Reproducibility of hemodynamic, cardiac autonomic modulation and blood flow assessments in patients with intermittent claudication

Objective: To identify, in patients with peripheral artery disease and intermittent claudication (IC), the reproducibility of heart rate (HR), blood pressure (BP), rate pressure product (RPP), heart rate variability (HRV), and forearm and calf blood flow (BF) and vasodilatory assessments. Methods: Twenty-nine patients with IC underwent test and retest sessions, 8-12 days apart. During each session, HR, BP, HRV, BF and vasodilatory responses were measured by electrocardiogram, auscultation, spectral analysis of HRV (low frequency, LFR-R; high frequency, HFR-R) and strain gauge plethysmography (baseline BF, post-occlusion BF, post-occlusion area under the curve, AUC). Reproducibility was determined by intraclass coefficient correlation (ICC), typical error, coefficient of variation (CV) and limits of agreement. Results: The ICC for HR and BP were > 0.8 with CV 0.9 while CV were 0.9 while CV were < 19%; variable ICC and CV for vasodilatory responses were exhibited for calf (0.653 – 0.770; 35.2 – 37.7%) and forearm (0.169 – 0.265; 46.2 – 55.5%). Conclusions: In male patients with IC, systemic hemodynamic (HR and BP), cardiac autonomic modulation (LFR-R and HFR-R) and forearm and calf baseline BF assessments exhibited excellent reproducibility, whereas the level of reproducibility for vasodilatory responses were moderate to poor. Assessment reproducibility has highlighted appropriate clinical tools for the regular monitoring of disease/intervention progression in patients with IC

Solução salina hipertônica aumenta a pressão de perfusão cerebral no transplante do fígado para hepatite fulminante: resultados preliminares

During orthotopic liver transplantation for fulminant hepatic failure, some patients may develop sudden deterioration of cerebral perfusion and oxygenation, mainly due to increased intracranial pressure and hypotension, which are likely responsible for postoperative neurological morbidity and mortality. In the present study, we hypothesized that the favorable effects of hypertonic saline solution (NaCl 7.5%, 4 mL/kg) infusion on both systemic and cerebral hemodynamics, demonstrated in laboratory and clinical settings of intracranial hypertension and hemorrhagic shock resuscitation, may attenuate the decrease in cerebral perfusion pressure that often occurs during orthotopic liver transplantation for fulminant hepatic failure. METHODS: 10 patients with fulminant hepatic failure in grade IV encephalopathy undergoing orthotopic liver transplantation with intracranial pressure monitoring were included in this study. The effect on cerebral and systemic hemodynamics in 3 patients who received hypertonic saline solution during anhepatic phase (HSS group) was examined, comparing their data with historical controls obtained from surgical procedure recordings in 7 patients (Control group). The maximal intracranial pressure and the corresponding mean arterial pressure values were collected in 4 time periods: (T1) the last 10 min of the dissection phase, (T2) the first 10 minutes at the beginning of anhepatic phase, (T3) at the end of the anhepatic phase, and (T4) the first 5 minutes after graft reperfusion. RESULTS: Immediately after hypertonic saline solution infusion, intracranial pressure decreased 50.4%. During the first 5 min of reperfusion, the intracranial pressure remained stable in the HSS group, and all these patients presented an intracranial pressure lower than 20 mm Hg, while in the Control group, the intracranial pressure increased 46.5% (P < 0.001). The HSS group was the most hemodynamically stable; the mean arterial pressure during the first 5 min of reperfusion increased 21.1% in the HSS group and decreased 11.1% in the Control group (P < 0.001). During the first 5 min of reperfusion, cerebral perfusion pressure increased 28.3% in the HSS group while in the Control group the cerebral perfusion pressure decreased 28.5% (P < 0.001). Serum sodium at the end of the anhepatic phase and 3 hours after reperfusion was significantly higher in the HSS group (153.00 &plusmn; 2.66 and 149.00 &plusmn; 1.73 mEq/L) than in the Control group (143.71 &plusmn; 3.30 and 142.43 &plusmn; 1.72 mEq/L), P = 0.003 and P < 0.001 respectively. CONCLUSION: Hypertonic saline solution can be successfully used as an adjunct in the neuroprotective strategy during orthotopic liver transplantation for fulminant hepatic failure, reducing intracranial pressure while restoring arterial blood pressure, promoting sustained increase in the cerebral perfusion pressure.Neste estudo testamos a hipótese de que os efeitos benéficos decorrentes da administração da solução salina hipertônica (NaCl 7,5%, 4 mL/kg) sobre a hemodinâmica sistêmica e cerebral na hipertensão intracraniana e no choque hemorrágico, possam atenuar a diminuição da pressão de perfusão cerebral que freqüentemente acompanha o transplante do fígado para hepatite fulminante. MÉTODO: Foram estudados 10 pacientes com hepatite fulminante em encefalopatia grau IV e monitorização de pressão intracraniana submetidos ao transplante do fígado. A hemodinâmica sistêmica e cerebral de 3 pacientes que receberam solução salina hipertônica durante a fase anepática (Grupo SSH) foi analisada comparando com os dados obtidos de 7 pacientes transplantados anteriormente nas mesmas condições (Grupo Controle). Os valores de pressão intracraniana máxima e a correspondente pressão arterial média foram coletados em quatro tempos: (T1) nos últimos 10 min da fase de disseccão, (T2) nos primeiros 10 minutos da fase anepática, (T3) no final da fase anepática e (T4) nos primeiros 5 min da reperfusão RESULTADO: Imediatamente após a infusão da solução salina hipertônica a pressão intracraniana diminuiu 50,4%. Nos primeiros 5 min da reperfusão a pressão intracraniana no Grupo SSH se manteve estável e todos os pacientes apresentavam pressão intracraniana menor que 20 mmHg enquanto no Grupo Controle a pressão intracraniana aumentou 46,5% (

