Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acute mountain sickness and high altitude cerebral edema are specific pathologies of high altitude exposure. The usual symptoms of acute mountain sickness are headache, nausea, vomiting, insomnia, lassitude, dizziness and ataxia. High altitude cerebral oedema is a severe state of acute mountain sickness with, in addition, alteration of mental status and consciousness. The pathophysiology of these 2 diseases are essentially due to an increase of intracranial pressure directly dependent of an increase of cerebral volume. Molecular and cellular mechanisms underlying acute mountain sickness and high altitude cerebral oedema are still poorly understood. The regulation of cerebral blood flow by nitric oxide seems to play a major role.
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PMID:[High altitude cerebral oedema]. 1281 24

Diabetic gastroparesis is a common and debilitating condition affecting millions of patients with diabetes mellitus worldwide. Although gastroparesis in diabetes has been known clinically for more than 50 years, treatment options remain very limited. Until recently, the scientific literature has offered few clues regarding the precise aetiology of gastric dysfunction in diabetes.Up to 50% of patients with diabetes may experience postprandial abdominal pain, nausea, vomiting and bloating secondary to gastric dysfunction. There is no clear association between length of disease and the onset of delayed gastric emptying. Gastroparesis affects both type 1 (insulin dependent) and type 2 (non- insulin dependent) forms of diabetes. Diagnosis requires identifying the proper symptom complex, while excluding other entities (peptic ulcer disease, rheumatological diseases, medication effects). The diagnosis of gastroparesis may be confirmed by demonstrating gastric emptying delay during a 4-hour scintigraphic study. Treatment options are limited and rely on dietary modifications, judicious use of available pharmacological agents, and occasionally surgical or endoscopic placement of gastrostomies or jejunostomies. Gastric pacing offers promise for patients with medically refractory gastroparesis but awaits further investigation. Current pharmacological agents for treating gastroparesis include metoclopramide, erythromycin, cisapride (only available via a company-sponsored programme) and domperidone (not US FDA approved). All of these drugs act as promotility agents that increase the number or the intensity of gastric contractions. These medications are not uniformly effective and all have adverse effects that limit their use. Cisapride has been removed from the open market as a result of over 200 reported cases of cardiac toxicity attributed to its use. Unfortunately, there is a paucity of clinical studies that clearly define the efficacy of these agents in diabetic gastroparesis and there are no studies that compare these drugs to each other. The molecular pathophysiology of diabetic gastroparesis is unknown, limiting the development of rational therapies. New studies, primarily in animals, point to a defect in the enteric nervous system as a major molecular cause of abnormal gastric motility in diabetes. This defect is characterised by a loss of nitric oxide signals from nerves to muscles in the gut resulting in delayed gastric emptying. Novel therapies designed to augment nitric oxide signalling are being studied.
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PMID:Current concepts in diabetic gastroparesis. 1282 60

Giardia lamblia (syn. G. duodenalis or G. intestinalis), the causative agent of giardiasis, is one of the most common causes worldwide of intestinal infections in humans. Symptomatic infection is characterized by diarrhoea, epigastric pain, nausea, vomiting, and weight loss, yet many infections are asymptomatic. The protozoan, unicellular parasite resides in the lumen and attaches to the epithelium and overlying mucus layers but does not invade the mucosa and causes little or no mucosal inflammation. Giardiasis is normally transient, indicating the existence of effective host defences, although re-infections can occur, which may be related to differences in infecting parasites and/or incomplete immune protection. Mucosal defences against Giardia must act in the small intestinal lumen in the absence of induction by classical inflammatory mediators. Secretory IgA antibodies have a central role in anti-giardial defence. B cell-independent mechanisms also exist and can contribute to eradication of the parasite, although their identity and physiological importance are poorly understood currently. Possible candidates are nitric oxide, antimicrobial peptides such as Paneth cell alpha-defensins, and lactoferrin. Elucidation of the key anti-giardial effector mechanisms will be important for selecting the best adjuvants in the rational development of vaccination strategies against Giardia.
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PMID:Mucosal defences against Giardia. 1296 44

