Background Approaches to the evaluation of pulmonary arterial hypertension (PAH) in premature calves by using lung-specific epithelial and endothelial biomarkers are needed. Objective To investigate the evaluation of PAH in premature calves with and without respiratory distress syndrome (RDS) by using lung-specific epithelial and endothelial biomarkers and determine the prognostic value of these markers in premature calves. Animals Fifty premature calves with RDS, 20 non-RDS premature calves, and 10 healthy term calves. Methods Hypoxia, hypercapnia, and tachypnea were considered criteria for RDS. Arterial blood gases (PaO2, PaCO2, oxygen saturation [SO2], base excess [BE], and serum lactate concentration) were measured to assess hypoxia. Serum concentrations of lung-specific growth differentiation factor-15 (GDF-15), asymmetric dimethylarginine (ADMA), endothelin-1 (ET-1), vascular endothelial growth factor (VEGF), and surfactant protein D (SP-D) were measured to assess PAH. Results Arterial blood pH, PaO2, SO2, and BE of premature calves with RDS were significantly lower and PaCO2 and lactate concentrations higher compared to non-RDS premature and healthy calves. The ADMA and SP-D concentrations of premature calves with RDS were lower and serum ET-1 concentrations higher than those of non-RDS premature and healthy calves. No statistical differences for GDF-15 and VEGF were found among groups. Conclusions and Clinical Importance Significant increases in serum ET-1 concentrations and decreases in ADMA and SP-D concentrations highlight the utility of these markers in the diagnosis of PAH in premature calves with RDS. Also, we found that ET-1 was a reliable diagnostic and prognostic biomarker for PAH and predicting mortality in premature calves.
Background: Osteoarthritis is a chronic joint disease that affects dogs and humans alike, with nonsteroidal anti‐inflammatory drugs (NSAIDs) being the primary drug treatment for pain relief. This study hypothesised that pentoxifylline could be a potent therapeutic option for canine osteoarthritis, offering superior benefits compared to meloxicam. The study aimed to mitigate inflammation and degeneration, safeguard joint integrity, and assess pentoxifylline's potential as a safer and more effective alternative to NSAIDs in osteoarthritis management. Methods: 12 dogs with stifle osteoarthritis were divided into two groups: meloxicam (0.1 mg/kg, subcutaneous) and pentoxifylline (10 mg/kg, intramuscular). Clinical, radiological and biochemical examinations were conducted on days 0, 15, 30 and 60. Results: The pain scores were significantly lower in the meloxicam group on days 30 and 60 ( p < 0.05). However, both groups had similar scores for other clinical evaluations ( p > 0.05). Serum C‐reactive protein (CRP) levels were lower in the pentoxifylline group on days 15 and 30, and serum IL‐1β levels were lower on days 15, 30 and 60 ( p < 0.05). Moreover, cartilage oligomeric matrix protein (COMP) and bone alkaline phosphatase (bALP) levels in the pentoxifylline group showed a significant reduction on day 15 ( p < 0.05). Pentoxifylline reduced osteocalcin in serum and hyaluronic acid concentrations in synovial fluid on days 15 and 30 ( p < 0.05). However, the level of cross‐linked C‐telopeptide of type 2 collagen in urine significantly decreased following meloxicam treatment. Conclusion: Meloxicam relieves pain by protecting joint cartilage, while even low doses of pentoxifylline enhance joint perfusion and combat inflammation. Future research should explore higher pentoxifylline doses and its potential synergy with NSAIDs for superior osteoarthritis management.
18 July 2024 in Journal of Pharmacy and Pharmacology
Objectives: The aim of this study was to determine the single and combined antidiabetic activity and side effects of the retinoid X receptor agonist bexarotene and the thioredoxin-interacting protein inhibitor and peroxisome proliferator-activated receptor γ and AMP-activated protein kinase activator icariin. Methods: The rats were grouped as healthy (control), diabetes, diabetes + bexarotene (20 mg/kg), diabetes + icariin (60 mg/kg), diabetes + bexarotene (10 mg/kg) + icariin (30 mg/kg) low-dose combination and diabetes + bexarotene (20 mg/kg) + icariin (60 mg/kg) high-dose combination groups. Key findings: Icariin treatment led to a significant reduction in glucose levels compared with the diabetes control group, a remarkable outcome observed 45 days after the initial application. HbA1c levels of the icariin and low-dose combination treatment groups were significantly lower than in the diabetes group. Notably, icariin treatment also significantly elevated HOMA-β levels, which is indicative of improved β-cell function. Icariin significantly decreased glucose levels at 30 and 120 min in the oral glucose tolerance test. Moreover, it ameliorated hepatocyte degeneration, hepatic cord dissociation, congestion, mononuclear cell infiltration in the liver, and degeneration in the pancreas. Conclusions: Icariin treatment exhibited robust antidiabetic effects with fewer side effects than other treatment options in this study. In future studies, long-term and varying doses of icariin will contribute to the development of novel antidiabetic drugs.
The purpose of the present study was to establish the development of acute kidney injury (AKI) and evaluate the usefulness of kidney-specific biomarkers in diagnosing AKI in premature calves with respiratory distress syndrome (RDS). Ten-term healthy and 70 premature calves with RDS were enrolled. Clinical examination, blood gases, and chemical analysis were performed at admission and 72 h. Serum concentrations of blood urea nitrogen (BUN), creatinine (Cre), phosphorus (P), cystatin-C (Cys-C), neutrophil gelatinase-associated lipocalin (NGAL), uromodulin (UMOD), and liver-type fatty acid-binding protein (L-FABP) were measured to evaluate kidney injury. Our findings showed that 38.5% of the premature calves with RDS developed AKI. The RDS-AKI group had a 4-fold higher mortality risk than the RDS-non-AKI group. Cys-C, with 90% and 89% specificity, and NGAL, with 100% sensitivity and 85% specificity, were the most reliable biomarkers to determine AKI in premature calves. The usefulness of any biomarker to predict mortality was not found to be convincing. In conclusion, AKI can develop as a consequence of hypoxia in premature calves and may increase the risk of mortality. In addition, serum Cys-C and NGAL concentrations may be useful in the diagnosis of AKI in premature calves with RDS.
Levofloxacin is a broad-spectrum antibacterial drug in the fluoroquinolone classthat is classified as category C during pregnancy. This study aimed to determine theeffects of levofloxacin administration on embryos at different developmental stages.It examined 420 fertile chicken eggs, divided into two main groups—levofloxacintreatment on days 7 and 14—each containing seven subgroups (n = 30 each): negativecontrol (no treatment), positive control (treated with saline), and five levofloxacindoses (5000, 2500, 1250, 625, and 312.5 μg/kg). On day 21, all eggs were hatched,the live–dead ratio was determined, and liver and kidney tissues were collected forhistopathological analysis. Administering levofloxacin to embryos at 7 and 14 days ofincubation had no lethal effect at doses up to 5000 μg/kg (p>0.05). Histopathologicalevaluations revealed no significant or clinically meaningful histopathologicaltoxicity was observed of levofloxacin on liver and kidney development (p>0.05). Inconclusion, when administered directly, levofloxacin does not have adverse effectson embryos at different developmental stages.