An oral sulfate salt solution (OSS), under development as a bowel cleansing agent for colonoscopy in humans, is studied in rats and dogs. In rats, amaximumpractical oral OSS dose (5 g/kg/d) is compared with an oral sodium phosphate (OSP) solution, both at about 7 times the clinical dose. OSS induces the intended effects of loose stools and diarrhea. In rats, higher urine sodium and potassium accompany higher clearance rates, considered adaptive to the osmotic load of OSS. OSS for 28 days is well tolerated in rats and dogs. In contrast, OSP causes increased mortality, reduced body weight and food consumption, severe kidney tubular degeneration, and calcium phosphate deposition in rats. These are accompanied by mineralization in the stomach and aorta, along with cardiac and hepatic degeneration and necrosis. The greater safety margin of OSS over OSP at similarmultiples of the clinical dose indicates its suitability for human use.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1177/1091581809335124 | DOI Listing |
Regul Toxicol Pharmacol
December 2024
Division of Nephrology, University of Utah Health, Salt Lake City, UT, USA.
Marketed endothelin receptor antagonists (ERAs) have been associated with testicular tubular atrophy and decreases in male animal fertility in chronic toxicity studies in rats and dogs. Consistent with these findings, reduced sperm count has been observed in the clinical setting and is considered a potential class risk with chronic administration of ERAs. In contrast, no such effects on male animal fertility are noted with angiotensin II type 1 receptor blocker (ARB) treatment.
View Article and Find Full Text PDFCytokine
December 2024
Cancer Research Unit, Sumitomo Pharma Co Ltd, Osaka, Japan. Electronic address:
Toll-like receptors (TLRs) are crucial for the detection of infections and activation of downstream signaling pathways that lead to the production of pro-inflammatory cytokines and interferons. Because of their strong immunostimulatory activity, TLRs are thought to be a "double-edged sword" for systemic treatment, even in the cancer field. To solve this, we have developed dextran-based TAM targeting activator conjugate (D-TAC) technology which successfully uses tumor-associated macrophages (TAMs) to deliver the TLR7 agonist DSP-0509.
View Article and Find Full Text PDFOne Health
December 2024
One Health Research Group, Universidad de Las Américas, Quito, Ecuador.
Leptospirosis is a neglected zoonotic disease that is endemic in tropical regions, including Ecuador. It is caused by spirochetes of the genus , which can infect humans through animal reservoirs such as rats and dogs, or through contact with contaminated water or soil. In March 2023, public health authorities declared a concerning outbreak of leptospirosis in Durán Cantón, located in the Coastal region of Ecuador.
View Article and Find Full Text PDFBiomaterials
May 2025
School of Pharmacy, Key Laboratory of Smart Drug Delivery (Ministry of Education), Fudan University, Shanghai, 201203, China. Electronic address:
This study aimed to address the challenges associated with the low oral bioavailability and the necessity for frequent dosing of breviscapine (BRE), a mainstream drug in the treatment of cardiovascular and cerebrovascular diseases. The poor solubility and permeability of BRE in the gastrointestinal tract were identified as significant barriers to effective drug absorption, thereby impacting therapeutic efficacy and patient compliance. To enhance the gastrointestinal absorption of BRE, particles loaded with BRE were engineered utilizing Cremophor EL (CrEL), an absorption enhancer, in conjunction with mesoporous silica, a biocompatible drug delivery vector, formulating mesoporous silica particles loaded with BRE and CrEL (BRE-CrEL@SiO).
View Article and Find Full Text PDFACS Pharmacol Transl Sci
December 2024
Department of Chemical Biology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany.
Despite the end of COVID-19 pandemic, only intravenous remdesivir was approved for treatment of vulnerable pediatric populations. Molnupiravir is effective against viruses beyond SARS-CoV-2 and is orally administrable without CYP-interaction liabilities but has a burden of potential bone or cartilage toxicity, observed at doses exceeding 500 mg/kg/day in rats. Especially, activity of molnupiravir against viruses, such as Ebola, with high fatality rates and no treatment option warrants the exploration of potentially effective but safe doses for pediatric populations, i.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!