In silico predicted epitopes from the COOH-terminal extension of cysteine proteinase B inducing distinct immune responses during Leishmania (Leishmania) amazonensis experimental murine infection

<p>Abstract</p> <p>Background</p> <p><it>Leishmania </it>parasites have been reported to interfere and even subvert their host immune responses to enhance their chances of survival and proliferation. Experimental <it>Leishmania </it>infection in mice has been widely used in the identification of specific parasite virulence factors involved in the interaction with the host immune system. Cysteine-proteinase B (CPB) is an important virulence factor in parasites from the <it>Leishmania (Leishmania) mexicana </it>complex: it inhibits lymphocytes Th1 and/or promotes Th2 responses either through proteolytic activity or through epitopes derived from its COOH-terminal extension. In the present study we analyzed the effects of <it>Leishmania (Leishmania) amazonensis </it>CPB COOH-terminal extension-derived peptides on cell cultures from murine strains with distinct levels of susceptibility to infection: BALB/c, highly susceptible, and CBA, mildly resistant.</p> <p>Results</p> <p>Predicted epitopes, obtained by <it>in silico </it>mapping, displayed the ability to induce cell proliferation and expression of cytokines related to Th1 and Th2 responses. Furthermore, we applied <it>in silico </it>simulations to investigate how the MHC/epitopes interactions could be related to the immunomodulatory effects on cytokines, finding evidence that specific interaction patterns can be related to <it>in vitro </it>activities.</p> <p>Conclusions</p> <p>Based on our results, we consider that some peptides from the CPB COOH-terminal extension may influence host immune responses in the murine infection, thus helping <it>Leishmania </it>survival.</p

Walking training improves systemic and local pathophysiological processes in intermittent claudication

Objective: This study examined the impact of submaximal walking training (WT) on local and systemic nitric oxide (NO) bioavailability, inflammation, and oxidative stress in patients with intermittent claudication (IC). Methods: The study employed a randomised, controlled, parallel group design and was performed in a single centre. Thirty-two men with IC were randomly allocated to two groups: WT (n = 16, two sessions/week, 15 cycles of two minutes walking at an intensity corresponding to the heart rate obtained at the pain threshold interspersed by two minutes of upright rest) and control (CO, n = 16, two sessions/week, 30 minutes of stretching). NO bioavailability (blood NO and muscle nitric oxide synthase [eNOS]), redox homeostasis (catalase [CAT], superoxide dismutase [SOD], lipid peroxidation [LPO] measured in blood and muscle), and inflammation (interleukin-6 [IL-6], C-reactive protein [CRP], tumour necrosis factor α [TNF-α], intercellular adhesion molecules [ICAM], vascular adhesion molecules [VCAM] measured in blood and muscle) were assessed at baseline and after 12 weeks. Results: WT statistically significantly increased blood NO, muscle eNOS, blood SOD and CAT, and muscle SOD and abolished the increase in circulating and muscle LPO observed in the CO group. WT decreased blood CRP, ICAM, and VCAM and muscle IL-6 and CRP and eliminated the increase in blood TNF-α and muscle TNF-α, ICAM and VCAM observed in the CO group. Conclusion: WT at an intensity of pain threshold improved NO bioavailability and decreased systemic and local oxidative stress and inflammation in patients with IC. The proposed WT protocol provides physiological adaptations that may contribute to cardiovascular health in these patients

Walking Training Increases microRNA-126 Expression and Muscle Capillarization in Patients with Peripheral Artery Disease

