The recent emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led society to live with a serious public health problem. In this sense, repositioning of antiretrovirals has ...captured the attention of the scientific community. Tenofovir disoproxil fumarate (TDF) is an antiretroviral compound that is used to treat acquired immune deficiency syndrome (AIDS) and hepatitis B. In this short report, we present a scale-up investigation of TDF by in situ infrared spectroscopy monitoring and a forced degradation study to describe a new degradation product. Finally, we have evaluated TDF in vitro for SARS-CoV-2 for the first time foreseeing the using of this medicine in pre-clinical and clinical investigations for the COVID-19 (coronavirus disease 2019) treatment.
•A high-fat diet causes hyperphagia in second-generation offspring.•A high-fat diet induced intergenerational inheritance in second-generation offspring.•A high-fat diet reduced hypothalamic ...sensitivity to insulin and leptin of second-generation offspring.
The aim was to investigate the intergenerational inheritance induced by a high-fat diet on sensitivity to insulin and leptin in the hypothalamic control of satiety in second-generation offspring, which were fed a control diet.
Progenitor rats were fed a high-fat or a control diet for 59 d until weaning. The first-generation and second-generation offspring were fed the control diet until 90 d of age. Body mass and adiposity index of the progenitors fed the high-fat diet and the second-generation offspring from progenitors fed the high-fat diet were evaluated as were the gene expression of DNA methyltransferase 3a, angiotensin-converting enzyme type 2, angiotensin II type 2 receptor, insulin and leptin signaling pathway (insulin receptor, leptin receptor, insulin receptor substrate 2, protein kinase B, signal transducer and transcriptional activator 3, pro-opiomelanocortin, and neuropeptide Agouti-related protein), superoxide dismutase activity, and the concentration of carbonyl protein and satiety-regulating neuropeptides, pro-opiomelanocortin and neuropeptide Agouti-related protein, in the hypothalamus.
The progenitor group fed a high-fat diet showed increased insulin resistance and reduced insulin-secreting beta-cell function and reduced food intake, without changes in caloric intake. The second-generation offspring from progenitors fed a high-fat diet, compared with second-generation offspring from progenitors fed a control diet group, had decreased insulin-secreting beta-cell function and increased food and caloric intake, insulin resistance, body mass, and adiposity index. Furthermore, second-generation offspring from progenitors fed a high-fat diet had increased DNA methyltransferase 3a, neuropeptide Agouti-related protein, angiotensin II type 1 receptor, and nicotinamide adenine dinucleotide phosphate oxidase p47phox gene expression, superoxide dismutase activity, and neuropeptide Agouti-related protein concentration in the hypothalamus. In addition, there were reduced in gene expression of the insulin receptor, leptin receptor, insulin receptor substrate 2, pro-opiomelanocortin, angiotensin II type 2 receptor, angiotensin-converting enzyme type 2, and angiotensin-(1–7) receptor and pro-opiomelanocortin concentration in the second-generation offspring from progenitors fed the high-fat diet.
Overall, progenitors fed a high-fat diet induced changes in the hypothalamic control of satiety of the second-generation offspring from progenitors fed the high-fat diet through intergenerational inheritance. These changes led to hyperphagia, alterations in the hypothalamic pathways of insulin, and leptin and adiposity index increase, favoring the occurrence of different cardiometabolic disorders in the second-generation offspring from progenitors fed the high-fat diet fed only with the control diet.
The Cerrado biome is a biodiversity hotspot with a rich biota, and intense anthropogenic pressures. Despite its importance, it is still poorly understood how insects occupy different spatial ...dimensions of the landscape.
We investigated how the beta diversity of plants influences the beta diversity of nymphalids at the regional‐scale (gallery forest vs. savannah) and local‐scale (transects). We expected greater beta‐diversity in nymphalid assemblages in gallery forests given the heterogeneity of plants and canopy structure.
