Evaluation of the effects of SPONDIAS MOMBIN extract as an alternative antimicrobial drug

The extract of Spondias mombin has constituents which may improve psychiatric disorders, in addition to having antiviral, antifungal, and antimicrobial activity. But despite having several benefits, it is necessary to assess whether the extract may interfere with cell metabolism so furthermore its microbicide potential can be explored. Fifteen Wistar rats were used, divided into four groups (control group; control with extract; hyperlipidemic diet; hyperlipidemic diet and extract). For 12 weeks, the animals were weighed and their blood glucose was assessed. Afterwards, they were euthanized, and the biological material was collected. The evaluation confirmed the efficacy of the extract of S. mombin against cell metabolism of rats, without negatively altering cell viability; the group of rats with an hyperlipidemic diet showed an increase in body weight; however, in the individual assessment of the organs, there were no significant changes. The glycemic index, liver parameters, lipids, and mineral ions did not show changes. Furthermore, the antimicrobial potential of S. mombin extract was observed against Staphylococcus aureus ATCC 29213 and Staphylococcus aureus BLACC. The results suggest that S. mombin extract did not interfere with cell viability, did not show cytotoxicity to cells that were exposed to it, nor did it interfere with the metabolism, organs, and biochemical indices of rats with a standard or hyperlipidemic diet. Considering such characteristics and the potential activities observed in this present study, additional evaluation should be conducted to further assess the role of S. mombin extract as a source of new alternative antimicrobial drug as well as its possible beneficial activity to the cardiovascular system.

Neurociência da música e ações da musicoterapia nos transtornos mentais: uma revisão sistemática / Neuroscience of music and actions of music therapy in mental disorders: a systematic review

Investigar o potencial musical no encéfalo humano como ferramenta terapêutica nos transtornos mentais. Realizou-se uma revisão sistemática com busca e seleção de estudos via Scielo, PubMed, Capes e BVS, relacionando a musicoterapia aos transtornos mentais. Para a busca, considerou-se publicações no período 2015 a 2020 em português ou inglês. Foram avaliados 11 artigos. A musicoterapia tem crescente destaque no manejo psicopatológico, possuindo diferentes aplicações terapêuticas, elevando a autopercepção e autorrealização, reduzindo ansiedade, depressão e afeto negativo. Evidenciou-se modificações encefálicas com aumento na conectividade funcional insular em esquizofrênicos e aumento da massa cinzenta no Tinnitus. Ademais, a musicoterapia aprimorou a resposta comportamental e relações interpessoais de idosos institucionalizados com demência e pacientes com Transtorno do Espectro do Autismo. A musicoterapia mostra forte potencial terapêutico nos transtornos mentais, induzindo alterações psicofisiológicas e cognitivo-comportamentais, sendo uma terapia eficaz, não invasiva e de baixo custo.

To investigate the musical potential in the human brain as a therapeutic tool in mental disorders. A systematic review was carried out with a search and selection of studies via Scielo, PubMed, Capes and VHL, relating music therapy to mental disorders. For the search, publications in the period 2015 to 2020, in Portuguese or English. Eleven articles were evaluated. Music therapy has an increasing prominence in psychopathological management, having different therapeutic applications, increasing self-perception and self-realization, reducing anxiety, depression, and negative affect. Brain changes were evidenced with an increase in insular functional connectivity in schizophrenics and an increase in gray matter in Tinnitus. In addition, music therapy improved the behavioral response and interpersonal relationships of institutionalized elderly people with dementia and patients with autism spectrum disorder. Music therapy shows strong therapeutic potential in mental disorders, inducing psychophysiological and cognitive-behavioral changes, being an effective, non-invasive, and low-cost therapy.

Effects of Green Banana Biomass (Musa spp.) on Laboratory Parameters of Animal Models of Wistar Mice under Hyperlipidic Diet.