A placebo-controlled, double-blind, parallel group study was performed with 58 patients to investigate effects of French maritime pine bark extract, Pycnogenol, on patients with hypertension. Supplementation of the patients with 100 mg Pycnogenol over a period of 12 weeks helped to reduce the dose of the calcium antagonist nifedipine in a statistically significant manner. The intake of Pycnogenol decreased endothelin-1 concentrations significantly compared to placebo while concentrations of 6-keto prostaglandin F1a in plasma were significantly higher compared to placebo. Values for nitric oxide (NO) in plasma increased in both groups, but the differences were not significant. Angiotensin II concentrations in plasma were lowered in the placebo group to a larger extent than in the Pycnogenol group. Heart rate, electrolytes and blood urea nitrogen were not changed during treatment in both groups of patients. Unwanted effects observed in both groups were of mild and transient nature, such as gastrointestinal problems, vertigo, headache and nausea. Differences in rate of side effects were not statistically significant between the two groups. Study results support a supplementation with Pycnogenol for mildly hypertensive patients.
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PMID:Pycnogenol, French maritime pine bark extract, improves endothelial function of hypertensive patients. 1465 74

During the administration of recombinant human TSH (rhTSH) to monitor differentiated thyroid carcinoma, mild side effects, such as nausea and headaches, often occur. The origin of these is not clear. Since changes in TSH and thyroid hormones can modulate some endothelial-derived factors, we aimed at testing whether rhTSH administration induces changes in nitric oxide. We studied 25 patients (56.6+/-12.6 yr) who had undergone thyroidectomy followed by ablative radioiodine for papillary thyroid cancer and who were under follow-up. While L-thyroxine therapy continued, thyroglobulin (Tg), TSH, free-T3, free-T4 and nitrite-plus-nitrate (NOx) concentrations were evaluated before and after rhTSH administration (0.9 mg i.m. on 2 consecutive days). Mean TSH showed a huge increase from baseline (0.1+/-0.0 mIU/l) to day 3 (216.3+/-17.5 mIU/l, p<0.001), which was not accompanied by changes in thyroid hormones. Mean baseline NOx levels were 12.6+/-1.2 micromoles/l and showed a significant increase on day 3 (20.1+/-1.2 micromoles/l, p<0.05 vs day 0), followed by progressive reduction from day 6 (18.1+/-2.8 micromoles/l) to day 9 (10.6+/-1.3 micromoles/l, p<0.05 vs day 0). There was a significant (p=0.04) correlation between the percentage increase in TSH and the percentage increase in NOx. On the other hand, increase in TSH did not correlate with the percentage decrease in NOx from day 6 to day 9. No correlation was noted between the increase in TSH or NOx and the occurrence or severity of the symptoms. Our study shows that, during rhTSH testing, circulating nitric oxide increases. This endothelial-derived factor might, in turn, mediate the occurrence of vasomotor headache and nausea in some particularly susceptible patients.
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PMID:Circulating nitric oxide is modulated by recombinant human TSH administration during monitoring of thyroid cancer remnant. 1505 71

The sudden onset of hearing impairment or hearing loss can be a characteristic sign of a vertebrobasilar circulatory disturbance. We report on a 65 year old male patient with an acute left-sided tinnitus followed by hearing loss as an initial symptom of an infarction of the left anterior inferior cerebellar artery (AICA). Successively, additional symptoms with vertigo, nausea, vomiting and a transient dysarthria and ataxia of the left upper extremity occurred. In the course of the illness, the hearing loss, ataxia and dysarthria completely recovered. MRI of the brain showed an infarction in the area of the anterior inferior cerebellar artery; neurosonographic examination of the basilar and vertebral arteries was normal. Therefore, in patients with acute hearing impairment or hearing loss, an AICA-ischemia should be considered and the patient carefully examined for additional brainstem symptoms, since this can be the first sign of an life-threatening basilar artery thrombosis.
HNO 2005 Sep
PMID:[Sudden hearing loss as the leading symptom of an infarction of the left anterior inferior cerebellar artery]. 1565 56

