Ketamine is associated with lower urinary tract signs and symptoms.

BACKGROUND: Case reports and series indicate that ketamine, an anesthetic agent, causes lower urinary tract symptoms (LUTS). This study explored whether ketamine users were more likely to report LUTS compared to other substance users. METHODS: Participants were recruited through an online survey on erowid.org, a drug information website. A notice posted on the website invited substance users to participate in a web-based survey on "drug use and health". The notice did not mention ketamine, or other aspects of the research questions, to avoid participation bias. The anonymous survey collected demographics, drug use history, and history of LUTS (urinary frequency, urgency, incontinence, hematuria, and dysuria). RESULTS: Of 18,802 participants, 18.7% and 5.8% reported ever (lifetime) and recent (past-6-month) use of ketamine, respectively. Prevalence of LUTS among ever, recent, and never users of ketamine were 28%, 30%, and 24% respectively. Multivariate analysis showed significant associations between recent ketamine use and urinary symptoms. For each additional day of ketamine use in the last 180 days, the odds of developing urinary frequency, urgency, dysuria, and hematuria increased by 1.6%, 1.4%, 1.7%, and 1.9% respectively. One excess case of urinary frequency was reported per 17 recent users of ketamine. CONCLUSION: Compared to non-users, recent ketamine users had increased odds of LUTS. This is the first large-scale community-based study assessing the association of non-medical ketamine use with LUTS. Associations between ketamine and urological symptoms should be confirmed through longitudinal studies.

Localization and expression of insulin-like growth factor in the teleost retina.

Teleost fish retinas continue to add neurons throughout life, and evidence from in vitro experiments have implicated insulin-like growth factors (IGFs) in this process. To discover whether these factors are expressed in vivo, we have examined their expression in the cichlid fish, Haplochromis burtoni. Three lines of evidence show that IGFs are present in the fish retina. An IGF-I specific antibody, sm 1.2, binds preferentially to the retinal outer plexiform layer, in areas of cone photoreceptor synaptic endings. Northern blots of mRNA hybridized with riboprobes from trout IGF-I and IGF-II genes revealed transcripts of approximately 6.5 and 4.9 kb, respectively. The IGF-I probe detected an additional transcript of 1.2 kb in liver but not in retinal mRNA. In situ hybridization with digoxigenin-labeled riboprobes revealed that the IGF gene product is localized in the cone photoreceptors. These results show that cone photoreceptors are the source of IGFs in the fish retina, consistent with the hypothesis that IGFs play a role in regulating production of new neurons in the teleost retina.

Egr-1 activation of rat adrenal phenylethanolamine N-methyltransferase gene.

The immediate early gene transcription factor Egr-1 increases luciferase reporter gene activity 3-4-fold when a rat phenylethanolamine N-methyltransferase (PNMT) promoter-luciferase construct and an Egr-1 expression construct are cotransfected into transformed PC12 cells (RS1). Egr-1 also stimulates endogenous PNMT mRNA expression in the RS1 cells. Furthermore, when transfected RS1 cells are treated with dexamethasone, both luciferase and endogenous PNMT mRNA rise an additional 2-fold although dexamethasone does not independently activate transcription from the PNMT promoter. While both Egr-1 sites (-45 and -165 base pairs) in the PNMT promoter appear necessary for maximum luciferase reporter gene expression, the -165 site appears to be the more important for mediating the Egr-1 response. When the upstream site is deleted or either or both sites are mutated in PNMT-reporter gene constructs, Egr-1-induced luciferase activity from the PNMT promoter is significantly reduced. In addition, the incremental activation by dexamethasone is lost when sequences containing the glucocorticoid response element are deleted or when the Egr-1 sites are mutated. In the transfected RS1 cells, a rise in nuclear Egr-1 protein accompanies the rise in endogenous PNMT mRNA. Similarly, reserpine-treated rats (10 mg/kg, intraperitoneally), which show an 8-fold elevation in adrenal PNMT mRNA at 6 h postdrug administration, also show a marked rise in Egr-1 protein in adrenal medullary cell nuclei. These studies provide the first direct evidence that a transcription factor, Egr-1, can activate PNMT gene expression and identify PNMT as a novel target gene for Egr-1. Finally, the incremental enhancement of the Egr-1 response by glucocorticoids suggests a potential interaction between Egr-1 and another transcription factor, the glucocorticoid receptor.

