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The aim of the study was to compare the effects of chronic oral treatment with carvedilol or amlodipine on blood pressure, blood pressure variability and target organ damage in N-nitro-l-arginine methyl ester (L-NAME) hypertensive rats. Wistar rats were treated with L-NAME administered in the drinking water for 8 weeks together with oral administration of carvedilol 30 mg/kg (n = 6), amlodipine 10 mg/kg (n = 6), or vehicle (n = 6). At the end of the treatment, echocardiographic evaluation, blood pressure, and short-term variability measurements were performed. Left ventricular and thoracic aortas were removed to assess activity of metalloproteinase 2 and 9 and expression levels of transforming growth factor β, tumor necrosis factor α, and interleukin 6. Histological samples were prepared from both tissues. Carvedilol and amlodipine induced a comparable reduction of systolic and mean arterial pressure and its short-term variability in L-NAME rats. The expression of transforming growth factor β, tumor necrosis factor α, and interleukin 6 decreased in both organs after carvedilol or amlodipine treatment and the activity of metalloproteinase was reduced in aortic tissue. Treatment with carvedilol or amlodipine completely prevented left ventricular collagen deposition and morphometric alterations in aorta. Oral chronic treatment with carvedilol or amlodipine significantly attenuates blood pressure variability and reduces target organ damage and biomarkers of tissue fibrosis and inflammation in L-NAME hypertensive rats. [ABSTRACT FROM AUTHOR]

Exposure to air particulate matter (PM) is associated with increased cardiovascular morbimortality. However, PM doesn't affect equally to all people, being the old cohort the most susceptible and studied. We hypothesized that another specific life phase, the middle-aged subpopulation, may be negatively affected. Therefore, the aim of this study was to analyze in vivo the acute biological impact of two environmental particles, Urban Air Particles from Buenos Aires and Residual Oil Fly Ash, on the cardiorespiratory system of middle-aged mice, evaluating oxidative metabolism and inflammation. Both PM provoked a local and systemic inflammatory response, leading to a reduced alveolar area in the lung, an epicard inflammation in the heart, an increment of IL-6, and a reduction on PON 1 activity in serum of middle-aged animals. The positive correlation of local parameters with systemic markers of oxidative stress and inflammation could be responsible for associations of cardiovascular morbimortality in this subpopulation. [ABSTRACT FROM AUTHOR]

Abstract: Background: The prevalence of obesity is growing worldwide and has reached epidemic proportions. Vertical sleeve gastrectomy, which requires irreversible removal of gastric tissue, is considered an effective weight loss treatment of severe obesity. The aim of the present study was to evaluate the feasibility of a reversible gastric sleeve magnetic implant that mimics the vertical sleeve gastrectomy without the gastrectomy for weight loss in a group of normal and obese rats. Methods: A group of Zucker fatty rats either underwent surgical implantation or a sham operation and were followed up for 6 weeks. Also, a group of Wistar rats underwent surgical implantation for 6 weeks, followed by surgical implant removal at 6 weeks, and recovery for an additional 4 weeks. Food intake and body weight were monitored after surgery to determine the efficacy of the device. A histologic examination for all rats was made to evaluate the change in the gastric wall in response to gastric sleeve magnetic implantation. Results: The implanted Zucker fatty and Wistar rats showed a statistically significant decrease in food intake and weight gain rate compared with the sham-operated rats (approximately 3%/wk of body weight loss in the treated group). Moreover, the decrease in the weight gain rate was sustained for 4 weeks after removal of the magnetic implant. The histologic evidence revealed an inflammatory mononuclear cell infiltration and mild fibrosis and hyperplasia of blood vessels, as expected for any implant. No significant structural damage, tissue ischemia, hemorrhage, or necrosis was found in the gastric wall. Conclusion: Our results have shown that the device is feasible in rats, results in effective weight loss, and can be easily removed. These findings, along with the lack of the need for resection of the native stomach, provide a compelling basis for additional development of the device in large animal models. [Copyright &y& Elsevier]