Mildronate (3-(2,2,2-trimethylhydrazinium)propionate; MET-88; meldonium, quaterine) is an antiischemic drug developed at the Latvian Institute of Organic Synthesis. Mildronate was designed to inhibit carnitine biosynthesis in order to prevent accumulation of cytotoxic intermediate products of fatty acid beta-oxidation in ischemic tissues and to block this highly oxygen-consuming process. Mildronate is efficient in the treatment of heart ischemia and its consequences. Extensive evaluation of pharmacological activities of mildronate revealed its beneficial effect on cerebral circulation disorders and central nervous system (CNS) functions. The drug is used in neurological clinics for the treatment of brain circulation disorders. It appears to improve patients' mood; they become more active, their motor dysfunction decreases, and asthenia, dizziness and nausea become less pronounced. Since the brain does not utilize fatty acids as fuel other mechanisms of action of mildronate in CNS should be considered. Several reports indicate the possible existence of an alternative, non-carnitine dependent mechanism of action of mildronate. Our recent findings suggest that CNS effects of mildronate could be mediated by stimulation of the nitric oxide production in the vascular endothelium by modification of the gamma-butyrobetaine and its esters pools. It is hypothesized that mildronate may increase the formation of the gamma-butyrobetaine esters. The latter are potent cholinomimetics and may activate eNOS via acetylcholine receptors or specific gamma-butyrobetaine ester receptors. This article summarizes known pharmacological effects of mildronate, its pharmacokinetics, toxicology, as well as the proposed mechanisms of action.
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PMID:Mildronate: an antiischemic drug for neurological indications. 1600 37

Opiates are the primary treatment for pain management in cancer patients reporting moderate to severe pain, and are being increasingly used for non-cancer chronic pain. However, prolonged administration of opiates is associated with significant problems including the development of antinociceptive tolerance, wherein higher doses of the drug are required over time to elicit the same amount of analgesia. High doses of opiates result in serious side effects such as constipation, nausea, vomiting, dizziness, somnolence, and impairment of mental alertness. In addition, sustained exposure to morphine has been shown to result in paradoxical pain in regions unaffected by the initial pain complaint, and which may also result in dose escalation, i.e. 'analgesic tolerance'. A concept that has been gaining considerable experimental validation is that prolonged use of opioids elicits paradoxical, abnormal pain. This enhanced pain state requires additional opioids to maintain a constant level of antinociception, and consequently may be interpreted as antinociceptive tolerance. Many substances have been shown to block or reverse antinociceptive tolerance. A non-inclusive list of examples of substances reported to block or reverse opioid antinociceptive tolerance include: substance P receptor (NK-1) antagonists, calcitonin gene-related peptide (CGRP) receptor antagonists, nitric oxide (NO) synthase inhibitors, calcium channel blockers, cyclooxygenase (COX) inhibitors, protein kinase C inhibitors, competitive and non-competitive antagonists of the NMDA (N-methyl-D-aspartate) receptor, AMPA (alpha-amino-3-hydroxy-5-methyl-4 isoxazolepropionic acid) antagonists, anti-dynorphin antiserum, and cholecystokinin (CCK) receptor antagonists. Without exception, these substances are also antagonists of pain-enhancing agents. Prolonged opiate administration indeed induces upregulation of substance P (SP) and calcitonin gene-related peptide (CGRP) within sensory fibers in vivo, and this is accompanied by an enhanced release of excitatory neurotransmitters and neuropeptides from primary afferent fibers upon stimulation. The enhanced evoked release of neuropeptides is correlated with the onset of abnormal pain states and opioid antinociceptive tolerance. Importantly, the descending pain modulatory pathway from the brainstem rostral ventromedial medulla (RVM) via the dorsolateral funiculus (DLF) is critical for maintaining the changes observed in the spinal cord, abnormal pain states and antinociceptive tolerance, because animals with lesion of the DLF did not show enhanced evoked neuropeptide release, or develop abnormal pain or antinociceptive tolerance upon sustained exposure to opiates. Microinjection of either lidocaine or a CCK antagonist into the RVM blocked both thermal and touch hypersensitivity as well as antinociceptive tolerance. Thus, prolonged opioid exposure enhances a descending pain facilitatory pathway from the RVM that is mediated at least in part by CCK activity and is essential for the maintenance of antinociceptive tolerance.
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PMID:Is paradoxical pain induced by sustained opioid exposure an underlying mechanism of opioid antinociceptive tolerance? 1621 2

