Gabapentin in pain management.
Explore the source record for details and available documents.
Acetates↗
Biomedical subjects
J Mao
Publications and source records attributed to J Mao.
Identification of a novel kidney-specific gene downregulated in acute ischemic renal failure.
To gain further insights into the molecular mechanisms involved in acute renal failure, we have isolated a new gene from rat and human, named KSP32 (kidney-specific protein with a molecular mass of 32 kDa). KSP32 encodes a novel gene that shows little homology to other mammalian proteins. It, however, shares extensive homology with several proteins found in the nematode Caenorhabditis elegans and plants. The expression of KSP32 mRNA is highly restricted to kidney. In situ hybidization analysis revealed that the expression of KSP32 mRNA was prominent in the boundary of kidney cortex and outer medulla, exhibiting a raylike formation extending from the medulla into the cortex. Finally, KSP32 mRNA was dramatically downregulated in rat following induction of acute ischemic renal failure. Rapid loss of KSP32 mRNA expression was observed beginning at approximately 5 h following renal injury and mRNA levels remained depressed for at least 96 h. Both KSP32 mRNA levels as well as renal function recovered 14 days after injury. Administration of an endothelin receptor antagonist (SB-209670), known to restore renal function, significantly increased KSP32 expression.
Acute Kidney Injury↗
Isolation and identification of urinary metabolites of porfiromycin in dogs and humans.
Porfiromycin (PM), a bioreductive alkylating agent, is currently under development for the treatment of head and neck cancers as an adjunct to radiation therapy in phase III clinical trials. After i.v. administration of a single dose of PM to patients at 40 mg/m2, urinary metabolites were isolated by HPLC and identified by atmospheric pressure chemical ionization mass spectrometry. In dogs, [methyl-3H]PM was administered i.v. to three Beagle dogs at a single dose of 2 mg/kg. Urinary excretion of radioactivity and PM at different times was determined by liquid scintillation counting and by HPLC, respectively. An average of 48.0% of total radioactivity given to the dogs was cumulatively excreted in urine over a period of 7 days. Unchanged parent drug excreted in urine accounted for 10.8% of the administered dose over the same period of time. The results indicated that the majority of excreted dose in dog urine was in the form of metabolites. Three phase I and four phase II metabolites of PM were identified in human and dog urine. The phase I metabolites are 2-methylamino-7-aminomitosene, 1,2-cis and 1,2-trans-1-hydroxy-2-methylamino-7-aminomitosenes. The phase II metabolites are a pair of isomeric N-acetylcysteine S-conjugates and a pair of isomeric cysteine S-conjugates of mitosenes at the C-1 and C-10 positions. Most of the identified metabolites were confirmed by comparison with synthetic reference standards using HPLC and liquid chromatography/mass spectrometry (LC/MS). The identification of mercapturic acids and cysteine S-conjugates in urine indicates that the metabolism of PM may be through GSH conjugation.
Animals↗
fMRI: methodology--acquisition and processing.
Explore the source record for details and available documents.
Artifacts↗
Clinical and pathological observations in men lacking the gap junction protein connexin 32.
The X-linked form of Charcot-Marie-Tooth disease has been associated with mutations in the connexin 32 (Cx 32) gene, which encodes a gap junction protein. The majority of identified mutations are missense, but a few nonsense mutations or frame-shifting microdeletions have been encountered. Functional assessments of the mutated gap junction protein have demonstrated altered or simple losses of function. Mutations segregate with a typical clinical phenotype, which is the result of an age-related, progressive neuropathy. The mechanisms that cause the nerve damage are unknown. This report describes the consequences of a unique deletion mutation that eliminates the entire coding sequence of Cx 32, resulting in the absence of the Cx 32 gap junction protein in affected, hemizygous men. The clinical expression of this unique mutation was studied by the clinical, electrophysiological, and pathological evaluation of this kinship of five generations. The resulting severe neuropathy combines features of demyelination, notably in paranodal distribution, and distal accentuated axonal degeneration. The predicted absence of Cx 32 gap junctions is shown to be associated with a severe dysfunction of the axon-Schwann cell unit. Observed changes resemble those of Cx 32-null mice. No central nervous system changes were demonstrated.
