ABSTRACT
Relapsing polychondritis is a relatively rare disease characterized by episodic inflammation and progressive destruction of cartilage involving ears, nasal and laryngotracheal cartilage, cardiovascular system and the eyes. The increasing awareness of its clinically distinct has resulted in recognition of at least 550 reported cases. Six cases are reported to demonstrate the wide variety of clinical pattern. The most common features of the disease are auricular and nasal cartilage inflammation and nondeforming arthritis. Ocular symptoms and vasculitis is relatively rare. Two cases of relapsing polychondritis with laryngotracheobronchial manifestations illustrate the severe clinical features of the disease. Relapsing polychondritis may associate with diverse forms of connective tissue disease, such as rheumatoid arthritis. It seems interesting to note the onset in childhood. Treatment has been primarily symptomatic. In situations of mild symptoms, initial treatment is with nonsteroidal antiinflammatory drugs. For cases with serious manifestation, corticosteroids and immunosuppressants are indicated.
Subject(s)
Polychondritis, Relapsing/diagnosis , Adult , Diagnosis, Differential , Female , Humans , Male , Middle AgedABSTRACT
Dopamine released from the lateral olivocochlear efferent system is thought to inhibit the toxic effect of the extreme glutamate outflow from the inner hair cells during ischemia or acoustic trauma. Using in vitro microvolume superfusion, we have studied the release of [(3)H]dopamine from the lateral olivocochlear efferent bundle of guinea pig in response to accumulation of [Na(+)](i), under condition characteristics of ischemia. Veratridine, that acts only on excitable membranes as a specific activator of voltage-sensitive sodium channels, significantly increased the electrically evoked release of [(3)H]dopamine, which was completely inhibited by tetrodotoxin. Dizocilpine (MK-801), a non-competitive NMDA-receptor antagonist, and GYKI-52466, a selective non-NMDA-receptor antagonist, had no effect on veratridine-induced [(3)H]dopamine release. Our data provide further evidence that the cochlear release of dopamine is of neural origin and possibly independent on a local effect of glutamate. The veratridine-induced transmitter release in the cochlea will be a very useful method in studying the effect of drugs on ischemic injury.
Subject(s)
Cochlea/drug effects , Cochlea/metabolism , Dopamine/metabolism , Veratridine/pharmacology , Animals , Excitatory Amino Acid Antagonists/pharmacology , Guinea Pigs , In Vitro Techniques , Male , Tetrodotoxin/pharmacology , Veratridine/antagonists & inhibitorsABSTRACT
A cDNA encoding a cytochrome P450 enzyme was isolated from a cDNA library of the corpora allata (CA) from reproductively active Diploptera punctata cockroaches. This P450 from the endocrine glands that produce the insect juvenile hormone (JH) is most closely related to P450 proteins of family 4 and was named CYP4C7. The CYP4C7 gene is expressed selectively in the CA; its message could not be detected in the fat body, corpora cardiaca, or brain, but trace levels of expression were found in the midgut and caeca. The levels of CYP4C7 mRNA in the CA, measured by ribonuclease protection assays, were linked to the activity cycle of the glands. In adult females, CYP4C7 expression increased immediately after the peak of JH synthesis, reaching a maximum on day 7, just before oviposition. mRNA levels then declined after oviposition and during pregnancy. The CYP4C7 protein was produced in Escherichia coli as a C-terminal His-tagged recombinant protein. In a reconstituted system with insect NADPH cytochrome P450 reductase, cytochrome b5, and NADPH, the purified CYP4C7 metabolized (2E,6E)-farnesol to a more polar product that was identified by GC-MS and by NMR as (10E)-12-hydroxyfarnesol. CYP4C7 converted JH III to 12-trans-hydroxy JH III and metabolized other JH-like sesquiterpenoids as well. This omega-hydroxylation of sesquiterpenoids appears to be a metabolic pathway in the corpora allata that may play a role in the suppression of JH biosynthesis at the end of the gonotrophic cycle.
Subject(s)
Cockroaches/metabolism , Cytochrome P-450 Enzyme System/genetics , Cytochrome P-450 Enzyme System/metabolism , Gene Expression Regulation, Developmental , Insect Proteins , Juvenile Hormones/biosynthesis , Mixed Function Oxygenases/genetics , Mixed Function Oxygenases/metabolism , Amino Acid Sequence , Animals , Base Sequence , Cloning, Molecular , Cockroaches/genetics , Cockroaches/growth & development , Cytochrome P-450 Enzyme System/chemistry , Cytochrome P450 Family 4 , DNA Primers , Escherichia coli , Female , Gene Expression Regulation, Enzymologic , Mixed Function Oxygenases/chemistry , Molecular Sequence Data , Mutagenesis, Site-Directed , Nuclear Magnetic Resonance, Biomolecular , Oviposition , Polymerase Chain Reaction , Recombinant Proteins/chemistry , Recombinant Proteins/metabolism , Sequence Alignment , Sequence Homology, Amino Acid , Transcription, GeneticABSTRACT
Most peptides have not proved useful as neuroactive drugs because they are blocked by the blood-brain barrier and do not reach their receptors within the brain. Intraperitoneally administered L-serinyl beta-D-glucoside analogues of [Met5]enkephalin (glycopeptides) have been shown to be transported across the blood-brain barrier to bind with targeted mu- and delta-opioid receptors in the mouse brain. The opioid nature of the binding has been demonstrated with intracerebroventricularly administered naloxone. Paradoxically, glucosylation decreases the lipophilicity of the peptides while promoting transport across the lipophilic endothelial layer. It is suggested that glucose transporter GLUT-1 is responsible for the transport of the peptide message. Profound and long-lasting analgesia has been observed in mice (tail-flick and hot-plate assays) with two of the glycopeptide analogues when administered intraperitoneally.
