Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0032290 (aspiration pneumonia)
 2,291 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The eosinophilia-myalgia syndrome (EMS) is a unique entity associated with products that contain L-tryptophan (L-trp). Studies of the underlying etiopathogenic processes are underway. EMS is a distinct syndrome, but shares features with eosinophilic fasciitis and other variants of systemic sclerosis. A wide spectrum of clinical manifestations has been described, but there is no consensus regarding treatment. We report the clinical and laboratory features of 12 patients. All were treated with nonsteroidal antiinflammatory drugs (NSAIDs) and analgesics with transient or minimal effect. Two received D-penicillamine (DP) and colchicine, with minimal improvement; one had no response to azathioprine (AZA). Eleven received corticosteroids and had improvement of general symptoms, arthralgias, arthritis, myalgias, skin changes, eosinophilia, and leukocytosis. Nevertheless, all but the latter two findings recurred when corticosteroids were tapered. Seven patients who were unresponsive to the former treatments received low-dose pulse oral methotrexate. Six exhibited continued improvement after a mean follow-up of 4.5 months, with good drug tolerance. Corticosteroids were tapered and, in some instances, discontinued without relapse or complications. One patient improved but later died of aspiration pneumonia. We conclude that methotrexate (MTX) is a therapeutic alternative for patients with severe or refractory EMS.
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PMID:Treatment of the eosinophilia-myalgia syndrome. 174 39

Dicarboxylic acids are prominent features of several diseases, including Reye's syndrome and inborn errors of mitochondrial and peroxisomal fatty acid oxidation. Moreover, dicarboxylic acids are potentially toxic to cellular processes. Previous studies [Tonsgard, Mendelson & Meredith (1988) J. Clin. Invest. 82, 1567-1573] demonstrated that long-chain dicarboxylic acids have a single high-affinity binding site and between one and three lower-affinity sites on albumin. Medium-chain-length dicarboxylic acids have a single low-affinity site. We further characterized dicarboxylic acid binding to albumin in order to understand the potential effects of drugs and other ligands on dicarboxylic acid binding and toxicity. Progesterone and oleate competitively inhibit octadecanedioic acid binding to the single high-affinity site. Octanoate inhibits binding to the low-affinity sites. Dansylated probes for subdomain 2AB inhibit dodecanedioic acid binding whereas probes for subdomain 3AB do not. In contrast, low concentrations of octadecanedioic acid inhibit the binding of dansylated probes to subdomain 3AB and 2AB. L-Tryptophan, which binds in subdomain 3AB, inhibits hexadecanedioic acid binding but has no effect on dodecanedioic acid. Bilirubin and acetylsalicylic acid, which bind in subdomain 2AB, inhibit the binding of medium-chain and long-chain dicarboxylic acids. Our results suggest that long-chain dicarboxylic acids bind in subdomains 2C, 3AB and 2AB. The single low-affinity binding site for medium-chain dicarboxylic acids is in subdomain 2AB. These studies suggest that dicarboxylic acids are likely to be unbound in disease states and may be potentially toxic.
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PMID:Characterization of the binding sites for dicarboxylic acids on bovine serum albumin. 206

Aspiration pneumonia remains a major cause of death in the elderly. However, fundamental and effective treatment has not been established yet. Onset of aspiration pneumonia is based on the presence of dysphagia, such as delayed triggering of the swallowing reflex. The swallowing reflex in the elderly is temperature sensitive, even if it is impaired. Swallowing reflex was delayed when the temperature of the food was close to body temperature. The actual swallowing time shortened when the temperature difference increases. The improvement of swallowing reflex by temperature stimuli could be mediated by the temperature-sensitive TRP channel. Administration of the TRPV1 agonists improves the delay of the swallowing reflex. Red wine polyphenols have been suggested to improve the swallowing reflex by increasing TRPV1 response. Food with menthol, an agonist of TRPM8 which is a cold temperature receptor, also decreased the delay in swallowing reflex. Olfactory stimuli, such as black pepper, can be a useful tool to improve swallowing reflex in people with lower ADL and consciousness levels. By combining these various sensory stimuli, we developed a protocol to start oral intake in patients with aspiration pneumonia This protocol shall continue to contribute to the ingestion of many older people.
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PMID:Stimulating oral and nasal chemoreceptors for preventing aspiration pneumonia in the elderly. 2212 60

Aspiration pneumonia is a major health problem in the elderly. A swallowing disorder, such as a delayed triggering of the swallowing reflex, predisposes in patients with aspiration pneumonia. Swallowing reflex was delayed when the temperature of the food is close to body temperature. The actual swallowing time shortened when the temperature difference increases. The improvement of swallowing reflex by temperature stimuli could be mediated by the temperature-sensitive TRP channel at pharynx. The administration of capsaicin as an agonist stimulus of TRPV1, a warm temperature receptor, decreased the delay in swallowing reflex. Food with menthol, agonist of TRPM8 which is a cold temperature receptor, also decreased the delay in swallowing reflex. Olfactory stimulation such as black pepper was useful to improve the swallowing reflex for people with low ADL levels or with decreased consciousness. Thus, we found anti-aspiration drugs with various site of actions on the hierarchical structure of neuronal control of swallowing. By combining anti-aspiration drugs and swallowing rehabilitations, we developed a protocol to start eating more efficiently and safely. Implementation of this protocol would help avoid re-aspiration in many elderly people with aspiration pneumonia. The combination of various anti-aspiration drugs may improve the swallowing disorders and prevent aspiration pneumonia.
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PMID:[Therapeutic approach targeting TRP channels and development of anti-aspiration drugs]. 2319 61

Despite the development of strong antibiotics, the pneumonia death is increasing all over the world in these decades. Among the people who died of pneumonia, the majority were 65 years old or over. Although pneumonia is recently categorized into several entities, aspiration pneumonia includes all entities. Therefore, targeting dysphagia and aspiration to treat pneumonia is a promising strategy and anti-aspiration drugs will be a part of pneumonia treatment. The swallowing reflex in elderly people was temperature-sensitive and the improvement of swallowing reflex by temperature stimuli could be mediated by the thermosensing TRP channels at pharynx. The administration of capsaicin as an agonist stimulus of TRPV1, a warm temperature receptor, decreased the delay in swallowing reflex. Red wine polyphenols improved swallowing reflex by enhancing TRPV1 response. Food with menthol, agonist of TRPM8 which is a cold temperature receptor, also decreased the delay in swallowing reflex. Olfactory stimulation such as black pepper was useful to improve the swallowing reflex for people with low ADL levels or with decreased consciousness. Thus, recent advancement of geriatrics found several anti-aspiration drugs such as thermosensing TRP channel agonists, black pepper odor, amantadine, cilostazol, theophylline and angiotensin- converting enzymes inhibitors. Thermosensing TRP channel agonists include capsaicin, capsiate, menthol, and red wine polyphenols. Controls of swallowing are mediated by various stages of neural system from peripheral sensory nerves to the entire cerebral cortex. Each anti-aspiration drug acts on various sites of neural axis of swallowing reflex. The combination of various anti-aspiration drugs may improve dysphagia and prevent aspiration pneumonia.
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PMID:Thermal taste and anti-aspiration drugs: a novel drug discovery against pneumonia. 2388 80