Histomorfometric Analysis of Duodenum of Rats Submitted to Food Stress / Análise Histomorfométrica do Duodeno de Ratos Submetidos ao Estresse Alimentar

Stress was interpreted as a nonspecific reaction of the organism to a situation that would threaten its homeostasis. Several factors in the modern world can be related to this condition: the search for a perfect body, the labor market dispute or the pressure to conquer everything as fast as possible. Associated with these factors, one can add the intense, naturally stressful, routine in which man is inserted. At the experimental level, several effects are observed at a systemic and behavioral level in rats that have been submitted to food restriction models, finding that the gastrointestinal system is quite vulnerable to stress in general. In specific cases of food stress, it was observed that the manifestations vary according to the life stage of the animal and the applied model. In this sense, the present research aims to evaluate the influence of food restriction on the intestinal tunica morphology of rats submitted to a chronic food stress model. For this, 27 animals were divided into control (n = 11) and test (n = 16) groups. From the 60 th day of life, the test group was submitted to four stages, each one being performed in one day: 1) palatable diet; 2) visual stimulation to the diet, but without access; 3) fasting; 4) standard diet of the biotery. The four steps were repeated until the animals completed 90 days. In the morphometry of the duodenum were analyzed: length, width and area of vill, as well as area of intestinal gland (Lieberkühn). Statistical inference of data showed that the applied stress model affected the morphology of the stressed group, since the intestinal villi appeared wider and with less area in this group. The villi length as well as the intestinal gland area did not undergo morphological changes. The alterations found reinforce that the fasting process acts as a stressor and a predisposing factor for morphological alterations, as observed in other studies in our laboratory. However, there are not many studies in the literature that allow the knowledge of the consequences of this type of stress. In this case, further research is needed on the relationship between the gastrointestinal tract and the experimental model applied to elucidate such findings

Effects of chronic food stress on morphometry and expression of nuclear organizing regions in the adult rats hippocampus Chronic food stress on morphometry and expression of agnor in the rats hippocampus / Efeitos do estresse alimentar crônico na morfometria e expressão das regiões de organização nuclear nos ratos adultos hipocampo Testemunho crônico de alimentação sobre morfometria e expressão do agnor no hippocampus das taxas

The aim of this study was to verify the immediate and late effects of chronic food stress on the expression of Nuclear Organizing Regions (NORs) in hippocampal neurons. Twenty Wistar rats were separated into two groups: test (n = 10) and control (n = 10). Food stress started from the 60th day of life and lasted for a month. After this time the animals were anesthetized, euthanized and had their hippocampus dissected. The obtained hippocampus were histologically processed, stained by the HE technique for morphological description and by the AgNOR technique for NOR analysis. From each image the total number of neurons, the number of neurons with NOR in Dispersion (NND), the total number of NORs (NNOR), and then performed a ratio of NNOR by the total number of neurons to obtain the number Of NOR by neuron (NNN). Of the analyzed variants, the number of neurons was higher (p <0.001) in the stressed group (41.98 ± 17), when compared with the control group (33.57 ± 14). In addition, NND was also higher in the stressed group (4.523 ± 4.04) than the control group (1.4 ± 2.20) with p <0.001. Thus, we have that chronic food stress increases the number of granular neurons in the hippocampus in rats as well as increases the number of NOR in dispersion. 

Estudos morfológico e morfométrico do coração e da artéria aorta em ratos adultos desmamados precocemente / Morphological and morphometric studies of the heart and aorta artery in preciously weed adult rats

Objetivo: Realizar uma investigação acerca dos efeitos do desmame precoce sobre a morfologia e morfometria do coração e da artéria aorta de ratos adultos submetidos ao desmame precoce no 15° dia de vida pós-natal. Método: Foram utilizados 16 ratos machos da linhagem Wistar. Os grupos experimentais foram formados pelos grupos DP15 (desmame no 15° dia pós-natal) e C30 (desmame no 30° dia pós-natal), com o 8 ratos cada grupo. Após o desmame, os animais foram separados em gaiolas individuais e no 100° dia de vida pós-natal, foram eutanasiados através da pefusão intracardíaca. O coração e a artéria aorta foram coletados e posteriormente processados para a microscopia de luz. As análises foram realizadas a partir de fotomicrografias e do software ImageJ. Foram avaliados o número de cárdiomiócitos, a área nuclear e a espessura da aorta. Resultado: Os resultados mostraram que o desmame precoce promoveu alterações significativas nas variáveis analisadas, provocando a redução da área nuclear dos cardiomiócitos (C: 16,77µm ± 5,95; DP: 12,48µm ± 7,03), hiperplasia do miocárdio (C: 30,42µm ± 11,38; DP: 48,87µm ± 13,62), diminuição na espessura da artéria aorta (C: 168,56µm ± 46,61; DP: 113,81µm ± 28,01) (C: 130,69µm ± 40,75; DP: 81,62µm ± 19,89). Baseado em nossos resultados podemos sugerir que o desmame precoce é uma agressão perinatal capaz de provocar alterações na morfologia e morfometria do coração e da artéria aorta de ratos. 

