ObjectiveTo study the effect of inter medin(IMD) on smooth muscle of rat seminal vesicles including the specific receptors and the signal pathways involved.MethodsThe contraction of the seminal vesicle in response to norepinephrine (NE) and ADM2/IMD was studied by the organ bath method. The effects of antagonists for calcitonin gene related peptide (CGRP), adrenomedullin (ADM) and IMD receptors, and inhibitors of nitric oxide synthase, [L-NG-Nitroarginine Methyl Ester, L-NAME) and cAMP-dependent protein kinase (PKA), KT5720] were also investigated. The first overshoot, amplitude, frequency and basal tone were measured.ResultsThere is no significant effect of IMD on the initial overshoot, frequency and the basal tone in the seminal vesicle contraction. Only the amplitude of the contraction induced by NE was inhibited by IMD. The IMD inhibitory actions on amplitude were completely blocked by hADM22-52 and L-NAME, but not by hCGRP8-37 or KT5720. Furthermore, the action was diminished by IMD17-47.ConclusionThe results demonstrated that the inhibitory action of IMD on NE-induced seminal vesicle contraction was mediated via the ADM receptor(s) and the nitric oxide production pathway, partially by the IMD receptor, but not by the CGRP receptor and the cAMP-PKA pathway. 相似文献
The fetal response to cutaneous injury has been investigated in a variety of models; most have studied the differences between fetal and adult healing mechanisms in vivo and in cell culture. Further disclosure of the cellular and biochemical events requires a model that can be manipulated to study single factors influencing fetal tissue repair without the complex interactions that occur in vivo, but in a system that more closely approximates normal skin than cell culture models. This paper presents a method for the organ culture of fetal skin and its advantages as a model to help elucidate fetal healing mechanisms. Skin sections (1 × 1 cm) excised from the backs of fetuses of New Zealand white rabbits on day 27 gestation (term = 31 days) were placed eccentrically in 65-mm culture dishes and fed daily with 2.5 mL of DMEM containing 10% fetal calf serum, antibiotics, and 10 mM ascorbic acid. A separate group, treated similarly, received 4-mm punch wounds to assess the in vitro response to wounding. Thespecimens were incubated at 37° Cin humidified room air on a rocker platform to provide alternate exposure of the skin to air and medium. Gross observation at 3 weeks showed cells extending into the central wound, indicating that viable cells were proliferating and/or migrating from the tissue. Skin was examined histologically and was viable over the 3-week period studied. Organ culture, by maintaining tissue in the natural extracellular matrix, allows cell-to-cell contact and communication to be maintained while allowing controlled environmental manipulation. In addition, the procedure is reproducible and assessment of tissue viability can be determined easily using histology. These advantages make fetal skin organ culture a valuable adjunct in the study of fetal skin and its response to wounding. 相似文献
Introduction: When investigating drugs that treat heart diseases, it is critical when choosing an animal model for the said model to produce data that is translatable to the human patient population, while keeping in mind the principles of reduction, refinement, and replacement of the animal model in the research.
Areas covered: In this review, the authors focus on mammalian models developed to study the impact of drug treatments on human heart failure. Furthermore, the authors address human patient variability and animal model invariability as well as the considerations that need to be made regarding choice of species. Finally, the authors discuss some of the most common models for the two most prominent human heart failure etiologies; increased load on the heart and myocardial ischemia.
Expert opinion: In the authors’ opinion, the data generated by drug studies is often heavily impacted by the choice of species and the physiologically relevant conditions under which the data are collected. Approaches that use multiple models and are not restricted to small rodents but involve some verification on larger mammals or on human myocardium, are needed to advance drug discovery for the very large patient population that suffers from heart failure. 相似文献
AbstractThis study aimed to characterize the effect of different running modes on serum irisin concentrations in rats. A total of 18, 10-week-old rats were divided into three groups; control group, 16° uphill running group (concentric exercise; CON) and, ?16° downhill running group (eccentric exercise; ECC). The running group’s rats ran on the inclined treadmill at 16?m/min, for a total of 90?min. Blood was drawn from the rats, 48?h after running, after which the rats were anesthetized. The serum concentrations of irisin were measured using enzyme-linked immunosorbent assays. Vastus intermedius was collected for immunohistochemical analysis. After multiple comparisons, the ECC showed a significantly high serum irisin concentration (ECC: 28.42?±?6.31?ng/ml, CON: 21.27?±?3.03?ng/ml) and a larger irisin antibody reactive cross-sectional area in vastus intermedius compared to the CON (p?<?0.05). This is the first study to reveal that single bout downhill running increases serum irisin concentrations in rats. 相似文献
ObjectivesUsing newly developed ultrasonic technology, we attempted to disclose the characteristics of the left ventricular (LV) contraction–extension (C–E) property, which has an important relationship to LV function.MethodsStrain rate (SR) distribution within the posterior wall and interventricular septum was microscopically measured with a high accuracy of 821 μm in spatial resolution by using the phase difference tracking method. The subjects were 10 healthy men (aged 30–50 years).ResultsThe time course of the SR distribution disclosed the characteristic C–E property, i.e. the contraction started from the apex and propagated toward the base on one hand, and from the epicardial side toward the endocardial side on the other hand. Therefore, the contraction of one area and the extension of another area simultaneously appeared through nearly the whole cardiac cycle, with the contracting part positively extending the latter part and vice versa. The time course of these propagations gave rise to the peristalsis and the bellows action of the LV wall, and both contributed to effective LV function.The LV contraction started coinciding in time with the P wave of the electrocardiogram, and the cardiac cycle was composed of 4 phases, including 2 types of transitional phase, as well as the ejection phase and slow filling phase. The sum of the measurement time duration of either the contraction or the extension process occupied nearly equal duration in normal conditions.ConclusionThe newly developed ultrasonic technology revealed that the SR distribution was important in evaluating the C–E property of the LV myocardium. The harmonious succession of the 4 cardiac phases newly identified seemed to be helpful in understanding the mechanism to keep long-lasting pump function of the LV. 相似文献