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Biomedical subjects

E Curran

Publications and source records attributed to E Curran.

At least 19 recordsLinked to original sources
PubMed2002

Abused drugs modulate RGS4 mRNA levels in rat brain: comparison between acute drug treatment and a drug challenge after chronic treatment.

While different classes of abused drugs interact with distinct signaling substrates, it appears that all utilize receptors in the mesolimbic dopamine system to mediate their reinforcing effects. The regulator of G-protein signaling (RGS) proteins modulate G-protein coupled receptor (GPCR) signaling by increasing the rate of GTP hydrolysis of G proteins. This study was undertaken to determine whether morphine, cocaine, or amphetamine would modulate RGS4 mRNA levels in relevant brain regions. Acute administration of morphine and cocaine decreased levels of RGS4 mRNA in the reticulotegmental pontine nucleus (RtTg) and locus coeruleus (LC). Increases in RGS 4 mRNA levels were observed in the nucleus accumbens (NAc) and dorsal central gray (CGD). Acute drug challenge after chronic drug administration increased RGS4 mRNA in the CGD and decreased RGS4 levels in the red nucleus and RtTg. Interestingly, the LC exhibited biphasic modulation, with decreased RGS4 mRNA levels after acute administration and increased levels after chronic administration. These findings indicate that RGS4 mRNA levels are modulated in a similar manner by different drugs of abuse and imply that a common substrate could mediate some effects of abused drugs.

Animals↗
PubMed2000

Expression analysis of BACE2 in brain and peripheral tissues.

Beta-site amyloid precursor protein cleaving enzyme (BACE) is a novel transmembrane aspartic protease that possesses all the known characteristics of the beta-secretase involved in Alzheimer's disease (Vassar, R., Bennett, B. D., Babu-Khan, S., Kahn, S., Mendiaz, E. A., Denis, P., Teplow, D. B., Ross, S., Amarante, P., Loeloff, R., Luo, Y., Fisher, S., Fuller, J., Edenson, S., Lile, J., Jarosinski, M. A., Biere, A. L., Curran, E., Burgess, T., Louis, J. -C., Collins, F., Treanor, J., Rogers, G., and Citron, M. (1999) Science 286, 735-741). We have analyzed the sequence and expression pattern of a BACE homolog termed BACE2. BACE and BACE2 are unique among aspartic proteases in that they possess a carboxyl-terminal extension with a predicted transmembrane region and together they define a new family. Northern analysis reveals that BACE2 mRNA is expressed at low levels in most human peripheral tissues and at higher levels in colon, kidney, pancreas, placenta, prostate, stomach, and trachea. Human adult and fetal whole brain and most adult brain subregions express very low or undetectable levels of BACE2 mRNA. In addition, in situ hybridization of adult rat brain shows that BACE2 mRNA is expressed at very low levels in most brain regions. The very low or undetectable levels of BACE2 mRNA in the brain are not consistent with the expression pattern predicted for beta-secretase.

Amino Acid Sequence↗
PubMed2000

Identification and characterization of proSAAS, a granin-like neuroendocrine peptide precursor that inhibits prohormone processing.

Five novel peptides were identified in the brains of mice lacking active carboxypeptidase E, a neuropeptide-processing enzyme. These peptides are produced from a single precursor, termed proSAAS, which is present in human, mouse, and rat. ProSAAS mRNA is expressed primarily in brain and other neuroendocrine tissues (pituitary, adrenal, pancreas); within brain, the mRNA is broadly distributed among neurons. When expressed in AtT-20 cells, proSAAS is secreted via the regulated pathway and is also processed at paired-basic cleavage sites into smaller peptides. Overexpression of proSAAS in the AtT-20 cells substantially reduces the rate of processing of the endogenous prohormone proopiomelanocortin. Purified proSAAS inhibits prohormone convertase 1 activity with an IC(50) of 590 nM but does not inhibit prohormone convertase 2. Taken together, proSAAS may represent an endogenous inhibitor of prohormone convertase 1.

Adrenal Glands↗
PubMed2000

Do health care workers need to wear masks when caring for patients with pulmonary tuberculosis?

Outbreaks of hospital acquired tuberculosis (TB) in the 1990s, some of which affected staff, highlight the fact that TB still poses a risk to health care workers (HCWs). This risk is best minimised by the primary controls of early identification and treatment, good infection control practice such as early isolation, patients covering mouths when coughing, and engineering controls such as negative pressure isolation. There is no direct evidence to prove that the use of respiratory protective devices has prevented HCWs from acquiring TB, but modelling has shown that environmental controls are not enough to prevent exposure. Masks that filter aerosols (including TB) and have at least 95% efficiency of filtering particles 0.3 micron in diameter can reduce exposure. Environmental controls in the United Kingdom (UK) do not (always) include a specified minimum number of air-changes per hour or negative pressure. Therefore it seems reasonable to advise that HCWs should use masks as advocated by national guidelines for high risk procedures. Masks are also of value when entering any body cavity or dissecting any viscus/organ in which TB is suspected, as in the necropsy room or operating theatre. This is recommended in current guidelines from the United States but not those from the UK.

Guidelines as Topic↗
PubMed1999

Beta-secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE.

