We compared the parameters related to glucose homeostasis, and liver and muscle proteomes in fluorosis-susceptible (A/J; S) and fluorosis-resistant (129P3/J; R) mice in response to fluoride (F) ...exposure and exercise. Ninety male mice (45 R-mice and 45 S-mice) were randomized into three groups: (SI; RI) No-F, No-Exercise, (SII; RII) 50 ppm F, No-Exercise, (SIII; RIII) 50 ppm F, Exercise. Overall, mean F concentrations in the plasma and femur were significantly higher in R-mice compared with S-mice. In R-mice, exercise resulted in an increase in F accumulation in the femur. In S-mice, the mean plasma glucose level was significantly higher in Group II compared with Groups I and III. There was an increase in liver proteins involved in energy flux and antioxidant enzymes in non-exercise groups (I, II) of S-mice in comparison with the corresponding groups of R-mice. The results also showed a decrease in muscle protein expression in Group I S-mice compared with their R-mice counterparts. In conclusion, the findings suggest an increased state of oxidative stress in fluorosis-susceptible mice that might be exacerbated by the treatment with F. In addition, fluorosis-susceptible mice have plasma glucose levels higher than fluorosis-resistant mice on exposure to F, and this is not affected by exercise.
Dexamethasone (DEX)‐induced hypertension is observed in normotensive rats, but little is known about the effects of DEX on spontaneously hypertensive animals (SHR). This study aimed to evaluate the ...effects of DEX on hemodynamics, cardiac hypertrophy and arterial stiffness in normotensive and hypertensive rats. Wistar rats and SHR were treated with DEX (50 μg/kg s.c., 14 d) or saline. Pulse wave velocity (PWV), echocardiographic parameters, blood pressure (BP), autonomic modulation and histological analyses of heart and thoracic aorta were performed. SHR had higher BP compared with Wistar, associated with autonomic unbalance to the heart. Echocardiographic changes in SHR (vs. Wistar) were suggestive of cardiac remodeling: higher relative wall thickness (RWT, +28%) and left ventricle mass index (LVMI, +26%) and lower left ventricle systolic diameter (LVSD, −19%) and LV diastolic diameter (LVDD, −10%), with slightly systolic dysfunction and preserved diastolic dysfunction. Also, SHR had lower myocardial capillary density and similar collagen deposition area. PWV was higher in SHR due to higher aortic collagen deposition. DEX‐treated Wistar rats presented higher BP (~23%) and autonomic unbalance. DEX did not change cardiac structure in Wistar, but PWV (+21%) and aortic collagen deposition area (+21%) were higher compared with control. On the other side, DEX did not change BP or autonomic balance to the heart in SHR, but reduced RWT and LV collagen deposition area (−12% vs. SHRCT). In conclusion, the results suggest a differential effect of dexamethasone on arterial stiffness, myocardial remodeling and blood pressure between normotensive and spontaneously hypertensive rats.
This study aimed to evaluate the effects of DEX on hemodynamics, cardiac hypertrophy, and arterial stiffness in normotensive and spontaneously hypertensive rats (SHR). DEX‐treated Wistar rats presented higher BP accompanied by autonomic unbalance to the heart and aortic stiffness. On the other side, hypertension, autonomic unbalance to the heart and arterial stiffness were maintained in SHR after DEX treatment, suggesting a differential effect of DEX between normotensive and hypertensive rats.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
This study was undertaken to describe the association of patient race/ethnicity and renal allograft survival among the national cohort of pediatric renal allograft recipients. Additionally, we ...determined whether racial and ethnic differences in graft survival exist among individuals living in low- or high-poverty neighborhoods and those with private or public insurance. Among 6216 incident, pediatric end-stage renal disease patients in the United States Renal Data System (kidney transplant from 2000 through September, 2011), 14.4% experienced graft failure, with a median follow-up time of 4.5 years. After controlling for multiple covariates, black race, but not Hispanic ethnicity, was significantly associated with a higher rate of graft failure for both deceased and living donor transplant recipients. Disparities were particularly stark by 5 years post transplant, when black living donor transplant recipients experienced only 63.0% graft survival compared with 82.8 and 80.8% for Hispanics and whites, respectively. These disparities persisted among high- and low-poverty neighborhoods and among both privately and publicly insured patients. Notably profound declines in both deceased and living donor graft survival rates for black, compared with white and Hispanic, children preceded the 3-year mark when transplant Medicare eligibility ends. Further research is needed to identify the unique barriers to long-term graft success among black pediatric transplant recipients.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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•Dexamethasone decreases microcirculation in soleus muscle.•Aerobic exercise training counteracts dexamethasone-induced apoptotic/angiogenic imbalance.•Pre-conditioning mitigates ...hypertension induced by dexamethasone.
