Dysregulation in erythrocyte dynamics caused by SARS-CoV-2 infection: possible role in shuffling the homeostatic puzzle during COVID-19

Abstract Introduction The evolving COVID-19 pandemic became a hallmark in human history, not only by changing lifestyles, but also by enriching scientific knowledge on viral infection and its consequences. Objective Although the management of cardiorespiratory changes is pivotal to a favorable prognosis during severe clinical findings, dysregulation of other systems caused by SARS-CoV-2 infection may imbalance erythrocyte dynamics, such as a bidirectional positive feedback loop pathophysiology. Method and Results Recent evidence shows that SARS-CoV-2 is capable of affecting the genetics and dynamics of erythrocytes and this coexists with a non-homeostatic function of cardiovascular, respiratory and renal systems during COVID-19. In hypothesis, SARS-CoV-2-induced systematical alterations of erythrocytes dynamics would constitute a setpoint for COVID-19-related multiple organ failure syndrome and death. Conclusion The present review covers the most frequent erythrocyte-related non-homeostatic findings during COVID-19 capable of providing mechanistic clues of SARS-CoV-2-induced infection and inspiring therapeutic-oriented scientific evidence.

Maternal postnatal early overfeeding induces sex-related cardiac dysfunction and alters sexually hormones levels in young offspring.

Postnatal early overfeeding (PO) is a risk factor for cardiometabolic disorders. However, remains unknown the cardiac effects in the second generation from postnatal overfed dams. Our aim was to investigate the effects of maternal PO on cardiac parameters in second generation (F2) offspring. For this, pregnant Wistar rats (F0) were divided into two groups: normal litter (NL, 9 pups) and small litter (SL, 3 pups). At P70, female offspring (F1) of both groups were mated with non-PO male rats. At P21 male and female F2 offspring (NLO and SLO) were weaned, and at P45 they were euthanized to evaluate the cardiac function and sample collection. Male and female SLO showed increased body weight, food intake and adiposity. Blood estradiol levels were increased in the male SLO and decreased in the female SLO. Blood testosterone levels increased in SLO females, but not change in SLO male rats. Although SLO offspring presented cardiac hypertrophy, only males had ex vivo functional impairments, such as reduction of the intraventricular systolic pressure and dP/dt. Male and female SLO had increased interstitial fibrosis; however, only the male SLO had increased perivascular fibrosis. In addition, only male rats from SLO group had decreased AKT and Type 2 Ang-2 receptor, increased catalase and type alpha estrogenic receptor protein levels. Maternal PO leads to obese phenotype and alters sex-steroid levels in both male and female offspring. Although both sexes showed cardiac hypertrophy, only male offspring showed cardiac dysfunction, which may be related with Ang2 and AKT signaling impairments.

Antiepileptic effects of long-term intracerebroventricular infusion of angiotensin-(1-7) in an animal model of temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) is the most frequent type of epilepsy and is often refractory to pharmacological treatment. In this scenario, extensive research has identified components of the renin-angiotensin system (RAS) as potential therapeutic targets. Therefore, the aim of the present study was to evaluate the effects of long-term treatment with angiotensin-(1-7) [Ang-(1-7)] in male Wistar rats with TLE induced by pilocarpine (PILO). Rats with TLE were submitted to intracerebroventricular (icv) infusion of Ang-(1-7) (200 ng/kg/h) for 28 days, starting at the first spontaneous motor seizure (SMS). Body weight, food intake, and SMS were evaluated daily. Behavioral tests and hippocampal protein levels were also evaluated at the end of the treatment. Ang-(1-7) treatment reduced the frequency of SMS and attenuated low anxiety levels, increased locomotion/exploration, and reduced body weight gain that was induced by TLE. Moreover, Ang-(1-7) positively regulated the hippocampal levels of antioxidant protein catalase and antiapoptotic protein B-cell lymphoma 2 (Bcl-2), as well as mammalian target of rapamycin (mTOR) phosphorylation, which were reduced by TLE. The hippocampal up-regulation of angiotensin type 1 receptor induced by TLE was also attenuated by Ang-(1-7), while the Mas receptor (MasR) was down-regulated compared with epilepsy. These data show that Ang-(1-7) presents an antiepileptic effect, increasing neuroprotection markers and reducing SMS frequency, body weight, and behavior impairments found in TLE. Therefore, Ang-(1-7) is a promising coadjutant therapeutic option for the treatment of TLE.

