Treadmill Exercise Training Prevents Myocardial Mechanical Dysfunction Induced by Androgenic-Anabolic Steroid Treatment in Rats

Elevated concentrations of testosterone and its synthetic analogs may induce changes in cardiovascular function. However, the effects of the combination of anabolic/androgenic steroid (AAS) treatment and exercise training on systolic and diastolic cardiac function are poorly understood. in the present study, we aimed to investigate the effects of low-dose steroid treatment (stanozolol) on cardiac contractile parameters when this steroid treatment was combined with exercise training in rats and the effects of chronic steroid treatment on the Frank-Starling (length-tension curves) relationship. Male Wistar rats were randomly assigned to one of four groups: U (untrained), US (untrained and treated with stanozolol 5 mg/kg/week), T (trained, 16 m/min/1 h) and TS (trained and treated with stanozolol 5 mg/kg/week). Continuous exercise training was conducted 5 days/week for 8 consecutive weeks. the speed of the treadmill was gradually increased to a final setting of 16 m/min/1 h. Experiments were divided into two independent series: 1) central hemodynamic analysis for mean arterial blood pressure (MAP) and cardiac output (CO) measurements and 2) isolated papillary muscle preparation in Krebs solution. Stanozolol treatment significantly increased the MAP and the heart size in untrained and trained rats (U 113 +/- 2; T 106 +/- 2; US 138 +/- 8 and TS 130 +/- 7 mmHg). Furthermore, stanozolol significantly decreased developed tension and dT/dt (maximal and minimal) in U rats. However, the developed tension was completely restored by training. the Frank/Starling relationship was impaired in rats treated with stanozolol; however, again, training completely restored diastolic function. Taken together, the present data suggest that AAS treatment is able to decrease cardiac performance (systolic and diastolic functions). the combination of stanozolol and physical training improved cardiac performance, including diastolic and systolic functions, independent of changes in central hemodynamic parameters. Therefore, changes in ventricular myocyte calcium transients may play a cardioprotective role.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Univ Sao Judas Tadeu, Dept Post Grad Phys Educ, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Physiol, Div Cardiovasc, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Med, Div Cardiol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Physiol, Div Cardiovasc, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Med, Div Cardiol, São Paulo, BrazilWeb of Scienc

Negative effects of ant-plant interaction on pollination: costs of a mutualism

The mutualism of ants and extrafloral nectary (EFN)-bearing plants is known to reduce rates of herbivory. However, ants may have negative impacts on other mutualisms such as pollination, constituting an indirect cost of a facultative mutualism. For instance, when foraging on or close to reproductive plant parts ants might attack pollinators or inhibit their visits. We tested the hypothesis that ants on EFN-bearing plants may negatively influence pollinator behavior, ultimately reducing plant fitness (fruit set). The study was done in a reserve at Brazilian savannah using the EFN-bearing plant Banisteriopsis malifolia (Malpighiaceae). The experimental manipulation was carried out with four groups: control (free visitation of ants), without ants (ant-free branches), artificial ants (isolated branches with artificial ants on flowers) and plastic circles (isolated branches with plastic circles on flowers). We made observations on flower visitors and their interactions, and measured fruit formation as a proxy for plant fitness. Our results showed that pollinators hesitated to visit flowers with artificial ants, negatively affecting pollination, but did not hesitate to visit flowers with plastic circles, suggesting that they recognize the specific morphology of the ants. Pollinators spent more time per flower on the ant-free branches, and the fruiting rate was lower in the group with artificial ants. Our results confirm an indirect cost in this facultative mutualism, where the balance between these negative and positive effects of ants on EFN-bearing plants are not well known

T Cell Factor 1-Expressing Memory-like CD8(+) T Cells Sustain the Immune Response to Chronic Viral Infections.

