo de Sobressalto/efeitos dos fármacos , Inibidores Seletivos de Recaptação de Serotonina/administração & dosagem , Vocalização Animal/efeitos dos fármacos
15.
Brain Res ; 1715: 156-164, 2019 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-30898678

RESUMO

Most diabetic patients describe moderate to severe pain symptoms whose pharmacological treatment is palliative and poorly effective. Cannabidiol (CBD) has shown promising results in painful conditions. Then, we aimed to investigate the potential antinociceptive effect of CBD over the mechanical allodynia in streptozotocin-induced diabetic (DBT) rats, as well as its involved mechanisms. Wistar adult male diabetic rats were treated acutely or sub-chronically (for 14 days) with CBD (0.1, 0.3 or 3 mg/kg, intraperitoneal; i.p.) and had their mechanical threshold assessed using the electronic Von Frey. Acute treatment with CBD (at doses of 0.3 and 3 mg/kg) exerted a significant anti-allodynic effect, which is not associated with locomotor impairment. The antinociceptive effect of CBD (3 mg/kg) was not altered by the pre-treatment with CB1 or CB2 receptor antagonists (AM251 and AM630; respectively; both at a dose of 1 mg/kg, i.p.) nor by glycine receptor antagonist (strychnine hydrochloride, 10 µg/rat, intrathecal, i.t.). However, this effect was completely prevented by the pre-treatment with the selective 5-HT1A receptor antagonist WAY 100135 (3 µg/rat, i.t.). Sub-chronic treatment with CBD (0.3 or 3 mg/kg) induced a sustained attenuation of the mechanical allodynia in DBT rats. DBT rats presented significantly lower spinal cord levels of serotonin, which was prevented by the daily treatment with CBD (0.3 mg/kg). Taken together, our data suggest that CBD may be effective in the treatment of painful diabetic neuropathy and this effect seems to be potentially mediated by the serotonergic system activation through 5-HT1A receptors.


Assuntos
Canabidiol/farmacologia , Hiperalgesia/tratamento farmacológico , Receptor 5-HT1A de Serotonina/efeitos dos fármacos , Animais , Canabidiol/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Modelos Animais de Doenças , Hiperalgesia/metabolismo , Masculino , Neuralgia/tratamento farmacológico , Piperazinas/farmacologia , Piperidinas/farmacologia , Pirazóis/farmacologia , Piridinas/farmacologia , Ratos , Ratos Wistar , Receptor 5-HT1A de Serotonina/metabolismo , Estreptozocina/farmacologia
16.
Rev. enferm. UFPE on line ; 13(3): 852-857, mar. 2019.
Artigo em Português | BDENF - Enfermagem | ID: biblio-1015887

RESUMO

Objetivo: realizar uma ação educativa sobre o aleitamento materno, para gestantes na sala de espera das consultas de pré-natal, em uma unidade municipal de saúde. Método: trata-se de um estudo descritivo, tipo relato de experiência. Refere-se a um jogo de perguntas aplicado a 15 gestantes, depois, ocorreu a discussão dos temas abordados. Resultados: percebeu-se que as gestantes ainda acreditam em muitos mitos que podem aumentar as chances de desmame precoce, baixo peso e adoecimento da criança, porém, estão cada vez mais informadas sobre a importância da amamentação, mas ainda precisam de orientações e atenção nesse momento da vida delas, pois ainda existem alguns mitos que prevalecem, podendo dificultar a adesão à amamentação exclusiva. Conclusão: tornam-se as ações em saúde relevantes, pois estimulam a troca de saberes entre profissionais e usuários e colaboram positivamente na promoção do aleitamento materno e no empoderamento dessas mulheres para a execução dessa prática. Desperta-se, nos acadêmicos, além disso, por meio de ações educativas em saúde, o lado educador inerente ao profissional enfermeiro.(AU)


