Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0241981 (loss of balance)
 452 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endothelin is a 21-amino-acid, vasoactive peptide. Sequence analysis of cloned cDNAs for porcine and human endothelin precursors showed that endothelin-1 (ET-1) is produced in the endothelial cells. The peptide, endothelin (ET), was first identified as a potent vasoconstrictor. It is one of the most potent endogenous vascular smooth-muscle constrictors, ten times more potent than angiotensin II, vasopressin, and neuropeptide Y. Shortly after the discovery of this vasoconstrictor peptide, it was revealed that endothelin also possesses vasodilator properties at doses lower than those necessary to produce vasoconstriction. However, controversy still exists over the mechanism(s) of action; prostacyclin and endothelium-derived relaxing factor (EDRF) have mainly been implicated as the source of the initial vasodepressor effect. ET also elicits markedly different regional hemodynamic response patterns. There is a heterogeneity in the observed vasodilation or vasoconstriction, depending on species and on vascular beds studied in the same species. Endothelin has been implicated in a number of pathologic situations, including tissue ischemia and vasospasm. ET seems to be produced more actively around the site of endothelial damage; the loss of balance between its vasodilator- and vasoconstrictor-induced responses could contribute to its patho-physiologic properties. Experimental results strongly support the concept that ET could be important in controlling vascular tonus, both in the healthy and the diseased vessel.
 ...
PMID:Endothelin: an endothelium-derived vasoactive peptide. 788 38

A loss of balance between excitatory and inhibitory signaling leads to excitoxicity, and contributes to ischemic cell death. Reduced synaptic inhibition as a result of dysfunction of the ionotropic GABAA receptor has been suggested as one of the major causes for this imbalance, although the underlying mechanisms remain poorly understood. In the present study, we investigated whether oxygen-glucose deprivation (OGD), an ischemia-like challenge, alters cell-surface expression of GABAA receptors in cultured hippocampal neurons, and thereby leads to excitotoxic cell death. Using cell culture ELISA as a cell surface receptor assay, we found that OGD produced a marked decrease in cell surface GABAA receptors, without altering the total amount of receptors. Furthermore, the reduction could be prevented by inhibition of receptor endocytosis with hypertonic sucrose treatment. Notably, insulin significantly limited OGD-induced changes in cell-surface GABAA receptors. In parallel, insulin protected cultured neurons against both glutamate toxicity and OGD, as assayed by mitochondrial reduction of Alamar Blue. Importantly, insulin-mediated neuroprotection was eliminated when bicuculline, a GABAA receptor antagonist, was co-applied with insulin during OGD. Together, our results strongly suggest that ischemia-like insults decrease cell surface GABAA receptors in neurons via accelerated internalization, and that insulin provides neuroprotection by counteracting this reduction.
 ...
PMID:Insulin exerts neuroprotection by counteracting the decrease in cell-surface GABA receptors following oxygen-glucose deprivation in cultured cortical neurons. 1560

Acute kidney injury (AKI) is frequently encountered in the intensive care unit, and from its inception, morbidity and mortality increase in these patients compared to those without AKI. Despite numerous clinical trials and newer pharmacological agents, very little progress has been made to reduce the deaths that occur in this population. An important emerging concept is that AKI does not occur in isolation and it frequently involves other organs. Clinical conditions such as shock, trauma, and sepsis lead to an increase in fluid volume, cytokines/chemokines, uremic toxins and other soluble mediators that are known to affect distant organs. This critical loss of balance of these mediators appears to be due both to a reduction in clearance and increase in production as demonstrated by experimental studies of bilateral nephrectomy and ischemia-reperfusion, respectively. The evidence and mechanisms for distant organ injury following AKI will be discussed.
 ...
PMID:The changing pattern of acute kidney injury: from one to multiple organ failure. 2042 65