Atrophy↗
[The effect of three kinds of anti-glaucoma eyedrops on ocular blood flow].
OBJECTIVE: Surveying the changes of ocular blood flow by continuous anti-glaucoma eyedrops for one week. METHODS: Thirty-two patients in glaucoma clinic were divided into three groups, one treated by 0.5% timolol, one by 0.5% levobunolol and the third by 0.1% dipivefrine, twice a day. Each patient got the retinal and choroidal angiography before and after the medication. We also made the intra- and inter-observer reproducibility test for verifying the credibility of the method used to determine the ocular blood flow. All the data were analyzed by Students't test. RESULTS: The reproducibility test revealed this method creditable. Timolol and levobunolol could decrease the choroidal blood flow significantly, there was a trend to decrease the optic nerve blood flow after continues application of timolol eyedrops. Dipivefrine did not induce any significant change on ocular blood flow except the mild artery constriction. CONCLUSION: The results suggest that it is necessary to be careful in choosing the anti-glaucoma eyedrops when ischemia plays an important role in glaucomatous damage.
Adult↗
[Infrared spectra and Raman spectra of monoclinic RblnS2 and CsInS2].
Monoclinic RbInS2 and CsInS2 were prepared by the traditional flux method and their IR and Raman spectra were studied. The IR and Raman absorption bands of CsInS2 shift to lower frequency compared with RbInS2. IR and Raman spectra show that monoclinic RbInS2 and CsInS2 exhibit good infrared transmission.
English Abstract↗
Suppression of glycogen synthase kinase activity is not sufficient for leukemia enhancer factor-1 activation.
Glycogen synthase kinase-3 (GSK) can be regulated by different signaling pathways including those mediated by protein kinase Akt and Wnt proteins. Wnt proteins are believed to activate a transcription factor leukemia enhancer factor-1 (LEF-1) by inhibiting GSK, and Akt was shown to phosphorylate GSK and inhibit its kinase activity. We investigated the effect of an activated Akt on the accumulation of cytosolic beta-catenin and LEF-1-dependent transcription. Although the activated Akt, mAkt, clearly inhibited the kinase activity of GSK, mAkt alone did not induce accumulation of cytosolic beta-catenin or activate LEF-1-dependent transcription. On the contrary, coexpressed Wnt-1 and Frat activated LEF-1 but did not show significant inhibition of GSK-mediated phosphorylation of a peptide substrate. However, mAkt could act synergistically with Wnt-1 or Frat to activate LEF-1. In addition, the interaction of GSK for Axin appeared to decrease in the presence of mAkt, whereas the interaction for Frat remained unchanged. Consistently, a GSK mutant with substitution of a Phe residue for residue Tyr-216, which showed one-fifth of kinase activity of the wild-type GSK, exhibited a reduced association for Axin than the wild-type GSK. These results suggest that inhibition of GSK kinase activity is not sufficient for activation of LEF-1 but may facilitate the activation by reducing the interaction of GSK for Axin. The additional mechanism for LEF-1 activation may require dissociation of GSK from Axin as Frat facilitates the dissociation of GSK from Axin.
3T3 Cells↗
A chiral rhodium complex for rapid asymmetric transfer hydrogenation of imines with high enantioselectivity.
[formula: see text] A chiral rhodium complex, (R)-Cp*RhCl[(1S,2S)-p-TsNCH(C6H5)CH(C6H5)NH2] (1a, (S,S)-Cp*RhClTsDPEN), generated from [Cp*RhCl2]2 and (1S,2S)-N-p-toluenesulfonyl-1,2-diphenylethylenediamine [(S,S)-TsDPEN], and its enantiomer 1b were found to provide superior catalysts for the rapid, high-yielding, asymmetric transfer hydrogenation of some heterocyclic imines, using an HCO2H-Et3N azeotrope as the hydrogen source.
Hydrogen↗
Axin and Frat1 interact with dvl and GSK, bridging Dvl to GSK in Wnt-mediated regulation of LEF-1.
