Current Issue : April-June Volume : 2026 Issue Number : 2 Articles : 5 Articles
Introduction: Cough is a common reflex that serves a protective role, but when persistent, it can severely affect patients’ quality of life. Despite its high prevalence, current treatment options remain limited. Traditional antitussives such as codeine and dextromethorphan present notable side effects, underscoring the need for safer and more effective alternatives. Methods: This study evaluated and compared the antitussive efficacy of classic (codeine, cloperastine, dextromethorphan, levodropropizine) and novel (gefapixant) agents using a citric acid-induced cough model in guinea pigs. Animals were pretreated with the selected compounds, and cough frequency, latency to first cough, and cough intensity were assessed using acoustic recordings and quantitative analysis. Results: Codeine, cloperastine, and gefapixant produced a significant reduction in cough frequency and markedly increased latency to the first cough, with comparable efficacy at the highest doses tested. In contrast, dextromethorphan and levodropropizine did not significantly affect these parameters. Additionally, cloperastine, codeine, and gefapixant reduced cough intensity, while none of the treatments significantly altered cough duration. Conclusions: In this preclinical model, cloperastine and gefapixant demonstrated antitussive effects comparable to codeine but without the known narcotic-associated risks. These findings highlight the potential clinical relevance of both centrally and peripherally acting non-opioid alternatives. Continued investigation of these agents may help address the unmet need for safer and more effective cough treatments....
Background/Objectives: Propofol is frequently used as an intravenous anesthetic and is rapidly metabolized. Therefore, if it could be administered non-invasively (e.g., orally) as premedication, it might hasten emergence from anesthesia, thereby improving patient safety. However, it undergoes extensive first-pass metabolism in the liver and intestines, limiting the route for premedication. We evaluated whether intranasal delivery of a propofol-encapsulated liposome solution improves systemic exposure and bioavailability in rabbits. Methods: A propofol-encapsulated liposome solution was administered to rabbits via the intravenous, oral, and intranasal routes. Blood propofol concentrations were measured for up to 60 min after administration and the area under the concentration– time curve (AUC0–60) and bioavailability of the propofol-encapsulated liposome solution were compared with those of the non-encapsulated propofol formulation. The differences were tested by two-way analysis of variance (ANOVA) with Šidák’s post hoc multiplecomparisons test and the Mann–Whitney test (α = 0.05). Results: The AUC0–60 for blood propofol concentrations after intravenous administration was significantly higher with the propofol-encapsulated liposome solution than with the non-encapsulated propofol formulation (3038.8 ± 661.5 vs. 1929.8 ± 58.2 ng·min/mL; p = 0.0286). By contrast, no increase in blood propofol concentrations was observed after oral administration, whereas intranasal administration increased blood propofol concentrations and yielded significantly higher bioavailability compared with the non-encapsulated propofol formulation (16.4 ± 7.3% vs. 2.0 ± 1.2%; p = 0.0286). Conclusions: The findings of the present study suggest that intranasal liposomal propofol increased systemic availability compared with a non-encapsulated formulation, supporting further evaluation as a candidate premedication approach for propofol....
Hypoxia-ischemia is a serious perinatal complication affecting neonates globally. Animal models have increased the understanding of its pathophysiology and have been used to investigate potential therapies. Exenatide, clinically used for the treatment of type 2 diabetes mellitus, also protects the rodent brain from hypoxia-ischemia. The rabbit brain has an earlier neurodevelopmental maturation than rodents, as well as similar postnatal maturation to humans. We hereby introduce a new, reproducible hypoxia-ischemia model in rabbit kits at postnatal day (P) 3–4. Following hypoxia-ischemia, rabbit kits received different exenatide concentrations: 170 μg/g (2-dose) or 500 μg/g (1- or 2-dose), or vehicle. The brains were collected seven days later for histological assessment showing that 500 μg/g exenatide, either as a 1- or 2-dose regimen, reduced brain tissue loss by 90% in hypoxia-ischemia experiments both at P3 and P4. A second cohort received a 1-dose 500 μg/g of exenatide or vehicle, and were sacrificed at different early time-points for glucose, ketone bodies, body weight, and temperature measurements. Our results showed a transient 2-fold increase in ketone bodies (0.6 to 1.3 mmol/L) at 6 h. Exenatide did not affect glucose, body temperature or weight gain and appears to be safe and well tolerated in the rabbit model of hypoxia-ischemia....
