PubMed Health⌕ Search

Biomedical subjects

Patricia Murphy

Publications and source records attributed to Patricia Murphy.

At least 19 recordsLinked to original sources
PubMed2006

The heat-shock protein 90 inhibitor 17-allylamino-17-demethoxygeldanamycin suppresses glial inflammatory responses and ameliorates experimental autoimmune encephalomyelitis.

The heat-shock response (HSR), a highly conserved cellular response, is characterized by rapid expression of heat-shock proteins (HSPs), and inhibition of other synthetic activities. The HSR can attenuate inflammatory responses, via suppression of transcription factor activation. A HSR can be induced pharmacologically by HSP90 inhibitors, through activation of the transcription factor Heat Shock Factor 1 (HSF1). In the present study we characterized the effects of 17-allylamino-17-demethoxygeldanamycin (17-AAG), a less toxic derivative of the naturally occurring HSP90 inhibitor geldanamycin, on glial inflammatory responses and the development of experimental autoimmune encephalomyelitis. In primary enriched glial cultures, 17-AAG dose dependently reduced lipopolysaccharide-dependent expression and activity of inducible nitric oxide synthase, attenuated interleukin (IL)-1beta expression and release, increased inhibitor of kappaB protein levels, and induced HSP70 expression. 17-AAG administration to mice immunized with myelin oligodendrocyte glycoprotein peptide prevented disease onset when given at an early time, and reduced clinical symptoms when given during ongoing disease. T cells from treated mice showed a reduced response to immunogen re-stimulation, and 17-AAG reduced CD3- and CD28-dependent IL-2 production. Together, these data suggest that HSP90 inhibitors could represent a new approach for therapeutic intervention in autoimmune diseases such as multiple sclerosis.

Animals↗
PubMed2006

The ketogenic diet causes a reversible decrease in activity level in Long-Evans rats.

Individuals with epilepsy also often exhibit symptoms of attention deficit hyperactivity disorder (ADHD). The ketogenic diet, which is a high fat, low protein, and low carbohydrate diet used in the treatment of intractable epilepsy, also appears to improve symptoms of ADHD in individuals with both disorders. Previous research suggests that the diet decreases the activity level of rats. The purpose of the present research was to further investigate the effects of the ketogenic diet on activity level, using an animal model. Two experiments were conducted. The first experiment examined the time frame and reversibility of the effect of the diet on activity level. The second experiment examined the relationship between activity level and anxiety level. In both experiments, adult male Long-Evans rats were placed on either a ketogenic diet or a control diet. The results of the first experiment show that the ketogenic diet can cause a decrease in activity level within 24 h and that the results are reversible. The results of Experiment 2 show that the decrease in activity level is not linked to a change in anxiety level. The ketogenic diet may be of use in the treatment of ADHD.

Animals↗
PubMed2006

Canadian guidelines for training in adult perioperative transesophageal echocardiography. Recommendations of the Cardiovascular Section of the Canadian Anesthesiologists' Society and the Canadian Society of Echocardiography.

PURPOSE: To establish Canadian guidelines for training in adult perioperative transesophageal echocardiography (TEE). METHODS: Guidelines were established by the Canadian Perioperative Echocardiography Group with the support of the cardiovascular section of the Canadian Anesthesiologists' Society (CAS) in conjunction with the Canadian Society of Echocardiography. Guidelines for training in echocardiography by the American Society of Echocardiography, the American College of Cardiology and the Society of Cardiovascular Anesthesiologists were reviewed, modified and expanded to produce the 2003 Quebec expert consensus for training in perioperative echocardiography. The Quebec expert consensus and the 2005 Guidelines for the provision of echocardiography in Canada formed the basis of the Canadian training guidelines in adult perioperative TEE. RESULTS: Basic, advanced and director levels of expertise were identified. The total number of echocardiographic examinations to achieve each level of expertise remains unchanged from the 2002 American Society of Echocardiography-Society of Cardiovascular Anesthesiologists guidelines. The increased proportion of examinations personally performed at basic and advanced levels, and the level of autonomy at the basic level suggested by the Quebec expert consensus are retained. These examinations can be performed in a perioperative setting and are not limited to intraoperative TEE. Training "on the job", the role of the perioperative transesophageal echocardiography examination, requirements for maintenance of competence, and duration of training are also discussed for each level of training. The components of a TEE report and comprehensive TEE examination are also outlined. CONCLUSION: The Canadian guidelines for training in adult perioperative TEE reflect the unique Canadian practice profile in perioperative TEE and address the training requirements to obtain expertise in this field.