Wnt proteins transduce their signals through dishevelled (Dvl) proteins to inhibit glycogen synthase kinase 3beta (GSK), leading to the accumulation of cytosolic beta-catenin and activation of TCF/LEF-1 transcription factors. To understand the mechanism by which Dvl acts through GSK to regulate LEF-1, we investigated the roles of Axin and Frat1 in Wnt-mediated activation of LEF-1 in mammalian cells. We found that Dvl interacts with Axin and with Frat1, both of which interact with GSK. Similarly, the Frat1 homolog GBP binds Xenopus Dishevelled in an interaction that requires GSK. We also found that Dvl, Axin and GSK can form a ternary complex bridged by Axin, and that Frat1 can be recruited into this complex probably by Dvl. The observation that the Dvl-binding domain of either Frat1 or Axin was able to inhibit Wnt-1-induced LEF-1 activation suggests that the interactions between Dvl and Axin and between Dvl and Frat may be important for this signaling pathway. Furthermore, Wnt-1 appeared to promote the disintegration of the Frat1-Dvl-GSK-Axin complex, resulting in the dissociation of GSK from Axin. Thus, formation of the quaternary complex may be an important step in Wnt signaling, by which Dvl recruits Frat1, leading to Frat1-mediated dissociation of GSK from Axin.
Adaptor Proteins, Signal Transducing↗
Molecular characterization of a ranavirus isolated from largemouth bass Micropterus salmoides.
An iridovirus, isolated from largemouth bass Micropterus salmoides following a die-off among adult fish and provisionally designated largemouth bass virus (LMBV), was characterized by analysis of viral protein synthesis in infected cells, viral DNA restriction fragment length polymorphisms (RFLP), and sequence determination of the major capsid protein and viral DNA methyltransferase genes. All 3 approaches yielded results consistent with the suggestion that LMBV was a member of the genus Ranavirus. Moreover, LMBV was nearly identical to 2 isolates from Southeast Asia which had been previously detected in imported ornamental fish. It remains to be determined whether infection of largemouth bass resulted from exposure to an imported virus, or whether the presence of similar viruses in southeast Asia and the southeastern United States indicates that iridovirus species are not geographically limited as suggested earlier, but rather globally distributed.
Amino Acid Sequence↗
Cellular mechanisms of neuropathic pain, morphine tolerance, and their interactions.
Compelling evidence has accumulated over the last several years from our laboratory, as well as others, indicating that central hyperactive states resulting from neuronal plastic changes within the spinal cord play a critical role in hyperalgesia associated with nerve injury and inflammation. In our laboratory, chronic constriction injury of the common sciatic nerve, a rat model of neuropathic pain, has been shown to result in activation of central nervous system excitatory amino acid receptors and subsequent intracellular cascades including protein kinase C translocation and activation, nitric oxide production, and nitric oxide-activated poly(ADP ribose) synthetase activation. Similar cellular mechanisms also have been implicated in the development of tolerance to the analgesic effects of morphine. A recently observed phenomenon, the development of "dark neurons," is associated with both chronic constriction injury and morphine tolerance. A site of action involved in both hyperalgesia and morphine tolerance is in the superficial laminae of the spinal cord dorsal horn. These observations suggest that hyperalgesia and morphine tolerance may be interrelated at the level of the superficial laminae of the dorsal horn by common neural substrates that interact at the level of excitatory amino acid receptor activation and subsequent intracellular events. The demonstration of interrelationships between neural mechanisms underlying hyperalgesia and morphine tolerance may lead to a better understanding of the neurobiology of these two phenomena in particular and pain in general. This knowledge may also provide a scientific basis for improved pain management with opiate analgesics.
Animals↗
hnRNP C and polypyrimidine tract-binding protein specifically interact with the pyrimidine-rich region within the 3'NTR of the HCV RNA genome.