AIM: Analyze the effects of green banana biomass (Musa spp.) on the biochemical parameters in Wistar male rats under standard and hyperlipidic diet. METHODS: Ethical approval for this study was obtained from Ethics Committee on the Use of Animals CEUA - PUC-GO and consisted in the division of 32 rats in 4 differentiated groups according to their diet (standard - CT; standard with green banana biomass - CTBM; hyperlipidic - HL and hyperlipidic with green banana biomass - HLBM). Through 8 weeks animals were weighted and their glycemia were measured. After this period, they were euthanized and biological material was collected to evaluate the biochemical parameters, which analysis used the ANOVA test. RESULTS: The weekly evaluation confirmed that the efficacy of the hyperlipidic model since the final weight was bigger in the HL group in comparison with the CT group, from the sixth to the eighth week. It was also possible to observe that the CTBM group had a smaller weight compared to the CT group. Besides, the measurement of glycemia, high-density lipoprotein, triglycerides, alanine aminotransferase, aspartate aminotransferase, serum total bilirubin, direct bilirubin, alkaline phosphatase, urea, serum creatine, uric acid, calcium, phosphor, magnesium and the hematological parameters from the 8 animal of each group were compared by the ANOVA test without any significative difference (p < 0.05) in the comparisons. CONCLUSIONS: This study it did not demonstrate significative changes of the green banana biomass on the observed laboratory parameters during the 8 weeks in comparison to the standard group, indicating an absence of interference of the probiotics in the laboratory parameters on the hyperlipidic model during the analyzed period. Therefore, it is necessary an evaluation of its efficacy in obesity treatment in longer studies with molecular parameters.

Avaliação dos parâmetros hematológicos em ratos Wistar descendentes de mães obesas / Evaluation of hematological parameters in Wistar rats descending from obese mothers

O modelo de obesidade em ratos por meio de uma dieta hiperlipídica têm se consolidado, sendo relevante compreender os componentes da hereditariedade nesta enfermidade. Por meio do hemograma é possível avaliar os elementos sanguíneos e as células responsáveis pela defesa do organismo, incluindo sua morfologia, bem como interpretando-as. Compreender esses fatores em ratos descendentes de mães obesas poderia contribuir na compreensão dos mecanismos imuno-hematológicos envolvidos na obesidade e na hereditariedade. Com isso, o objetivo deste estudo é avaliar os parâmetros hematológicos e leucocitários de ratos alimentados com dieta hiperlipídica descendentes de mães obesas. Foram utilizadas 20 ratas Wistar (peso inicial 200g) alimentadas com dieta padrão (CT) ou com dieta hiperlipídica (HL). Posteriormente, alocou-se 3 fêmeas com 1 macho por 4 dias, certificando o cruzamento. Após 23 dias do nascimento da ninhada, foi feita a separação da prole em 4 grupos com 5 animais cada, e submetidos à dieta HL ou CT. Ficando então os grupos CT, CT+ HL, HL, HL + CT. Após 20 semanas de dieta, os animais foram anestesiados e tiveram peritônio exposto para coleta de sangue, que serviu para a realização e análise do hemograma, por diferenciação celular. Todos os procedimentos foram realizados de acordo com as diretrizes da utilização de animais para fins científicos (Lei 11.794/08), e protocolada no CEUA sob o n° 9062310117. As ratas HL tiveram um ganho de peso significativamente maior a partir da 10ª semana, comparando as ratas CT. Já em relação à prole, após 13 semanas, o grupo HL obteve um ganho de peso maior em relação aos demais grupos: CT: 144,8 ± 12,15 g; CT+HL (ratos descendentes de mães CT alimentados com ração HL): 138,6 ± 5,34 g; HL+CT (ratos descendentes de mães HL alimentados com ração CT): 152,2 ± 5,23 g; HL 161 ± 10,75 g. Nos parâmetros hematológicos da prole, foi observada diferença entre o grupo CT e experimental, os monócitos apresentaram uma redução significativa de 1,6± 0,89, hemoglobina 13,8 ± 1,07, hematócrito 37,9 ± 5,51 nos grupos que receberam dieta CT comparado à CT+HL, VCM apresentou aumento de 50,4 ± 0,55 no grupo CT e 53,5 ± 0,58 na dieta HL. Dentro das condições experimentais deste trabalho e com base nos resultados obtidos, conclui-se que a dieta hiperlipídica é capaz de induzir a obesidade, com capacidade de influenciar a proliferação e a diferenciação hematopoiética, porém a prole alimentada com ração padrão (CT) consegue adaptar a dieta independente do fator hereditário em relação à obesidade.

