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Biomedical subjects

M Gilbert

Publications and source records attributed to M Gilbert.

At least 271 records · Page 15Linked to original sources
PubMedDate not supplied

Identification of detomidine carboxylic acid as the major urinary metabolite of detomidine in the horse.

Horse urine was investigated for metabolites by chromatography and mass spectrometry following the oral administration of the large animal analgesic sedative detomidine to two stallions and intravenous administration of [3H]-detomidine to a mare. Detomidine carboxylic acid and hydroxydetomidine glucuronic acid conjugate were identified in the urine after the oral doses. In addition, traces of free hydroxydetomidine were observed. About half of the radioactivity of [3H]-detomidine was excreted in the urine in 12 h after the i.v. dose (80 micrograms/kg). Most of the excretion occurred between 5 and 12 h in contrast to urine output which was highest 2-5 h after the dosing. The major radioactive metabolite in the urine was detomidine carboxylic acid. It comprised more than two thirds of the total metabolites in all the urine fractions collected. Its excretion profile was similar to that of total radioactivity. Hydroxydetomidine glucuronide was also excreted. It contributed 10-20% of the total metabolites in the urine. The free aglycone was only seen in the samples collected during the peak urine flow. A minor metabolite was tentatively characterized as the glucuronide of N-hydroxydetomidine.

Analgesics↗
PubMedDate not supplied

Differential effects of long chain n-3 fatty acids on the expression of PGH synthase isoforms in bovine aortic endothelial cells.

Primary cultures of bovine aortic endothelial cells were used at confluency to evaluate the effect of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids on the expression of both the constitutive and inducible isoforms of PGH synthase (PGHS), PGHS-1 and PGHS-2, respectively. After a 22 h period enrichment of cell lipid stores with each fatty acid, the expression of PGH synthase isoforms was measured by western blotting. EPA and DHA, but not oleate, significantly decreased the immunoreactive PGHS-1 and to a similar extent the corresponding mRNA, as measured by northern blotting. Studies on mRNA stability failed to show any difference between DHA-enriched and control cells, indicating that the decreased expression observed was likely from transcriptional origin. Under the enrichment conditions, EPA and DHA, but not oleate, moderately but significantly induced an oxidative stress as judged by malondialdehyde formation. Interestingly, hydrogen peroxide was able to mimic the effect of EPA and DHA in decreasing the expression of PGHS-1. On the other hand, the PMA-induced PGHS-2 expression could be potentiated by cell pre-enrichment with DHA, whereas hydrogen peroxide alone could induce such an expression. We conclude that the long chain n-3 fatty acids EPA and DHA may differently affect the expression of PGH synthase isoforms, possibly via an oxidative stress.

Animals↗
PubMedDate not supplied

Effect of ultrasonication on the stability of oligonucleotides adsorbed on nanoparticles and liposomes.

In the present study, oligonucleotides were adsorbed onto the surface of cationic liposomes and nanoparticles at different ratios. As a result, the surface charges of the colloidal carriers were decreased with increasing oligonucleotide concentration. At a certain oligonucleotide concentration, complete charge neutralization led to the aggregation of the carrier systems. Further increasing oligonucleotide concentrations reversed the surface charge of liposomes and nanoparticles to a negative one. Ultrasonication was investigated as a possible means for the homogenization of the formed aggregates. However, the use of ultrasonication led to a time-dependent damage of oligonucleotides adsorbed onto AH-Chol liposomes and MMAEMC-nanoparticles, as well as of unbound oligonucleotides. Nearly 60% of the oligonucleotides adsorbed to MMAEMC-nanoparticles and 65% of ODNs adsorbed to the liposomes were degraded by the effect of cavitation produced by ultrasonication within 10 min. In contrast, the oligonucleotides were protected from degradation when DEAE-stabilized PHCA-nanoparticles were employed as ODN carriers. More than 80% of the oligonucleotides entangled in the surface matrix of these nanoparticles remained intact.