Adult↗
PubMed2006

Canadian guidelines for training in adult perioperative transesophageal echocardiography. Recommendations of the Cardiovascular Section of the Canadian Anesthesiologists' Society and the Canadian Society of Echocardiography.

PURPOSE: To establish Canadian guidelines for training in adult perioperative transesophageal echocardiography (TEE). METHODS: Guidelines were established by the Canadian Perioperative Echocardiography Group with the support of the cardiovascular section of the Canadian Anesthesiologists' Society in conjunction with the Canadian Society of Echocardiography. Guidelines for training in echocardiography by the American Society of Echocardiography, the American College of Cardiology and the Society of Cardiovascular Anesthesiologists were reviewed, modified and expanded to produce the 2003 Quebec expert consensus for training in perioperative echocardiography. The Quebec expert consensus and the 2005 guidelines for the provision of echocardiography in Canada formed the basis of the Canadian training guidelines in adult perioperative TEE. RESULTS: Basic, advanced and director levels of expertise were identified. The total number of echocardiographic examinations to achieve each level of expertise remains unchanged from the 2002 American Society of Echocardiography and the Society of Cardiovascular Anesthesiologists guidelines. The increased proportion of examinations personally performed at basic and advanced levels, as well as the level of autonomy at the basic level suggested by the Quebec expert consensus are retained. These examinations may be performed in a perioperative setting and are not limited to intraoperative TEE. Training 'on-the-job', the role of the perioperative TEE examination, the requirements for maintenance of competence and the duration of training are also discussed for each level of training. The components of a TEE report and comprehensive TEE examination are also outlined. CONCLUSION: The Canadian guidelines for training in adult perioperative TEE reflect the unique Canadian practice profile in perioperative TEE and address the training requirements to obtain expertise in this field.

Adult↗
PubMed2006

Adding bupivacaine to high-potassium cardioplegia improves function and reduces cellular damage of rat isolated hearts after prolonged, cold storage.

BACKGROUND: Bupivacaine retards myocardial acidosis during ischemia. The authors measured function of rat isolated hearts after prolonged storage to determine whether bupivacaine improves cardiac protection compared with standard cardioplegia alone. METHODS: After measuring cardiac function on a Langendorff apparatus, hearts were perfused with cardioplegia alone (controls), cardioplegia containing 500 microm bupivacaine, or cardioplegia containing 2 mm lidocaine; were stored at 4 degrees C for 12 h; and were then reperfused. Heart rate and left ventricular developed pressures were measured for 60 min. Maximum positive rate of change in ventricular pressure, oxygen consumption, and lactate dehydrogenase release were also measured. RESULTS: All bupivacaine-treated, four of five lidocaine-treated, and no control hearts beat throughout the 60-min recovery period. Mean values of heart rate, left ventricular developed pressure, maximum positive rate of change in ventricular pressure, rate-pressure product, and efficiency in bupivacaine-treated hearts exceeded those of the control group (P < 0.001 at 60 min for all). Mean values of the lidocaine group were intermediate. Oxygen consumption of the control group exceeded the other groups early in recovery, but not at later times. Lactate dehydrogenase release from the bupivacaine group was less than that from the control group (P < 0.001) but did not differ from baseline. CONCLUSIONS: Adding bupivacaine to a depolarizing cardioplegia solution reduces cell damage and improves cardiac function after prolonged storage. Metabolic inhibition may contribute to this phenomenon, which is not entirely explained by sodium channel blockade.

Anesthetics, Local↗
PubMed2005

Are germinal inclusion cysts markers of ovulation?