The obesity model in rats maintained by a hyper-lipidic diet is well known, and thus, there is a need to understand the components of heredity in this disease. Using HEM, it is possible to study the blood elements and cells involved in the defense of the organism, including cell morphology and its interpretation. Understanding these factors in rats descending from obese mothers may contribute to the comprehension of the immunity and hematologic mechanisms involved in both obesity and heredity. The purpose of this study is to evaluate the hematologic and leukocyte parameters of rats fed with a hyper-lipidic diet descending from obese mothers. A total of twenty Wistar female rats (initial weight 200g) fed standard diet (SD) or hyperlipidic diet (HD) were used. Subsequently, 3 females were housed with a male for 4 days in order to get inseminated. Twenty-three days after born, the animals were separated into 4 groups, with 5 animals in each group. The groups were organized as follows: SD, SD+HD, HD, SD+HD. The animals were kept on a diet for 20 weeks. In the end of that period, animals were anesthetized and had their peritoneum exposed for the collection of blood, which was used for performing the erythrogram and leukogram analysis via cellular differentiation. All procedures were performed according the animal welfare guidelines (Law No. 11.794/08) and approved by CEUA (number 9062310117). After 10 weeks, HL mothers presented an increased body weight when compared with SD mothers. In relation to the offspring, after 13 weeks, the HD group presented greater weight gain when compared to the other groups, as follows: SD: 144.8 ± 12.15 g; SD+HD (rats from SD mothers fed with HD feed): 138.6 ± 5.34 g; HD + SD (offspring from HL mothers fed with SD feed): 152.2 ± 5.23 g; HD 161 ± 10.75 g. The offspring hematological parameters presented differences between the SD and the experimental group, where the monocytes presented a significant reduction (1.6 ± 0.89), hemoglobin (13.8 ± 1.07), hematocrit (37.9 ± 5.51) in the groups that received a SD diet compared with the SD + HD; the MCV presented an increase of 50.4 ± 0.55 in the SD group and 53.5 ± 0.58 in the group on HD diet. Conclusion: Based on the results, it can be concluded that a hyper-lipidic diet is capable of inducing obesity and may also influence hematopoietic proliferation and differentiation. However, the offspring fed with standard diet (SD) is able to adapt the diet regardless of the hereditary factor in relation to obesity.

Overexpression of AT2R in the solitary-vagal complex improves baroreflex in the spontaneously hypertensive rat.

The aim of this study was to investigate the physiological effects of increased angiotensin II type 2 receptor (AT2R) expression in the solitary-vagal complex (nucleus of the solitary tract/dorsal motor nucleus of the vagus; NTS/DVM) on baroreflex function in non-anaesthetised normotensive (NT) and spontaneously hypertensive rats (SHR). Ten week old NT Holtzman and SHR were microinjected with either an adeno-associated virus expressing AT2R (AAV2-CBA-AT2R) or enhanced green fluorescent protein (control; AAV2-CBA-eGFP) into the NTS/DVM. Baroreflex and telemetry recordings were performed on four experimental groups: 1) NTeGFP, 2) NTAT2R, 3) SHReGFP and 4) SHRAT2R (n=4-7/group). Following in-vivo experimental procedures, brains were harvested for gene expression analysis. Impaired bradycardia in SHReGFP was restored in SHR rats overexpressing AT2R in the NTS/DMV. mRNA levels of angiotensin converting enzyme decreased and angiotensin converting enzyme 2 increased in the NTS/DMV of SHRAT2R compared to SHReGFP. Increased levels of pro-inflammatory cytokine mRNA levels in the SHReGFP group also decreased in the SHRAT2R group. AT2R overexpression did not elicit any significant change in mean arterial pressure (MAP) in all groups from baseline to 4weeks post viral transfection. Both SHReGFP and SHRAT2R showed a significant elevation in MAP compared to the NTeGFP and NTAT2R groups. Increased AT2R expression within the NTS/DMV of SHR was effective at improving baroreflex function but not MAP. We propose possible mediators involved in improving baroreflex are in the ANG II/ACE2 axis, suggesting a potential beneficial modulatory effect of AT2R overexpression in the NTS/DMV of neurogenic hypertensive rats.