Introduction: The histopathologic evolution of myocardial infarct and of remote zones in rabbit hearts was studied. Methods: The left coronary artery of 55 rabbits was ligated and rabbits were sacrificed at 2, 4, 6, 8, 12, 14, 16, 18, 26, 35 and 56 days post-ligature (n=5 per group). Two rabbits were used as control and four were sham-operated. The hearts were excised, cut in slices and stained with hematoxylin-eosin, Masson''s trichrome and picrosirius red. The histological evaluation was semiquantitative (scale: 0 to ++). Results: At day 2, the presence of neutrophils was ++, decreasing suddenly at day 4 and disappearing completely at day 6. The proliferation of cells with features of fibroblasts increased from days 4 to 14 post-occlusion. Coagulation necrosis in mid-myocardium during the first week was ++. Subendocardial myocytolysis was evident from day 2 up to day 56 post-infarction. During the second week, proliferation of lymphocytes and macrophages (++), granulation tissue formation (++) and incipient traces of fibrosis that peaked at day 35 were observed. Scarring was complete at day 56 (++). In remote zones (right ventricle and septum), the proliferation of cells+ on Vimentin was observed at day 2, and perivascular, interstitial and endocardial fibrosis started to increase at day 6 and peaked at day 16. Conclusion: Although myocardial infarction in rabbits maintains the essence of the infarct chronology, some differences as the early presence of cells+ on Vimentin and subendocardial fibrosis in infarcted areas, and also the rapid increase and early disappearance of neutrophils appear when other species are considered. An interesting finding was the early proliferation of cells with features of fibroblasts in remote zones. [Copyright &y& Elsevier]

Abstract: Apoptosis is a pathologic feature of cardiomyocytes in acute myocardial infarction (AMI) and heart failure. The temporal course of apoptosis in the peri-infarct area in the weeks following an AMI is still uncompletely defined. In order to study the time course of apoptosis after AMI, 16 rabbits underwent left coronary artery ligation and were sacrificed at 16, 26, 35, and 56 days after surgery. Increased apoptotic rate (AR) was observed at in the peri-infarct region than in remote myocardium (5.4% [2.5–9.6] vs 0.4% [0.1–0.9], respectively, P <0.001) and than in sham-operated cases (0.01% [0–0.02], P <0.001). A gradual decrease of AR in the peri-infarct region was observed over time with a 90% reduction at 8 weeks after coronary ligation. [Copyright &y& Elsevier]

We have previously reported that the N-terminal domain of the antigen Tc52 (NTc52) is the section of the protein that confers the strongest protection against Trypanosoma cruzi infection. To improve vaccine efficacy, we conducted here a prime-boost strategy (NTc52PB) by inoculating two doses of pcDNA3.1 encoding the NTc52 DNA carried by attenuated Salmonella (SNTc52), followed by two doses of recombinant NTc52 expressed in Picchia pastoris plus ODN-CpG as adjuvant. This strategy was comparatively analyzed with the following protocols: (1) two doses of NTc52 + ODN-CpG by intranasal route followed by two doses of NTc52 + ODN-CpG by intradermal route (NTc52CpG); (2) four doses of SNTc52; and (3) a control group with four doses of Salmonella carrying the empty plasmid. All immunized groups developed a predominant Th1 cellular immune response but with important differences in antibody development and protection against infection. Thus, immunization with just SNTc52 induces a strong specific cellular response, a specific systemic antibody response that is weak yet functional (considering lysis of trypomastigotes and inhibition of cell invasion), and IgA mucosal immunity, protecting in both the acute and chronic stages of infection. The group that received only recombinant protein (NTc52CpG) developed a strong antibody immune response but weaker cellular immunity than the other groups, and the protection against infection was clear in the acute phase of infection but not in chronicity. The prime-boost strategy, which combines DNA and protein vaccine and both mucosal and systemic immunizations routes, was the best assayed protocol, inducing strong cellular and humoral responses as well as specific mucosal IgA, thus conferring better protection in the acute and chronic stages of infection. [ABSTRACT FROM AUTHOR]