Like other members of the Flaviviridae family, the 3' non-translated region (NTR) of the hepatitis C virus (HCV) is believed to function in the initiation and regulation of viral RNA replication by interacting with components of the viral replicase complex. To inves-tigate the possibility that host components may also participate in this process, we used UV cross-linking assays to determine if any cellular proteins could bind specifically to the 3'NTR RNA. We demonstrate the specific interaction of two host proteins with the extensive pyrimidine-rich region within the HCV 3'NTR. One host protein migrates as a doublet with a molecular weight of 57 kDa and is immunoreactive with antisera specific for polypyrimidine tract-binding protein (PTB), and the other protein (35 kDa) is recognized by a monoclonal antibody specific for heterogeneous nuclear ribonucleoprotein C (hnRNP C). These results suggest that recognition of the large pyrimidine-rich region by PTB and hnRNP C may play a role in the initiation and/or regulation of HCV RNA replication.
3' Untranslated Regions↗
Dishevelled proteins lead to two signaling pathways. Regulation of LEF-1 and c-Jun N-terminal kinase in mammalian cells.
Dishevelled (Dsh/Dvl) proteins are known to mediate Wnt signaling by up-regulating beta-catenin levels and stimulating T cell factor (TCF)/LEF-1-dependent transcription. We have identified a new Dvl-mediated signaling pathway in that mouse Dvl proteins, when expressed in COS-7 cells, stimulate c-Jun-dependent transcription activity and the kinase activity of the c-Jun N-terminal kinase (JNK). The DEP domain of Dvl1 is essential for JNK activation. By contrast, all three conserved domains of Dvl, including DIX, PDZ, and DEP, are required for up-regulation of beta-catenin and for stimulation of LEF-1-mediated transcription in mammalian cells. Thus, Dvl can lead to two different signaling pathways. Furthermore, the small G proteins of Cdc42 or Rac1, which are involved in JNK activation by many stimuli, do not appear to play a major role in Dvl-mediated JNK activation, because the dominant negative mutants of Cdc42 and Rac1 could not inhibit Dvl-induced JNK activation. This suggests that Dvl may activate JNK via novel pathways.
3T3 Cells↗
NMDA and opioid receptors: their interactions in antinociception, tolerance and neuroplasticity.
Over the last several years, significant progress has been made in our understanding of interactions between the N-methyl-D-aspartate (NMDA) and opioid receptors. Such interactions have been demonstrated at two distinct sites: (1) modulation of NMDA receptor-mediated electrophysiological events by opioids; and (2) intracellular events involving interactions between NMDA and opioid receptors. Furthermore, a considerable number of studies have shown the involvement of such interactions in neural mechanisms of nociceptive transmission, antinociception in acute and chronic pain states, opioid tolerance/dependence, and neuroplasticity. Importantly, emerging evidence indicates that activation of NMDA receptors may differentially modulate functions mediated by distinct opioid receptor subtypes, namely mu, delta, and kappa receptors. These studies have greatly enriched our knowledge regarding both NMDA and opioid receptor systems and have shed light on neurobiology of both acute and chronic pain. The advancement of such knowledge also promotes new strategies for better clinical management of pain patients.
Animals↗
Molecular characterization of iridoviruses isolated from sympatric amphibians and fish.
Iridoviruses infect invertebrates (primarily insects and crustaceans) and ectothermic vertebrates (fish, amphibians, and reptiles). Identical, or nearly identical viruses, have been isolated from different animals within the same taxonomic class, indicating that infection by a given virus is not limited to a single species. Although inter-class infections have been documented following experimental infection with vertebrate iridoviruses, it is not clear whether such infections occur in nature. Here we report the isolation of apparently identical iridoviruses from wild sympatric fish (the threespine stickleback, Gasterostelus aculeatus) and amphibians (the red-legged frog, Rana aurora). Viruses isolated from sticklebacks (stickleback virus, SBV) and from a red-legged frog tadpole (tadpole virus 2, TV2) replicated in fathead minnow (FHM) cells and synthesized proteins which co-migrated with those of frog virus 3 (FV3). Following restriction endonuclease digestion of viral DNA with Hind III and Xba I, gel analysis showed that the profiles of SBV and TV2 were identical to each other and distinct from FV3. Using oligonucleotide primers specific for a highly conserved region of the iridovirus major capsid protein, an approximately 500 nucleotide DNA fragment was amplified from SBV and TV2. Sequence analysis showed that within this 500 nucleotide region SBV and TV2 were identical to each other and to FV3. Taken together these results provide the first evidence that iridoviruses naturally infect animals belonging to different taxonomic classes, and strengthen the suggestion that fish may serve as a reservoir for amphibian viruses or vice versa.