Increased expression of angiotensin II type 2 receptors in the solitary-vagal complex blunts renovascular hypertension.

Angiotensin II increases and decreases arterial pressure by acting at angiotensin type 1 and type 2 receptors, respectively. Renovascular hypertensive rats exhibit a high level of activity of the peripheral and central renin-angiotensin system. Therefore, in the present study, we evaluated the effect of increasing the expression of angiotensin type 2 receptors in the solitary-vagal complex (nucleus of the solitary tract/dorsal motor nucleus of the vagus), a key brain stem region for cardiovascular regulation, on the development of renovascular hypertension. Holtzman normotensive rats were implanted with a silver clip around the left renal artery to induce 2-kidney 1-clip renovascular hypertension. Three weeks later, rats were microinjected in the solitary-vagal complex with either an adenoassociated virus to increase the expression of angiotensin type 2 receptors or with a control vector. We observed that increasing angiotensin type 2 receptor expression in the solitary-vagal complex attenuated the development of renovascular hypertension and also reversed the impairment of the baroreflex and the increase in the low-frequency component of systolic blood pressure observed in renovascular hypertensive rats. Furthermore, an observed decrease in mRNA levels of angiotensin-converting enzyme 2 in the solitary-vagal complex of renovascular hypertensive rats was restored to control levels after viral-mediated increases in angiotensin type 2 receptors at this site. Collectively, these data demonstrate specific and beneficial effects of angiotensin type 2 receptors via the brain of hypertensive rats and suggest that central angiotensin type 2 receptors may be a potential target for therapeutics in renovascular hypertension.

Macrophage migration inhibitory factor in the nucleus of solitary tract decreases blood pressure in SHRs.

AIMS: The macrophage migration inhibitory factor (MIF) is an intracellular inhibitor of the central nervous system actions of angiotensin II on blood pressure. Considering that angiotensin II actions at the nucleus of the solitary tract are important for the maintenance of hypertension in spontaneously hypertensive rats (SHRs), we tested if increased MIF expression in the nucleus of the solitary tract of SHR alters the baseline high blood pressure in these rats. METHODS AND RESULTS: Eight-week-old SHRs or normotensive rats were microinjected with the vector AAV2-CBA-MIF into the nucleus of the solitary tract, resulting in MIF expression predominantly in neurons. Rats also underwent recordings of the mean arterial blood pressure (MAP) and heart rate (via telemetry devices implanted in the abdominal aorta), cardiac- and baroreflex function. Injections of AAV2-CBA-MIF into the nucleus of the solitary tract of SHRs produced significant decreases in the MAP, ranging from 10 to 20 mmHg, compared with age-matched SHRs that had received identical microinjections of the control vector AAV2-CBA-eGFP. This lowered MAP in SHRs was maintained through the end of the experiment at 31 days, and was associated with an improvement in baroreflex function to values observed in normotensive rats. In contrast to SHRs, similar increased MIF expression in the nucleus of the solitary tract of normotensive rats produced no changes in baseline MAP and baroreflex function. CONCLUSION: These results indicate that an increased expression of MIF within the nucleus of the solitary tract neurons of SHRs lowers blood pressure and restores baroreflex function.