Objective: to carry out an educational action on breastfeeding for pregnant women in the waiting room for prenatal consultations in a municipal health unit. Method: it is a descriptive study, type of experience report. Refers to a game of questions applied to 15 pregnant women, after which the discussion of the topics discussed took place. Results: pregnant women still believe in many myths that may increase their chances of early weaning, low weight and illness, but they are increasingly informed about the importance of breastfeeding, but they still need guidance and attention. of their lives, as there are still some myths that prevail, which may make adherence to exclusive breastfeeding difficult. Conclusion: relevant health actions become important, since they stimulate the exchange of knowledge between professionals and users and collaborate positively in the promotion of breastfeeding and in the empowerment of these women to carry out this practice. In the academics, moreover, the educational side inherent to the nurse professional is awakened through educational actions in health.(AU)


Objetivo: realizar una acción educativa sobre lactancia materna, para gestantes en la sala de espera de consultas prenatales, en una unidad municipal de salud. Método: se trata de un estudio descriptivo, tipo relato de experiencia. Se refiere a un juego de preguntas aplicado a 15 gestantes, enseguida, ocurrió una discusión de os temas abordados. Resultados: se percibió que las gestantes todavía creen en muchos mitos que pueden aumentar las chances de destete precoz, bajo peso y enfermedad del niño, sin embargo, están cada vez más informadas sobre la importancia del amamantamiento, pero todavía necesitan de orientaciones y atención en este momento de sus vidas, pues aún existen algunos mitos que prevalecen, pudiendo dificultar la adhesión al amamantamiento exclusivo. Concusión: se convierten las acciones en salud relevantes, pues estimulan el cambio de saberes entre profesionales y usuarios y colaboran positivamente en la promoción de la lactancia materna y en el empoderamiento de esas mujeres para la ejecución de esta práctica. Se despierta, en los académicos, además de eso, por medio de acciones educativas en salud, el lado educador inherente al profesional enfermero. (AU)


Assuntos
Humanos , Feminino , Gravidez , Recém-Nascido , Lactente , Cuidado Pré-Natal , Atenção Primária à Saúde , Aleitamento Materno , Educação em Saúde , Saúde Materno-Infantil , Saúde do Lactente , Promoção da Saúde , Relações Enfermeiro-Paciente , Epidemiologia Descritiva
18.
Eur Neuropsychopharmacol ; 26(10): 1590-600, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27544303

RESUMO

The pathophysiology associated with increased prevalence of depression in diabetics is not completely understood, although studies have pointed the endocannabinoid system as a possible target. Then, we aimed to investigate the role of this system in the pathophysiology of depression associated with diabetes. For this, diabetic (DBT) male Wistar rats were intraperitoneally treated with cannabinoid CB1 (AM251, 1mg/kg) or CB2 (AM630, 1mg/kg) receptor antagonists followed by anandamide (AEA, 0.005mg/kg) and then submitted to the forced swimming test (FST). Oxidative stress parameters, CB1 receptor expression and serotonin (5-HT) and noradrenaline levels in the hippocampus (HIP) and prefrontal cortex (PFC) were also performed. It was observed that DBT animals presented a more pronounced depressive-like behavior and increase of CB1 receptor expression in the HIP. AEA treatment induced a significant improvement in the depressive-like behavior, which was reversed by the CB1 antagonist AM251, without affecting the hyperglycemia or weight gain. AEA was also able to restore the elevated CB1 expression and also to elevate the reduced level of 5-HT in the HIP from DBT animals. In addition, AEA restored the elevated noradrenaline levels in the PFC and induced a neuroprotective effect by restoring the decreased reduced glutathione and increased lipid hydroperoxides levels along with the decreased superoxide dismutase activity observed in HIP or PFC. Together, our data suggest that in depression associated with diabetes, the endocannabinoid anandamide has a potential to induce neuroadaptative changes able to improve the depressive-like response by its action as a CB1 receptor agonist.


