To elucidate a putative role of beta-adrenoceptors in the modulation of intrathymic T-cell maturation, the expression of major differentiational antigens (CD4/CD8 and TCR alphabeta) on the thymocytes from both immature (aged 21 day at the beginning of the treatment) and adult (aged 75 days at the beginning of treatment) male rats subjected to a 15-day-long propranolol treatment (0.40 mg/100 g/day, s.c.) was analyzed by two- and one-color flow cytometry, respectively. Rats of matched age injected with saline served as controls. The propranolol treatment in immature but not adult rats caused a significant reduction in both the relative thymus weight and total thymocyte yield. In addition, a significant increase in the percentage of CD4+ 8+ double-positive cells, with a proportional decrease in the relative proportion of CD4+ 8- single positive cells, was found in immature rats. In contrast, a slight but significant decrease in the percentage of CD4+ 8+ cells with a parallel increase in the relative proportion of CD4+ 8- cells was found in adult rats. In both groups of rats, the percentage of TCR alphabeta(total) thymocytes was increased: in immature rats this was due to an increase in the percentage of TCR alphabeta(low) thymocytes, while in the adult rats it reflected a rise in the relative proportion of TCR alphabeta(high) cells. In conclusion, the study revealed that propranolol treatment in both immature and adult rats alters the relative proportion of CD4+ 8+ and CD4+ 8- thymocytes, but in opposite fashion, and the data suggest that this treatment affects distinct fractions within the population of CD4+ 8+ thymocytes with respect to expression of TCR alphabeta. The results also indicate that, regardless of rat sexual maturity, the development of thymocytes towards CD4- 8+ T-cells is relatively insensitive to long-lasting beta-adrenoceptor blockade.
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PLoS One
January 2025
Department of Biology, College of Science, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia.
A common heavy metal in many facets of daily life is aluminum (AlCl3), which can be found in food, toothpaste, cosmetics, food additives, and numerous pharmaceutical items. The hippocampus, liver, and kidneys have the highest concentrations of this powerful neurotoxin, which also accumulates over time and contributes to the development of a number of cognitive disorders. Long-term overconsumption of AlCl3 results in hepatic and renal toxicity as well as neuronal inflammation.
View Article and Find Full Text PDFJ Med Chem
January 2025
Department of Chemistry, Fudan University, 2205 Songhu Road, Shanghai 200438, China.
The combination of ultralong-acting neuromuscular block and subsequent on-demand rapid reversal may provide prolonged surgeries with improved conditions by omitting continuous or repetitive blocker administration, enabling a more stable and predictable hemodynamic profile and eliminating residual block. For this target, we prepared 19 imidazolium-incorporated tetracationic macrocycles. In vivo studies with rats revealed that one macrocycle (IMC-14) displays extremely high blocking activity.
View Article and Find Full Text PDFPLoS One
January 2025
Department of Nutritional Physiology, National Institute of Medical and Nutritional Sciences "Salvador Zubirán", Mexico City, Mexico.
Childhood obesity increases the risk of developing metabolic diseases in adulthood, since environmental stimuli during critical windows of development can impact on adult metabolic health. Studies demonstrating the effect of prepubertal diet on adult metabolic disease risk are still limited. We hypothesized that a prepubertal control diet (CD) protects the adult metabolic phenotype from diet-induced obesity (DIO), while a high-fat diet (HFD) would predispose to adult metabolic alterations.
View Article and Find Full Text PDFEur J Pain
March 2025
Department of Life Sciences, South Kensington, Imperial College London, London, UK.
Background: Healthy individuals demonstrate considerable heterogeneity upon dynamic quantitative sensory testing assessment of endogenous pain modulatory mechanisms. For those who stratify into a 'pro-nociceptive profile' cohort, consisting of inefficient conditioned pain modulation (CPM) and elevated temporal summation of pain (TSP), the optimal approach for balancing the net output of pain modulatory processes towards anti-nociception remains unresolved. In this translational healthy human and rat study, we examined whether descending modulation countered spinal amplification during concurrent application of a CPM and TSP paradigm alongside pupillometry since pontine activity was previously linked to functionality of endogenous pain modulatory mechanisms and pupil dilation.
View Article and Find Full Text PDFPharmacol Rep
January 2025
Department of Neuroscience, School of Translational Medicine, Monash University, Melbourne, VIC, 3004, Australia.
Background: Due to its availability and perceived safety, paracetamol is recommended even during pregnancy and for neonates. It is used frequently alone or in combination with other drugs required for the treatment of various chronic conditions. The aim of this study was to investigate potential effects of drug interactions on paracetamol metabolism and its placental transfer and entry into the developing brain.
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