Chronic infections promote the terminal differentiation (or "exhaustion") of T cells and are thought to preclude the formation of memory T cells. In contrast, we discovered a small subpopulation of virus-specific CD8(+) T cells that sustained the T cell response during chronic infections. These cells were defined by, and depended on, the expression of the transcription factor Tcf1. Transcriptome analysis revealed that this population shared key characteristics of central memory cells but lacked an effector signature. Unlike conventional memory cells, Tcf1-expressing T cells displayed hallmarks of an "exhausted" phenotype, including the expression of inhibitory receptors such as PD-1 and Lag-3. This population was crucial for the T cell expansion that occurred in response to inhibitory receptor blockade during chronic infection. These findings identify a memory-like T cell population that sustains T cell responses and is a prime target for therapeutic interventions to improve the immune response in chronic infections

Unlocking the potential of snake venom-based molecules against the malaria, Chagas disease, and leishmaniasis triad

Funding Information: This work received financial support from PT national funds ( FCT/MCTES , Fundação para a Ciência e Tecnologia and Ministério da Ciência, Tecnologia e Ensino Superior) through the project CIRCNA/BRB/0281/2019 . Funding Information: This work received financial support from PT national funds (FCT/MCTES, Fundação para a Ciência e Tecnologia and Ministério da Ciência, Tecnologia e Ensino Superior) through the project CIRCNA/BRB/0281/2019.The authors further thank FCT/MCTES for supporting Research Units LAQV-REQUIMTE (UIDB/50006/2020), GHTM (UID/Multi/04413/2020). Publisher Copyright: © 2023 The AuthorsMalaria, leishmaniasis and Chagas disease are vector-borne protozoal infections with a disproportionately high impact on the most fragile societies in the world, and despite malaria-focused research gained momentum in the past two decades, both trypanosomiases and leishmaniases remain neglected tropical diseases. Affordable effective drugs remain the mainstay of tackling this burden, but toxicicty, inneficiency against later stage disease, and drug resistance issues are serious shortcomings. One strategy to overcome these hurdles is to get new therapeutics or inspiration in nature. Indeed, snake venoms have been recognized as valuable sources of biomacromolecules, like peptides and proteins, with antiprotozoal activity. This review highlights major snake venom components active against at least one of the three aforementioned diseases, which include phospholipases A2, metalloproteases, L-amino acid oxidases, lectins, and oligopeptides. The relevance of this repertoire of biomacromolecules and the bottlenecks in their clinical translation are discussed considering approaches that should increase the success rate in this arduous task. Overall, this review underlines how venom-derived biomacromolecules could lead to pioneering antiprotozoal treatments and how the drug landscape for neglected diseases may be revolutionized by a closer look at venoms. Further investigations on poorly studied venoms is needed and could add new therapeutics to the pipeline.publishersversionepub_ahead_of_prin

Metabolite Profiles of Sugarcane Culm Reveal the Relationship Among Metabolism and Axillary Bud Outgrowth in Genetically Related Sugarcane Commercial Cultivars

Metabolic composition is known to exert influence on several important agronomic traits, and metabolomics, which represents the chemical composition in a cell, has long been recognized as a powerful tool for bridging phenotype–genotype interactions. In this work, sixteen truly representative sugarcane Brazilian varieties were selected to explore the metabolic networks in buds and culms, the tissues involved in the vegetative propagation of this species. Due to the fact that bud sprouting is a key trait determining crop establishment in the field, the sprouting potential among the genotypes was evaluated. The use of partial least square discriminant analysis indicated only mild differences on bud outgrowth potential under controlled environmental conditions. However, primary metabolite profiling provided information on the variability of metabolic features even under a narrow genetic background, typical for modern sugarcane cultivars. Metabolite–metabolite correlations within and between tissues revealed more complex patterns for culms in relation to buds, and enabled the recognition of key metabolites (e.g., sucrose, putrescine, glutamate, serine, and myo-inositol) affecting sprouting ability. Finally, those results were associated with the genetic background of each cultivar, showing that metabolites can be potentially used as indicators for the genetic background

Maternal Melatonin Programs the Daily Pattern of Energy Metabolism in Adult Offspring