This work investigated the mechanisms induced by exercise training that may contribute to attenuate dexamethasone (DEX)-induced microvascular rarefaction and hypertension. Wistar rats underwent training protocol or were kept sedentary for 8 weeks. Dexamethasone was administered during the following 14-days and hemodynamic parameters were recorded at the end. Capillary density (CD) and capillary-to-fiber ratio (C:F ratio) were obtained in soleus muscle (SOL). Also, vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor-2 (VEGFR-2), endothelial nitric oxide synthase (eNOS), B-cell lymphoma 2 (Bcl-2), Bcl-2-like protein 4 (Bax), p-BAX and caspase-3 cleaved protein levels were analyzed. DEX treatment significantly increased blood pressure (+14%), which was associated with reduced C:F ratio (−41.0%) and CD (−43.1%). Reduction of vessel density was associated with decreased VEGF (−15.6%), VEGFR-2 (−14.6%), Bcl-2 (−18.4%), Bcl-2/Bax ratio (−29.0%) and p-Bax/Bax (−25.4%), and also with increased caspase-3 cleaved protein level (25%). Training, on the other hand, prevented microvessels loss by mitigating all proteins changes induced by DEX. In addition, angiogenic and apoptotic proteins were significantly correlated with CD, which, in turn, was associated with blood pressure. Therefore, we may point out that exercise training is a good strategy to attenuate DEX-induced microvascular rarefaction in soleus muscle and this response involves a better balance between apoptotic and angiogenic proteins, which may contribute for the attenuation of hypertension.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The generation of dendrimers is a powerful tool in the control of the size and biodistribution of polyion complexes (PIC). Using a combinatorial screening of six dendrimers (18–243 terminal groups) ...and five oppositely charged PEGylated copolymers, a dendrimer‐to‐PIC hierarchical transfer of structural information was revealed with PIC diameters that increased from 80 to 500 nm on decreasing the dendrimer generation. This rise in size, which was also accompanied by a micelle‐to‐vesicle transition, is interpreted according to a cone‐ to rod‐shaped progression in the architecture of the unit PIC (uPIC). This precise size tuning enabled dendritic PICs to act as nanorulers for controlled biodistribution. Overall, a domino‐like control of the size and biological properties of PIC that is not attainable with linear polymers is feasible through dendrimer generation.
PIC and choose: The size and biodistribution of polyion complexes (PICs) can be hierarchically tuned with the generation of a dendrimer component in a way not attainable with linear polymers.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Arterial stiffness, frequently associated with hypertension, is associated with disorganization of the vascular wall and has been recognized as an independent predictor of all-cause mortality. The ...identification of the molecular mechanisms involved in aortic stiffness would be an emerging target for hypertension therapeutic intervention. This study evaluated the effects of perindopril on pulse wave velocity (PWV) and on the differentially expressed proteins in aorta of spontaneously hypertensive rats (SHR), using a proteomic approach. SHR and Wistar rats were treated with perindopril (SHR
) or water (SHRc and Wistar rats) for 8 weeks. At the end, SHR
presented higher systolic blood pressure (SBP, +70%) and PWV (+31%) compared with Wistar rats. SHR
had higher values of nitrite concentration and lower PWV compared with SHR
. From 21 upregulated proteins in the aortic wall from SHR
, most of them were involved with the actin cytoskeleton organization, like
and
. After perindopril treatment, there was an upregulation of the
(
), which normally inhibits the
pathway and may contribute to decreased arterial stiffening. In conclusion, the results of the present study revealed that treatment with perindopril reduced SBP and PWV in SHR. In addition, the proteomic analysis in aorta suggested, for the first time, that the
pathway may be inhibited by perindopril-induced upregulation of
or increases in NO bioavailability in SHR. Therefore, we may propose that activation of
or inhibition of
pathway could be a possible strategy to treat arterial stiffness.