Background: Karwinskia humboldtiana (Kh) is a toxic plant that produces a fruit that, when ingested in large quantities, causes damage to the lungs, liver, kidneys, pancreas, and duodenum. Pancreatic damage was measured using a semiquantitative score, revealing that it is progressive and characterized by selective apoptosis and necrosis of the exocrine portion. However, renal injury has not been evaluated using injury scales and has only been reported descriptively. Pancreatic adenocarcinoma is one of the top five causes of cancer death in the United States, and options for its treatment are limited. One of the toxins extracted from the fruit (T-514) has been tested as a possible antineoplastic agent in various cancer cell lines. In order to preliminarily assess its possible usefulness against pancreatic cancer, we decided to re-evaluate kidney damage using a semi-quantitative scale, hoping to obtain a lesser injury intensity than that reported in the pancreas. Methods: We analyzed kidney samples from the same model of acute pancreatitis by Kh by semiquantitative scoring to compare the results with those previously reported in the pancreas, and performed a TUNEL assay to analyze cell death in the kidney. Results: The renal injury that occurs in this model of Kh poisoning consists mainly of hydropic degeneration and loss of microvilli in proximal tubules. According to the scale used in this work, the following percentages of kidney injury were obtained: 8.26 ± 0.93% for the control group, 9.65 ± 1.60%, 11.04 ± 1.36%, 12.78 ± 2.46%, 14.03 ± 1.83% and 15.76 ± 3.73% for the groups 24 h, 48 h, 72 h, 96 h and 120 h after Kh administration. In contrast, the following were reported for the pancreas: 0.28 ± 0.83% for the control group, 14.81 ± 7.64%, 35.63 ± 12.05%, 67.13 ± 5.27%, 85.28 ± 13.14% and 87.13 ± 11.17% for the groups 24 h, 48 h, 72 h, 96 h and 120 h after Kh administration. These results indicate that pancreatic injury is 71.37% more intense than renal injury at 120 h after Kh. No evidence of nuclear chromatin fragmentation was found in the kidney. Conclusions: The renal damage in this model of acute pancreatitis is of lower intensity than the pancreatic damage, suggesting that Kh and its toxins may be useful in the treatment of pancreatic cancer and their study in an in vitro or in vivo cancer model is justified....
A hypercaloric diet is associated with oxidative stress and the dysfunction of ATP-Binding Cassette transporter A1 (ABCA1), a key element in high-density lipoprotein (HDL) biogenesis and reverse cholesterol transport. Nicotinamide (NAM) presents antioxidant properties, which may contribute to maintaining lipid metabolism. Therefore, we aimed to evaluate the effect of NAM on HDL-cholesterol (HDL-C) level, oxidative stress markers, and the gene expression and protein levels of ABCA1 in Sprague-Dawley rats fed a hypercaloric diet. Forty male rats were divided into five groups: one group received a standard diet, and the remaining groups received a single high-fat, high-fructose diet (HFDF). Three of the HFDF groups received NAM treatment (5, 10, and 15 mM) in drinking water for 16 weeks (5 h/day). While HDL-C and oxidative stress were measured in serum samples, oxidative stress markers, and the gene expression and protein levels of ABCA1 were quantified in liver samples. The HDL-C level altered by the HFDF was improved by treatment with NAM. Furthermore, NAM reduces systemic lipid peroxidation levels and enhances the hepatic antioxidant response affected by the HFDF. In addition, NAM modulates the hepatic ABCA1 gene expression and protein level, altered by the HFDF. Our results suggest that NAM may modify the serum HDL-C level by an improvement of antioxidant response, and a possible modulation of the hepatic ABCA1 gene and protein expression. Further metabolic and molecular studies are needed to support the potential therapeutic role of NAM to prevent or treat lipid alterations promoted by a hypercaloric diet....
Loading....