Fat Embolism Does Not Alter Cardiac Structure or Induce Pathological Changes in a Rat Model.

Introduction: Fat embolism (FE) encompasses conditions in which fatty substance becomes embedded in a tissue/organ. Fat emboli most commonly affect the lungs in a trauma setting. This can lead to both significant pathology locally and systemically including changes in structure, inflammatory response, activation of the renin-angiotensin system, and subsequent hypoxia.

Renin-Angiotensin Blockade Reduces Readmission for Acute Chest Syndrome in Sickle Cell Disease.

Rationale Acute chest syndrome (ACS) is a life-threatening complication of sickle cell disease (SCD). Current treatment is supportive-supplemental oxygen, transfusions, and antibiotics. Prevention of ACS may reduce morbidity and mortality in patients with SCD.

Cod Liver Oil, but Not Retinoic Acid, Treatment Restores Bone Thickness in a Vitamin A-Deficient Rat.

Vitamin A plays a prominent role for maintaining optimal bone status, but its impact upon the bone in response to vitamin A deficiency is not well defined. The purpose of this study was to evaluate how replenishing vitamin A by either whole food cod liver oil (COD) or the active metabolite of vitamin A, retinoic acid (RA), altered bone thickness of vitamin A-deficient (VAD) rats. Weanling rats were administered a control diet (CTRL) or VAD diet for 9 weeks.

Evidence for angiotensin mediation of the late histopathological effects of pulmonary fat embolism: Protection by losartan in a rat model.

Purpose: In a model of fat embolism using triolein-treated rats, we have reported that the acute pulmonary histopathological changes at 48 hrs were ameliorated by the angiotensin AT1 receptor blocker losartan, the angiotensin converting enzyme inhibitor captopril, and the direct renin inhibitor aliskiren. Although much of the pathology had declined by 3 weeks, the changes persisted at 6 weeks. The purpose of the study was to extends the time course investigation to 10 weeks and to examines whether the fat embolism effects continue to be blocked by losartan when given at a late time period.

Preclinical Safety Evaluation of HIV-1 gp120 Responsive Microbicide Delivery System in C57BL/6 Female Mice.

Many novel vaginal/rectal microbicide formulations failed clinically due to safety concerns, indicating the need for the early investigation of lead microbicide formulations. In this study, the preclinical safety of an HIV-1 gp120 and mannose responsive microbicide delivery system (MRP) is evaluated in C57BL/6 mice. MRP was engineered through the layer-by-layer coating of calcium carbonate (CaCO) with Canavalia ensiformis lectin (Con A) and glycogen.

Spray-Dried Thiolated Chitosan-Coated Sodium Alginate Multilayer Microparticles for Vaginal HIV Microbicide Delivery.

It is hypothesized that novel thiolated chitosan-coated multilayer microparticles (MPs) with enhanced drug loading are more mucoadhesive than uncoated MPs and safe in vivo for vaginal delivery of topical anti-HIV microbicide. Formulation optimization is achieved through a custom experimental design and the alginate (AG) MPs cores are prepared using the spray drying method. The optimal MPs are then coated with the thiolated chitosan (TCS) using a layer-by-layer method.

The renin inhibitor aliskiren protects rat lungs from the histopathologic effects of fat embolism.

Background: Fat embolism (FE) and the consequent FE syndrome occurring after trauma or surgery can lead to serious pulmonary injury, including ARDS and death. Current treatment of FE syndrome is limited to supportive therapy. We have shown in a rat model that the renin angiotensin system plays a significant role in the pathophysiology of FE because drugs interfering with the renin angiotensin system, captopril and losartan reduce the histopathologic pulmonary damage.

Tenofovir Containing Thiolated Chitosan Core/Shell Nanofibers: In Vitro and in Vivo Evaluations.

It is hypothesized that thiolated chitosan (TCS) core/shell nanofibers (NFs) can enhance the drug loading of tenofovir, a model low molecular weight and highly water-soluble drug molecule, and improve its mucoadhesivity and in vivo safety. To test this hypothesis, poly(ethylene oxide) (PEO) core with TCS and polylactic acid (PLA) shell NFs are fabricated by a coaxial electrospinning technique. The morphology, drug loading, drug release profiles, cytotoxicity and mucoadhesion of the NFs are analyzed using scanning and transmission electron microscopies, liquid chromatography, cytotoxicity assays on VK2/E6E7 and End1/E6E7 cell lines and Lactobacilli crispatus, fluorescence imaging and periodic acid colorimetric method, respectively.

