The expression of sigma-2 receptors was investigated in nine urothelial tumours of the urinary bladder of cattle. Each tumour was associated with the presence of DNA of bovine papillomavirus type-2 (BPV-2) and expression of the E5 viral oncoprotein. Five tumours were classified as low-grade carcinoma on the basis of morphological criteria and calculation of mean nuclear area (MNA) and mean nuclear perimeter (MNP). Four tumours were classified as high-grade carcinoma. Sigma-2 receptors were overexpressed in both types of carcinoma. In control normal bovine bladder tissue the density of receptors (expressed as the B(max)) was 0.37 pmol/mg of protein. Low-grade carcinomas had a mean B(max) of 1.37+/-0.32 pmol/mg of protein (range 1.03-1.86) and in high-grade carcinomas the mean B(max) was 10.9+/-2.8 pmol/mg of protein (range 8.2-14). The difference in B(max) between low- and high-grade carcinomas was statistically significant (P=0.0001).
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http://dx.doi.org/10.1016/j.jcpa.2009.06.001 | DOI Listing |
Eur J Pharm Sci
January 2025
Centre for Applied Pharmacokinetic Research, University of Manchester, UK.
Access of drugs to the central nervous system is limited by the blood-brain barrier, and this in turn affects drug efficacy/toxicity. To date, most drug discovery optimization paradigms have relied heavily on in vitro transporter assays and preclinical species pharmacokinetic evaluation to provide a qualitative assessment of human brain penetration. Because of the lack of human brain pharmacokinetic data, mechanistic models for preclinical species, combined with in vitro and in silico data, are useful for translation to human.
View Article and Find Full Text PDFMuscle Nerve
January 2025
Faculty of Health Sciences, Kobe Tokiwa University, Kobe, Japan.
Introduction: A 20 kDa fragment at the N-terminus of titin is highly excreted in the urine of patients with Duchenne muscular dystrophy (DMD), making urine titin a prominent biomarker for muscle breakdown. This N-terminal fragment is presumed to be a product of degradation by a protein-degrading enzyme, calpain 3; however, whether calpain 3 is required remains unclear. We aimed to determine whether urine titin elevation occurs in the absence of calpain 3.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Department of Pharmaceutical Sciences, Tohoku University Hospital, Sendai 980-8574, Japan.
The involvement of drug-metabolizing enzymes and transporters in plasma clozapine (CLZ) dynamics has not been well examined in Japanese patients with treatment-resistant schizophrenia (TRS). Therefore, this clinical study investigated the relationship between single nucleotide polymorphisms (SNPs) of various pharmacokinetic factors (drug-metabolizing enzymes and transporters) and dynamic changes in CLZ. Additionally, we aimed to determine whether CLZ acts as a substrate for pharmacokinetic factors using in vitro assays and molecular docking calculations.
View Article and Find Full Text PDFClin Chim Acta
January 2025
Graduate School of Science, Technology and Innovation, Kobe University, Kobe, Japan.
Background: Becker muscular dystrophy (BMD) is a dystrophinopathy caused by a pathological variant of the DMD gene. Urinary titin, a degradation product of the giant protein titin present in muscle sarcomeres, has been used as a biomarker to reflect muscle degradation in Duchenne muscular dystrophy, a more severe dystrophinopathy. However, the clinical significance of urinary titin levels in BMD remains unclear.
View Article and Find Full Text PDFSci Rep
November 2024
Department of Pathophysiology, Third Faculty of Medicine, Charles University, Ruska 87, Prague, 100 00, Czech Republic.
The molecular mechanisms linking obstructive sleep apnea syndrome (OSA) to obesity and the development of metabolic diseases are still poorly understood. The role of hypoxia (a characteristic feature of OSA) in excessive fat accumulation has been proposed. The present study investigated the possible effects of hypoxia (4% oxygen) on de novo lipogenesis by tracking the major carbon sources in differentiating 3T3-L1 adipocytes.
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