Timing and Rationale of Treatment: Achieving the "Best Result".

Various clinical disciplines defend the modality of therapy available to them (eg, medical vs surgery) when, in fact, multi-modality therapy is usually in the best interest of the patient. The aim of any modality of treatment is to obtain the best possible result for a given patient. To successfully achieve that aim for infantile hemangiomas (IH) and all vascular anomalies, defining what is meant by the best possible result and by when to achieve that, the result needs to be defined.

C-reactive protein (CRP) as a biomarker of pulmonary exacerbation presentation and treatment response.

Background: C-reactive protein (CRP) has been proposed as a biomarker for pulmonary exacerbation (PEx) diagnosis and treatment response. CRP >75mg/L has been associated with increased risk of PEx treatment failure. We have analyzed CRP measures as biomarkers for clinical response during the STOP2 PEx study (NCT02781610).

Temperature sensitive liposomes combined with thermal ablation: Effects of duration and timing of heating in mathematical models and in vivo.

Background: Temperature sensitive liposomes (TSL) are nanoparticles that rapidly release the contained drug at hyperthermic temperatures, typically above ~40°C. TSL have been combined with various heating modalities, but there is no consensus on required hyperthermia duration or ideal timing of heating relative to TSL administration. The goal of this study was to determine changes in drug uptake when heating duration and timing are varied when combining TSL with radiofrequency ablation (RF) heating.

Recanalization and clinical outcome of occlusion sites at baseline CT angiography in the Interventional Management of Stroke III trial.

Purpose: To use baseline computed tomographic (CT) angiography to analyze imaging and clinical end points in an Interventional Management of Stroke III cohort to identify patients who would benefit from endovascular stroke therapy.

Materials And Methods: The primary clinical end point was 90-day dichotomized modified Rankin Scale (mRS) score. Secondary end points were 90-day mRS score distribution and 24-hour recanalization.

Bleomycin delivery by osmotic minipump: similarity to human scleroderma interstitial lung disease.

The interstitial lung diseases (ILD) include a large number of chronic, progressive, irreversible respiratory disorders involving pulmonary fibrosis, the most common of which are idiopathic pulmonary fibrosis and scleroderma lung disease (SSc ILD). Because bleomycin causes lung fibrosis when used in cancer chemotherapy, it is used to model human ILD in rodents. In most studies, bleomycin has been delivered directly into the lung by intratracheal or intraoral administration.

Inflammasomes are important mediators of cyclophosphamide-induced bladder inflammation.

Bladder inflammation (cystitis) underlies numerous bladder pathologies and is elicited by a plethora of agents such as urinary tract infections, bladder outlet obstruction, chemotherapies, and catheters. Pattern recognition receptors [Toll-like receptors (TLRs) and Nod-like receptors (NLRs)] that recognize pathogen- and/or damage-associated molecular patterns (PAMPs and/or DAMPs, respectively) are key components of the innate immune system that coordinates the production (TLRs) and maturation (NLRs) of proinflammatory IL-1β. Despite multiple studies of TLRs in the bladder, none have investigated NLRs beyond one small survey.

Cytoskeletal role in protection of the failing heart by β-adrenergic blockade.

Formation of a dense microtubule network that impedes cardiac contraction and intracellular transport occurs in severe pressure overload hypertrophy. This process is highly dynamic, since microtubule depolymerization causes striking improvement in contractile function. A molecular etiology for this cytoskeletal alteration has been defined in terms of type 1 and type 2A phosphatase-dependent site-specific dephosphorylation of the predominant myocardial microtubule-associated protein (MAP)4, which then decorates and stabilizes microtubules.

Role of integrins in angiotensin II-induced proliferation of vascular smooth muscle cells.

Angiotensin II (AII) binds to G protein-coupled receptor AT(1) and stimulates extracellular signal-regulated kinase (ERK), leading to vascular smooth muscle cells (VSMC) proliferation. Proliferation of mammalian cells is tightly regulated by adhesion to the extracellular matrix, which occurs via integrins. To study cross-talk between G protein-coupled receptor- and integrin-induced signaling, we hypothesized that integrins are involved in AII-induced proliferation of VSMC.

