Introduction:
Dexamethasone (DEX)-induced hypertension and cardiac remodeling are still unclear, especially in spontaneously hypertensive rats (SHR). On the other side, exercise training is a good ...strategy to control hypertension. Therefore, this study investigated the effects of DEX treatment and physical training on arterial pressure and cardiac remodeling in SHR.
Material and Methods:
SHR underwent treadmill training (5 days/week, 1h/session, at 50-60% of maximal capacity, 0% degree, 75 days) and received low-dose of DEX (50µg/kg, s.c.) during the last 15 days. Sedentary Wistar rats (W) were used as control. Echocardiography and artery catheterization were performed for cardiac remodeling and function, arterial pressure and autonomic nervous system analyses. In addition, left ventricle (LV) capillary density, myocyte diameter and collagen deposition area were analyzed using specific histological staining.
Results:
Low-dose of DEX treatment did not exacerbate arterial pressure of SHR and trained groups had lower values, regardless of DEX. DEX and training decreased relative left ventricle wall thickness (RWT) and determined LV angiogenesis (+19%) and lower collagen deposition area (−22%). In addition, it determined increased left ventricular diastolic diameter. These changes were followed by improvements on systolic and diastolic function, since it was observed increased posterior wall shortening velocity (PWSV) and reduced isovolumetric relaxation time (IVRT).
Conclusion:
In conclusion, this study is unique to indicate that low-dose of DEX treatment does not exacerbate arterial pressure in SHR and, when associated with training, it improves LV systolic and diastolic function, which may be due to LV angiogenesis and reduction of wall collagen deposition area.
Diabetes mellitus is a degenerative disease that has deleterious effects on male reproductive function, possibly through an increase in oxidative stress. This study was conducted in order to clarify ...the mechanisms by which oxidative stress influences animal models for both type 1 (streptozotocin-treated rats, STZ) and type 2 (Goto-Kakizaki (GK) rats) diabetes. We determined the extent of lipid peroxidation, protein oxidation, lactate levels, adenine nucleotides, adenylate energy charge and the activity of glutathione peroxidase, glutathione reductase and lactate dehydrogenase, in isolated testicular cells of control and diabetic rats. We have also correlated these parameters with sperm count and motility. Sperm concentration and motility were decreased in STZ-treated rats. ATP levels were lower in rats treated with STZ for 3 months, in contrast to GK and rats treated with STZ for 1 month, suggesting an adaptative response. STZ-treated rats showed increased lipid peroxidation after 1 week and 3 months of treatment. Glutathione reductase (G-red) activity was found to be higher in GK rats. Glutathione peroxidase activity was lower in GK and rats treated with STZ for 1 month, which is in accordance with the proposal of functional recovery in these animals. We conclude that hyperglycemia has an adverse effect in sperm concentration and motility via changes in energy production and free radical management. Furthermore, both animal models, particularly GK rats and rats treated with STZ for 1 month, present some metabolic adaptations, increasing the efficiency of mitochondrial ATP production, in order to circumvent the deleterious effects promoted by the disease.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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•Lean mass decreases earlier than body weight during dexamethasone treatment.•Myostatin protein level may be involved in triggering muscle atrophy.•MuRF-1 protein level may be ...important for the maintenance of muscle atrophy.
This study was designed to describe the time-course changes of catabolic proteins following muscle atrophy induced by 10days of dexamethasone (DEX). Rats underwent DEX treatment for 1, 3, 5, 7 and 10days. Body weight (BW) and lean mass were obtained using a dual energy X-ray absorptiometry (DEXA) scan. Muscle ringer finger1 (MuRF-1), atrogin-1 and myostatin protein levels were analyzed in the tibialis anterior (TA), flexor hallucis longus (FHL) and soleus muscles. DEX treatment reduced lean mass since day-3 and reduced BW since day-5. Specific muscle weight reductions were observed after day-10 in TA (−23%) and after day-5 in FHL (−16%, −17% and −29%, for days 5, 7 and 10, respectively). In TA, myostatin protein level was 36% higher on day-5 and its values were normalized in comparison with controls on day-10. MuRF-1 protein level was increased in TA muscle from day-7 and in FHL muscle only on day-10. This study suggests that DEX-induced muscle atrophy is a dynamic process which involves important signaling factors over time. As demonstrated by DEXA scan, lean mass declines earlier than BW and this response may involve other catabolic proteins than myostatin and MuRF-1. Specifically for TA and FHL, it seems that myostatin may trigger the catabolic process, and MuRF-1 may contribute to maintain muscle atrophy. This information may support any intervention in order to attenuate the muscle atrophy during long period of treatment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Here, we evaluate how cationic gallic acid-triethylene glycol (GATG) dendrimers interact with bacteria and their potential to develop new antimicrobials. We demonstrate that GATG dendrimers ...functionalised with primary amines in their periphery can induce the formation of clusters in Vibrio harveyi, an opportunistic marine pathogen, in a generation dependent manner. Moreover, these cationic GATG dendrimers demonstrate an improved ability to induce cluster formation when compared to poly(N-3-(dimethylamino)propylmethacrylamide) p(DMAPMAm), a cationic linear polymer previously shown to cluster bacteria. Viability of the bacteria within the formed clusters and evaluation of quorum sensing controlled phenotypes (i.e. light production in V. harveyi) suggest that GATG dendrimers may be activating microbial responses by maintaining a high concentration of quorum sensing signals inside the clusters while increasing permeability of the microbial outer membranes. Thus, the reported GATG dendrimers constitute a valuable platform for the development of novel antimicrobial materials that can target microbial viability and/or virulence.