We aimed to investigate the role of early administration of Enalapril (Enal) on post-myocardial infarction (MI) ventricular remodeling and diastolic dysfunction in rabbits. White New Zealand rabbits that underwent coronary artery ligature or Sham were divided in three experimental groups: (1) Sham, (2) MI, and (3) MI + Enal. Enal was given by gavage at a dose of 10 mg/kg/day starting at 3 h after surgery for 35 days. At the end of the protocol, we measured (1) mean arterial pressure, (2) left ventricular (LV)+dP/dt max , (3) LV end-diastolic pressure (LVEDP) and isovolumic relaxation (Tau), (4) LV dimensions, (5) LV ejection and shortening fraction, (6) infarct size (Masson's trichrome-stained slices), (7) fibrosis in the infarct and remote zone (Picrosirius red-stained slices), and (8) myocyte cross-sectional area (MCSA) in WGA-stained section. Enal reduced the mean arterial pressure by 30% as compared with untreated animals and Sham ( P < .05). MI reduced LV + dP/dt max and LV − dP/dt max (mmHg/s), increased LVEDP (mmHg), Tau (ms), and t 50 (ms) values, suggesting a decrease in the relaxation rate. LV end-diastolic dimension and LV end-systolic dimension (LVESD, mm) increased in untreated MI ( P < .05 vs. Sham). In contrast, Enal markedly prevented post-MI diastolic dysfunction by significantly decrease LVEDP from 8.2 ± 0.2 to 5.1 ± 0.3 mmHg, Tau from 19.8 ± 0.8 to 15.3 ± 0.9 ms, and t 50 from 12.4 ± 0.5 to 9.6 ± 0.8 ms as well as reduced LVESD from 15 ± 1.1 to 12 ± 0.8 mm ( P < .05 MI vs. MI + Enal). Collagen concentration in the scar was unaffected, but chronic treatment with Enal prevented myocardial fibrosis and MCSA in the remote zone. In summary, chronic early administration of Enal to rabbits with experimental MI has a favorable effect on ventricular remodeling and diastolic function by reducing MCSA and fibrosis, without affecting the wound healing. [ABSTRACT FROM AUTHOR]

Abstract: Background: It is not known whether overexpansion modifies stent recoil, symmetric distribution of struts, and neointimal hyperplasia. Objectives: The objectives were (a) to evaluate whether stent overexpansion modifies the geometric configuration of the stent in the arterial wall, (b) to determine the relationship between overexpansion and stent recoil, and (c) to evaluate the relationship between the distribution of struts and neointimal hyperplasia. Methods: Twenty tubular stainless steel 316L stents (3.0 and 3.5 mm in diameter) were implanted at 20 and 10 atm, respectively, in the abdominal aorta of New Zealand rabbits fed a hypercholesterolemic diet (1% cholesterol). Sham operations were also performed in seven animals. Eight weeks after implantation or sham operation, an intravascular ultrasound (IVUS) study was performed to measure stent recoil and aid in stent classification (symmetric or asymmetric) according to strut distribution. The degree of injury and neointimal hyperplasia were also evaluated in hematoxylin-eosin stained sections. Results: The symmetry/asymmetry of stents assessed by IVUS, as well as the neointimal hyperplasia, was similar in both groups. Stent recoil was significantly greater in the 3.0-mm stent (overexpanded) group (0.28±0.02 mm), as compared with stent recoil in the 3.5-mm stent group (0.10±0.01 mm, P<.05). The neointimal hyperplasia in histological slices, independent of the implant technique, was predominantly in zones with higher strut concentration as compared with zones with fewer struts. Conclusions: Stent overexpansion enhanced stent recoil and did not modify symmetric and asymmetric strut distribution. Neointimal hyperplasia was not modified by the implant technique. Interestingly, significant hyperplasia was observed in locations with greater strut concentration, independent of overexpansion. [Copyright &y& Elsevier]

Abstract: Background: Apoptosis plays a major role in the transition to heart failure (HF) in systemic hypertension although the underlying mechanisms are still unclear. The aim of this study was to determine the relationship between apoptosis, left ventricular remodeling, heart failure and the myocyte expression of survivin, an inhibitor of apoptosis. Methods: Spontaneously hypertensive rats (SHR) were used as a model of hypertensive cardiopathy, and Wistar Kyoto Stars rats (WKY) were used as controls. Animals were allowed to survive up to 18 months of age. The animals underwent echocardiography (EDD, ESD and FS were measured). The median section of the heart was processed for in situ end-labeling of DNA fragmentation (TUNEL) and for survivin expression by immunohistochemistry. Results: All SHR presented features of adverse cardiac remodeling. Apoptotic cells were increased in SHR compared with WKY, measured as apoptotic cells per high power field (1.08±0.43 vs. 0.27±0.15, P <0.001), and as apoptotic rate (0.16±0.06% vs. 0.04±0.02%, P <0.001). The incidence of apoptosis showed a positive correlation with unfavorable ventricular remodeling, assessed by echocardiogram. Survivin expression was found in all cases, but the survivin expression index was significantly lower in SHR vs. WKY (43±40% vs. 86±18%, respectively, P =0.014). Moreover the survivin expression index was inversely correlated with features of adverse remodeling (i.e., Heart Weight, R =−0.79, P <0.001) and with apoptosis (i.e., apoptotic rate, R =−0.52, P =0.050). Conclusion: Survivin myocardial expression in aging SHR is associated with reduced apoptosis and more favorable cardiac remodeling. Modulation of this pathway may prove beneficial in preventing pressure overload cardiac remodeling and heart failure. [Copyright &y& Elsevier]