Blood pressure-lowering effects of a Bowman-Birk inhibitor and its derived peptides in normotensive and hypertensive rats.

Bioactive plant peptides have received considerable interest as potential antihypertensive agents with potentially fewer side effects than antihypertensive drugs. Here, the blood pressure-lowering effects of the Bowman-Birk protease inhibitor, BTCI, and its derived peptides, PepChy and PepTry, were investigated using normotensive (Wistar-WR) and spontaneously hypertensive rats (SHR). BTCI inhibited the proteases trypsin and chymotrypsin, respectively, at 6 µM and 40 µM, a 10-fold greater inhibition than observed with PepTry (60 µM) and PepChy (400 µM). These molecules also inhibited angiotensin converting enzyme (ACE) with IC50 values of 54.6 ± 2.9; 24.7 ± 1.1; and 24.4 ± 1.1 µM, respectively, occluding its catalytic site, as indicated by molecular docking simulation, mainly for PepChy and PepTry. Gavage administration of BTCI and the peptides promoted a decrease of systolic and diastolic blood pressure and an increase of renal and aortic vascular conductance. These effects were more expressive in SHR than in WR. Additionally, BTCI, PepChy and PepTry promoted coronary vasodilation and negative inotropic effects in isolated perfused hearts. The nitric oxide synthase inhibitor blunted the BTCI and PepChy, with no cardiac effects on PepTry. The findings of this study indicate a therapeutic potential of BTCI and its related peptides in the treatment of hypertension.

The influence of MTHFR C677T polymorphism in chronic lymphocytic leukemia.

Some factors have been associated with the etiology of chronic lymphocytic leukemia (CLL), among them the Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism. The aim of this study was to evaluate the role of MTHFR C677T polymorphism in CLL. A case-control study was conducted with 219 individuals from Brazilian central population. MTHFR C677T polymorphism was determined through PCR-RFLP followed by PAGE. The T allele frequence was higher in patients diagnosed with CLL than healthy subjects. However, when stratified by gender, the TT genotype was exclusively found in men diagnosed with CLL (p < 0.05). Adjusted multiple logistic regression analysis demonstrated that age was significantly linked to CLL predisposition (odds ratio = 1.08; p < 0.001). Studies evaluating the influence of genetic factors may provide insights on susceptibility for CLL.

Role of the Carotid Bodies in the Hypertensive and Natriuretic Responses to NaCl Load in Conscious Rats.

Hyperosmotic challenges trigger a hypertensive response and natriuresis mediated by central and peripheral sensors. Here, we evaluated the importance of the carotid bodies for the hypertensive and natriuretic responses to acute and sub-chronic NaCl load in conscious rats. Male Wistar rats (250-330 g) submitted to bilateral carotid body removal (CBX) or sham surgery were used. One day after the surgery, the changes in arterial blood pressure (n = 6-7/group) and renal sodium excretion (n = 10/group) to intravenous infusion of 3 M NaCl (1.8 mL/kg b.w. during 1 min) were evaluated in non-anesthetized rats. Another cohort of sham (n = 8) and CBX rats (n = 6) had access to 0.3 M NaCl as the only source of fluid to drink for 7 days while ingestion and renal excretion were monitored daily. The sodium balance was calculated as the difference between sodium infused/ingested and excreted. CBX reduced the hypertensive (8 ± 2 mmHg, vs. sham rats: 19 ± 2 mmHg; p < 0.05) and natriuretic responses (1.33 ± 0.13 mmol/90 min, vs. sham: 1.81 ± 0.11 mmol/90 min; p < 0.05) to acute intravenous infusion of 3 M NaCl, leading to an increase of sodium balance (0.38 ± 0.11 mmol/90 min, vs. sham: -0.06 ± 0.10 mmol/90 min; p < 0.05). In CBX rats, sub-chronic NaCl load with 0.3 M NaCl to drink for 7 days increased sodium balance (18.13 ± 4.45 mmol, vs. sham: 5.58 ± 1.71 mmol; p < 0.05) and plasma sodium concentration (164 ± 5 mmol/L, vs. sham: 140 ± 7 mmol/L; p < 0.05), without changing arterial pressure (121 ± 9 mmHg, vs. sham: 116 ± 2 mmHg). These results suggest that carotid bodies are important for the maintenance of the hypertensive response to acute hypertonic challenges and for sodium excretion to both acute and chronic NaCl load.