ANÁLISE COMPARATIVA DO USO DA ESTATINA E DO ÁCIDO NICOTÍNICO NO TRATAMENTO DA SÍNDROME METABÓLICA

Considering metabolic syndrome (MS) as a pathophysiological condition characterized by arterial hypertension, central obesity, insulin resistance, dyslipidemia, and hyperglycemia, this study aims to compare the use of statins and nicotinic acid in the treatment of MS. To this end, a comparative analysis based on relevant clinical and epidemiological studies was conducted. Thus, it is observed that statins significantly reduce LDL cholesterol by about 50% and decrease the risk of cardiovascular events by 25% to 35%, with an odds ratio (OR) of improvement between 0.70 and 0.80. Statins are widely available and accessible, especially in generic versions, and have a relatively manageable adverse effect profile. In contrast, nicotinic acid reduces LDL cholesterol by 15% to 25%, increases HDL cholesterol, and reduces triglycerides, but with less consistent efficacy in preventing cardiovascular events (OR ranging from 0.90 to 1.10) and significant side effects, such as skin flushing and hepatotoxicity. The cost and availability of nicotinic acid are more limited compared to statins. It is concluded that statins are the preferred choice for the treatment of MS due to their robust efficacy and accessibility, while nicotinic acid may be considered in specific cases, with caution due to its adverse effects.Considerando a síndrome metabólica (SM) como uma condição fisiopatológica caracterizada por hipertensão arterial, obesidade central, resistência à insulina, dislipidemia e hiperglicemia, este estudo objetiva comparar o uso de estatinas e ácido nicotínico no tratamento da SM. Para tanto, procede-se a uma análise comparativa baseada em estudos clínicos e epidemiológicos relevantes. Desse modo, observa-se que as estatinas reduzem significativamente o LDL-colesterol em cerca de 50% e diminuem o risco de eventos cardiovasculares em 25% a 35%, com odds ratio (OR) de melhora entre 0,70 e 0,80. As estatinas são amplamente disponíveis e acessíveis, especialmente nas versões genéricas, e apresentam um perfil de efeitos adversos relativamente manejável. Em contraste, o ácido nicotínico reduz o LDL-colesterol em 15% a 25%, aumenta o HDL-colesterol e reduz os triglicerídeos, mas com uma eficácia menos consistente na prevenção de eventos cardiovasculares (OR variando de 0,90 a 1,10) e efeitos colaterais significativos, como rubor cutâneo e hepatotoxicidade. O custo e a disponibilidade do ácido nicotínico são mais limitados em comparação às estatinas. Conclui-se que as estatinas são a escolha preferida para o tratamento da SM devido à sua eficácia robusta e acessibilidade, enquanto o ácido nicotínico pode ser considerado em casos específicos, com precaução devido aos seus efeitos adversos

Fístula arteriovenosa dural intracraniana da junção craniocervical com drenagem venosa perimedular espinhal: um raro relato de caso

Fístulas arteriovenosas durais (FAVDs) são lesões adquiridas, que consistem em uma ou mais conexões fistulosas no interior dos folhetos da dura-máter, com envolvimento das paredes de um seio venoso dural ou então das veias leptomeníngeas adjacentes. Sua incidência é de difícil determinação, no entanto, segundo estudos, ela é estimada em 10% a 15% de todas as malformações cerebrovasculares diagnosticadas por angiografia. Os fatores predisponentes ao desenvolvimento das FAVDs são o traumatismo cranioencefálico, tromboflebite cerebral, neurocirurgia prévia e infecções. O objetivo deste estudo é apresentar um caso de Fístula Arteriovenosa Dural Intracraniana em um paciente de 58 anos, ressaltando os aspectos imagenológicos, etiológicos, fisiopatológicos e, sobretudo, os tipos de classificação da doença e a terapia utilizada. W.S.D., sexo masculino, 58 anos, natural e procedente de São Paulo – SP, deu entrada no pronto-socorro de um hospital de referência da capital paulista queixando-se de parestesia de membros superiores (MMSS) há 3 meses. Foi realizado exame físico e anamnese de forma minuciosa, na qual o paciente negou cefaleia e outros sintomas associados. Foi submetido à investigação com uma ressonância magnética (RNM) da região cerebral e medular em ponderações T1 e T2, as quais demonstraram efeito tumefativo que comprometia a transição bulbo-medular e a medula cervical de C2, as quais encontravam-se edemaciadas. Além disso, estavam proeminentes os vasos leptomeníngeos nos hemisférios cerebelares, estes patognomônicos da FAVD. Ademais, foi observado hipersinal em T2, com padrão estriado/tigroide, típico de degeneração mielínica progressiva. O paciente apresentava agressivo refluxo venoso cortical com drenagem perimedular espinhal na veia cortical e, dessa forma, enquadrou-se na Classificação de Cognard tipo V, sendo considerado um paciente portador de FAVD maligna. Foi então realizado tratamento endovascular com embolização transarterial, o qual proporcionou fechamento completo da fístula e, dessa forma, o paciente obteve um prognóstico favorável. As fístulas arteriovenosas durais, por serem uma condição rara e com variadas manifestações clínicas, podem passar despercebidas pelo profissional médico. Dessa forma, é de fundamental importância o conhecimento da doença, com o intuito de proporcionar ao paciente um diagnóstico precoce e uma terapia eficaz