Patients with peripheral artery disease (PAD) have reduced muscle capillary density. Walking training (WT) is recommended for PAD patients. The goal of the study was to verify whether WT promotes angiogenesis in PAD-affected muscle and to investigate the possible role of miRNA-126 and the vascular endothelium growth factor (VEGF) angiogenic pathways on this adaptation. Thirty-two men with PAD were randomly allocated to two groups: WT (n = 16, 2 sessions/week) and control (CO, n = 16). Maximal treadmill tests and gastrocnemius biopsies were performed at baseline and after 12 weeks. Histological and molecular analyses were performed by blinded researchers. Maximal walking capacity increased by 65% with WT. WT increased the gastrocnemius capillary-fiber ratio (WT = 109 ± 13 vs. 164 ± 21 and CO = 100 ± 8 vs. 106 ± 6%, p < 0.001). Muscular expression of miRNA-126 and VEGF increased with WT (WT = 101 ± 13 vs. 130 ± 5 and CO = 100 ± 14 vs. 77 ± 20%, p < 0.001; WT = 103 ± 28 vs. 153 ± 59 and CO = 100 ± 36 vs. 84 ± 41%, p = 0.001, respectively), while expression of PI3KR2 decreased (WT = 97 ± 23 vs. 75 ± 21 and CO = 100 ± 29 vs. 105 ± 39%, p = 0.021). WT promoted angiogenesis in the muscle affected by PAD, and miRNA-126 may have a role in this adaptation by inhibiting PI3KR2, enabling the progression of the VEGF signaling pathway

Orange Pectin Mediated Growth and Stability of Aqueous Gold and Silver Nanocolloids

International audienceThe role of orange based pectin in the nucleation and growth of silver and gold nanoparticles is addressed. Pectin is a complex polysaccharide found in fruits such as oranges, lemons, passion fruits or apples. It displays smooth and hairy chain regions contg. hydroxyl-​, ester-​, carboxylate- and eventually amine groups that can act as surface ligands interacting under various pH conditions more or less efficiently with growing nanometals. Here, a high methoxy pectin (>50​% esterified) was used as a stabilizer​/reducing agent in the prepn. of gold, silver and silver-​gold nanoparticles. Com. pectin (CP) and pectin extd. from orange bagasse (OP) were used. Optionally, trisodium citrate or oxalic acid we used to reduce AgNO3 and HAuCl4 in aq. environment. Characterization methods included UV-​vis absorption spectroscopy, transmission electron microscopy, electron diffraction and energy-​dispersive X-​ray spectroscopy. The results show that under different pH conditions, pectin and reducing agents allow producing various nanostructures shapes (triangles, spheres, rods, octahedrons and decahedrons) often with high polydispersity and sizes ranging between 5 nm and 30 nm. In addn., depending on Ag​/Au-​ratio and pH, the surface plasmon bands can be continuously shifted between 410 nm and 600 nm. Finally, pectin seems to be a highly efficient stabilizer of the colloidal systems that show a remarkable stability and unchanged optical spectral response even after five years

Metabolic Profiling of Inga Species with Antitumor Activity.

Funding: This research received no external funding. Acknowledgments: The authors thank Brazilian Research Agencies CNPq, CAPES, and FAPESP, as well as Albrn Care, India.Peer reviewedPublisher PD

Arabidopsis thaliana rosette habit is controlled by combined light and energy signaling converging on transcriptional control of the TALE homeobox gene ATH1

In the absence of light signals, Arabidopsis plants fail to develop the rosette habit typical for this species. Instead, plants display caulescent growth due to elongation of rosette internodes. This aspect of photomorphogenic development has been paid little attention and molecular events involved, downstream of photoreceptor signaling, remain to be identified. Using a combination of genetic and molecular approaches, we show that Arabidopsis rosette habit is a photomorphogenic trait controlled by induction of ARABIDOPSIS THALIANA HOMEOBOX GENE1 (ATH1) as downstream target of multiple photoreceptors. ATH1 induction prevents rosette internode elongation by maintaining the shoot apical meristem (SAM) rib zone area inactive and requires inactivation of photomorphogenesis inhibitors, including PHYTOCHROME INTERACTING FACTOR (PIF) proteins. ATH1 activity results in tissue-specific inhibition of PIF expression, establishing double-negative feedback-regulation at the SAM. Light-requirement for ATH1 expression can be overcome by high sugar availability to the SAM. Both sugar and light signals that induce ATH1 and, subsequently, rosette habit are mediated by TOR kinase. Collectively, our data reveal a SAM-specific, double-negative ATH1-PIF feedback loop at the basis of rosette habit. Upstream, TOR kinase functions as central hub integrating light and energy signals that control this for Arabidopsis quintessential trait

O desenvolvimento do projeto tutoria química essencial da Universidade Federal de Mato Grosso

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Post-embryonic Hourglass Patterns Mark Ontogenetic Transitions in Plant Development

The historic developmental hourglass concept depicts the convergence of animal embryos to a common form during the phylotypic period. Recently, it has been shown that a transcriptomic hourglass is associated with this morphological pattern, consistent with the idea of underlying selective constraints due to intense molecular interactions during body plan establishment. Although plants do not exhibit a morphological hourglass during embryogenesis, a transcriptomic hourglass has nevertheless been identified in the model plant Arabidopsis thaliana. Here, we investigated whether plant hourglass patterns are also found postembryonically. We found that the two main phase changes during the life cycle of Arabidopsis, from embryonic to vegetative and from vegetative to reproductive development, are associated with transcriptomic hourglass patterns. In contrast, flower development, a process dominated by organ formation, is not. This suggests that plant hourglass patterns are decoupled from organogenesis and body plan establishment. Instead, they may reflect general transitions through organizational checkpoints