Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dopamine pretreatment has been used to confer protection against cellular injury following hypothermia or anoxia, especially in vascular endothelial cells. Ischemia/reperfusion-associated tissue alterations still represent a major drawback in liver transplantation. The present study was aimed to investigate the effect of dopamine as an ex vivo adjunct, added to the cold storage solution, on cold preservation of the liver. Rat livers were excised 30 min after cardiac arrest, flushed with preservation solution and cold stored for 18 h. Dopamine (10, 50 or 100 microM) was added to the preservation solution in other livers. Organ viability was evaluated by 120 min of warm reperfusion in vitro (n = 6, resp.). Dopamine induced a dose related up to fourfold (at 50 mum) reduction in parenchymal (ALT, LDH) and mitochondrial (GLDH) enzyme release and significantly reduced histologic signs of tissue injury. Bile production and tissue ATP was doubled by dopamine. On the molecular level, dopamine enhanced postischemic phosphorylation of protein kinase A and p42/44 MAP kinase. Inhibition of cAMP-PKA pathway by simultaneous application of RP-cAMPs had no effect on P42/44 phosphorylation, or functional recovery of dopamine-treated grafts. Dopamine supplementation of the flush-out solution appears as a simple way for ex vivo augmentation of liver viability during preservation, not mediated via the catecholamine-cAMP signal cascade.
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PMID:Dopamine as additive to cold preservation solution improves postischemic integrity of the liver. 2021 Sep 35

Neurotensin (NT) exerts naloxone-insensitive antinociceptive action through its binding to both NTS1 and NTS2 receptors and NT analogs provide stronger pain relief than morphine on a molecular basis. Here, we examined the analgesic/adverse effect profile of a new NT(8-13) derivative denoted JMV2009, in which the Pro10 residue was substituted by a silicon-containing unnatural amino acid silaproline. We first report the synthesis and in vitro characterization (receptor-binding affinity, functional activity and stability) of JMV2009. We next examined its analgesic activity in a battery of acute, tonic and chronic pain models. We finally evaluated its ability to induce adverse effects associated with chronic opioid use, such as constipation and analgesic tolerance or related to NTS1 activation, like hypothermia. In in vitro assays, JMV2009 exhibited high binding affinity for both NTS1 and NTS2, improved proteolytic resistance as well as agonistic activities similar to NT, inducing sustained activation of p42/p44 MAPK and receptor internalization. Intrathecal injection of JMV2009 produced dose-dependent antinociceptive responses in the tail-flick test and almost completely abolished the nociceptive-related behaviors induced by chemical somatic and visceral noxious stimuli. Likewise, increasing doses of JMV2009 significantly reduced tactile allodynia and weight bearing deficits in nerve-injured rats. Importantly, repeated agonist treatment did not result in the development of analgesic tolerance. Furthermore, JMV2009 did not cause constipation and was ineffective in inducing hypothermia. These findings suggest that NT drugs can act as an effective opioid-free medication for the management of pain or can serve as adjuvant analgesics to reduce the opioid adverse effects.
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PMID:Pain relief devoid of opioid side effects following central action of a silylated neurotensin analog. 3253 76