The role of P-glycoprotein in limiting intestinal regional absorption of digoxin in rats.

The objective of this work was to study the role of regional intestinal efflux activity of P-glycoprotein (Pgp) in situ in anesthetized rats in limiting the absorption of digoxin. A 10-cm portion of duodenum or jejunum, or 5-cm of colon was perfused single-pass with saline containing [(3)H]digoxin while the appearance of radioactivity in the blood was measured. Verapamil in the perfusate was used as a modulator of Pgp in the intestinal mucosa. Net water absorption, mucosal integrity, and intestinal motility of the isolated segment were monitored, as well as heart rate and blood pressure. Excretion of i.v. administered unlabelled digoxin, 1 mg/kg, into the intestine while perfusing the duodenum-proximal jejunum region, was studied for comparison. At a perfusate concentration of 1 mM, verapamil caused a dramatic increase in [(3)H]digoxin absorption rate from duodenum and jejunum, while the effect in colon was insignificant. At concentrations of 0.1, 1, and 2.5 mM in the duodenal perfusate, verapamil increased the absorption rate of [(3)H]digoxin in a dose-dependent manner. The lowest concentration almost doubled the rate without having any significant effects on the cardiovascular system, intestinal motility, or net absorption of water. The excretion rate of unlabelled digoxin from the blood into the gut lumen was found to be halved in the presence of 0.5 mM verapamil in the perfusate. Absorption rate of [(3)H]digoxin in the rat is likely limited by Pgp-mediated efflux. The data indicate that Pgp plays an important role for digoxin efflux in the small intestine only.     

Metronidazole-induced encephalopathy: a systematic review

Journal of Neurology - Metronidazole, a commonly used antibiotic drug, can cause adverse effects in the central nervous system termed metronidazole-induced encephalopathy, leading to diagnostic...     

Heterogeneity of cancer‐associated fibroblasts: Opportunities for precision medicine

Despite marked development in cancer therapies during recent decades, the prognosis for advanced cancer remains poor. The conventional tumor–cell‐centric view of cancer can only explain part of cancer progression, and thus a thorough understanding of the tumor microenvironment (TME) is crucial. Among cells within the TME, cancer‐associated fibroblasts (CAFs) are attracting attention as a target for cancer therapy. However, CAFs present a heterogeneous population of cells and more detailed classification of CAFs and investigation of functions of each subset is needed to develop novel CAF‐targeted therapies. In this context, application of newly developed approaches to single‐cell analysis has already made an impact on our understanding of the heterogeneity of CAFs. Here, we review the recent literature on CAF heterogeneity and function, and discuss the possibility of novel therapies targeting CAF subsets.     

Carbohydrate-deficient transferrin (CDT) in serum in women with early alcohol addiction

Carbohydrate-deficient transferrin (CDT) in serum was determined by micro anion exchange chromatography and a transferrin radioimmune assay in 58 consecutive women treated for early alcohol dependence compared, with 62 healthy females with an alcohol consumption of 0-15 g of ethanol/day. The upper normal CDT level was 74 mg/l. CDT was elevated above this value in 83% of the alcoholic women with an intake of 60 g of ethanol/day or more for at least 7 days within the preceding two weeks. CDT values were significantly positively correlated with daily alcohol consumption but not with GT, ASAT, ALAT or MCV. During abstinence CDT level declined exponentially with a half-life of 14 +/- 3 days. The results indicated that CDT may be as sensitive and specific a marker in women with early alcohol addiction as in previously studied male alcoholics. The amount of alcohol consumed appeared to be more important than sex or liver function. Determination of CDT may thus offer a means for early objective diagnosis and adequate treatment also of women in early stages of alcoholism.     

Protection against noise trauma by pre-exposure to a low level acoustic stimulus

Guinea pigs were pre-exposed to a low level acoustic stimulus prior to exposure to a stimulus known to yield a permanent threshold shift. This pre-treatment resulted in: 1) approximately a 20 dB reduction in the threshold shift relative to animals not pre-exposed, and 2) complete recovery from the threshold shift after 2 months.     

Patient‐reported outcomes (PROs) in chronic urticaria

Chronic urticaria is an itching skin disease which persists for more than 6 weeks. Chronic urticaria has great impact on the daily life of the patient, and the fluctuating nature of the symptoms complicates the monitoring and treatment of the disease. Currently, there are no reliable biomarkers to identify and measure disease activity in chronic spontaneous urticaria. Consequently, use of patient‐reported outcomes (PROs) is crucial when evaluating and monitoring different aspects of chronic urticaria such as disease activity/severity, disease control, and quality of life. We present an overview of seven different PROs used in chronic urticaria and highlight their strengths, limitations, and use in clinical practice and research.