Stimuli-sensitive thiolated hyaluronic acid based nanofibers: synthesis, preclinical safety and in vitro anti-HIV activity.

Aim: To develop a seminal enzyme bioresponsive, mucoadhesive nanofibers (NFs) as safe and effective nanocarriers for the prevention of HIV vaginal transmission.

Methods: A novel thiolated hyaluronic acid (HA-SH) polymer was synthesized to fabricate tenofovir (TFV)-loaded electrospun NFs (HA-SH-NFs) and characterized in vitro/in vivo.

Results: A triggered drug release (87% w/w) from the engineered HA-SH-NFs (mean diameter ∼75 nm) occured within 1 h under the influence of seminal hyaluronidase enzyme.

Fat embolism sensitizes rats to a "second hit" with lipopolysaccharide: An animal model of pulmonary fibrosis.

Background: Pulmonary fat embolism (FE) in patients after major bone fracture and other trauma may lead to acute respiratory distress, but few clinical evidence of lung injury remains, and there is a dearth of histopathologic information after the initial recovery. We recently reported histologic changes in the lungs of a patient who died after cesarian delivery, which were similar to a rat model of FE. In this model, we found that despite an apparent full recovery, modest fibrotic damage persisted up to 6 weeks.

Dietary Flaxseed Oil Protects against Bleomycin-Induced Pulmonary Fibrosis in Rats.

Bleomycin, a widely used antineoplastic agent, has been associated with severe pulmonary toxicity, primarily fibrosis. Previous work has shown a reduction in bleomycin-induced lung pathology by long-chain omega-3 fatty acids. Treatment by short-chain omega-3 fatty acids, α-linolenic acid, found in dietary flaxseed oil may also reduce lung fibrosis, as previously evidenced in the kidney.

Effect of exendin (exenatide)--GLP 1 receptor agonist on the thyroid and parathyroid gland in a rat model.

Exenatide or Exendin-4 is a 39-amino acid agonist of the glucagon like peptide (GLP-1) receptor approved for the adjunctive treatment for type 2 diabetes. Recent reports suggest that GLP-1 agonists may also have distant effects including C-cell thyroid hyperplasia. The aim of this study was to evaluate the effect of exendin-4 on the thyroid and parathyroid cells in a rat model.

Persistent and progressive pulmonary fibrotic changes in a model of fat embolism.

Background: Fat embolism (FE) after trauma and some orthopedic procedures is known to cause acute lung injury, including acute respiratory distress syndrome. However, its potential long-term effects on the lung are unknown. A previous study using a rat model of FE found significant histopathologic changes in the lungs after intravenous injection of triolein for up to 11 days.

Mitigating effects of captopril and losartan on lung histopathology in a rat model of fat embolism.

Background: Fat embolization (FE) is an often overlooked and poorly understood complication of skeletal trauma and some orthopedic procedures. Fat embolism can lead to major pulmonary damage associated with fat embolism syndrome (FES).

Methods: A model of FE in unanesthetized rats, using intravenous injection of the neutral fat triolein, was used to study the potential therapeutic effect on lung histopathology of altering the production of, or response to, endogenous angiotensin (Ang) II.

Treatment with omega-3 fatty acids but not exendin-4 improves hepatic steatosis.

Background: Nonalcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease in the Western world. The aim of this study was to evaluate the biochemical and histological effects of omega-3 fatty acid and exendin-4 treatment on NAFLD in an animal model.

Methods: Sixty-three 8-week-old outbred Sprague-Dawley male rats were used for this study.

Fat embolism: evolution of histopathological changes in the rat lung.

The pathophysiology of Fat Embolism Syndrome (FES) is poorly understood and subject to some controversy. Evaluation of the evolution of histological changes in the lungs of patients with FES is impractical. The current theories of FES were established through acute clinical observations and acute animal experiments, but sequential changes in the histology of lungs over a prolonged period have not been made.

Phthalate-Induced Liver Protection against Deleterious Effects of the Th1 Response: A Potentially Serious Health Hazard.

Infection with Mycobacterium tuberculosis (TB) induces pulmonary immunopathology mediated by classical Th1 type of acquired immunity with hepatic involvement in up to 80% of disseminated cases. Since PPAR agonists cause immune responses characterized by a decrease in the secretion of Th1 cytokines, we investigated the impact of activating these receptors on hepatic pathology associated with a well-characterized model of Th1-type pulmonary response. Male Fischer 344 rats were either maintained on a drug-free diet (groups I and II), or a diet containing diethylhexylphthalate (DEHP), a compound transformed in vivo to metabolites known to activate PPARs, for 21 days (groups III and IV).