OBJECTIVES: Germinal inclusion cysts (GICs) of the ovary are possible precursor lesions for epithelial ovarian cancer. These cysts have been postulated to form as stigmata of ovulation. It is known that oral contraceptives, breastfeeding, and pregnancy, which decrease lifetime ovulations, confer protection against epithelial ovarian cancer. This study was undertaken to determine if ovarian density of epithelial inclusion cysts corresponds to a woman's frequency of ovulation. METHODS: One hundred two cases of women undergoing incidental oophorectomy at the time of surgery for benign gynecological conditions were interviewed for information relating to ovulation. Review of multiple sections of ovarian tissue was performed to count numbers of GICs. RESULTS: There was a modest correlation between the average number of germinal inclusion cysts and ovulatory age (Spearman's rho = 0.2, P = 0.06). There were fewer GICs in current smokers and ever-users of oral contraceptives; however these associations were not significant (P > 0.1). CONCLUSIONS: This study showed increased numbers of GICs in women of greater ovulatory age, and those who were not current smokers or ever used oral contraceptives. This provides some evidence that GICs may be caused by ovulation. The small number of subjects limited our ability to evaluate associations.

Adult↗
PubMed2005

Breaking the cycles of violence.

Violence begets violence and it is important to understand how cycles of violence are perpetuated if we are to find solutions to the global problems they present. A multi-disciplinary group of The International Work Group on Death, Dying and Bereavement has developed a model of the cyclical events that perpetuate violence at all levels including the family, community, nation, and world. This includes the Violent Act(s), the Perception of the Violent Act(s), the Immediate Response, Legitimising Authority, Destructive Codes, and Inflammatory/Polarising Strategies. It is possible at each point to break the cycle, examples are given and recommendations made.

Conflict, Psychological↗
PubMed2005

A controlled 2-mo dietary fat reduction and soy food supplementation study in postmenopausal women.

BACKGROUND: Low intake of dietary fat and high intake of soy foods have been suggested to partly explain the lower breast cancer rates in Asia, perhaps because of lower endogenous estrogens. OBJECTIVE: The objective was to assess the hormonal and nonhormonal effects of diets resembling an Asian diet in terms of total fat and soy food contents. DESIGN: Fifty-seven postmenopausal women participated in a randomized, controlled, dietary intervention study. The subjects consumed a very-low-fat diet (VLFD; 11% of energy as fat), a Step I diet (25% of energy as fat) supplemented with soy food (SFD; 50 mg isoflavones/d), or a control Step I diet (CD; 27% of energy as fat) with no soy food. All diets were prepared at the General Clinical Research Center of the University of Southern California. Serum hormones and other markers were measured at baseline and every 2 wk during the 8 wk of intervention. RESULTS: There were no significant differences in total estradiol and sex hormone binding globulin at the completion of the intervention between women in the SFD and VLFD groups and those in the CD group. Serum insulin decreased significantly in the SFD group, and leptin decreased significantly in the SFD and VLFD groups; however, these changes did not differ significantly from the changes in the CD group. CONCLUSIONS: This study does not provide evidence that ingestion of soy food or a VLFD significantly reduces estrogen concentrations in postmenopausal women. However, short-term changes in diet may have significant and beneficial effects on blood insulin and leptin concentrations.

Dietary Fats↗
PubMed2005

Use of the ketogenic diet as a treatment for epilepsy refractory to drug treatment.

The ketogenic diet is a high-fat, low-carbohydrate and low-protein diet used in the treatment of epilepsy that does not respond to antiepileptic drugs. The diet has been found to be very effective in treating intractable epilepsy in children. There is also some evidence that the diet is useful in treating drug-resistant epilepsy in infants, adolescents and adults. This paper traces the history and development of the ketogenic diet and reviews the clinical and animal research investigating its effects.

Animals↗
PubMed2004

The antidepressant properties of the ketogenic diet.

BACKGROUND: The ketogenic diet is used to treat epilepsy refractory to anticonvulsant medication. Individuals with epilepsy often have behavioral problems and deficits in attention and cognitive functioning. The ketogenic diet has been found to effect improvements in these domains. It has also been suggested that the ketogenic diet may act as a mood stabilizer. METHODS: The present research used the Porsolt test, an animal model of depression, to determine whether the ketogenic diet has antidepressant properties. Porsolt test scores of rats on the ketogenic diet were compared with those of rats on a control diet. RESULTS: The rats on the ketogenic diet spent less time immobile, suggesting that rats on the ketogenic diet, like rats treated with antidepressants, are less likely to exhibit "behavioral despair." CONCLUSIONS: It is concluded that the ketogenic diet may have antidepressant properties.