Cyanoacrylates↗
PubMedDate not supplied

Management of the patient with a pituitary tumor resection.

The resection of a pituitary tumor represents a challenging diagnosis for the critical care nurse. There are important nursing assessments that can assist in identifying post-surgical complications. Detailed teaching instructions by the critical care nurses will also assist in minimizing the patient's postoperative complications.

Critical Care↗
PubMedDate not supplied

Halogenated general anesthetics in visual photoreceptor membranes as examined by static and dynamic properties of rhodopsin.

The visual pigment rhodopsin was used as an intrinsic probe to measure the effect of incorporation of enflurane into bovine rod outer segment disk membranes. At moderately low enflurane concentration, we find that, while extrinsic probes show little membrane perturbation, rhodopsin may experience large changes with respect to the native lipid-protein interactions which modulate some of its properties. Enflurane induces a small blue shift in the pigment lambda max and a strong inhomogeneity in its photochemical behavior. As a function of enflurane concentration, there appears to be an increasing population of rhodopsin molecules for which the metarhodopsin I-->II transition is blocked, while it is accelerated in the remaining population. Under these conditions, electrophoresis and partial membrane solubilization indicate that an increasing amount of rhodopsin does not behave like a free monomeric species. These results are all consistent with a reduction of the membrane order accompanied by lateral aggregation of rhodopsin in the presence of enflurane. By comparison with the perturbation probed by a spin label, the large molecular environment change experienced by the rhodopsin molecule suggests that enflurane may concentrate at the lipid-protein interface.

Animals↗
PubMedDate not supplied

Stimulation of transcriptional regulatory activity by substance P.

The neuropeptide substance P (SP) is one of the principal mediators of neurogenic inflammation as well as a neurotransmitter in nociceptive affect neurons. The mechanisms by which binding of SP to its receptor stimulates diverse downstream biologic effects remain unknown. In order to elucidate this process we have established stably transfected cell lines expressing functional rat SP receptors (KNRK-SPR). When stimulated by SP, KNRK-SPR cells respond by simultaneously mobilizing intracellular Ca2+ and increasing cAMP levels. To determine if SP stimulation activates downstream transcriptional regulatory factors, we transfected KNRK-SPR cells with plasmids containing the activator protein 1 (AP-1) and cAMP-responsive (CRE) enhancer elements coupled to the chloramphenicol acetyltransferase (CAT) reporter gene. Stimulation with SP 1-1,000 nM caused a 1.5- to 2-fold increase in CAT activity in both AP-1-CAT- and CRE-CAT-transfected KNRK-SPR cells. Northern and Western blot analyses demonstrate that the mechanism by which SP stimulates AP-1 enhancer activity involves increases in both c-jun mRNA and protein. Moreover, gel retardation assays with oligomers containing the AP-1 and CRE binding sites showed that SP induces specific retardation bands consistent with increases in AP-1 and CRE complexes. These experiments suggest that SP-mediated stimulation of cells involves the participation of two signaling pathways resulting in several transcriptional regulatory mechanisms being activated.

Animals↗
PubMedDate not supplied

Microbial growth patterns in a total parenteral nutrition formulation containing lipid emulsion.

Microbial growth of Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Candida albicans was evaluated in a standard amino acid-dextrose-based total parenteral nutrition (TPN) solution, 10% lipid emulsion, and a combined TPN formulation containing amino acids, dextrose, and lipid emulsion. At an initial inoculum of 10(4) CFU/ml, all three bacterial organisms grew well in 10% lipid emulsion, died in the standard solution and grew only minimally or died in the combined formulation. C. albicans grew in all three formulations at an initial inoculum of 10(4) CFU/ml; however, at an initial inoculum of 10(2) CFU/ml, which approximates touch contamination, growth of Candida in the standard and combined formulations was less than 1 log at 24 hr in contrast to the 10% lipid emulsion which showed significant growth greater than 2 log at 24 hr. It is concluded that a 24-hr infusion time is safe for the combined TPN formulation used in this study. This should result in significant cost savings compared to the previously recommended 12-hr infusion time.