Binding of metal ions to polysaccharides. V. Potentiometric, spectroscopic, and viscosimetric studies of the binding of cations to chondroitin sulfate and chondroitin in neutral and acidic aqueous media.

Binding of cations to chondroitin sulfate A and C, chondroitin, and D-glucuronate was investigated in neutral and acidic aqueous media using H+, Cu2+, and Na+ ion-specific electrodes, viscometry, electron spin resonance (esr), and ligand-field spectroscopy. Site binding to the carboxylate group and only electrostatic interaction with the sulfate group could describe the results well. The nitrogen atom of the N-acetyl group appeared not to be involved in bonding of cations to chondroitin(sulfate) systems. The interaction of the divalent metal ions follows the Irving-Williams series. The value of the electrostatic potential at the carboxylate group of chondroitin(sulfate), as experienced by a cation, was determined in dependence of cation bonding. It proved to be difficult to establish the composition of a complex of a metal ion with a polyion by means of a molar ratio curve.

A 13C-n.m.r. study of the binding of ytterbium(III) to chondroitin sulphate and chondroitin.

13C-N.m.r. spectra of chondroitin 4- and 6-sulphates, chondroitin, beta-D-glucuronate, and beta-D-glucose 6-sulphate were measured in the presence of ytterbium(III) in deuterium oxide. The structure of the ytterbium-polysaccharide compounds in solution was found to be similar to that reported for calcium chondroitin 4-sulphate in a stretched film. In the glucuronate complex, Yb(III) coordinates to the carboxylate group. For beta-D-glucose 6-sulphate, the ytterbium-induced shifts are too small to allow the structure to be determined.

Mode of action of copper complexes of some 2,2'-bipyridyl analogs on Paracoccus denitrificans.

Copper complexes of 2,2'-bipyridyl and related compounds and CuSO4 inhibited the growth of paracoccus denitrificans. The copper(I) complex of 2,9-dimethyl-1,10-phenanthroline [Cu(DMP)2NO3] showed the highest activity, whereas the copper(II) complex of 1,10-phenanthroline and CuSO4 inhibited the growth to a lesser extent. The uncomplexed ligands (1,10-phenanthroline and 2,9-dimethyl-1,10-phenanthroline) showed little activity, but in the presence of noninhibitory amounts of CuSO4 this activity increased markedly. Copper ions therefore proved to be essential for the growth-inhibitor effect. The extent of inhibition appeared to be strongly dependent on the initial cell density and on the growth medium. No selective inhibition of deoxyribonucleic acid, ribonucleic acid, or protein synthesis was observed with Cu(DMP)2NO3. Respiratory electron transport of P. denitrificans appeared to be strongly inhibited by Cu(DMP)2NO3 and to a somewhat lesser extent by CuSO4. Both aerobic and anaerobic respirations were inhibited to the same extent, and from the cytochrome redox kinetics it is concluded that the site of this inhibition in the respiratory electron transport chain must be located before cytochrome b. Cu(DMP)2NO3 did not significantly influence the H+/O ratio with whole cells of P. denitrificans, suggesting that the efficiency of oxidative phosphorylation is not affected by CU(DMP)2NO3. Growing cultures of P. denitrificans showed a decrease in intracellular potassium ion content in the presence of increasing amounts of Cu(DMP)2NO3. It is concluded that interference with the cytoplasmic membrane, resulting in inhibition of respiratory electron transport, probably constitutes the main mode of action of copper complexes of 2,2'-bipyridyl analogs on P. denitrificans.