Diabetes Mellitus (DM), a state of chronic hyperglycemia, is a major cause of serious micro and macrovascular diseases, affecting, therefore, nearly every system in the body. Growing evidence ...indicates that oxidative stress is increased in diabetes due to overproduction of reactive oxygen species (ROS) and decreased efficiency of antioxidant defences, a process that starts very early and worsens over the course of the disease. During the development of diabetes, oxidation of lipids, proteins and DNA increase with time. Mitochondrial DNA mutations have also been reported in diabetic tissues, suggesting oxidative stress-related mitochondrial damage. Diabetes-related oxidative stress may also be the trigger for many alterations on sexual function, which can also include decreased testicular mitochondrial function. Although sexual disorders have been extensively studied in diabetic men, possible changes in the sexual function of diabetic women have only recently received attention. The prevalence of sexual dysfunction in diabetic men approaches 50%, whereas in diabetic women it seems to be slightly lower. Testicular dysfunction, impotence, decreased fertility potential and retrograde ejaculations are conditions that have been described in diabetic males. Diabetes is also the most common cause of erectile dysfunction in men. Poor semen quality has also been reported in diabetic men, including decreased sperm motility and concentration, abnormal morphology and increased seminal plasma abnormalities. In addition, diabetic men may have decreased serum testosterone due to impaired Leydig cell function. Among diabetic women neuropathy, vascular impairment and psychological complaints have been implicated in the pathogenesis of decreased libido, low arousability, decreased vaginal lubrication, orgasmic dysfunction, and dyspareunia. An association between the production of excess radical oxygen species and disturbed embryogenesis in diabetic pregnancies has also been suggested. In fact, maternal diabetes during pregnancy is associated with an increased risk of complications in the offspring, such as altered fetal growth, polyhydramnios, fetal loss and congenital malformations. In addition, hypocalemia and reduced bone mineral content are found in neonates of diabetic mothers. Abnormalities in gametogenesis and sexual function have also been documented in animal models for both types of Diabetes, which thus constitute an important research tool to both study the effects of the disease, and to test novel therapeutical interventions. Because sexuality and fertility are important aspects in the lives of individuals and couples, and considering that over 124 million individuals worldwide suffer from Diabetes, this review highlights the impact of Diabetes and associated oxidative stress on sexual function.