Ajustes cardiovasculares e do equilibrio hidroeletrolítico induzidos por soluções hipertônicas em ratos com lesão do núcleo do trato solitário comissural / Cardiovascular and hydroelectrolytic balance adjustments induced by hypertonic solutions in rats with commissural nucleus of tract solitary lesions

O sistema nervoso central (SNC) tem um papel fundamental na regulação de mecanismos que controlam a osmolaridade dos líquidos corporais. O núcleo do trato solitário (NTS) é o sítio primário das aferências cardiovasculares e de osmorreceptores periféricos e se projeta à áreas prosencefálicas envolvidas com a regulação cardiovascular e do equilíbrio hidroeletrolítico. Demonstramos anteriormente que animais com lesão da porção comissural do NTS (commNTS) tem maior ingestão de água, natriurese e resposta pressora frente a sobrecarga intragástrica (ig) de NaCl 2 M. Os mecanismos responsáveis por estas alterações ainda não foram determinados. Uma vez que o estímulo com NaCl 2 M ig (2 ml) ativa osmorreceptores centrais e periféricos, não sabemos até o momento os efeitos da lesão do commNTS sobre as respostas observadas após a estimulação específica de osmorreceptores periféricos, que pode ser feita com NaCl 0,6 M ig. (2 ml). Desta forma os nossos objetivos foram: a) estudar os mecanismos que medeiam o aumento da pressão arterial e da natriurese após a sobrecarga de NaCl 2 M em animais com lesão do commNTS; b) verificar as alterações na expressão da proteína c-Fos após NaCl 2 M ig em ratos com lesão fictícia (sham) ou lesão do commNTS; c) verificar as alterações na expressão gênica no PVN após NaCl 2 M ig, d) estudar os efeitos na pressão arterial, na ingestão de água e na excreção renal subseqüentes a administração de NaCl 0,6 M ig, bem como os mecanismos responsáveis pelas alterações, em ratos com lesão fictícia (sham) ou lesão do commNTS; e) verificar as alterações na expressão da proteína c-Fos após NaCl 0,6 M ig em ratos com lesão fictícia (sham) ou lesão do commNTS. Ratos Holtzman (280-320 g) foram utilizados. A lesão eletrolítica ou lesão fictícia (sham) do commNTS, e todos os experimentos foram realizados na fase crônica da lesão (14 a 21 dias. Para a lesão do commNTS, uma craniotomia parcial foi realizada e a superfície dorsal do bulbo foi exposta. A lesão eletrolítica foi realizada por meio de duas correntes de 1 mA por 5 s, com intervalo de 30 s entre elas. Nos ratos sham, o eletrodo foi posicionado nas mesmas coordenadas, exceto que não foi passada corrente elétrica. Observamos que os ratos com lesão eletrolítica do commNTS a resposta pressora do quimiorreflexo, testado com KCN (iv), foi reduzida, enquanto que o barorreflexo manteve-se inalterado. Nos ratos com lesão do commNTS, a sobrecarga de NaCl 2 M promoveu aumento da pressão arterial, que foi dependente de vasopressina. A gavagem com NaCl 2 M também promoveu pronunciada expressão de c-Fos nas regiões magnocelular do núcleo paraventricular do hipotálamo (mPVN) e no núcleo supra-óptico (SON) e essa foi significantemente maior nos ratos com lesão do commNTS do que nos ratos sham. Ambos os grupos tiveram aumento da secreção de vasopressina e ocitocina após NaCl 2 M ig, embora ratos com lesão do commNTS a secreção de vasopressina foi maior. Após a sobrecarga de NaCl 0,6 M, que ativa osmorreceptores periféricos, observamos que os ratos com lesão do commNTS tiveram resposta pressora mediada por vasopressina, incremento da resposta dipsogênica, bem como um maior aumento na expressão de c-Fos no SON comparado com animais sham. Em conclusão, nossos resultados mostram que a lesão do commNTS facilita a ingestão de água e a hipertensão dependente de vasopressina após aumento sobrecarga de NaCl hipertônico, seja a solução hipertônica capaz de alterar a osmolaridade plasmática (ativação de osmorreceptores centrais e periféricos) ou apenas a osmolaridade da região hepato-portal (ativação de osmorreceptores periféricos). As alterações na natriurese em ratos lesados submetidos a gavagem com NaCl 2 M parece ser dependente do aumento na pressão arterial nestes animais. Esses resultados sugerem que o commNTS faz parte de uma circuitaria neural inibitória que controla a pressão arterial, secreção de vasopressina, ingestão de água e ativação de áreas prosencefálicas frente à hiperosmolaridade, que ativa os osmorreceptores centrais e/ou periféricos

