A Murine Model of Vesicant-Induced Acute Lung Injury.

Burn injuries including those caused by chemicals can result in systemic effects and acute lung injury (ALI). Cutaneous exposure to Lewisite, a warfare and chemical burn agent, also causes ALI. To overcome the limitations in conducting direct research on Lewisite-induced ALI in a laboratory setting, an animal model was developed using phenylarsine oxide (PAO) as a surrogate for Lewisite.

Pulmonary pathogenesis in a murine model of inhaled arsenical exposure.

Arsenic trioxide (ATO), an inorganic arsenical, is a toxic environmental contaminant. It is also a widely used chemical with industrial and medicinal uses. Significant public health risk exists from its intentional or accidental exposure.

Sex differences in cardiopulmonary effects of acute bromine exposure.

Accidental occupational bromine (Br>) exposures are common, leading to significant morbidity and mortality; however, the specific effects of Br> inhalation in female victims are unclear. Our studies demonstrated that acute high-concentration Br> inhalation is fatal, and cardiac injury and dysfunction play an important role in Br> toxicity in males. In this study, we exposed female Sprague Dawley rats, age-matched to those males from previously studied, to 600 ppm Br> for 45 min and assessed their survival, cardiopulmonary injury and cardiac function after exposure.

Echocardiographic, Biochemical, and Electrocardiographic Correlates Associated With Progressive Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is a progressive proliferative vasculopathy associated with mechanical and electrical changes, culminating in increased vascular resistance, right ventricular (RV) failure, and death. With a main focus on invasive tools, there has been an underutilization of echocardiography, electrocardiography, and biomarkers to non-invasively assess the changes in myocardial and pulmonary vascular structure and function during the course of PAH. A SU5416-hypoxia rat model was used for inducing PAH.

Behavioral and Neuronal Effects of Inhaled Bromine Gas: Oxidative Brain Stem Damage.

The risk of accidental bromine (Br) exposure to the public has increased due to its enhanced industrial use. Inhaled Br damages the lungs and the heart; however, adverse effects on the brain are unknown. In this study, we examined the neurological effects of inhaled Br in Sprague Dawley rats.

Epigenetic underpinnings of inflammation: Connecting the dots between pulmonary diseases, lung cancer and COVID-19.

Inflammation is an essential component of several respiratory diseases, such as chronic obstructive pulmonary disease (COPD), asthma and acute respiratory distress syndrome (ARDS). It is central to lung cancer, the leading cancer in terms of associated mortality that has affected millions of individuals worldwide. Inflammation and pulmonary manifestations are also the major causes of COVID-19 related deaths.

Chronic cardiac structural damage, diastolic and systolic dysfunction following acute myocardial injury due to bromine exposure in rats.

Accidental bromine spills are common and its large industrial stores risk potential terrorist attacks. The mechanisms of bromine toxicity and effective therapeutic strategies are unknown. Our studies demonstrate that inhaled bromine causes deleterious cardiac manifestations.

MicroRNA-mediated inflammation and coagulation effects in rats exposed to an inhaled analog of sulfur mustard.

Exposure of rats to 2-chloroethyl ethyl sulfide (CEES), an analog of sulfur mustard, can cause acute lung injury (ALI), resulting in increased inflammation and coagulation and altered levels of plasma microRNAs (miRNAs). Rats were exposed to aerosolized CEES and euthanized 12 h later for collection of tissue and plasma. Profiling of miRNAs in plasma, using a TaqMan-based RT-PCR array, revealed 14 differentially expressed miRNAs.

Cutaneous lewisite exposure causes acute lung injury.

Lewisite is a strong vesicating and chemical warfare agent. Because of the rapid transdermal absorption, cutaneous exposure to lewisite can also elicit severe systemic injury. Lewisite (2.

Obesogenic diet in aging mice disrupts gut microbe composition and alters neutrophil:lymphocyte ratio, leading to inflamed milieu in acute heart failure.

Calorie-dense obesogenic diet (OBD) is a prime risk factor for cardiovascular disease in aging. However, increasing age coupled with changes in the diet can affect the interaction of intestinal microbiota influencing the immune system, which can lead to chronic inflammation. How age and calorie-enriched OBD interact with microbial flora and impact leukocyte profiling is currently under investigated.

Bromine inhalation mimics ischemia-reperfusion cardiomyocyte injury and calpain activation in rats.

Halogens are widely used, highly toxic chemicals that pose a potential threat to humans because of their abundance. Halogens such as bromine (Br) cause severe pulmonary and systemic injuries; however, the mechanisms of their toxicity are largely unknown. Here, we demonstrated that Br and reactive brominated species produced in the lung and released in blood reach the heart and cause acute cardiac ultrastructural damage and dysfunction in rats.

Blueberry supplementation attenuates oxidative stress within monocytes and modulates immune cell levels in adults with metabolic syndrome: a randomized, double-blind, placebo-controlled trial.

Background: Blueberries (BB) have been shown to improve insulin sensitivity and endothelial function in obese and pre-diabetic humans, and decrease oxidative stress and inflammation, and ameliorate cardio-renal damage in rodents. This indicates that blueberries have a systemic effect and are not limited to a particular organ system. In order for blueberries to exert beneficial effects on the whole body, the mechanism would logically have to operate through modulation of cellular humoral factors.

Disruption of desmin-mitochondrial architecture in patients with regurgitant mitral valves and preserved ventricular function.

Objective: Recent studies have demonstrated improved outcomes in patients receiving early surgery for degenerative mitral regurgitation (MR) rather than adhering to conventional guidelines for surgical intervention. However, studies providing a mechanistic basis for these findings are limited.