The initiation or progression of periodontitis might involve a local renin-angiotensin system (RAS) in periodontal tissue. The aim of this study was to further characterize the local RAS in human and ...rat periodontal tissues between healthy and periodontally-affected tissue. Components of the RAS were investigated using in vitro, ex vivo and in vivo experiments involving both human and Wistar rat periodontium. Although not upregulated when challenged with P. gingivalis-lipopolysaccharide, human gingival and periodontal ligament fibroblasts expressed RAS components. Likewise, healthy and inflamed human gingiva expressed RAS components, some of which were shown to be functional, yet no differences in expression were found between healthy and diseased gingiva. However, in inflamed tissue the immunoreactivity was greater for the AT1R compared to AT2R in fibroblasts. When compared to healthy tissue, ACE activity was increased in human gingiva from volunteers with gingivitis. Human-gingiva homogenates generated Ang II, Ang 1-9 and Ang 1-7 when incubated with precursors. In gingiva homogenates, Ang II formation from Ang I was nearly abolished only when captopril and chymostatin were combined. Ang 1-7 formation was significantly greater when human gingiva homogenates were incubated with chymostatin alone compared to incubation without any inhibitor, only captopril, or captopril and chymostatin. In rat gingiva, RAS components were also found; their expression was not different between healthy and experimentally induced periodontitis (EP) groups. However, renin inhibition (aliskiren) and an AT1R antagonist (losartan) significantly blocked EP-alveolar-bone loss in rats. Collectively, these data are consistent with the hypothesis that a local RAS system is not only present but is also functional in both human and rat periodontal tissue. Furthermore, blocking AT1R and renin can significantly prevent periodontal bone loss induced by EP in rats.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Although viruses are well-established causes of acute gastroenteritis, few data on the circulation of these pathogens in Porto Velho, state of Rondônia, Brazil, are available. Thus, faecal samples ...from hospitalised diarrhoeic children, under six years of age, were collected and tested for the presence of norovirus (NoV), adenovirus (AdV) and astrovirus (AstV) from February 2010-February 2012. Specimens were screened by reverse-transcription polymerase chain reaction and viruses were found in 10.7% (63/591) of the cases. NoV, AdV and AstV were detected in 7.8%, 2% and 0.8% of the samples, respectively. NoV infection was observed at all ages and was most prevalent in zero-18-month-old children (84.7%; p = 0.002). A higher incidence of NoV was detected from February-April 2010, when it was found in 52.2% of the cases. Co-infections involving these viruses, rotavirus and enteropathogenic bacteria were detected in 44.4% (28/63) of the children with viral diarrhoea. Nosocomial infections were demonstrated in 28.6% (18/63) of the cases in which viruses were detected. The present paper reports, for the first time, the circulation of NoV and AstV among the paediatric population of Porto Velho and it contributes to our understanding of the roles of these pathogens in gastrointestinal infections.
The aim of the present study was to investigate the effectiveness of photobiomodulation therapy (PBMT) on muscle recovery based on inflammation (interleukin-10 IL-10; tumor necrosis factor-α TNFα), ...muscle damage markers (creatine kinase CK; lactate dehydrogenase LDH), delay onset muscle soreness (DOMS), and countermovement jump performance (CMJ) after two sprint interval training (SIT) sessions compared with a placebo condition (part-I), as well as to compare the effectiveness of PBMT with active recovery (AR) and cold-water immersion (CWI) (part-II).
Part-I was conducted as a double-blind, randomized and placebo-controlled study and part-II as a parallel-group study. Thirty-six men participated in the studies (12 participants in part-I and 36 participants in part-II). Volunteers performed two SITs interspaced by 24-h (SIT
and SIT
) to mimic the effect of accumulating 2 consecutive days of SIT. In part-I, only after SIT
, PBMT Total energy: 600J (300J per leg in 5 spots); wavelength: 660-850 nm or placebo interventions were performed, while in part-II PBMT (part-I data), AR (15-min; 50% of the maximal aerobic power), or CWI (10-min; 10°C) were carried out, also after SIT
. Blood samples were collected before (i.e., baseline), and 0.5, 1, 24, 48, and 72-h after SIT
, while CMJ and DOMS were measured before, 24, 48, and 72-h after SIT
.
In part-I, there were no interactions between PBMT and placebo conditions for any blood markers (
≥ 0.313), DOMS (
= 0.052), and CMJ (
= 0.295). However, an effect of time was found with increases in LDH, CK, and IL-10 (
≤ 0.043) as well as a decrease in DOMS at 72-h compared with 24-h (
= 0.012). In part-II, there were no interactions between the PBMT, AR, and CWI groups for any markers at the same moments (
≥ 0.189) and for the peak and integral values (
≥ 0.193), for DOMS (
= 0.314) and CMJ (
= 0.264). However, an effect of time was found with an increase in CK and IL-10 (
= 0.003), while DOMS decreased at 48 and 72-h compared with 24-h (
= 0.001).
In summary, PBMT had no effect on inflammation, muscle damage, CMJ performance, or DOMS after two consecutive sprint interval training sessions compared to placebo, CWI, and AR strategies.
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