The mechanism(s) involved in determining the voiding cycle of the rat urinary bladder have been investigated in urethan-anesthetized animals. Fluid emission is almost confined to that phase of the voiding cycle which is characterized by the presence of a series of high-frequency oscillations in intraluminal pressure (IPHFO). During this phase the mean urethral flow rate reached a maximum and fluid was expelled in a stream-like fashion. The index obtained by multiplying the amplitude of IPHFO by their duration was significantly related to the maximal value of urethral flow rate. The IPHFO were selectively abolished by administration of d-tubocurarine at a dose that barely affects detrusor contractility. Moreover, d-tubocurarine reduced mean urethral flow rate and increased residual volume. The reflex (hexamethonium sensitive) mechanism(s) responsible for the generation of IPHFO is more developed in male than female rats. This mechanism, which involves activation of skeletal muscle, plays a significant role in determining bladder voiding in this species.
The intestinal epithelial monolayer constitutes a physical and functional barrier between the organism and the external environment. It regulates nutrients absorption, water and ion fluxes, and represents the first defensive barrier against toxins and enteric pathogens. Epithelial cells are linked together at the apical junctional complex by tight junctions that reduce the extracellular space and the passage of charge entities while forming a physical barrier to lipophilic molecules. Cultured intestinal epithelial cells have been extensively used to study intestinal absorption of newly synthesized drugs and the regulation of tight junctions structure and function. In vitro mild irritants, proinflammatory cytokines, toxins and pathogens, and adverse environmental conditions open tight junctions and increase paracellular permeability, an effect often accompanied by immune activation of the enterocytes. Conversely, inhibition of proinflammatory cytokines, exposure to growth factors and probiotics, among others, exert a protective effect. Impaired barrier function results from activation of signalling pathways that lead to alteration of junctional proteins expression and/or distribution. In vivo, intestinal barrier dysfunction is associated with various intestinal and non-intestinal disorders including inflammatory bowel disease, celiac disease, and diarrhoeal infection. This review will describe the current knowledge of the mechanisms regulating tight junctions and intestinal permeability, how these findings have lead to a better understanding of barrier alteration in human intestinal disorders, and what the emerging therapies to treat these pathologies are.
The postnatal development of the micturition reflex and factors related to its initiation have been investigated by means of cystometric techniques under urethan anesthesia. In rats less than 10 days of age, micturition is not elicited in response to bladder distension. In these animals voiding is triggered by application of a somatic stimulus in the perineal area. In rats greater than or equal to 15 days of age the response to bladder filling is similar to that observed in adults. In rats 10-15 days of age an intermediate pattern is frequently observed; i.e., bladder filling elicited micturition at high values of pressure threshold. The myogenic (tetrodotoxin insensitive) contractile activity of the bladder is absent at birth and developed postnatally, similar to that described in the isolated organ [C. A. Maggi, P. Santicioli, and A. Meli. Am. J. Physiol. 247 (Regulatory Integrative Comp. Physiol. 16): R972-R978, 1985]. The ability of topical capsaicin to induce tetrodotoxin-sensitive contractions of rat bladder (micturition reflex) appeared at day 10 and increases thereafter in parallel with ability of the bladder to respond to distension. These findings demonstrate that peripheral factors, such as myogenic contractile activity and sensory innervation, which are involved in the initiation of bladder voiding undergo a postnatal development in rats.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.