The effect of basic fibroblast growth factor on the blood flow and morphologic features of a latissimus dorsi cardiomyoplasty

AbstractPrevious studies designed to determine whether latissimus cardiomyoplasty could be used to revascularize ischemic myocardium showed that after operation the latissimus was ischemic and had severely deteriorated. This study was undertaken to determine whether basic fibroblast growth factor, a potent angiogenic peptide, would improve the vascularity of the latissimus and enhance collateral formation between the muscle of the cardiomyoplasty and ischemic myocardium. In goats, myocardial ischemia was induced with an ameroid constrictor and cardiomyoplasty performed. The latissimus was continuously stimulated electrically at 2 Hz for 6 weeks and given four weekly bolus injections of human recombinant basic fibroblast growth factor (80 μg infused into the left subclavian artery). In eight animals, rates of regional blood flow were measured and both the heart and latissimus were evaluated histochemically. The latissimus blood flow rate was 0.114 ± 0.029 ml/gm per minute, which was three times greater than that of historical controls (chronically stimulated latissimus cardiomyoplasty without basic fibroblast growth factor treatment; 0.042 ± 0.007 ml/gm per minute, p < 0.05). Associated with the improved blood flow, there was significantly less evidence of skeletal muscle fiber dropout and muscle fibrosis in the animals treated with basic fibroblast growth factor. Latissimus-derived collateral flow to ischemic myocardium developed in five of the eight goats and averaged 0.288 ± 0.075 ml/gm per minute. This flow was 42.8% ± 15.7% ( n = 5) of the flow required by normal myocardium (which was 0.728 ± 0.095 ml/gm per minute). This value for latissimus-derived collateral blood flow was almost twice that of the historical controls (24.0% ± 3.9%), but the increase did not achieve statistical significance ( p = 0.08). These results hold the promise that basic fibroblast growth factor treatment might enhance the formation of extramyocardial collaterals to the heart and improve skeletal muscle function. (J THORAC CARDIOVASC SURG 1996;111:19-28

Lymphocyte Homing to Bronchus-associated Lymphoid Tissue (BALT) Is Mediated by L-selectin/PNAd, α4β1 Integrin/VCAM-1, and LFA-1 Adhesion Pathways

Bronchus-associated lymphoid tissue (BALT) participates in airway immune responses. However, little is known about the lymphocyte–endothelial adhesion cascades that recruit lymphocytes from blood into BALT. We show that high endothelial venules (HEVs) in BALT express substantial levels of VCAM-1, in marked contrast to HEVs in other secondary lymphoid tissues. BALT HEVs also express the L-selectin ligand PNAd. Anti–L-selectin, anti-PNAd, and anti–LFA-1 mAbs almost completely block the homing of B and T lymphocytes into BALT, whereas anti–α4 integrin and anti–VCAM-1 mAbs inhibit homing by nearly 40%. α4β7 integrin and MAdCAM-1 are not involved. Importantly, we found that mAbs against α4 integrin and VCAM-1 significantly block the migration of total T cells (80% memory phenotype) but not naive T and B cells to BALT. These results suggest that an adhesion cascade, which includes L-selectin/PNAd, α4β1 integrin/VCAM-1, and LFA-1, targets specific lymphocyte subsets to BALT. This high level of involvement of α4β1 integrin/VCAM-1 is unique among secondary lymphoid tissues, and may help unify lymphocyte migration pathways and immune responses in BALT and other bronchopulmonary tissues

Water Quality Monitoring System Using 3G Network

This paper presents a water quality monitoring system through the acquisition of data parameters such as temperature, pH level, turbidity, and amount of dissolved oxygen. The prototype consists of hardware such as sensors, Gizduino, Raspberry Pi, and 3G Pocket Wifi. Software element includes Raspbian as an operating system, Python as a programming language and MySQL for the database. The power source of the prototype comprises a battery and a solar panel. The testing of the prototype was done in three different bodies of water such as tap water, “Wawa” dam water and “Pasig” river. The raw data gathered from the testing were validated using calibration methods for the temperature sensor and pH sensor while the turbidity sensor follows the ISO 7027 and for the dissolved oxygen parameter, interpolation with the temperature values was computed. Also, the results revealed a minimal standard deviation for each of the parameters for all of the testing done from three bodies of water which validates the consistency of the data gathered. In terms of power supply, no power failure was encountered during the three testing sites. The data from the sensors were also transmitted to the database using MySQL through a 3G network

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes.