We sampled nymphalids in each habitat monthly for 1 year and observed 3459 individuals from 62 species. Nymphalidae abundance was significantly higher in the understory than in the canopy. Specifically, only 18% of the individuals were captured in the canopy of gallery forests compared to 11% in savannah canopies. Species richness was higher in gallery forests (55 species) compared to savannahs (34 species).
Savannah transects were very similar in plant species composition and butterfly assemblages within the understory and canopy, whereas the species composition of plants and butterflies in gallery forests was highly heterogeneous which is consistent with the habitat heterogeneity hypothesis.
Gallery forests are spatially more complex, which probably results in higher niche availability that may contribute to reduce the community saturation and help to maintain greater beta diversity in these habitats.
The Cerrado biome has different habitat types ranging from grasslands to forests. In the present study, we have investigated how spatial heterogeneity influences the beta diversity of Nymphalidae species.
Nymphalidae species composition has changed from understory to canopy in gallery forests. Moreover, beta diversity of both plants and nymphalids were greater in gallery forest than in savannah transects.
Gallery forests are spatially more complex, which probably reflects in higher niche availability that may contribute to reduce community saturation, thus maintaining greater beta diversity in this habitat.
The metabolic syndrome (MS) is characterized by variable coexistence of metabolic and pathophysiological alterations which are important risk factors for developing of type II diabetes and/or ...cardiovascular diseases. Increased of MS patients in worldwide has stimulated the development of experimental models. However, it is still challenging to find an dietetic model that most closely approximates human MS and, in addition, is not yet fully established the effect of different diets of MS in lipid metabolism in rats of different ages. The aim of this study was to evaluate the effect of different diets of MS in lipid metabolism and ectopic fat deposition and define the most appropriate diet for inducing the characteristic disturbances of the human MS in rats of different ages.
Young (4 weeks old) and adult rats (12 weeks old) were given a high-fat (FAT) or high-fructose diet (FRU) for 13 weeks and biochemical, physiological, histological and biometric parameters were evaluated.
In young rats, the FAT diet induced increased mean blood pressure (MAP) and heart rate (HR), body weight after 6 to 10 weeks, and in the 13th week, increased the liver, mesenteric, retroperitoneal and epididymal fat weights, fasting glucose, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and reduced HDL cholesterol; and also induced non-alcoholic fatty liver disease (NAFLD) and renal inflammatory infiltrates. In adult rats, the FRU diet induced transient elevations of MAP and HR in the 6th week, and, at 13 weeks, increased fasting glucose, triglycerides, total cholesterol, AST and ALT; increased liver, kidneys and retroperitoneal fat weights; and induced macrovesicular and microvesicular NAFLD, the presence of fat cells in the kidney, glomerular sclerosis, and liver and kidney inflammation. Additionally, the FAT and FRU diets induced, respectively, increases in liver glycogen in adults and young rats.
Our data show that FRU diet in adult rats causes biggest change on metabolism of serum lipids and lipid accumulation in liver and kidney, while the FAT diet in young rats induces elevation of MAP and HR and higher increased visceral lipid stores, constituting the best nutritional interventions to induce MS in rats.
is a highly diverse genus within the Sternopygidae family, comprising 30 species. Due to its complex taxonomy, molecular analyses have been crucial for species delimitation within this group. ...Therefore, the present study presents a genetic analysis using sequences of the mitochondrial gene cytochrome
oxidase subunit 1 (
) in specimens previously identified through alpha taxonomy as
(with unpublished data),
, and
, originating from various locations within the Upper Paraná and Paraguay River basins in Brazil. The molecular data confirm the taxonomic complexity of the genus, as individuals morphologically identified as
and
shared the same haplotype (H52). Furthermore, the results of the species delimitation tests suggest that specimens morphologically identified as
belong to the species
. In addition, samples morphologically identified as
may correspond to more than one Operational Taxonomic Units (
). Furthermore, the intraspecific Kimura-2-parameter (
) distances within the different studied populations are significant. This study has contributed valuable information about genetic diversity in
, emphasizing the importance of using integrative analyses to resolve taxonomic conflicts within the group. It also supports biogeographical studies and assists in biodiversity conservation efforts.