Strength training reverses ovariectomy-induced bone loss and improve metabolic parameters in female Wistar rats.

Menopause induces osteoporosis, sarcopenia, insulin resistance, and dyslipidemia. Ovariectomized (OVX) rat is an animal model, which mimetics postmenopausal conditions. The present study aimed to test the effects of strength training protocol on bone mineral density and metabolic parameters in OVX rats. Female Wistar rats were randomly separated in four groups: non-ovariectomized rats (Sham); ovariectomized rats (OVX); OVX treated with 17ß-estradiol (HR); and OVX trained group (TR). At 70-days-old OVX groups were submitted to a bilateral ovariectomy. Hormonal replacement and strength training were performed three times per week, for 60 days. 17ß-estradiol was administered by intramuscular injection (50 µg/kg of BW) and strength training protocol was composed by four series of 12 repetitions with 65-75% of 1RM. As expected, OVX impaired glucose homeostasis, promoted weight and adiposity gain, dyslipidemia, sarcopenia and osteoporosis, but hormonal replacement and strength training improved most of these parameters. Both HR and TR normalize glucose homeostasis; however, only TR restores blood insulin. OXV also reduced the maximum force in 42%, but TR improved this parameter in 110%, in addition TR prevents sarcopenia and fat mass gain. Interestingly, strength training was able to improve significantly BMD. Taken together, these data suggest that strength training can be effective in the treatment of damage caused by OVX, which in a translational context, becomes an effective non-pharmacological strategy to improve the health of postmenopausal women, reducing costs with secondary symptoms, mainly caused by weight gain, sarcopenia and osteoporosis.

Emotional intelligence as a competence for the animal science professional / A inteligência emocional como competência para o profissional de ciência animal

ABSTRACT: Corporations started to invest in human capital to employ professionals that presented a holistic view of the commercial area and that were able to utilize the available resources in each demanded situation consciously. Moreover, professionals should also be emotionally centered regarding emotional intelligence (EI) and should have personal and vocational skills. In addition, the labor market demands zootechnicians to be competent at having satisfactory work performance together with the EI abilities. The EI contributes to the presence of a precise particularity in the zootechnician, which will act in different contexts, including the organizational area to promote the training, management of human capital and the physical resources of the agroindustrial organizations.

RESUMO: As corporações começaram a investir no capital humano, buscando profissionais que possuíssem uma visão holística no âmbito comercial, e que fossem capazes de utilizar de forma consciente os recursos disponíveis em cada situação. Estes sendo centrados emocionalmente, no que tange a inteligência emocional (IE), e que possuam habilidades e competências de caráter pessoal e profissional. Adicionalmente, o mercado de trabalho visa zootecnistas que possuam competências para o desempenho satisfatório no trabalho, ressaltando a necessidade de outras habilidades e competências, incluindo a IE. De modo suplementar, a IE contribui para que esse diferencial seja nítido no zootecnista, em que atuará em todas as esferas, incluindo o âmbito organizacional promovendo o treinamento, a gestão do capital humano e dos recursos físicos das organizações agroindustriais.

Preclinical Assessment of Cardiovascular Alterations Induced by Birch Polypore Mushroom, Piptoporus betulinus (Agaricomycetes).

Piptoporus betulinus has been used in folk medicine for millennia. However, no data currently exist regarding its potential cardiovascular activity. In this work, the crude ethanolic extract and fractions (hexane, ethyl acetate, and water) with increased polarity from the partitioning process, as well as stigmasterol (the major metabolite isolated from P. betulinus), were administered orally at different doses to normotensive male Wistar rats an hour before recording mean arterial pressure, heart rate, renal blood flow, renal vascular conductance, arterial blood flow, and arterial vascular conductance. The acute oral administration of crude ethanolic extract and all fractions did not alter mean arterial pressure when compared with the control group, which received a vehicle. In addition, subchronic (14 days) oral administration of crude ethanolic extract, fractions, and stigmasterol did not alter cardiovascular parameters. In conclusion, our findings demonstrate that oral administration of organic extracts of P. betulinus did not induce cardiovascular alterations.