Abstract BACKGROUND: The cardiovascular effects of adding once-weekly treatment with exenatide to usual care in patients with type 2 diabetes are unknown. METHODS: We randomly assigned patients with type 2 diabetes, with or without previous cardiovascular disease, to receive subcutaneous injections of extended-release exenatide at a dose of 2 mg or matching placebo once weekly. The primary composite outcome was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The coprimary hypotheses were that exenatide, administered once weekly, would be noninferior to placebo with respect to safety and superior to placebo with respect to efficacy. RESULTS: In all, 14,752 patients (of whom 10,782 [73.1%] had previous cardiovascular disease) were followed for a median of 3.2 years (interquartile range, 2.2 to 4.4). A primary composite outcome event occurred in 839 of 7356 patients (11.4%; 3.7 events per 100 person-years) in the exenatide group and in 905 of 7396 patients (12.2%; 4.0 events per 100 person-years) in the placebo group (hazard ratio, 0.91; 95% confidence interval [CI], 0.83 to 1.00), with the intention-to-treat analysis indicating that exenatide, administered once weekly, was noninferior to placebo with respect to safety (P<0.001 for noninferiority) but was not superior to placebo with respect to efficacy (P=0.06 for superiority). The rates of death from cardiovascular causes, fatal or nonfatal myocardial infarction, fatal or nonfatal stroke, hospitalization for heart failure, and hospitalization for acute coronary syndrome, and the incidence of acute pancreatitis, pancreatic cancer, medullary thyroid carcinoma, and serious adverse events did not differ significantly between the two groups. CONCLUSIONS: Among patients with type 2 diabetes with or without previous cardiovascular disease, the incidence of major adverse cardiovascular events did not differ significantly between patients who received exenatide and those who received placebo. (Funded by Amylin Pharmaceuticals; EXSCEL ClinicalTrials.gov number, NCT01144338 .)

A survey of political interference patterns and modalities in national roadworks in the Philippines

This study surveys and describes the patterns or modalities of political interference in national roadworks in the Philippines based on an examination of the literature and interviews using process-level frameworks, specifically the project management cycle and the budget cycle framework. Political interference here refers to non-legitimate interventions by politicians in government processes and programs. We argue that it is a form of political corruption. Evidence suggests that this type of interference tends to be prominent in national roadworks. Executive interference occurs at various stages of the project management and budget processes. The abuse of executive discretion in national road development is observed from project selection and prioritization to project maintenance and evaluation. Legislator interference appears to occur at various stages of the project management cycle based on collusive and kickback arrangements. In the budget cycle, this is most notable during the budget legislation stage. Given these vulnerabilities, a comprehensive review of existing project and budget management systems is necessary with the view of reducing such abuse. Finally, understanding the historical and institutional (socio, economic, political, and cultural) context under which these systems operate is necessary to identify context-specific solutions. © 2018 by De La Salle University

Título: Operum

Lugar de impresion tomado de final de textoMarca tip. en port., de donde se ha tomado el impresorSign.: 2a-2g\p8\s, 2h\p4\s, a-z\p8\s, A-R\p8\sPort. orlada y a dos tintasTexto a dos col. con apostillas marginalesIniciales decoradas con figuras y motivos vegetale

Decrypting the chloroplastic [Fe-S] cluster assembly machinery

International audienc

Decrypting the chloroplastic [fe-s] cluster assembly machinery

Iron-Sulfur ([Fe-S]) clusters are metal cofactors of proteins involved in many fundamental metabolic pathways and cellular processes occurring in both prokaryotes and eukaryotes ( e.g. respiration, photosynthesis). [Fe-S] clusters participate in electrontransfer, substrate binding/activation, iron and sulfur storage, regulation of gene expression, and enzyme activity. The [Fe-S] cluster biogenesis machinery is composed of scaffold proteins that build the cluster de novo and of carrier proteins that transfer the [Fe-S] prosthetic groups to their target proteins (also called apoproteins). In plants three different machineries lead to [Fe-S] cluster assembly, namely the mitochondrial ISC (Iron Sulfer Cluster) system, the chloroplastic SUF (SUlFur mobilization) system and the cytosolic CIA (Cytosolic Iron-sulfur cluster Assembly) system. Our team focuses mainly on the chloroplastic SUF system and specifically on the characterization of a [Fe-S] carrier proteins named NFU2 ( NiFU-LIKE PROTEIN 2) and its potential role on the maturation of the 45 putative chloroplastic [Fe-S] cluster proteins. The [Fe-S] cluster acquisition of only 5 targets among the 45 putative chloroplastic [Fe-S] cluster proteins has already been explored. Thus, the identification of the carriers that act on the other 40 targets is still a big challenge. In order to shed new light on this process, we have initiated the global characterisation of the nfu2 mutant using proteomic (quantitative label free mass-spectrometry strategy) and metabolomic approaches. Results obtained within the frame of this work will be discussed