Adapted physical activity programs have shown promising results in reducing the physical, social and psychological side effects associated with breast cancer, but the extent to which they can be ...effectively adopted, implemented and maintained is unclear. The aim of this study is to use the framework to guide the planning and evaluation of programs according to the 5 following keys: Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) framework to evaluate a fencing program under the French acronym RIPOSTE (Reconstruction, Image de soi, Posture, Oncologie, Santé, Thérapie, Escrime) literally in English (Reconstruction, Self-Image, Posture, Oncology, Health, Therapy, Fencing). This program is an innovative intervention focused on improving the quality of life (QoL) of breast cancer surgery patients through fencing.
A convergent mixed methods pilot study was conducted to preliminary evaluate the different RE-AIM dimension of the pilot program. Twenty-four participants who have just undergone surgery for invasive breast cancer were randomly allocated in two groups: one group started immediately after their inclusion (Early RIPOSTE group) and the other started 3 months following their inclusion (Delayed RIPOSTE group). Participants answered a questionnaire at inclusion and at the end of the program on QoL, shoulder functional capacity, fatigue, anxiety-depression and physical activity.
RIPOSTE program was able to reach mainly young and dynamic participants, attracted by the originality of fencing and keen to improve their physical condition. Regarding effectiveness, our results suggest a trend to the improvement of QoL, shoulder functional capacity, fatigue and anxiety-depression state, even without any significant differences between the Early RIPOSTE group and the Delayed RIPOSTE group.
The cooperation, exchanges and cohesion within the group greatly facilitated the adoption of the program, whereas interruptions during school vacations were the main barriers. The intervention was moderately well implemented and adherence to the protocol was suitable.
RIPOSTE is an acceptable and effective program for involving breast cancer survivors in physical activity, that needs to be tested at a larger scale to investigate its effectiveness, but has the potential to be transferred and scaled up worldwide.
In this study, we investigated some mechanisms involved in sodium-dependent hypertension of rats exposed to chronic salt (NaCl) intake from weaning until adult age. Weaned male Wistar rats were ...placed under high (0.90% w/w, HS) or regular (0.27% w/w, Cont) sodium diets for 12 weeks. Water consumption, urine output and sodium excretion were higher in HS rats compared to control. Blood pressure (BP) was directly measured by the arterial catheter and found 13.8% higher in HS vs Cont rats. Ganglionic blockade with hexamethonium caused greater fall in the BP of HS rats (33%), and central antagonism of AT
receptors (losartan) microinjected into the lateral ventricle reduced BP level of HS, but not of Cont group. Heart rate variability analysis revealed sympathetic prevalence on modulation of the systolic interval. HS diet did not affect creatinine clearance. Kidney histological analysis revealed no significant change in renal corpuscle structure. Sodium and potassium concentrations in CSF were found higher in HS rats despite no change in plasma concentration of these ions. Taken together, data suggest that animals exposed to chronic salt intake to a level close to that reported for human' diet since weaning lead to hypertension, which appears to rely on sodium-driven neurogenic mechanisms.
New Findings
What is the central question of this study?
How does swimming exercise training impact hydro‐electrolytic balance, renal function, sympathetic contribution to resting blood pressure and ...cerebrospinal fluid (CSF) Na+ in rats fed a high‐sodium diet from weaning?
What is the main finding and its importance?
An exercise‐dependent reduction in blood pressure was associated with decreased CSF Na+, sympathetically driven vasomotor tonus and renal fibrosis indicating that the anti‐hypertensive effects of swimming training in rats fed a high‐sodium diet might involve neurogenic mechanisms regulated by sodium levels in the CSF rather than changes in blood volume.
