Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085437 (bacterial meningitis)
 4,038 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This paper describes a gradient system for separating D- and L-isomers of Dns-amino acids by mixed chelate complexation through the addition of histidine methyl ester and copper sulfate to the mobile phase. Most of the biologically important amino acids were separated in a single analysis. With a simple solvent gradient consisting of increasing concentrations of acetonitrile in L-histidine methyl ester buffer all the common amino acids were resolved except cysteine and all optical isomers were resolved except those of threonine, alanine and proline. Analysis time was 90 min. Use of this system for determining non-protein amino acids in human cerebrospinal fluid showed the amino acids to be L-isomers, as expected. The pattern in fluid from a patient with bacterial meningitis was different from that of most of the others.
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PMID:Stereoselective D- and L-amino acid analysis by high-performance liquid chromatography. 673 58

The sulfonamides constitute an important class of drugs, with several types of pharmacological agents possessing antibacterial, anticarbonic anhydrase, diuretic, hypoglycemic, and antithyroid activity among others. A large number of structurally novel sulfonamide derivatives have ultimately been reported to show substantial protease inhibitory properties. Of particular interest are some metalloprotease inhibitors belonging to this class, which by inhibiting several matrix metalloproteases (MMPs) show interesting antitumor properties. Some of these compounds are currently being evaluated in clinical trials. The large number of sulfonamide MMP inhibitors ultimately reported also lead to the design of effective tumor necrosis factor-alpha converting enzyme (TACE) inhibitors, potentially useful in the treatment of inflammatory states of various types. Since both MMPs and TACE contribute synergistically to the pathophysiology of many diseases, such as arthritis, bacterial meningitis, tumor invasion; the dual inhibition of these enzymes emerged as an interesting target for the drug design of anticancer/antiinflammatory drugs, and many such sulfonamide derivatives were recently reported. Human neutrophyl elastase (HNE) inhibitors of the sulfonamide type may also be useful in the treatment of inflammatory conditions, such as emphysema, cystic fibrosis, chronic bronchitis, ischemia reperfusion injury, and acute respiratory distress syndrome. Inhibition of some cysteine proteases, such as several caspase and cathepsin isozymes, may lead to the development of pharmacological agents effective for the management of several diseases, such as rheumatoid arthritis, inflammatory bowel disease, brain damage, and stroke. Another research line that progressed much in the last time regards different sulfonamides with remarkable antiviral activity. Some clinically used HIV protease inhibitors (such as amprenavir) possess sulfonamide moieties in their molecules, which are critical for the potency of these drugs, as shown by means of X-ray crystallography, whereas a very large number of other derivatives are constantly being synthesized and evaluated in order to obtain compounds with lower toxicity or augmented activity against viruses resistant to the such first generation drugs. Other viral proteases, such as those isolated from several types of herpes viruses may be inhibited by sulfonamide derivatives, leading thus to more effective classes of antiviral drugs.
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PMID:Protease inhibitors of the sulfonamide type: anticancer, antiinflammatory, and antiviral agents. 1278 86

Despite antibiotic therapy, supportive intensive care, and adjunctive treatment with dexamethasone, the mortality and morbidity remain high in patients with bacterial meningitis. The intracranial complications that mainly contribute to the poor outcome are in part a result of the production of reactive oxygen and nitrogen species. Experimental studies have shown that the prognosis for bacterial meningitis can be improved by the administration of antioxidants. Especially adjunctive therapy with N-acetyl-L-cystein (NAC) was shown to have mainly positive effects. Since NAC is already in clinical use in high doses for treating other diseases (e.g., acetaminophen intoxication) and only minor side effects have been observed, there is justified hope that adjunctive therapy with NAC could improve the prognosis of patients with bacterial meningitis.
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PMID:[N-acetyl-L-cysteine as a therapeutic option in bacterial meningitis]. 1723 23

Pneumococcal meningitis remains a serious disease with a case fatality rate of 15%-25%. Furthermore, long-term residues affect up to 50% of survivors. One of the most frequent sequelae is sensorineural hearing loss, which occurs in 26% of survivors of pneumococcal meningitis. Unfortunately, sufficient treatment regimens are still missing. New insights into the pathology and pathophysiology of meningitis-associated hearing loss have come from animal models of bacterial meningitis. Most likely, bacteria reach the cochlea through the cochlear aquaeduct. Once arrived in the perilymphatic spaces, they induce a severe suppurative labyrinthitis. The blood-labyrinth barrier breaks, hair cells are damaged, and neurons in the spiral ganglion undergo cell death, leading to meningitis-associated hearing loss. Reactive oxygen and nitrogen species, in particular peroxynitrite, seem to be among the crucial mediators of cochlear damage and hearing loss during meningitis. In our rat model of pneumococcal meningitis, adjunctive therapy with the antioxidants and peroxynitrite scavengers Mn(III)tetrakis(4-bencoic acid)-porphyrin (MnTBAP) and N-Acetyl-L-Cystein (NAC) significantly attenuated acute and long-term hearing loss. In several other animal studies of pneumococcal meningitis, adjunctive antioxidant therapy also protected infected animals from intracranial complications. Therefore, the use of antioxidants seems to be a promising future treatment option in pneumococcal meningitis.
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PMID:Nitrogen and oxygen molecules in meningitis-associated labyrinthitis and hearing impairment. 1808 15