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•Dexamethasone increased systolic arterial pressure and decreased baroreflex activity.•Training attenuated hypertension and improved baroreflex activity.•Neither DEX nor training ...caused expressive changes in RAS components.
Dexamethasone-induced hypertension may be caused by baroreflex alterations or renin-angiotensin system (RAS) exacerbation. Aerobic training has been recommended for hypertension treatment, but the mechanisms responsible for reduction of arterial pressure (AP) in dexamethasone (DEX) treated rats are still inconclusive.This study evaluated whether mechanisms responsible for training-induced attenuation of hypertension involve changes in autonomic nervous system and in RAS components. Rats underwent aerobic training protocol on treadmill or were kept sedentary for 8 weeks. Additionally, animals were treated with DEX during the last 10 days of exercise. Body weight (BW), AP and baroreflex activity were analyzed. Tibialis anterior (TA), soleus (SOL) and left ventricle (LV) were collected for evaluation of RAS components gene expression and protein levels. Dexamethasone decreased BW (20%), caused TA atrophy (16%) and increased systolic AP (SAP, 16%) as well as decreased baroreflex activity. Training attenuated SAP increase and improved baroreflex activity, although it did not prevent DEX-induced BW reduction and muscle atrophy. Neither DEX nor training caused expressive changes in RAS components. In conclusion, exercise training was effective in attenuating hypertension induced by DEX and this response may be mediated by a better autonomic balance through an improvement of baroreflex activity rather than changes in RAS components.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
This study investigated whether exercise training could prevent the negative side effects of dexamethasone. Rats underwent a training period and were either submitted to a running protocol (60% ...physical capacity, 5 days/week for 8 weeks) or kept sedentary. After this training period, the animals underwent dexamethasone treatment (1 mg/kg per day, i.p., 10 days). Glycemia, insulinemia, muscular weight and muscular glycogen were measured from blood and skeletal muscle. Vascular endothelial growth factor (VEGF) protein was analyzed in skeletal muscles. Dexamethasone treatment evoked body weight loss (−24%), followed by muscular atrophy in the tibialis anterior (−25%) and the extensor digitorum longus (EDL, −15%). Dexamethasone also increased serum insulin levels by 5.7-fold and glucose levels by 2.5-fold compared to control. The exercise protocol prevented atrophy of the EDL and insulin resistance. Also, dexamethasone-treated rats showed decreased muscular glycogen (−41%), which was further attenuated by the exercise protocol. The VEGF protein expression decreased in the skeletal muscles of dexamethasone-treated rats and was unaltered by the exercise protocol. These data suggest that exercise attenuates hyperglycemia and may also prevent insulin resistance, muscular glycogen loss and muscular atrophy, thus suggesting that exercise may have some benefits during glucocorticoid treatment.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Physical activity is a major component of treatment for adolescents with obesity and prediabetes or type 2 diabetes; however, sedentary behavior remains pervasive. An SMS text message-based ...intervention paired with financial incentives may be an effective way to promote physical activity in this population.
This study aims to obtain end-user feedback on SMS text message content and assess the acceptability of a planned SMS text messaging intervention with financial incentives to motivate youth with prediabetes or type 2 diabetes to increase physical activity.
Adolescents with overweight or obesity and prediabetes or type 2 diabetes who attended a large academic pediatric endocrinology clinic were recruited to participate in group interviews (2-4/group) via videoconferencing. Participants were asked to share their thoughts on the use of SMS text messages and financial incentives to remind and motivate them to be more physically active. They rated and provided feedback on specific messages to be used in clinical trials. Participants were also asked about their personal experience with rewards to motivate behavior change and their anticipated reactions to rewards provided for goal attainment (gain-framing) versus those provided and then taken away if a goal was not met (loss-framing). The interviews were conducted by 2 trained interviewers and a note-taker. Content analysis was used to explore themes.
