Annual review of physiology
-
Annu. Rev. Physiol. · Jan 2003
ReviewThe role of exogenous surfactant in the treatment of acute lung injury.
A number of conditions, such as pneumonia, trauma, or systemic sepsis arising from the gut, may result in the acute respiratory distress syndrome (ARDS). Because of its significant morbidity and mortality, ARDS has been the focus of extensive research. ⋯ Several studies have demonstrated that alterations of surfactant contribute to the lung dysfunction associated with ARDS, which has led to investigations into the use of exogenous surfactant as a therapy for this syndrome. Clinical experience with surfactant therapy has been variable owing to a number of factors including the nature of the injury at the time of treatment, the specific surfactant preparation utilized, the dose and delivery method chosen, the timing of surfactant administration over the course of the disease, and the mode of ventilation used during and after surfactant administration.
-
Annu. Rev. Physiol. · Jan 2002
ReviewHuman and murine phenotypes associated with defects in cation-chloride cotransport.
The diuretic-sensitive cotransport of cations with chloride is mediated by the cation-chloride cotransporters, a large gene family encompassing a total of seven Na-Cl, Na-K-2Cl, and K-Cl cotransporters, in addition to two related transporters of unknown function. The cation-chloride cotransporters perform a wide variety of physiological roles and differ dramatically in patterns of tissue expression and cellular localization. The renal-specific Na-Cl cotransporter (NCC) and Na-K-2Cl cotransporter (NKCC2) are involved in Gitelman and Bartter syndrome, respectively, autosomal recessive forms of metabolic alkalosis. ⋯ These studies implicate the Na-K-2Cl cotransporter NKCC1 in hearing, salivation, pain perception, spermatogenesis, and the control of extracellular fluid volume. Targeted deletion of the neuronal-specific K-Cl cotransporter KCC2 generates mice with a profound seizure disorder and confirms the central role of this transporter in modulating neuronal excitability. Finally, the comparison of human and murine phenotypes associated with loss-of-function mutations in cation-chloride cotransporters indicates important differences in physiology of the two species and provides an important opportunity for detailed physiological and morphological analysis of the tissues involved.
-
Astrocytes, a sub-type of glia in the central nervous system, are dynamic signaling elements that integrate neuronal inputs, exhibit calcium excitability, and can modulate neighboring neurons. Neuronal activity can lead to neurotransmitter-evoked activation of astrocytic receptors, which mobilizes their internal calcium. ⋯ This capability, that has now been demonstrated in several studies, raises the untested possibility that astrocytes are an integral element of the circuitry for synaptic plasticity. Because the highest ratio of glia-to-neurons is found at the top of the phylogenetic tree in the human brain, these recent demonstrations of dynamic bi-directional signaling between astrocytes and neurons leave us with the question as to whether astrocytes are key regulatory elements of higher cortical functions.
-
Nephrogenic diabetes insipidus, which can be inherited or acquired, is characterized by an inability to concentrate urine despite normal or elevated plasma concentrations of the antidiuretic hormone arginine vasopressin. Polyuria, with hyposthenuria, and polydipsia are the cardinal clinical manifestations of the disease. About 90% of patients with congenital nephrogenic diabetes insipidus are males with the X-linked recessive form of the disease (OMIM 304800) who have mutations in the arginine vasopressin receptor 2 gene (AVPR2), which codes for the vasopressin V2 receptor. ⋯ Similarly, aquaporin-2 mutant proteins are misrouted and cannot be expressed at the luminal membrane. Chemical or pharmacological chaperones have been found to reverse the intracellular retention of aquaporin-2 and arginine vasopressin receptor 2 mutant proteins. Because many hereditary diseases stem from the intracellular retention of otherwise functional proteins, this mechanism may offer a new therapeutic approach to the treatment of those diseases that result from errors in protein kinesis.