Animals↗
Development of a parenteral formulation of an investigational anticancer drug, 3-aminopyridine-2-carboxaldehyde thiosemicarbazone.
The objective of this study was to develop an injectable formulation of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP) suitable for intravenous infusion. The solubility of 3-AP in different solvents and pH conditions was determined. The developed formulation underwent stability assessment and compatibility testing with large volume parenteral (LVP) solutions. The aqueous solubility of 3-AP was found to be 0.1 mg/ml and could only be increased marginally by altering the pH or adding surfactants. To achieve the desired concentration (> 4 mg/ml), 3-AP was formulated at 5-10 mg/ml in a nonaqueous system consisting of 70% polyethylene glycol 300 and 30% ethanol. However, 3-AP readily precipitated from this formulation when diluted with LVP solutions. Dilution-induced drug precipitation was eliminated by acidifying the solution with citric acid. Ascorbic acid, 0.1%, was found to minimize oxidative degradation of 3-AP. Accelerated stability data indicated that the formulation is compatible with the packaging components and is chemically stable at 2-8 degrees C, and retained > 90% of 3-AP at 40 degrees C for 3 months. Simulated infusion studies showed that the citric acid formulation was compatible with LVP solutions. However, because of the potential of extraction of plasticizers from polyvinyl chloride (PVC) plastic containers, it is recommended that the formulation be diluted in glass containers prior to administration.
Antineoplastic Agents↗
Reproductive, metabolic, and endocrine responses to feed restriction and GnRH treatment in primiparous, lactating sows.
The current experiment was carried out to determine whether exogenous GnRH treatment in primiparous, lactating sows undergoing feed restriction would improve reproductive performance after weaning. Sows were allocated to one of three treatments: AA sows (n = 8) were fed to appetite throughout a 28-d lactation, AR (n = 12) and AR + GnRH (n = 12) sows were fed as AA sows from farrowing to d 21 of lactation, and feed intake was reduced to 50% of the ad libitum intakes from d 22 to 28. The AR + GnRH sows received 800 ng of GnRH i.v. every 6 h from d 22 to 28 of lactation, and AA and AR sows received saline. Sow weight, backfat, and litter weight were recorded weekly. Within 2 d after farrowing, litter size was standardized to 8 to 10. At d 17 of lactation, an indwelling jugular catheter was surgically implanted in each sow. Blood samples were taken for characterization of plasma LH, FSH, insulin, IGF-I, and leptin by RIA at d 21 and before and after weaning on d 28 of lactation. After weaning, all sows were given ad libitum access to feed, checked for onset of standing estrus twice daily with mature vasectomized boars, and inseminated 12 and 24 h after onset of standing estrus with pooled semen from the same fertile boars (3 x 10(9) sperm/AI). After breeding, feed allowance was reduced to NRC (1988) requirements for gestation. At d 28 +/- 3 of gestation, sows were killed and ovulation rate and embryo survival were determined. Restricted sows lost more weight during lactation than AA sows (P < .02). During the period of feed restriction, plasma IGF-I and postprandial insulin and leptin in AR and AR + GnRH sows, and LH pulse frequency in AR sows, were lower than those in AA sows (P < .04). Associations (P < .004) between plasma insulin and leptin and between leptin and mean LH concentrations were established. The LH pulse frequency in AR + GnRH sows did not differ from that in AA sows before weaning. After weaning, maximum, mean, and minimum LH concentrations in the AA and AR sows, and FSH concentrations in AR sows, increased (P < .05) in response to weaning. Paradoxically, GnRH treatment in lactation seemed to suppress the expected LH and FSH responses to weaning. Ovulation rate and embryo survival were not different among the three groups. In conclusion, although exogenous GnRH therapy restored LH secretion in feed-restricted sows, it did not improve overall reproductive performance.
Adipose Tissue↗