Mimotope-Based Vaccines of <i>Leishmania infantum</i> Antigens and Their Protective Efficacy against Visceral Leishmaniasis

<div><p>Background</p><p>The development of cost-effective prophylactic strategies to prevent leishmaniasis has become a high-priority. The present study has used the phage display technology to identify new immunogens, which were evaluated as vaccines in the murine model of visceral leishmaniasis (VL). Epitope-based immunogens, represented by phage-fused peptides that mimic <i>Leishmania infantum</i> antigens, were selected according to their affinity to antibodies from asymptomatic and symptomatic VL dogs' sera.</p><p>Methodology/Main Findings</p><p>Twenty phage clones were selected after three selection cycles, and were evaluated by means of <i>in vitro</i> assays of the immune stimulation of spleen cells derived from naive and chronically infected with <i>L. infantum</i> BALB/c mice. Clones that were able to induce specific Th1 immune response, represented by high levels of IFN-γ and low levels of IL-4 were selected, and based on their selectivity and specificity, two clones, namely B10 and C01, were further employed in the vaccination protocols. BALB/c mice vaccinated with clones plus saponin showed both a high and specific production of IFN-γ, IL-12, and GM-CSF after <i>in vitro</i> stimulation with individual clones or <i>L. infantum</i> extracts. Additionally, these animals, when compared to control groups (saline, saponin, wild-type phage plus saponin, or non-relevant phage clone plus saponin), showed significant reductions in the parasite burden in the liver, spleen, bone marrow, and paws' draining lymph nodes. Protection was associated with an IL-12-dependent production of IFN-γ, mainly by CD8⁺ T cells, against parasite proteins. These animals also presented decreased parasite-mediated IL-4 and IL-10 responses, and increased levels of parasite-specific IgG2a antibodies.</p><p>Conclusions/Significance</p><p>This study describes two phage clones that mimic <i>L. infantum</i> antigens, which were directly used as immunogens in vaccines and presented Th1-type immune responses, and that significantly reduced the parasite burden. This is the first study that describes phage-displayed peptides as successful immunogens in vaccine formulations against VL.</p></div

Involvement of IL-12, CD4⁺ and CD8⁺ T cells in the IFN-γ production after <i>L. infantum</i> infection.

<p>Single-cells suspensions were obtained from the spleens of mice that were immunized with B10 clone plus saponin (<b>A</b>) or C01 clone plus saponin (<b>B</b>), 10 weeks after <i>L. infantum</i> infection. Levels of IFN-γ were measured in culture supernatants by capture ELISA of spleen cells cultures stimulated with SLA (20 µg mL⁻¹) for 48 h at 37°C, 5% CO₂. Cultures were incubated in the absence (positive control) or in the presence of 5 µg mL⁻¹ of monoclonal antibodies (mAb) against mouse IL-12 (C017.8), CD4 (GK 1.5), or mouse CD8 (53-6.7). Statistically significant differences between non-treated control cells and cultures incubated with anti-CD4, anti-CD-8 and anti-IL-12 monoclonal antibodies were observed (***<i>P <</i>0.0001). Each bar represents the mean ± standard deviation (SD) of the IFN-γ levels of the different groups.</p

Amino acid sequences from target peptides present in the selected phage clones.

<p>Amino acid sequences from target peptides present in the selected phage clones.</p

Protection of BALB/c mice vaccinated with phage clones plus saponin against <i>L. infantum.</i>

<p>Mice inoculated with saline, saponin, wild-type phage (WTP), B10 or C01 phage clones plus saponin were subcutaneously infected with 1×10⁷ stationary phase promastigotes of <i>L. infantum.</i> The number of parasites in the liver (<b>A</b>), spleen (<b>B</b>), pawś draining lymph nodes (<b>C</b>), and bone marrow (<b>D</b>) was measured, 10 weeks after challenge by a limiting-dilution technique. Each bar represents the mean ± standard deviation (SD) of the groups. Statistically significant differences in the parasite load in all evaluated organs between the B10 and C01 clones plus saponin and control groups are showed (***<i>P</i> <0.0001). Data shown are representative of two independent experiments, which presented similar results.</p