Fourier Transform Infrared Spectroscopic Imaging-Derived Collagen Content and Maturity Correlates with Stress in the Aortic Wall of Abdominal Aortic Aneurysm Patients.

Abdominal aortic aneurysm (AAA) is a degenerative disease of the aorta characterized by severe disruption of the structural integrity of the aortic wall and its major molecular constituents. From the early stages of disease, elastin in the aorta becomes highly degraded and is replaced by collagen. Questions persist as to the contribution of collagen content, quality and maturity to the potential for rupture.

Distinct macrophage phenotype and collagen organization within the intraluminal thrombus of abdominal aortic aneurysm.

Objective: Little is known about the etiologic factors that lead to the occurrence of intraluminal thrombus (ILT) during abdominal aortic aneurysm (AAA) development. Recent work has suggested that macrophages may play an important role in progression of a number of other vascular diseases, including atherosclerosis; however, whether these cells are present within the ILT of a progressing AAA is unknown. The purpose of this work was to define the presence, phenotype, and spatial distribution of macrophages within the ILT excised from six patients.

Fourier transform infrared spectroscopy to quantify collagen and elastin in an in vitro model of extracellular matrix degradation in aorta.

Extracellular matrix (ECM) is a key component and regulator of many biological tissues including aorta. Several aortic pathologies are associated with significant changes in the composition of the matrix, especially in the content, quality and type of aortic structural proteins, collagen and elastin. The purpose of this study was to develop an infrared spectroscopic methodology that is comparable to biochemical assays to quantify collagen and elastin in aorta.

Validation of the modified Vesikari score in children with gastroenteritis in 5 US emergency departments.

Objectives: The burden of acute gastroenteritis (AGE) in US children is substantial. Research into outpatient treatment strategies has been hampered by the lack of easily used and validated gastroenteritis severity scales relevant to the populations studied. We sought to evaluate, in a US cohort, the reliability, construct validity, and generalizability of a gastroenteritis severity scale previously derived in a Canadian population, the modified Vesikari score (MVS).

Heme oxygenase-1-mediated autophagy protects against hepatocyte cell death and hepatic injury from infection/sepsis in mice.

Unlabelled: Adaptive responses to sepsis are necessary to prevent organ failure and death. Cellular signaling responses that limit cell death and structural damage allow a cell to withstand insult from sepsis to prevent irreversible organ dysfunction. One such protective pathway to reduce hepatocellular injury is the up-regulation of heme oxygenase-1 (HO-1) signaling.

Lipopolysaccaride induces autophagic signaling in macrophages via a TLR4, heme oxygenase-1 dependent pathway.

Toll-like receptor (TLR) signaling is an important part of the innate immune response. One of the downstream responses to TLR4 signaling upon lipopolysaccharide (LPS) stimulation is the induction of autophagy, which is a key response to multiple stressors. An additional adaptive signaling molecule that is involved in the response to stress is heme oxygenase-1 (HO-1).

Nitrite potently inhibits hypoxic and inflammatory pulmonary arterial hypertension and smooth muscle proliferation via xanthine oxidoreductase-dependent nitric oxide generation.

Background: Pulmonary arterial hypertension is a progressive proliferative vasculopathy of the small pulmonary arteries that is characterized by a primary failure of the endothelial nitric oxide and prostacyclin vasodilator pathways, coupled with dysregulated cellular proliferation. We have recently discovered that the endogenous anion salt nitrite is converted to nitric oxide in the setting of physiological and pathological hypoxia. Considering the fact that nitric oxide exhibits vasoprotective properties, we examined the effects of nitrite on experimental pulmonary arterial hypertension.

Heme oxygenase 1 protects against hepatic hypoxia and injury from hemorrhage via regulation of cellular respiration.

Heme oxygenase 1 (HO-1) is an important regulator of the cellular response to stress and inflammation. These investigations test the hypothesis that HO-1 overexpression protects against hemorrhage-induced hypoxia by regulating cellular respiration and oxygen availability. Male C57BL/6 mice or primary mouse hepatocytes were treated with adenoviral gene transfer of HO-1 (AdHO-1) or beta-galactosidase (AdLacZ).

Carbon monoxide activates NF-kappaB via ROS generation and Akt pathways to protect against cell death of hepatocytes.

Heme oxygenase overexpression or exogenous carbon monoxide (CO) protects against hepatocyte apoptosis and fulminant hepatitis. The prevention of hepatocyte apoptosis by CO has been shown to require activation of NF-kappaB. The purpose of these investigations was to determine the mechanism of CO-induced hepatocyte NF-kappaB activation and protection against apoptosis.

Prolonged exposure to reduced levels of androgen accelerates prostate cancer progression in Nkx3.1; Pten mutant mice.

In this report, we have investigated the relationship between androgen levels and prostate tumorigenesis in Nkx3.1; Pten mutant mice, a genetically engineered mouse model of human prostate cancer. By experimentally manipulating serum levels of testosterone in these mice for an extended period (i.

Carbon monoxide signals via inhibition of cytochrome c oxidase and generation of mitochondrial reactive oxygen species.

Carbon monoxide (CO), which is produced endogenously in the breakdown of heme, has been recognized as an important physiological second messenger similar to NO. Additionally, pharmacological delivery of CO is protective in numerous models of injury, including ischemia/reperfusion, transplantation, hemorrhagic shock, and endotoxemia. However, the mechanism of action of CO is only partially elucidated focused primarily on how it modulates the cellular response to stress.

Nitric oxide-induced inhibition of smooth muscle cell proliferation involves S-nitrosation and inactivation of RhoA.

Nitric oxide (NO) acts as a vasoregulatory molecule that inhibits vascular smooth muscle cell (SMC) proliferation. Studies have illustrated that NO inhibits SMC proliferation via the extracellular signal-regulated kinase (ERK) pathway, leading to increased protein levels of the cyclin-dependent kinase inhibitor p21(Waf1/Cip1). The ERK pathway can be pro- or antiproliferative, and it has been demonstrated that the activation status of the small GTPase RhoA determines the proliferative fate of ERK signaling, whereby inactivation of RhoA influences ERK signaling to increase p21(Waf1/Cip1) and inhibit proliferation.

Carbon monoxide reverses established pulmonary hypertension.

Pulmonary arterial hypertension (PAH) is an incurable disease characterized by a progressive increase in pulmonary vascular resistance leading to right heart failure. Carbon monoxide (CO) has emerged as a potently protective, homeostatic molecule that prevents the development of vascular disorders when administered prophylactically. The data presented in this paper demonstrate that CO can also act as a therapeutic (i.

Metformin adjunctive therapy with insulin improves glycemic control in patients with type 1 diabetes mellitus: a pilot study.

Metformin lowers blood glucose by reducing hepatic glucose output and improving insulin sensitivity without requiring an increase in circulating insulin concentration. We hypothesized that metformin could be used adjunctively with insulin to improve glycemic control in type 1 diabetes mellitus (DM). We conducted a 6-month open-label pilot study in 10 adolescents and young adults with type 1 DM, 19.