High sodium intake is an important factor associated with hypertension. High‐sodium intake with exercise training can modify homeostatic hydro‐electrolytic balance, but the effects of this association are mostly unknown. In this study, we sought to investigate the effects of swimming training (ST) on cerebrospinal fluid (CSF) Na+ concentration, sympathetic drive, blood pressure (BP) and renal function of rats fed a 0.9% Na+ (equivalent to 2% NaCl) diet with free access to water for 22 weeks after weaning. Male Wistar rats were assigned to two cohorts: (1) fed standard diet (SD) and (2) fed high‐sodium (HS) diet. Each cohort was further divided into trained and sedentary groups. ST normalised BP levels of HS rats as well as the higher sympathetically related pressor activity assessed by pharmacological blockade of ganglionic transmission (hexamethonium). ST preserved the renal function and attenuated the glomerular shrinkage elicited by HS. No change in blood volume was found among the groups. CSF Na+ levels were higher in sedentary HS rats but were reduced by ST. Our findings showed that ST effectively normalised BP of HS rats, independent of its effects on hydro‐electrolytic balance, which might involve neurogenic mechanisms regulated by Na+ levels in the CSF as well as renal protection.
Physical training (PT) has been considered as a treatment in metabolic syndrome (MS), since it induces thermogenic activity in brown (BAT) and white (WAT) adipose tissues. We evaluated the ...therapeutic effect of PT on activity of WAT and BAT in rats with MS induced by high-fat diet (30% lard) for 13 weeks and submitted, for the last 6 weeks, to swimming or kept sedentary (SED) rats. MS-SED rats compared to control diet (CT-SED) rats showed low physical fitness and high levels of glucose, insulin, homeostasis evaluation of insulin resistance (HOMA-IR), homeostasis evaluation of the functional capacity of β-cells (HOMA-β), and blood pressure. The gastrocnemius muscle decreased in peroxisome proliferator-activated receptor gamma coactivator 1-alpha and beta (PGC-1α, PGC-1β), and uncoupled protein 2 and 3 (UCP2 and UCP3) expressions. Both WAT and BAT increased in the adipocyte area and decreased in blood vessels and fibroblast numbers. WAT increased in expression of pro-inflammatory adipokines and decreased in anti-inflammatory adipokine and adiponectin. WAT and gastrocnemius showed impairment in the insulin signaling pathway. In response to PT, MS rats showed increased physical fitness and restoration of certain biometric and biochemical parameters and blood pressure. PT also induced thermogenic modulations in skeletal muscle, WAT and BAT, and also improved the insulin signaling pathway. Collectively, PT was effective in treating MS by inducing improvement in physical fitness and interchangeable effects between skeletal muscle, WAT and BAT, suggesting a development of brown-like adipocyte cells.
In prevention studies of metabolic syndrome (MetS), Ang-(1-7) has shown to improve the insulin signaling. We evaluated the HPβCD/Ang-(1-7) treatment on lipid metabolism, renin-angiotensin system ...(RAS) components, oxidative stress, and insulin pathway in the liver and gastrocnemius muscle and hepatic steatosis in rats with established MetS. After 7 weeks of high-fat (FAT) or control (CT) diets, rats were treated with cyclodextrin (HPβCD) or HPβCD/Ang-(1-7) in the last 6 weeks. FAT-HPβCD/empty rats showed increased adiposity index and body mass, gene expression of ACE/ANG II/AT1R axis, and oxidative stress. These results were accompanied by imbalances in the insulin pathway, worsening of liver function, hyperglycemia, and dyslipidemia. Oral HPβCD/Ang-(1-7) treatment decreased ACE and AT1R, increased ACE2 gene expression in the liver, and restored thiobarbituric acid reactive substances (TBARS), catalase (CAT), superoxide dismutase (SOD), insulin receptor substrate (Irs-1), glucose transporter type 4 (GLUT4), and serine/threonine kinase 2 (AKT-2) gene expression in the liver and gastrocnemius muscle improving hepatic function, cholesterol levels, and hyperglycemia in MetS rats. Overall, HPβCD/Ang-(1-7) treatment restored the RAS components, oxidative stress, and insulin signaling in the liver and gastrocnemius muscle contributing to the establishment of blood glucose and lipid homeostasis in MetS rats.
PDF
