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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cancer anorexia frequently characterizes the clinical journey of patients with cancer and affects patients' morbidity, mortality, and quality of life. A constellation of symptoms concur to the diagnosis of anorexia, and early satiety, changes in taste/smell, and nausea are the more frequently reported. The pathogenesis of cancer anorexia is multifactorial, but accumulating evidence indicates that the hypothalamic melanocortin and neuropeptide Y systems become resistant to peripheral inputs. This results in increased melanocortin activity and reduced neuropeptide Y function, thereby leading to the promotion of catabolic stimuli (i.e., reduced energy intake, increased energy expenditure, possibly increased muscle proteolysis, and adipose tissue loss). Interestingly, hypothalamic proinflammatory cytokines and serotonin, among other factors, are key in triggering hypothalamic resistance. In the clinical setting, cancer anorexia develops with heterogeneous presenting symptoms (i.e., early satiety and/or nausea and/or changes of taste) and varying degrees of severity. Available evidence suggests that the constellation of symptoms characterizing this syndrome should be considered, at least in part, as different phenotypes of common neurochemical/metabolic alterations in the presence of a chronic inflammatory state.
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PMID:NPY and brain monoamines in the pathogenesis of cancer anorexia. 1866 59

About half of all cancer patients show a syndrome of cachexia, characterized by anorexia and loss of adipose tissue and skeletal muscle mass. Numerous cytokines have been postulated to play a role in the etiology of cancer cachexia. Cytokines can elicit effects that mimic leptin signaling and suppress orexigenic ghrelin and neuropeptide Y signaling, inducing sustained anorexia and cachexia not accompanied by the usual compensatory response. Furthermore, cytokines have been implicated in the induction of cancer-related muscle wasting. In particular, tumor necrosis factor-alpha, interleukin-1, interleukin-6 and interferon-gamma have been implicated in the induction of cancer-related muscle wasting. Cytokine-induced skeletal muscle wasting is probably a multifactorial process, which involves a depression in protein synthesis, an increase in protein degradation or a combination of both. Cancer patients suffer from the reduction in physical function, tolerance to anti-cancer therapy and survival, while many effective chemotherapeutic agents for cancer are burdened by toxicities that can reduce patient's quality of life or hinder their effective use. Herbal medicines have been widely used to help improve such conditions. Recent studies have shown that herbal medicines such as rikkunshito enhance ghrelin signaling and consequently improve nausea, appetite loss and cachexia associated with cancer or cancer chemotherapy, which worsens the quality of life and life expectancy of the patients. The multicomponent herbal medicines capable of targeting multiple sites could be useful for future drug discovery. Mechanistic studies and identification of active compounds could lead to new discoveries in biological and biomedical sciences.
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PMID:Cancer cachexia pathophysiology and translational aspect of herbal medicine. 2373 6

Neuropeptides are the largest class of intercellular signaling molecules, contributing to a wide variety of physiological processes. Neuropeptide receptors are therapeutic targets for a broad range of drugs, including medications to treat pain, addiction, sleep disorders, and nausea. In addition to >100 peptides with known functions, many peptides have been identified in mammalian brain for which the cognate receptors have not been identified. Similarly, dozens of "orphan" G protein-coupled receptors have been identified in the mammalian genome. While it would seem straightforward to match the orphan peptides and receptors, this is not always easily accomplished. In this review we focus on peptides named PEN and big LEN, which are among the most abundant neuropeptides in mouse brain, and their recently identified receptors: GPR83 and GPR171. These receptors are co-expressed in some brain regions and are able to interact. Because PEN and big LEN are produced from the same precursor protein and co-secreted, the interaction of GPR83 and GPR171 is physiologically relevant. In addition to interactions of these two peptides/receptors, PEN and LEN are co-localized with neuropeptide Y and Agouti-related peptide in neurons that regulate feeding. In this review, using these peptide receptors as an example, we highlight the multiple modes of regulation of receptors and present the emerging view that neuropeptides function combinatorially to generate a network of signaling messages. The complexity of neuropeptides, receptors, and their signaling pathways is important to consider both in the initial deorphanization of peptides and receptors, and in the subsequent development of therapeutic applications.
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PMID:Orphan neuropeptides and receptors: Novel therapeutic targets. 2917 50

The most common side effects of cisplatin chemotherapy are nausea and vomiting, and the overwhelming majority of research studies on the mechanism of cisplatin-induced nausea have been focused on the "vomiting center." As a modulatory center of gastric motility, the roles of the hypothalamus in nausea and vomiting remain unclear. In the present study, we investigated the effects of exogenous orexin-A injected into the arcuate nucleus (ARC) on cisplatin-induced nausea and vomiting, and the possible underlying mechanism. Kaolin intake was calculated daily in cisplatin-treated and saline-treated rats. Gastric motility recording, injections into the ARC, and lesions of the paraventricular nucleus (PVN) were used to study the effects of orexin-A and the hypothalamic nucleus on disorders of gastrointestinal function in cisplatin-treated rats. The pathway from the ARC to the PVN was observed through Fluoro-Gold retrograde tracing. Furthermore, an NPY Y1 receptor antagonist was administered to explore the possible mechanisms involved in the effects of orexin-A in the ARC. We illustrated that exogenous orexin-A injected into the ARC reduced kaolin intake and promoted gastric motility in cisplatin-treated rats, and these effects could have been blocked by an ipsilateral PVN lesion or co-injected antagonist of orexin-A-SB334867. Additional results showed that orexin-A-activated neurons in the ARC communicated directly with other neurons in the PVN that express neuropeptide Y (NPY). Furthermore, activation of the downstream NPY pathway was required for the observed effects of orexin in the ARC on cisplatin-induced nausea and vomiting. These findings reveal a novel neurobiological circuit from the ARC to the PVN that might provide a potential target for the prevention and treatment of cisplatin-induced nausea and vomiting.
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PMID:Arcuate Nucleus Orexin-A Signaling Alleviates Cisplatin-Induced Nausea and Vomiting Through the Paraventricular Nucleus of the Hypothalamus in Rats. 3061 23