Effects of dietary calorie restriction or exercise on the PI3K and Ras signaling pathways in the skin of mice.

Weight control by exercise and dietary calorie restriction (DCR) has been associated with reduced cancer risk, but the underlying mechanisms are not well understood. This study was designed to compare the effects of weight loss by increasing physical activity or decreasing calorie intake on tumor promoter-induced Ras-MAPK and PI3K-Akt pathways. SENCAR mice were randomly assigned to one of the following five groups: ad libitum-fed sedentary control, ad libitum-fed exercise (AL+Exe), exercise but pair-fed at the amount as controls (PF+Exe), 20% DCR, and 20% DCR plus exercise (DCR+Exe).

Effects on cytokines and histology by treatment with the ACE inhibitor captopril and the antioxidant retinoic acid in the monocrotaline model of experimentally induced lung fibrosis.

Monocrotaline (MCT), a pyrrolizidine alkaloid extracted from the shrub Crotalaria spectabilis, induces in the lungs of many mammalian species severe hypertension and fibrosis. Previous work with MCT-induced lung disease in rats has shown that some of the steps to progressive fibrosis can be interrupted or decreased by intervention with retinoic acid (RA) or with the angiotensin converting enzyme inhibitor, captopril. This report emphasizes the pathology and cytokines present in lungs of rats in the MCT model of hypertension and fibrosis in 8 treatment groups, six per group: (1) controls, not treated; (2) captopril; (3) RA; (4) combined captopril and RA.

Effect of an angiotensin II receptor blocker and two angiotensin converting enzyme inhibitors on transforming growth factor-beta (TGF-beta) and alpha-actomyosin (alpha SMA), important mediators of radiation-induced pneumopathy and lung fibrosis.

Progressive, irreversible fibrosis is one of the most clinically significant consequences of ionizing radiation on normal tissue. When applied to lungs, it leads to a complication described as idiopathic pneumonia syndrome (IPS) and eventually to organ fibrosis. For its high mortality, the condition precludes treatment with high doses of radiation.

Vitamin A and emphysema.

Within the last several years, research scientists and clinicians have been intrigued with the potential use of an active form of vitamin A, retinoic acid (RA), for the treatment and prevention of emphysema. The interest in this area can be largely attributed to the work of Massaro and Massaro (1996, 1997, 2000) in which they presented evidence that RA partially protects against and to some degree restores elastase-induced emphysema in rats. The mechanism for this protective effect of RA is in part related to elastin metabolism.

Potential deployment of angiotensin I converting enzyme inhibitors and of angiotensin II type 1 and type 2 receptor blockers in cancer chemotherapy.

There is significant evidence that both angiotensin I converting enzyme inhibitors (ACEI) and type 1 and type 2 angiotensin 2 (A2) receptor blockers may inhibit tumor growth. The finding is supported by many reports where these two classes of drugs showed cytostatic effects on the cultures of several lines of both normal and neoplastic cells. These drugs often transformed the cellular biochemical structures, especially in neoplastic cell lines.

Transplant-related bronchiolitis obliterans (BOS) demonstrates unique cytokine profiles compared to toxicant-induced BOS.

Bronchiolitis obliterans (BOS - bronchiolitis obliterans syndrome - clinical diagnosis; CBO-histopathologic diagnosis), is a chronic disease process of fibrosis and cellular deposition in airways, complicating long term survival following lung transplantation. BOS is also the result of sporadic toxicant exposure, with airway signs, symptoms, and histology indistinguishable from allograft rejection. This study establishes a transplant BOS model in MHC-mismatched rats and compares their cytokine profiles and histopathology to that of our established toxicant-induced BOS model.

The effect of treatment with a protease inhibitor on mycobacterial infection.

Mycobacterial infection occurs frequently in patients that receive protease inhibitors, which are drugs used to treat AIDS, but are known for metabolic effects. Proteases of microbial antigens have been recognized as important regulators of host inflammation and cellular response. To evaluate protease inhibitor effect on a mycobacterial infection, a pilot animal model was established.

Vitamin A depletion induced by cigarette smoke is associated with the development of emphysema in rats.

We showed previously that vitamin A deficiency per se causes emphysema. Benzo(a)pyrene, a constituent in cigarette smoke, induces vitamin A depletion when administered to rats; therefore, we tested the hypothesis that cigarette smoke induces vitamin A depletion, which is associated with the development of emphysema. Male weanling rats were fed a purified AIN-93G diet and divided into two groups.