Assuntos
Ácidos Araquidônicos/uso terapêutico , Comportamento Animal/efeitos dos fármacos , Química Encefálica/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/uso terapêutico , Depressão/tratamento farmacológico , Depressão/etiologia , Diabetes Mellitus Experimental/psicologia , Endocanabinoides/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Alcamidas Poli-Insaturadas/uso terapêutico , Receptor CB1 de Canabinoide/efeitos dos fármacos , Animais , Indóis/farmacologia , Masculino , Norepinefrina/metabolismo , Piperidinas/farmacologia , Pirazóis/farmacologia , Ratos , Ratos Wistar , Receptor CB1 de Canabinoide/biossíntese , Serotonina/metabolismo , Natação/psicologia
19.
Mol Neurobiol ; 53(10): 6997-7009, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-26671617

RESUMO

Diabetes is a chronic disease associated with depression whose pathophysiological mechanisms that associate these conditions are not fully elucidated. However, the activation of the indoleamine-2,3-dioxygenase (IDO), an enzyme that participate of the tryptophan metabolism leading to a decrease of serotonin (5-HT) levels and whose expression is associated with an immune system activation, has been proposed as a common mechanism that links depression and diabetes. To test this hypothesis, diabetic (DBT) and normoglycemic (NGL) groups had the cytokines (TNFα, IL-1ß, and IL-6) and 5-HT and norepinephrine (NE) levels in the hippocampus (HIP) evaluated. Moreover, the effect of the selective serotonin reuptake inhibitor fluoxetine (FLX), IDO direct inhibitor 1-methyl-tryptophan (1-MT), anti-inflammatory and IDO indirect inhibitor minocycline (MINO), or non-selective cyclooxygenase inhibitor ibuprofen (IBU) was evaluated in DBT rats submitted to the modified forced swimming test (MFST). After the behavioral test, the HIP was obtained for IDO expression by Western blotting analysis. DBT rats exhibited a significant increase in HIP levels of TNFα, IL-1ß, and IL-6 and a decrease in HIP 5-HT and NA levels. They also presented a depressive-like behavior which was reverted by all employed treatments. Interestingly, treatment with MINO, IBU, or FLX but not with 1-MT reduced the increased IDO expression in the HIP from DBT animals. Taken together, our data support our hypothesis that neuroinflammation in the HIP followed by IDO activation with a consequent decrease in the 5-HT levels can be a possible pathophysiological mechanism that links depression to diabetes.


Assuntos
Depressão/tratamento farmacológico , Diabetes Mellitus Experimental/psicologia , Indolamina-Pirrol 2,3,-Dioxigenase/antagonistas & inibidores , Cinurenina/metabolismo , Terapia de Alvo Molecular , Animais , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Comportamento Animal , Glicemia/metabolismo , Citocinas/metabolismo , Depressão/sangue , Depressão/patologia , Depressão/fisiopatologia , Diabetes Mellitus Experimental/sangue , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/uso terapêutico , Fluoxetina/farmacologia , Fluoxetina/uso terapêutico , Hipocampo/metabolismo , Hipocampo/patologia , Ibuprofeno/farmacologia , Ibuprofeno/uso terapêutico , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Mediadores da Inflamação/metabolismo , Masculino , Minociclina/farmacologia , Minociclina/uso terapêutico , Atividade Motora/efeitos dos fármacos , Norepinefrina/metabolismo , Ratos Wistar , Serotonina/metabolismo , Natação , Triptofano/análogos & derivados , Triptofano/farmacologia , Triptofano/uso terapêutico , Aumento de Peso/efeitos dos fármacos
20.
Mitochondrial DNA A DNA Mapp Seq Anal ; 27(3): 2293-4, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-25469815

RESUMO

The first complete mitochondrial genome for the Anostomidae fish family has been announced. Piracema fishes are the potamodromous migratory species from South America, which undergo lengthy and dramatic yearly reproductive upstream runs. The piracema species Leporinus piavussu has recently been described after a long misidentification history. Its mitogenome, assembled using NGS data and Sanger sequencing, consists in a 16,682 bp circular molecule (GenBank accession number KM886569). The exact sequence and position of 37 mitochondrial genes and the control region is established. A possible case of heteroplasmy was found with NGS and corroborated by Sanger sequencing. These results will positively contribute to the debate about this group's taxonomy, evolution and conservation.


Assuntos
Caraciformes/genética , Genoma Mitocondrial , Animais , Códon , DNA Mitocondrial/química , DNA Mitocondrial/isolamento & purificação , DNA Mitocondrial/metabolismo , Sequenciamento de Nucleotídeos em Larga Escala , RNA Ribossômico 16S/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA
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