Group interviews were completed with 20 participants (11/20, 55% women; 15/20, 75% with type 2 diabetes; 5/20, 25% with prediabetes) with a mean age of 15 (SD 1; range 12-18) years and a mean BMI of 41 (SD 5) kg/m
(all >95th percentile for age and sex). Most participants were non-Hispanic Black (14/20, 70%) and 10% (2/20) were Hispanics. Participants frequently cited near-continuous smartphone use and agreed that SMS text messages would serve as good reminders to be physically active, but the consensus about the need for short messages was strong. Favorable content included references to what they were likely to be doing when messages were sent (eg, homework or watching television) and messages that were upbeat or informative. Specific physical activity suggestions were rated favorably. Attitudes toward financial incentives varied, with differing opinions about whether loss-framed incentives would be motivating or discouraging. Many participants highlighted the role of intrinsic, rather than extrinsic, motivation in achieving and sustaining behavior change.
The engagement of adolescents with obesity and diabetes or prediabetes allowed for the refinement of SMS text messages for our planned intervention, with an emphasis on short, upbeat, relatable, and informative messages. Although an SMS text messaging intervention using financial incentives to motivate youth with prediabetes or type 2 diabetes to be more physically active is theoretically acceptable, the impact on actual activity levels in this population requires prospective evaluation in a clinical trial.
Cigarette smoking is usually associated with hypertension and may modify vasoconstrictor response.
The present study aimed to analyze and compare the interaction of passive cigarette smoking and ...hypertension on epinephrine and felypressin blood pressure effects after intravascular injection.
45-day male Wistar rats had the main left renal artery partially constricted and the right kidney removed (1K1C model). Rats were placed in the chamber for exposition to passive cigarette smoking (10 cigarettes) during 10 min (6 days a week). Hypertensive rats received atenolol (90 mg/kg/day) by gavage for two weeks. Hypotensive and hypertensive response, response duration and heart rate were recorded from direct blood pressure values. The significance level was 5%.
Passive cigarette smoking increased maximal hypertensive response to epinephrine in normotensive and 1K1C-atenolol treated rats and to felypressin only in 1K1C-atenolol treated rats; it also reduced epinephrine hypotensive response. Epinephrine increased heart rate in normotensive and hypertensive passive smokers or non-smoker rats. Comparing the two vasoconstrictors, epinephrine showed greater hypertensive response in normotensive smokers, 1K1C-atenolol treated smokers and non-smokers. However, in normotensive-nonsmoker rats, felypressin showed a greater and longer hypertensive effect.
Our results suggest that passive cigarette smoking may reduce epinephrine vasodilation and increase hypertensive response when compared to felypressin. Therefore, felypressin may be safe for hypertensive patients to avoid tachycardia and atenolol interaction, but for normotensive and non-smoker patients, epinephrine may be safer than felypressin.
Tamoxifen therapy is a standard in the treatment of estrogen receptor (ER)-positive breast cancer; however, its efficacy varies widely among patients. In addition to interpatient differences in the ...tamoxifen-metabolizing capacity, there is growing evidence that crosstalk between ER and growth factor signaling contributes to tamoxifen resistance. We focused on TC21, a member of the Ras superfamily, to investigate the influence of the TC21 -582C>T promoter polymorphism on TC21 expression and treatment outcome. Immunohistochemical analyses of breast tumors revealed a higher TC21 expression in ER-negative compared with ER-positive tumors. Expression in ER-positive tumors was higher in carriers of the T allele in an allele dose-dependent manner. Quantitative real-time PCR analyses showed that TC21 mRNA expression is decreased after transfection of ERalpha in ER-negative breast cancer cells MDA-MB-231, UACC893, and BT-20. In MCF7 ER-positive cells, TC21 expression decreased with 17beta-estradiol treatment and increased after treatment with tamoxifen metabolites, 4-OH-tamoxifen, or endoxifen. In patients treated with adjuvant mono tamoxifen, high cytoplasmic TC21 tumor expression or the carriership of the -582T allele conferred increased recurrence rates n=45: hazard ratio (HR), 3.06; 95% confidence interval (95% CI), 1.16-8.05; n=206: HR, 1.79; 95% CI, 1.08-3.00, respectively. A combined analysis with the data of the known tamoxifen predictor CYP2D6 showed an improvement of outcome prediction compared with CYP2D6 or TC21 genotype status alone (per mutated gene HR, 2.35; 95% CI, 1.34-4.14). Our functional and patient-based results suggest that the TC21 -582C>T polymorphism improves prediction of tamoxifen treatment outcome in breast cancer.
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