Abstract: Background: The effects of losartan (Los) on ventricular remodeling (VR) remain controversial. The objective was to determine whether early administration of Los to rabbits with myocardial infarction (MI) modifies VR. Methods: New Zealand rabbits underwent left coronary artery ligation. Four groups were analyzed: Sham (G1; n=13), MI (G2; n=13), Sham+Los (G3; n=13), and MI+Los (G4; n=13). Los (12.5 mg/kg/day) was administered from 3 h post-MI and during 35 days. At the end of the protocol, the hearts were isolated and perfused to determine pressure–volume curves (P/V). Hearts were weighed, cut, and stained with picrosirius red. The heart weight (HW)/body weight (BW) ratio was determined. Infarct size (IS;%), septum (SeT, mm) and scar thickness (ST, mm), myocyte area (μm2), and width (μm) were measured. Results (X±S.E.M.): Los shifted the diastolic left ventricular (LV) P/V relationship to the right in sham and MI (P<.05 vs. sham), with no changes in the systolic relation. IS was G2=25.38±5.31 and G4=21.85±4.13 (NS); HW/BW was 0.34±0.01, 0.35±0.02, 0.29±0.02 (P<.05 vs. G1 and G2), and 0.32±0.02 in G1, G2, G3, and G4, respectively. Scar collagen concentration (%) was lower in G4 (P<.05 vs. G2). SeT was lower in G3 and G4 (P<.05 vs. G2). The width and area of the septum myocytes increased in the untreated infarct, and Los suppressed that increase. Conclusion: The early administration of Los unfavorably modified post-MI VR, increasing ventricular dilation, reducing scar collagen concentration and thickness, and inhibiting myocytes width and area increase. The dilation observed in sham animals'' hearts suggests that infarct was not the main factor in the dilation of the cavity. [Copyright &y& Elsevier]

Adverse Childhood Experiences (ACE) are associated with substance use in adolescence and adulthood. However, there is a lack of longitudinal research examining the effect of ACE on substance use trajectories from adolescence through emerging adulthood. This study examined the role of ACE in substance use trajectories among Hispanic emerging adults. We surveyed a cohort of Hispanic adolescents (n = 1399) in Southern California across eight survey waves (beginning in 9th grade and continuing through emerging adulthood). Growth curve models were used to examine the effect of ACE on past 30-day cigarette, marijuana, and alcohol use over seven time points, and an interaction term of ACE ∗ time was included to investigate the cross-level effect of ACE. ACE was a significant predictor at 9th grade across all substances. Every additional ACE was associated with significantly higher past 30-day cigarette use (β = 0.05, 95%CI = 0.01, 0.10), marijuana use, (β = 0.15, 95%CI = 0.06, 0.25) and alcohol use (β = 0.14, 95%CI = 0.06, 0.21). Across all models, cross level interactions between ACE and time indicated that young adults exposed to more ACE experience significantly steeper inclining trajectories of 30-day cigarette use (β = 0.05, 95%CI = 0.02, 0.68), marijuana use (β = 0.07, 95%CI = 0.03, 0.11), and alcohol use (β = 0.02, 95%CI = 0.02, 0.68) than young adults with fewer ACE. ACE continue to have an impact on substance use trends through emerging adulthood. Results highlight the graded effect of ACE on substance use during and beyond adolescence and illustrate that ACE exposure is linked to an escalation of substance use frequency. • There is a dose-response relationship with ACE and substance use in adolescence and in emerging adulthood. • The cross-level effect of ACE indicates that ACE is a critical risk factor in substance use trajectories. • Substance use trajectories in those with more ACE are not constant, rather higher levels of ACE may exacerbate use. • ACE effects are ubiquitous across populations, including Hispanics, and highlight the need for ACE screening and prevention. [ABSTRACT FROM AUTHOR]