The total extracellular fluid volume and distribution in plasma and interstitial spaces, and the microvascular permeability properties were studied in 16 nonedematous patients with congestive heart failure (CHF) due to idiopathic dilated cardiomyopathy and 17 such patients who underwent heart transplantation (HT) by analyzing the 3-hour plasma disappearance curve of polyfructosan. Eighteen healthy subjects served as controls. Polyfructosan (3.5 kD) is an extracellular marker and inulin analog transported almost solely by diffusion. The initial capillary membrane plasma clearance (i.e., the permeability-surface area product), the interstitial plasma clearance determined at 10 minutes (clearance[10), and the extracellular volume were determined from the polyfructosan curves. I-131-albumin was used as a plasma volume reference. Permeability-surface area product was elevated in both patient groups (6.6 +/- 1.9 ml/ kg/min in the CHF group and 6.7 +/- 2.0 ml/kg/min in the HT group vs 5.1 +/- 1.3 ml/kg/min in controls, p <0.01 for both), whereas clearance(10) was normalized in the HT group (4.5 +/- 0.9 ml/kg/min in the HT group, 4.4 +/- 0.7 ml/kg/min in controls vs 5.0 +/- 0.9 ml/kg/ min in the CHF group, p <0.1 and p <0.05, respectively). The normalization of interstitial plasma clearance of polyfructosan was associated with time since HT (r = 0.49, p <0.05). Plasma volumes were similar in all 3 groups (41 +/- 8 ml/kg in controls, 44 +/- 13 in the CHF group and 39 +/- 8 in the HT group). In contrast, total extracellular volume was elevated in both patients groups (177 +/- 27 ml/kg in the CHF group and 173 +/-27 in the HT group vs 152 +/- 12 in controls, p <0.01). The results strongly suggest a microvascular permeability defect in both patient groups that perhaps plays a role in the extravascular distribution of the excess extracellular fluid volume.
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http://dx.doi.org/10.1016/s0002-9149(99)00878-4 | DOI Listing |
Front Pharmacol
January 2025
Waisman Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States.
Introduction: 7,8-Dihydroxyflavone (7,8-DHF) is a promising translational therapy in several brain injury models, including the neonatal hypoxia-ischemia (HI) model in mice. However, the neuroprotective effect of 7,8-DHF was only observed in female, but not male, neonatal mice with HI brain injury. It is unknown whether HI-induced physiological changes affect brain distribution of 7,8-DHF differently for male versus female mice.
View Article and Find Full Text PDFAnesthesiology
January 2025
Department of Anesthesiology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
Background: Tranexamic acid is an anti-fibrinolytic agent routinely used during hip and knee joint replacement surgery to minimize bleeding. Chronic kidney disease is a common chronic health problem seen among adults requiring major arthroplasty surgery. Tranexamic acid is renally cleared and may accumulate in chronic kidney disease.
View Article and Find Full Text PDFClin Pharmacol Ther
January 2025
Division of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, Food & Drug Administration, Silver Spring, Maryland, USA.
In response to increased illicit use of synthetic opioids, various μ-receptor antagonist formulations, with varied pharmacological characteristics, have been and are being developed. To understand how pharmacologic characteristics such as absorption rate and clearance rate affect reversal in treating community opioid overdose, we used our previously published translational opioid model. We adapted this model with in vitro receptor binding data and clinical pharmacokinetic data of three intranasal nalmefene formulations along with an intranasal naloxone formulation to study the reversal of fentanyl and carfentanil-induced respiratory depression in chronic opioid users.
View Article and Find Full Text PDFGynecol Endocrinol
December 2025
Department of Gynecological Endocrinology, Poznan University of Medical Sciences, Poznan, Poland.
Objective: To evaluate the effects of a combination of carnitines, L-arginine, L-cysteine and myo-inositol on metabolic and reproductive parameters in PCOS overweight/obese patients.
Methods: This was a retrospective study analyzing information of a group of PCOS ( = 25) overweight/obesity patients, not requiring hormonal treatment, selected from the database of the ambulatory clinic of the Gynecological Endocrinology Center at the University of Modena and Reggio Emilia, Modena, Italy. The hormonal profile, routine exams and insulin and C-peptide response to oral glucose tolerance test (OGTT) were evaluated before and after 12 weeks of a daily oral complementary treatment with L-carnitine (500 mg), acetyl-L-carnitine (250 mg), L-arginine (500 mg), L-cysteine (100 mg) and myo-inositol (1 gr).
Naunyn Schmiedebergs Arch Pharmacol
January 2025
Department of Pharmacology and Toxicology, School of Pharmacy, University of Health and Allied Sciences, Ho, Ghana.
Purpose: Major depressive disorder is one of the most common and burdensome psychiatric disorders worldwide. This study evaluated the anxiolytic- and antidepressant-like activity of three semi-synthetic derivatives of xylopic acid (XA) to identify the most promising derivative based on mechanism(s) of action, in vivo pharmacokinetics and in vitro cytotoxicity.
Methods: The anxiolytic potential and the involvement of GABAergic mechanisms were assessed in the elevated plus-maze and open field tests in mice.
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