We have previously shown that nitric oxide (NO) and cyclic guanosine monophosphate (GMP) may cause headache and migraine. However, not all findings in previous studies can be explained by an activation of the NO-cGMP pathway. Calcitonin gene-related peptide (CGRP) causes headache and migraine in migraine patients, but CGRP receptor activation causes an increase in cyclic adenosine monophosphate (cAMP). In order to investigate the role of cAMP in vascular headache pathogenesis, we studied the effect of cilostazol, an inhibitor of cAMP degradation, in our human experimental headache model. Twelve healthy volunteers were included in a double-blind, randomized, crossover study. Placebo or cilostazol (200 mg p.o.) was administered on two separate study days. Headache was scored on a verbal rating scale (0-10) and mechanical pain thresholds were measured with von Frey hairs. The median peak headache score 0-16 h postdose was 0 (range 0-2) after placebo and 3.5 (range 0-7) after cilostazol (P = 0.003). The median headache curve peaked at 6-9 h postdose. The headaches induced were usually bilateral and pulsating. Nausea occurred in two volunteers, photo- and phonophobia were not seen. Two volunteers had a headache that fulfilled International Headache Society criteria for migraine without aura after cilostazol. No change in mechanical pain thresholds in the forehead was seen (P = 0.25). The headache after cilostazol was equal to or more severe than headache induced by glyceryl trinitrate in previous experiments. The present study thus indicates that increased levels of cAMP may play a role in headache and migraine pathogenesis.
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PMID:The headache-inducing effect of cilostazol in human volunteers. 1705 37

Oral supplements of arginine and citrulline increase local nitric oxide (NO) production in the small intestine and this may be harmful under certain circumstances. Gastrointestinal toxicity was therefore reviewed with respect to the intestinal physiology of arginine, citrulline, ornithine, and cystine (which shares the same transporter) and the many clinical trials of supplements of the dibasic amino acids or N-acetylcysteine (NAC). The human intestinal dibasic amino acid transport system has high affinity and low capacity. L-arginine (but not lysine, ornithine, or D-arginine) induces water and electrolyte secretion that is mediated by NO, which acts as an absorbagogue at low levels and as a secretagogue at high levels. The action of many laxatives is NO mediated and there are reports of diarrhea following oral administration of arginine or ornithine. The clinical data cover a wide span of arginine intakes from 3 g/d to>100 g/d, but the standard of reporting adverse effects (e.g. nausea, vomiting, and diarrhea) was variable. Single doses of 3-6 g rarely provoked side effects and healthy athletes appeared to be more susceptible than diabetic patients to gastrointestinal symptoms at individual doses>9 g. This may relate to an effect of disease on gastrointestinal motility and pharmacokinetics. Most side effects of arginine and NAC occurred at single doses of >9 g in adults (>140 mg/kg) often when part of a daily regime of approximately>30 g/d (>174 mmol/d). In the case of arginine, this compares with the laxative threshold of the nonabsorbed disaccharide alcohol, lactitol (74 g or 194 mmol). Adverse effects seemed dependent on the dosage regime and disappeared if divided doses were ingested (unlike lactitol). Large single doses of poorly absorbed amino acids seem to provoke diarrhea. More research is needed to refine dosage strategies that reduce this phenomenon. It is suggested that dipeptide forms of arginine may meet this criterion.
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PMID:Adverse gastrointestinal effects of arginine and related amino acids. 1751 49


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