Pivotal role of JNK-dependent FOXO1 activation in downregulation of kallistatin expression by oxidative stress.

Oxidative stress has been shown to suppress endothelial nitric oxide synthase expression through activation of the transcription factor forkhead box O 1 (FOXO1) in cultured endothelial cells. We previously reported that circulating kallistatin levels are markedly reduced in rats with chronic oxidative organ damage. In this study, we investigated the potential role of oxidative stress in suppression of kallistatin expression via FOXO1 activation.

Changes in protein profiles during course of experimental glomerulonephritis.

Better characterization of the molecular mechanisms underlying glomerular cell proliferation may improve our understanding of the pathogenesis of glomerulonephritis and yield disease-specific markers. We used two-dimensional gel electrophoresis (2DE) and mass spectrometry (MS) to generate expression profiles of glomerular proteins in the course of anti-Thy-1 nephritis. Glomeruli were isolated from Wistar rats by sieving, and proteins were separated by 2DE.

Intermedin ameliorates vascular and renal injury by inhibition of oxidative stress.

Intermedin (IMD) is a newly discovered peptide related to calcitonin gene-related peptide and adrenomedullin, and has been shown to reduce blood pressure and reactive oxygen species formation in vivo. In this study, we determined whether IMD exerts vascular and renal protection in DOCA-salt hypertensive rats by intravenous injection of adenovirus harboring the human IMD gene. Expression of human IMD was detected in the rat kidney via immunohistochemistry.

Activation of the oxygen-sensing signal cascade prevents mitochondrial injury after mouse liver ischemia-reperfusion.

The mitochondrial permeability transition (MPT) plays an important role in hepatocyte death caused by ischemia-reperfusion (IR). This study investigated whether activation of the cellular oxygen-sensing signal cascade by prolyl hydroxylase inhibitors (PHI) protects against the MPT after hepatic IR. Ethyl 3,4-dihyroxybenzoate (EDHB, 100 mg/kg ip), a PHI, increased mouse hepatic hypoxia-inducible factor-1alpha and heme oxygenase-1 (HO-1).

The role of Sp1 in IL-1beta and H. pylori-mediated regulation of H,K-ATPase gene transcription.

Helicobacter pylori infection of the gastric body induces transient hypochlorhydria and contributes to mucosal progression toward gastric carcinoma. Acid secretion is mediated by parietal cell H,K-ATPase, in which the catalytic alpha-subunit (HKalpha) promoter activity in transfected gastric epithelial [gastric adenocarcinoma (AGS)] cells is repressed by H. pylori through NF-kappaB p50 homodimer binding to the promoter.

The prolyl hydroxylase oxygen-sensing pathway is cytoprotective and allows maintenance of mitochondrial membrane potential during metabolic inhibition.

The cellular oxygen sensor is a family of oxygen-dependent proline hydroxylase domain (PHD)-containing enzymes, whose reduction of activity initiate a hypoxic signal cascade. In these studies, prolyl hydroxylase inhibitors (PHIs) were used to activate the PHD-signaling pathway in cardiomyocytes. PHI-pretreatment led to the accumulation of glycogen and an increased maintenance of ATP levels in glucose-free medium containing cyanide.

ERK promotes hydrogen peroxide-induced apoptosis through caspase-3 activation and inhibition of Akt in renal epithelial cells.

Reactive oxygen species, including hydrogen peroxide (H(2)O(2)), are generated during ischemia-reperfusion and are critically involved in acute renal failure. The present studies examined the role of the extracellular signal-regulated kinase (ERK) pathway in H(2)O(2)-induced renal proximal tubular cells (RPTC) apoptosis. Exposure of RPTC to 1 mM H(2)O(2) resulted in apoptosis and activation of ERK1/2 and Akt.

Selective spatiotemporal induction of matrix metalloproteinase-2 and matrix metalloproteinase-9 transcription after myocardial infarction.