The central nervous system has an important role controlling the mechanisms involved in the regulation of body fluid osmolality. The nucleus of the solitary tract (NTS) is the primary site of cardiovascular and peripheral osmoreceptors afferents and projects to prosencephalic areas involved in hydroelectrolytic balance and cardiovascular regulation. We have demonstrated that commissural NTS (commNTS) lesioned rats had an increase in arterial pressure and a greater increase in water intake and natriuresis after 2 M NaCl intragastric (ig) load. The mechanisms involved in these responses are not known. Since 2 M NaCl ig (2 ml) activates central and peripheral osmoreceptors, it is not known the effects of the commNTS lesion on the responses induced only by the activation of the peripheral osmoreceptors, which can be done by 0.6 M NaCl (2 ml) ig. Thus, the aims of this study were: a) to study the mechanisms involved in the increase of the arterial pressure and natriuresis in commNTS lesioned rats after 2 M NaCl ig; b) to verify the changes in c-Fos expression after 2 M NaCl ig in sham and commNTS lesioned rats; c) to verify the changes in gene expression in PVN after 2 M NaCl ig in naïve rats; d) to study the effects on arterial pressure, water intake and renal excretion after 0.6 M NaCl, as well as, the mechanisms involved in these responses, in sham and in commNTS lesioned rats; e) to verify the changes in c-Fos expression after 0.6 M NaCl ig in sham and commNTS lesioned rats. Male Holtzman rats (280-320 g) were used. Electrolytic lesion of the commNTS and all experiments were be performed in chronic period of lesion (14 to 21 days. For the lesion, a partial craniotomy of the occipital bone was performed, and the dorsal surface of the brainstem was exposed. The electrolytic lesion was performed using a cathodal current (1 mA during 5 seconds, for two times). Sham lesioned rats had the electrode placed along the same coordinates, except that no current was passed. We observed that the pressor response to chemoreflex, tested with KCN (iv), was reduced in commNTS lesioned rats, while baroreflex remained intact. In the commNTS lesioned rats, 2 M NaCl ig induced a vasopressin dependent-pressor response for at least 60 min. After 2 M NaCl, we observed that the number of the cFos expressing cells in the magnocelular paraventricular nucleus (mPVN) and in the supra-optic nucleus of the hypothalamus were greater in the commNTS lesioned rats, indeed both groups had increase in vasopressin and oxcitocin in plasma after 2 M NaCl load, but in commNTS lesioned animals the increase in vasopressin was bigger. After 0.6 M NaCl that activates only peripheral osmoreceptors, it was observed that commNTS lesioned rats presented an increase in arterial pressure dependent on vasopressin, a greater increase in water intake, and also a greater cFos expression in SON compared to sham. In conclusion, the present data demonstrated that the commNTS lesion facilitates the water intake and the hypertension dependent on vasopressin secretion after hypertonic NaCl overload, regardless the hypertonic solution is able to activate central and/or peripheral osmorreceptors. The changes in the natriuresis observed in lesioned rats after 2 M NaCl seems to be dependent on the increase in arterial pressure in these animals. These results suggest that the commNTS is parte of an inhibitory circuitry that controls arterial pressure, vasopressin secretion and water intake and activation of prosencephalic areas after hyperosmotic stimuli, which activate central and/or peripheral osmoreceptors