Background: Shift work was recently described as a factor that increases the risk of Type 2 diabetes mellitus. In addition, rats born to mothers subjected to a phase shift throughout pregnancy are glucose intolerant. However, the mechanism by which a phase shift transmits metabolic information to the offspring has not been determined. Among several endocrine secretions, phase shifts in the light/dark cycle were described as altering the circadian profile of melatonin production by the pineal gland. The present study addresses the importance of maternal melatonin for the metabolic programming of the offspring. Methodology/Principal Findings: Female Wistar rats were submitted to SHAM surgery or pinealectomy (PINX). The PINX rats were divided into two groups and received either melatonin (PM) or vehicle. The SHAM, the PINX vehicle and the PM females were housed with male Wistar rats. Rats were allowed to mate and after weaning, the male and female offspring were subjected to a glucose tolerance test (GTT), a pyruvate tolerance test (PTT) and an insulin tolerance test (ITT). Pancreatic islets were isolated for insulin secretion, and insulin signaling was assessed in the liver and in the skeletal muscle by western blots. We found that male and female rats born to PINX mothers display glucose intolerance at the end of the light phase of the light/dark cycle, but not at the beginning. We further demonstrate that impaired glucose-stimulated insulin secretion and hepatic insulin resistance are mechanisms that may contribute to glucose intolerance in the offspring of PINX mothers. The metabolic programming described here occurs due to an absence of maternal melatonin because the offspring born to PINX mothers treated with melatonin were not glucose intolerant. Conclusions/Significance: The present results support the novel concept that maternal melatonin is responsible for the programming of the daily pattern of energy metabolism in their offspring.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)CNPq (Conselho Nacional de Aperfeicoameno Cientifico)CNPq (Conselho Nacional de Aperfeicoameno Cientifico

Impacto de um programa para profilaxia de tromboembolismo venoso em pacientes clínicos em quatro hospitais de Salvador

OBJETIVO: Implementar um programa hospitalar de profilaxia de TEV através da criação de uma comissão, da realização de palestras e da distribuição de algoritmos baseados na Diretriz Brasileira para Profilaxia de TEV em Pacientes Clínicos e avaliar seu impacto na adequação da utilização de profilaxia em quatro hospitais de Salvador, Bahia. MÉTODOS: Foram realizados dois estudos de corte-transversal, um antes e um depois da implementação do programa, e comparadas as proporções de pacientes em risco de TEV e as mudanças na adequação da profilaxia. RESULTADOS: Foram avaliados 219 pacientes clínicos antes e 292 depois do programa. As taxas daqueles com pelo menos um fator de risco para TEV e daqueles com contra indicação (CI) para heparina foram semelhantes nos dois grupos: 95% vs. 98% (p=0,13) e 42% vs. 34% (p=0,08), respectivamente. Nos dois estudos, 75% vs. 82% (p=0,06) eram candidates para profilaxia, e 44% vs. 55% (p =0,02) eram candidatos sem qualquer CI para heparina. Após o programa, utilizou-se mais profilaxia mecânica, 0,9% vs. 4,5% (p=0,03) e menos profilaxia farmacológica, 55,3% vs. 47,9% (p=0,04), embora tenha havido um aumento significativo na utilização das doses corretas das heparinas, 53% vs. 75% (pThere is a discrepancy between guideline recommendations and practice of venous thromboembolism (VTE) prophylaxis in hospitals worldwide. OBJECTIVE: To implement a program using a risk-assessment tool (RAT) for VTE and educational lectures based on the Brazilian Guidelines for VTE Prophylaxis for Medical Patients and to evaluate the impact of these tools on adequacy of VTE prophylaxis in 4 hospitals in Salvador, Bahia. METHODS: We performed two cross-sectional surveys before and after the implementation of the program to compare the proportion of patients at-risk of VTE and the changes in the adequacy of VTE prophylaxis. RESULTS: We compared the data of 219 medical patients before with 292 patients after the program. The rates of patients with at least one risk factor for VTE and with contraindications (CI) for heparins were similar: 95% vs. 98% (p=0.13), and 42% vs. 34% (p=0.08), respectively. In both studies, 75% vs. 82% (p=0.06) were candidates for prophylaxis, and 44% vs. 55% (p =0.02) were candidates for prophylaxis and had no CI for heparin. After the program there was an increase in the use of mechanical prophylaxis 0.9% vs. 4.5% (p=0.03) and a decrease in pharmacological prophylaxis, 55.3% vs. 47.9% (p=0.04). However, there was a significant increase of use of the recommended doses of heparins, 53% vs. 75 (p<0.001). CONCLUSION: There is underutilization of VTE prophylaxis in Brazilian hospitals. Strategies based on passive distribution of RAT and educational lectures were not sufficient to improve the practice of prophylaxis, but improved the adequacy of VTE prophylaxis in hospitalized patients