Bacteria↗
PubMedDate not supplied

Temporal and spatial regulation of the expression of BAD2, a MAP kinase phosphatase, during seizure, kindling, and long-term potentiation.

Recent studies indicate that stimulation of NMDA receptors in cultured hippocampal cells activates MAP kinase. Although the pathway whereby MAP kinase is activated has been been characterized, little is known about the mechanisms that shut off MAP kinase. In the course of analyzing several immediate-early genes identified previously by differential screen as inducible by seizure activity, we found that one of them, BAD2, encodes dual purpose, threonine/tyrosine phosphates with specific activity directed against MAP kinase (MKP-1). In situ hybridization of BAD2 demonstrates that stimuli that produce seizure, kindling, and long-term potentiation cause a rapid increase in BAD2 mRNA (within 0.5-1 hr after stimulation) that has, in each case, a distinctive pattern of expression in the brain. In these regions, the induction of a MAP kinase-specific phosphatase may provide a negative feedback control associated with long-term synaptic changes.

Amino Acid Sequence↗
PubMedDate not supplied

Correlation of tumor p53 and PCNA with response and survival of glioblastoma in patients treated with an ECOG protocol of pre-irradiation chemotherapy.

BACKGROUND: The ability to predict treatment responsiveness and survival of patients with glioblastoma multiforme, the most malignant and most common primary brain tumor, would be a valuable asset. Tumor and proliferation markers such as p53 and PCNA have been immunohistochemically defined and have been useful in other tumors in determining prognosis. Therefore, the authors studied the correlation of responsiveness to treatment, time to progression and survival with p53 and PCNA labeling indices in a pre-irradiation chemotherapy study of the glioblastoma multiforme. METHODS: Immunohistopathology for labeling indices for p53 and PCNA using formalin-fixed, paraffin-embedded tissue from the glioblastomas of 23 patients entered into a phase II ECOG trial of pre-irradiation chemotherapy were defined using the streptavidin-peroxidase technique with AEC chromogen. The labeling indices were correlated with response to treatment time to progression and overall survival. Most patients received three cycles of BCNU for three days over three months and cisplatin monthly for three days over three months prior to external beam irradiation. RESULTS: There were no significant differences in treatment response, time to progression or overall survival in glioblastoma, patients with positive p53 labeling index (> 5%) versus a negative p53 labeling index (< or = 5%) or positive PCNA labeling (> 10%) versus a negative labeling index (< or = 10%) or any combination of P53 and PCNA labeling indices. CONCLUSIONS: Using this protocol of pre-irradiation chemotherapy, p53 and PCNA labeling indices in the glioblastoma multiforme did not predict treatment benefit.

Adult↗
PubMedDate not supplied

Determining the relationship between end-of-life decisions expressed in advance directives and resuscitation efforts during cardiopulmonary resuscitation.

In recent years, there has been an increased focus on end-of-life decisions and the use of medical technology. It is not well documented in the literature whether or not and to what extent patients' advance directives are used for directing resuscitative efforts. The purpose of this study was to determine how useful patients' advance directives were to members of the health care team in determining treatment and end-of-life decisions among patients who received cardiopulmonary resuscitation (CPR) efforts. Medical records of 135 adult patients who had undergone CPR efforts within the previous year were reviewed to determine if and to what extent advance directives were useful in directing end-of-life care and treatment decisions. Only 35 of these patients had advance directives. Three categories for advance directives emerged: those that were "independently directive," those that were "vague and required further clarification," and those that were "nondirective." Information from this study may be used to clarify treatment options for end-of-life care and to determine if and what further interventions are required to ensure that advance directives can be executed as meaningful documents.

Advance Directive Adherence↗