Adverse Impact of Diet-Induced Hypercholesterolemia on Cardiovascular Tissue Homeostasis in a Rabbit Model: Time-Dependent Changes in Cardiac Parameters

ABSTRACT Amphotericin B lipid complex (ABLC) was recently approved by the Food and Drug Administration for treatment of patients with invasive fungal infections who are intolerant of or refractory to conventional amphotericin B therapy. Little is known, however, about the pharmacokinetics of this new antifungal compound. We therefore investigated the pharmacokinetics of ABLC in comparison with those of conventional desoxycholate amphotericin B (DAmB) in rabbits. The pharmacokinetics of DAmB in a rabbit model were similar to those previously reported in humans. The pharmacokinetics of ABLC differed substantially from those of DAmB. Plasma amphotericin B levels following ABLC administration were 10 times lower than those following administration of an equal dosage of DAmB. The levels of ABLC in whole blood were approximately 40 times greater than those in plasma. The ABLC model differed from the DAmB model by (i) a dose- and time-dependent uptake and return between the plasma compartment and apparent cellular components of the blood-sediment compartment and (ii) time-dependent tissue uptake and return to plasma from serially connected compartments. Following infusion of ABLC, there was a nonlinear uptake into the apparent cellular components of the blood-sediment compartment. This uptake was related to the reciprocal of the integral of the total amount of drug infused (i.e., the more drug infused the greater the fractional uptake between 0.5 and 5 mg/kg of body weight for ABLC). The transfer of drug from plasma to the cellular components of the blood-sediment compartment resulted in initial uptake followed by rapid redistribution back to the plasma. The study describes a detailed model of the pharmacokinetics of ABLC and characterizes a potential role of the cellular components of the blood-sediment compartment in the distribution of this new antifungal compound in tissue.

Download Full-text

Sex Differences and Regulatory Actions of Estrogen in Cardiovascular System

Frontiers in Physiology ◽

10.3389/fphys.2021.738218 ◽

2021 ◽

Vol 12 ◽

Author(s):

Kazutaka Ueda ◽

Nobuaki Fukuma ◽

Yusuke Adachi ◽

Genri Numata ◽

Hiroyuki Tokiwa ◽

...

Keyword(s):

Heart Failure ◽

Sex Differences ◽

Hormone Replacement ◽

Tissue Homeostasis ◽

Cardiovascular Tissue ◽

Full Extent ◽

Great Progress ◽

Regulatory Actions ◽

Made In

Great progress has been made in the understanding of the pathophysiology of cardiovascular diseases (CVDs), and this has improved the prevention and prognosis of CVDs. However, while sex differences in CVDs have been well documented and studied for decades, their full extent remains unclear. Results of the latest clinical studies provide strong evidence of sex differences in the efficacy of drug treatment for heart failure, thereby possibly providing new mechanistic insights into sex differences in CVDs. In this review, we discuss the significance of sex differences, as rediscovered by recent studies, in the pathogenesis of CVDs. First, we provide an overview of the results of clinical trials to date regarding sex differences and hormone replacement therapy. Then, we discuss the role of sex differences in the maintenance and disruption of cardiovascular tissue homeostasis.

Download Full-text

931: Time Dependent Variations in Inflammatory Reaction and Scar Formation of Cadaveric Fascia, Porcine Dermis, Porcine Small Intestine Submucosa, Polypropylene Mesh and Autologous Fascia in the Rabbit Model: Implications for Pubov Aginal Sling Surgery

The Journal of Urology ◽

10.1016/s0022-5347(18)35087-0 ◽

2005 ◽

Vol 173 (4S) ◽

pp. 252-252 ◽

Cited By ~ 1

Author(s):

Amy E. Krambeck ◽

Chandler D. Dora ◽

David S. DiMarco ◽

Thomas J. Sebo ◽

Mark E. Zobitz ◽

...

Keyword(s):

Small Intestine ◽

Inflammatory Reaction ◽

Polypropylene Mesh ◽

Rabbit Model ◽

Scar Formation ◽

Time Dependent ◽

Small Intestine Submucosa ◽

Porcine Dermis ◽

Sling Surgery ◽

Porcine Small Intestine Submucosa

Download Full-text

Harnessing Mechanosensation in Next Generation Cardiovascular Tissue Engineering

Biomolecules ◽

10.3390/biom10101419 ◽

2020 ◽

Vol 10 (10) ◽

pp. 1419

Author(s):

Gloria Garoffolo ◽

Silvia Ferrari ◽

Stefano Rizzi ◽

Marianna Barbuto ◽

Giacomo Bernava ◽

...

Keyword(s):

Gene Expression ◽

Tissue Homeostasis ◽

Extracellular Matrices ◽

Cell Behavior ◽

Next Generation ◽

Cardiovascular Tissue ◽

Physical Information ◽

Intracellular Pathways ◽

Complex Architecture ◽

Mechanical Sensing

The ability of the cells to sense mechanical cues is an integral component of ”social” cell behavior inside tissues with a complex architecture. Through ”mechanosensation” cells are in fact able to decrypt motion, geometries and physical information of surrounding cells and extracellular matrices by activating intracellular pathways converging onto gene expression circuitries controlling cell and tissue homeostasis. Additionally, only recently cell mechanosensation has been integrated systematically as a crucial element in tissue pathophysiology. In the present review, we highlight some of the current efforts to assess the relevance of mechanical sensing into pathology modeling and manufacturing criteria for a next generation of cardiovascular tissue implants.

Download Full-text