Ajustes Cardiovasculares Induzidos pela Desidratação Crônica nas Fases Iniciais do Período Pós-Natal em Ratos Acordados / Cardiovascular Adjustments Induced by Chronic Dehydration in the Early Stages of PostNatal in Awake Rats

Alterações da osmolaridade do compartimento extracelular podem alterar o volume, o metabolismo e a função celular. Em virtude disso,varias complicações podem ser observadas, dentre elas a hipertensão arterial. Assim, a regulação precisa do volume e da osmolaridade docompartimento extracelular é fundamental para a manutenção das funções normais do organismo e da sobrevivência. O objetivo desse estudofoi avaliar os parâmetros hemodinâmicos através de desidratação induzida por furosemide em ratos jovens não anestesiados. Foram utilizados,ratos Wistar com cinco dias de idade, divididos em dois grupos experimentais, um controle (n=10) e um submetido ao tratamento comFurosemide (10mg/kg de massa corpórea, n=12), administrado três vezes por semana, durante dois meses. Após o tratamento, os animaisforam anestesiados para cateterização com cânulas inseridas na artéria e veia femorais, através de um corte inguinal de um dos lados. Ascânulas foram transpassadas subcutaneamente através do dorso do animal e foram exteriorizadas. Os experimentos foram realizados apósuma recuperação de 48h do procedimento cirúrgico, utilizando um amplificador e um software. Os resultados obtidos demonstraram que nãohouve diferenças nos testes induzidos de ingestão de água durante os 120 minutos analisados, quando comparados o grupo controle e o grupofurosemide, respectivamente. Na análise da pressão arterial méia e frequência cardíaca, não foi observada modificação dos níveis basais. Essepadrão de resposta também foi obtido quando analisado a PAS e PAD. Com esses resultados, concluímos que a depleção do compartimentoextracelular induzido pela administração de furosemide em ratos jovens não é fator determinante para alteração dos parâmetros hemodinâmicosna fase adulta.

Changes in osmolarity of the extracellular compartment may change the volume, metabolism and cellular function. As a result, manycomplications can be observed, among them hypertension. Thus, precise regulation of the volume and osmolality of the extracellularcompartment is critical to maintaining normal body functions and survival. Previous results demonstrated that despite anesthetized ratssubmitted to chronic diuretic treatment showed no change in sensitivity to sodium and water, an increased arterial pressure was observed. Thepresent study aims to assess hemodynamic parameters through furosemide-induced dehydration in anaesthetized young rats. Five days oldWistar rats divided into two groups, a control (n = 10) and a group subjected to subcutaneous treatment with the diuretic Furosemide (10mg/kg of body weight, n = 12) were used. After treatment, the animals were anesthetized for the implantation of the polyethylene tubes, which wereinserted into the artery (for records cardiovascular variables) and femoral vein through a cut inguinal one side (left / right). The cannulaswere transfixed subcutaneously through the back of the animal and were exteriorized. Data were recorded after a 48h recovery of the surgicalprocedure, using an amplifier and software. No differences in induced intake test of water within 120 minutes were observed. With respect tomean arterial pressure and heart rate, no modification on baseline levels were observed (PAM: 99.4 ± 1.9 mmHg, control vs 102.7 ± 1 mmHg,furosemide; FC: 362.5 ± 5.2 bpm, control vs 364.9 ± 7 bpm, furosemide). This response pattern was also obtained for SBP (124.3 ± 6 mmHg,control vs 130 ± 1.6 mmHg, furosemide) and DBP (82.2 ± 1.9 mmHg, control vs 82.1 ± 1 mmHg, furosemide). We concluded that depletionof the extracellular compartment induced by furosemide administration in young rats is not a determining factor to change the hemodynamicparameters in adulthood.

