Erythrocytic metabolism of ATLX-0199: An agent that increases minute ventilation.

Both L- and D-isomers of S-nitrosocysteine (CSNO) can bind to the intracellular domain of voltage-gated potassium channels in vitro. CSNO binding inhibits these channels in the carotid body, leading to increased minute ventilation in vivo. However, only the l-isomer is active in vivo because it requires the l-amino acid transporter (LAT) for transmembrane transport.

S-Nitroso-l-cysteine and ventilatory drive: A pediatric perspective.

Though endogenous S-nitroso-l-cysteine (l-CSNO) signaling at the level of the carotid body increases minute ventilation (v̇ ), neither the background data nor the potential clinical relevance are well-understood by pulmonologists in general, or by pediatric pulmonologists in particular. Here, we first review how regulation of the synthesis, activation, transmembrane transport, target interaction, and degradation of l-CSNO can affect the ventilatory drive. In particular, we review l-CSNO formation by hemoglobin R to T conformational change and by nitric oxide (NO) synthases (NOS), and the downstream effects on v̇ through interaction with voltage-gated K (Kv) channel proteins and other targets in the peripheral and central nervous systems.

Transepithelial Transport of PAMAM Dendrimers Across Isolated Human Intestinal Tissue.

Poly(amido amine) (PAMAM) dendrimers have shown transepithelial transport across intestinal epithelial barrier in rats and across Caco-2 cell monolayers. Caco-2 models innately lack mucous barriers, and rat isolated intestinal tissue has been shown to overestimate human permeability. This study is the first report of transport of PAMAM dendrimers across isolated human intestinal epithelium.

Regional Morphology and Transport of PAMAM Dendrimers Across Isolated Rat Intestinal Tissue.

Intestinal permeability of PAMAM dendrimers has been observed, giving rationale for their use in oral drug delivery as potential carriers of associated molecules. This study assessed the apparent permeability coefficients (Papp) of dendrimers across isolated rat intestinal regional mucosae, along with estimation of the maximum non-toxic concentration. Caco-2 monolayers were also used to assess the comparative Papp values between isolated mucosae and cell culture models.

Transepithelial transport of PAMAM dendrimers across isolated rat jejunal mucosae in ussing chambers.

Oral delivery remains a challenge for poorly permeable hydrophilic macromolecules. Poly(amido amine) (PAMAM) dendrimers have shown potential for their possible oral delivery. Transepithelial transport of carboxyl-terminated G3.

In vivo biodistribution and pharmacokinetics of silica nanoparticles as a function of geometry, porosity and surface characteristics.

The in vivo biodistribution and pharmacokinetics of silica nanoparticles (SiO(2)) with systematically varied geometries, porosities, and surface characteristics were investigated in immune-competent CD-1 mice via the intravenous injection. The nanoparticles were taken up extensively by the liver and spleen. Mesoporous SiO(2) exhibited higher accumulation in the lung than nonporous SiO(2) of similar size.

Size and surface charge significantly influence the toxicity of silica and dendritic nanoparticles.

The influence of size, surface charge and surface functionality of poly(amido amine) dendrimers and silica nanoparticles (SNPs) on their toxicity was studied in immunocompetent mice. After systematic characterization of nanoparticles, they were administered to CD-1 (caesarean derived-1) mice to evaluate acute toxicity. A distinct trend in nanotoxicity based on surface charge and functional group was observed with dendrimers regardless of their size.