Cerebral deposition of amyloid beta peptide (Abeta) is an early and critical feature of Alzheimer's disease. Abeta generation depends on proteolytic cleavage of the amyloid precursor protein (APP) by two unknown proteases: beta-secretase and gamma-secretase. These proteases are prime therapeutic targets. A transmembrane aspartic protease with all the known characteristics of beta-secretase was cloned and characterized. Overexpression of this protease, termed BACE (for beta-site APP-cleaving enzyme) increased the amount of beta-secretase cleavage products, and these were cleaved exactly and only at known beta-secretase positions. Antisense inhibition of endogenous BACE messenger RNA decreased the amount of beta-secretase cleavage products, and purified BACE protein cleaved APP-derived substrates with the same sequence specificity as beta-secretase. Finally, the expression pattern and subcellular localization of BACE were consistent with that expected for beta-secretase. Future development of BACE inhibitors may prove beneficial for the treatment of Alzheimer's disease.

Alzheimer Disease↗
PubMed1999

Intra-articular tenoxicam improves postoperative analgesia in knee arthroscopy.

PURPOSE: Non Steroidal Anti-inflammatory drugs have a well documented benefit in the relief of postoperative pain. This study was designed to compare the analgesic effect of intra-articular tenoxicam 20 mg with intravenous tenoxicam on postoperative pain in 88 patients undergoing day case knee arthroscopy. METHODS: A prospective, double blind, randomized trial was performed. All patients received a standard general anesthetic. Patients in group A received 20 mg tenoxicam made up to 40 ml with normal saline intra-articularly (ia) and 2 ml normal saline i.v. Patients in group B received 40 ml normal saline intra-articularly and 2 ml, 20 mg of tenoxicam, i.v. RESULTS: Both groups of patients were similar with respect to age, weight, sex and tourniquet inflation time. Patients receiving ia tenoxicam had lower pain scores (at rest and upon movement) at 30, 60, 120 and 180 min postoperatively (0.8+/-0.2 vs. 2.5+/-0.2 at rest and 1.24+/-0.2 vs. 3.4+/-0.2 at movement at 60 min; P< 0.0001). Fewer patients required additional analgesia in the first four hours postoperatively (33% vs. 84%; P<0.00001) and the time to first analgesia (23.7+/-11.2 vs. 9.4+/-0.6; P<0.02) was longer in those receiving ia tenoxicam. CONCLUSION: Intra-articular tenoxicam provides superior postoperative analgesia and reduces postoperative analgesic requirements compared with i.v. tenoxicam in patients undergoing day case knee arthroscopy.

Adult↗
PubMed1994

Fatal nosocomial Legionnaires' disease: relevance of contamination of hospital water supply by temperature-dependent buoyancy-driven flow from spur pipes.

The investigation, epidemiology, and effectiveness of control procedures during an outbreak of Legionnaires' disease involving three immunosuppressed patients are described. The source of infection appeared to be a network of fire hydrant spurs connected directly to the incoming hospital mains water supply. Removal of these hydrants considerably reduced, but failed to eliminate, contamination of water storage facilities. As an emergency control procedure the incoming mains water was chlorinated continuously. Additional modifications to improve temperature regulation and reduce stagnation also failed to eliminate the legionellae. A perspex test-rig was constructed to model the pre-existing hospital water supply and storage system. This showed that through the hydraulic mechanism known as 'temperature buoyancy', contaminated water could be efficiently and quickly exchanged between a stagnant spur pipe and its mains supply. Contamination of hospital storage tanks from such sources has not previously been considered a risk factor for Legionnaires' disease. We recommend that hospital water storage tanks are supplied by a dedicated mains pipe without spurs.

Adult↗
PubMed1989

Solvent dependency of rotational barriers in ethamivan and comparison to nikethamide.

Carbon-13 nuclear magnetic resonance (NMR) techniques were employed to examine the effects of solvent environment on rotational barriers in two drugs known to cause widespread stimulation in the mammalian central nervous system: ethamivan and nikethamide. Total NMR bandshape analysis was performed for the exchanging alkyl carbon resonances of these compounds as a function of temperature in six solvent systems: D2O, CH3OD, CH3CH2OD, CDCl3, C6D6 and CF3CH2OH. The rate constants for rotation about the amide bond obtained in this way were used to calculate free energy (delta G++), enthalpy (delta H++) and entropy (delta S++) of activation parameters for this process. Our results indicate that the magnitude of rotational barriers is affected markedly by (1) the size and polarity of the solvent molecules, and (2) the nature of the aromatic ring system attached to the amide grouping. Comparative interpretation of the thermodynamic parameters in light of the structures of nikethamide and ethamivan (in the various solvent systems examined) has further clarified the manner in which hydrogen bonding interactions between solvent molecules and the carbonyl oxygen of these analogues stabilize transition state conformers.

Acetonitriles↗
PubMedDate not supplied

Reducing the risk of healthcare-acquired infection.

Many patients experience increased hospital stays, poor health outcomes, or die each year, as a result of healthcare-acquired infections. Evonne Curran discusses the most common types of infection and suggests how nurses can minimise the risks of infection in clinical settings.

Anti-Bacterial Agents↗
PubMedDate not supplied

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