Bowman-Birk protease inhibitor from Vigna unguiculata seeds enhances the action of bradykinin-related peptides.

The hydrolysis of bradykinin (Bk) by different classes of proteases in plasma and tissues leads to a decrease in its half-life. Here, Bk actions on smooth muscle and in vivo cardiovascular assays in association with a protease inhibitor, Black eyed-pea trypsin and chymotrypsin inhibitor (BTCI) and also under the effect of trypsin and chymotrypsin were evaluated. Two synthetic Bk-related peptides, Bk1 and Bk2, were used to investigate the importance of additional C-terminal amino acid residues on serine protease activity. BTCI forms complexes with Bk and analogues at pH 5.0, 7.4 and 9.0, presenting binding constants ranging from 103 to 104 M-1. Formation of BTCI-Bk complexes is probably driven by hydrophobic forces, coupled with slight conformational changes in BTCI. In vitro assays using guinea pig (Cavia porcellus) ileum showed that Bk retains the ability to induce smooth muscle contraction in the presence of BTCI. Moreover, no alteration in the inhibitory activity of BTCI in complex with Bk and analogous was observed. When the BTCI and BTCI-Bk complexes were tested in vivo, a decrease of vascular resistance and consequent hypotension and potentiating renal and aortic vasodilatation induced by Bk and Bk2 infusions was observed. These results indicate that BTCI-Bk complexes may be a reliable strategy to act as a carrier and protective approach for Bk-related peptides against plasma serine proteases cleavage, leading to an increase in their half-life. These findings also indicate that BTCI could remain stable in some tissues to inhibit chymotrypsin or trypsin-like enzymes that cleave and inactivate bradykinin in situ.

Prevalence of eating disorder attitudes among men and women with exercise dependence symptoms: a non-athlete population study / Prevalência de transtornos alimentares entre homens e mulheres com sintomas de dependência de exercícios: um estudo na população de não atletas / Prevalencia de los trastornos alimentarios entre hombres y mujeres con síntomas de dependencia de ejercicios: estudio de la población no deportista

The present study sought to describe the prevalence of Secondary Exercise Dependence (ScED, i.e. eating disorders attitudes along with exercise dependence symptoms) may differ between men and women in a broader exercising population. In this study, 174 regularly exerciser, aged 18-62 years old, who were invited to respond the Exercise Dependence Scale (EDS) and the Eating Attitudes Test (EAT-26). There were more women than men with ScED. However, only men in the sample presented exercise dependence symptoms without eating disorders attitudes. Eating disorders may or may not exist in those who are exercise dependent in the broad exercising population, although there is a higher prevalence of ScED in women than men.

O presente estudo buscou descrever a prevalência da Dependência de Exercícios Secundário (DESc, ou seja, atitudes alimentares de risco associadas com sintomas de dependência de exercícios) entre homens e mulheres em uma população não-atleta. Neste trabalho, 174 praticantes regulares de exercícios físicos, entre 18 e 62 anos, quando abordados responderam à Escala de Dependência de Exercícios (EDE) e ao Eating Attitudes Test (EAT-26). Houve mais mulheres do que homens com DESc. Contudo, somente os homens apresentaram sintomas de dependência de exercícios com ausência de atitudes alimentares de risco. Os transtornos alimentares podem ou não ocorrer entre não-atletas dependentes de exercícios físicos, embora haja uma maior prevalência de DESc entre as mulheres.

El estudio tiene como objetivo describir la prevalencia de la Dependencia de Ejercicio Secundaria (DESc, a saber riesgo de trastornos alimentarios asociado con los síntomas de dependencia de ejercicios) entre hombres y mujeres en una población no atleta. En este trabajo, 174 practicantes de ejercicios físicos regulares, entre 18 y 62 años, cuando abordados respondieron a la Escala de Dependencia del Ejercicio (EDE) y Eating Attitudes Test (EAT-26). Hubo más mujeres que hombres con DESc. Todavía, sólo los hombres mostraron síntomas de dependencia de ejercicios desasociado de los riesgos de trastorno alimentarios. Trastornos alimentarios pueden existir entre los practicantes de ejercicios no deportistas, aunque hay una mayor prevalencia de mujeres con DESc.