Myocardial remodeling after myocardial infarction (MI) is associated with increased levels of the matrix metalloproteinases (MMPs). Levels of two MMP species, MMP-2 and MMP-9, are increased after MI, and transgenic deletion of these MMPs attenuates post-MI left ventricular (LV) remodeling. This study characterized the spatiotemporal patterns of gene promoter induction for MMP-2 and MMP-9 after MI.

Lipopolysaccharide-binding protein modulates hepatic damage and the inflammatory response after hemorrhagic shock and resuscitation.

Hemorrhagic shock and resuscitation cause endotoxemia and hepatocellular damage. Because lipopolysaccharide-binding protein (LBP) enhances cellular responses to endotoxin, our aim was to determine whether LBP contributes to hemorrhage/resuscitation-induced injury by comparing LBP knockout and wild-type mice. Under pentobarbital anaesthesia, wild-type and LBP-deficient mice were hemorrhaged to 30 mmHg for 3 h and then resuscitated with shed blood plus half the volume of lactated Ringer solution.

Indoxyl sulfate induces complex redox alterations in mesangial cells.

Indoxyl sulfate is a protein metabolite that is concentrated in the serum of patients with chronic renal insufficiency. It also is a uremic toxin that has been implicated in the progression of chronic renal disease in rodent models. We have shown previously that mesangial cell redox status is related to activation of mitogen-activated protein kinases and cell proliferation, which are factors related to glomerular damage.

Matrix metalloproteinase-9 gene deletion facilitates angiogenesis after myocardial infarction.

Matrix metalloproteinases (MMPs) are postulated to be necessary for neovascularization during wound healing. MMP-9 deletion alters remodeling postmyocardial infarction (post-MI), but whether and to what degree MMP-9 affects neovascularization post-MI is unknown. Neovascularization was evaluated in wild-type (WT; n = 63) and MMP-9 null (n = 55) mice at 7-days post-MI.

Bax translocates from cytosol to mitochondria in cardiac cells during apoptosis: development of a GFP-Bax-stable H9c2 cell line for apoptosis analysis.

The proapoptotic protein Bax plays an important role in cardiomyocytic cell death. Ablation of this protein has been shown to diminish cardiac damage in Bax-knockout mice during ischemia-reperfusion. Presently, studies of Bax-mediated cardiac cell death examined primarily the expression levels of Bax and its prosurvival factor Bcl-2 rather than the localization of this protein, which dictates its function.

Kallikrein gene transfer reduces renal fibrosis, hypertrophy, and proliferation in DOCA-salt hypertensive rats.

In DOCA-salt hypertension, renal kallikrein levels are increased and may play a protective role in renal injury. We investigated the effect of enhanced kallikrein levels on kidney remodeling of DOCA-salt hypertensive rats by systemic delivery of adenovirus containing human tissue kallikrein gene. Recombinant human kallikrein was detected in the urine and serum of rats after gene delivery.

Mechanisms through which bradykinin promotes glomerular injury in diabetes.

In diabetes, mesangial cell proliferation and extracellular matrix expansion are critical components in the development of glomerulosclerosis. We reported that diabetes alters the activity of the kallikrein-kinin system and that these alterations contribute to the development of diabetic nephropathy. The present study examined the influence of streptozotocin-induced diabetes on the renal expression of bradykinin (BK) B2 receptors (B2KR), connective tissue growth factor (CTGF), transforming growth factor-beta (TGF-beta), and TGF-beta type II receptor (TGF-betaRII) and assessed the signaling mechanisms through which B2KR activation may promote glomerular injury.

Mechanisms of angiotensin II-induced expression of B2 kinin receptors.

Although the primary roles of the kallikreinkinin system and the renin-angiotensin system are quite divergent, they are often intertwined under pathophysiological conditions. We examined the effect of ANG II on regulation of B(2) kinin receptors (B2KR) in vascular cells. Vascular smooth muscle cells (VSMC) were treated with ANG II in a concentration (10(-9)-10(-6) M)- and time (0-24 h)-dependent manner, and B2KR protein and mRNA levels were measured by Western blots and PCR, respectively.