Methods: Left ventricular (LV) myocardium from 22 patients undergoing mitral valve repair for American Heart Association class I indications was evaluated for desmin, the voltage-dependent anion channel, α-B-crystallin, and α, β-unsaturated aldehyde 4-hydroxynonenal by fluorescence microscopy.

Proximal tubule PPARα attenuates renal fibrosis and inflammation caused by unilateral ureteral obstruction.

We examined the effects of increased expression of proximal tubule peroxisome proliferator-activated receptor (PPAR)α in a mouse model of renal fibrosis. After 5 days of unilateral ureteral obstruction (UUO), PPARα expression was significantly reduced in kidney tissue of wild-type mice but this downregulation was attenuated in proximal tubules of PPARα transgenic (Tg) mice. When compared with wild-type mice subjected to UUO, PPARα Tg mice had reduced mRNA and protein expression of proximal tubule transforming growth factor (TGF)-β1, with reduced production of extracellular matrix proteins including collagen 1, fibronectin, α-smooth muscle actin, and reduced tubulointerstitial fibrosis.

Interaction of TNF with angiotensin II contributes to mitochondrial oxidative stress and cardiac damage in rats.

Recent evidence suggests that tumor necrosis factor alpha (TNF) and angiotensin II (ANGII) induce oxidative stress contribute to cardiovascular disease progression. Here, we examined whether an interaction between TNF and ANGII contributes to altered cardiac mitochondrial biogenesis and ATP production to cause cardiac damage in rats. Rats received intraperitoneal injections of TNF (30 µg/kg), TNF + losartan (LOS, 1 mg/kg), or vehicle for 5 days.

Vasoreactivity before and after handgrip training in chronic heart failure patients.

Unlabelled: The purpose of this study was to investigate the vasodilatory and vasoconstrictor responses of the brachial artery in patients with chronic heart failure (CHF) and controls (CON) before and after a period of training and detraining.

Methods: CHF (n = 10; age = 62 ± 8 yrs) and CON (n = 10; age = 55 ± 5 yrs) subjects completed 4 weeks of bilateral handgrip training (20 min; 60% of maximal handgrip strength; 15 grips*min(-1); 4 days*week(-1)). Handgrip strength was measured using a hand dynamometer.

Biopolymer gel matrix as acellular scaffold for enhanced dermal tissue regeneration.

Biological grafts have drawbacks such as donor scarcity, disease transmission, tissue infection, while the scaffolds of either collagen or chitosan fabrics fail to become part of the tissue at the wound site, though they favor the formation of connective tissue matrix. This study developed a novel composite consisting of the combination of atelocollagen and chitosan in order to provide a biodegradable molecular matrix in gel form as a biomimetic surface for cell attachment, to promote the wound healing in excision wounds. We found that the topical application of biopolymer composite on the wound promoted cell proliferation, migration and collagen deposition overtime.

Angiotensin II-induced hypertension is modulated by nuclear factor-κBin the paraventricular nucleus.

Hypertension is considered a low-grade inflammatory condition, and understanding the role of transcription factors in guiding this response is pertinent. A prominent transcription factor that governs inflammatory responses and has become a focal point in hypertensive research is nuclear factor-κB (NFκB). Within the hypothalamic paraventricular nucleus (PVN), a known brain cardioregulatory center, NFκB becomes potentially even more important in ultimately coordinating the systemic hypertensive response.

A blueberry-enriched diet attenuates nephropathy in a rat model of hypertension via reduction in oxidative stress.

Objective And Background: To assess renoprotective effects of a blueberry-enriched diet in a rat model of hypertension. Oxidative stress (OS) appears to be involved in the development of hypertension and related renal injury. Pharmacological antioxidants can attenuate hypertension and hypertension-induced renal injury; however, attention has shifted recently to the therapeutic potential of natural products as antioxidants.

Aging is associated with hypoxia and oxidative stress in adipose tissue: implications for adipose function.

As a part of aging there are known to be numerous alterations which occur in multiple tissues of the body, and the focus of this study was to determine the extent to which oxidative stress and hypoxia occur during adipose tissue aging. In our studies we demonstrate for the first time that aging is associated with both hypoxia (38% reduction in oxygen levels, Po(2) 21.7 mmHg) and increases reactive oxygen species in visceral fat depots of aging male C57Bl/6 mice.

Central TNF inhibition results in attenuated neurohumoral excitation in heart failure: a role for superoxide and nitric oxide.

This study examined the effect of central tumor necrosis factor-alpha (TNF) blockade on the imbalance between nitric oxide and superoxide production in the paraventricular nucleus (PVN) and ventrolateral medulla (VLM), key autonomic regulators, and their contribution to enhanced sympathetic drive in mice with congestive heart failure (CHF). We also used a TNF gene knockout (KO) mouse model to study the involvement of TNF in body fluid homeostasis and sympathoexcitation in CHF. After implantation of intracerebroventricular (ICV) cannulae, myocardial infarction (MI) was induced in wild-type (WT) and KO mice by coronary artery ligation.

HDAC inhibition attenuates inflammatory, hypertrophic, and hypertensive responses in spontaneously hypertensive rats.

Reactive oxygen species and proinflammatory cytokines contribute to cardiovascular diseases. Inhibition of downstream transcription factors and gene modifiers of these components are key mediators of hypertensive response. Histone acetylases/deacetylases can modulate the gene expression of these hypertrophic and hypertensive components.