3-Hydroxybutyric Acid↗
PubMed2004

Effect of the ketogenic diet on the activity level of Wistar rats.

Children, adolescents, and adults with epilepsy often also show symptoms associated with attention-deficit/hyperactivity disorder (ADHD). The ketogenic diet, which is administered to children with epilepsy refractory to drug therapy, seems to improve behavior in individuals with symptoms of ADHD. The basis for this improvement is unknown, although it seems to be unrelated to seizure control. The present research was designed to investigate the effect of two ketogenic diets on the behavior of normal adult male rats. Two experiments were conducted. In experiment 1, 36 subjects were placed on one of three diets: a control diet, a 6.3:1 ketogenic diet, and a 4:1 ketogenic diet. In experiment 2, 20 subjects were placed either on a control diet or on a 4:1 ketogenic diet. The activity level of each subject was measured using an open field test. Time spent immobile, grooming, and in exploratory behavior was measured for 600 s. Subjects were tested once before initiation of the diets and once while on the diets. No significant group differences were found in activity level before initiation of the diets. After initiation of the diets, subjects in both ketogenic groups showed a significantly lower activity level than the rats on the control diet. The ketogenic diet decreases activity level in an animal model. This behavioral change may relate to the improved behavior seen when children with symptoms of ADHD are placed on the diet.

Adolescent↗
PubMed2004

A novel interaction of Cap-binding protein complexes eukaryotic initiation factor (eIF) 4F and eIF(iso)4F with a region in the 3'-untranslated region of satellite tobacco necrosis virus.

Satellite tobacco necrosis virus (STNV) RNA is naturally uncapped at its 5' end and lacks polyadenylation at its 3' end. Despite lacking these two hallmarks of eukaryotic mRNAs, STNV-1 RNA is translated very efficiently. A approximately 130-nucleotide translational enhancer (TED), located 3' to the termination codon, is necessary for efficient cap-independent translation of STNV-1 RNA. The STNV-1 TED RNA fragment binds to the eukaryotic cap-binding complexes, initiation factor (eIF) 4F and eIF(iso)4F, as measured by nitrocellulose binding and fluorescence titration. STNV-1 TED is a potent inhibitor of in vitro translation when added in trans. This inhibition is reversed by the addition of eIF4F or eIF(iso)4F, and the subunits of eIF4F and eIF(iso)4F cross-link to STNV-1 TED, providing additional evidence that these factors interact directly with STNV-1 TED. Deletion mutagenesis of the STNV-1 TED indicates that a minimal region of approximately 100 nucleotides is necessary to promote cap-independent translation primarily through interaction with the cap binding subunits (eIF4E or eIF(iso)4E) of eIF4F or eIF(iso)4F.

3' Untranslated Regions↗
PubMed2003

Anticonvulsant properties of acetone, a brain ketone elevated by the ketogenic diet.

The ketogenic diet (KD), a treatment for drug-resistant epilepsy, elevates brain acetone. Acetone has been shown to suppress experimental seizures. Whether elevation of acetone is the basis of the anticonvulsant effects of the KD and whether acetone, like the KD, antagonizes many different types of seizures, however, is unknown. This study investigated the spectrum of the anticonvulsant effects of acetone in animal seizure models. Rats were injected with acetone intraperitoneally. Dose-response effects were measured in four different models: (1) the maximal electroshock test, which models human tonic-clonic seizures; (2) the subcutaneous pentylenetetrazole test, which models human typical absence seizures; (3) the amygdala kindling test, which models human complex partial seizures with secondary generalization; and (4) the AY-9944 test, which models chronic atypical absence seizures, a component of the Lennox-Gastaut syndrome. Acetone suppressed seizures in all of the models, with the following ED(50)'s (expressed in mmol/kg): maximal electroshock, 6.6; pentylenetetrazole, 9.7; generalized kindled seizures, 13.1; focal kindled seizures, 26.5; AY-9944, 4.0. Acetone appears to have a broad spectrum of anticonvulsant effects. These effects parallel the effects of the KD. Elevation of brain acetone therefore may account for the efficacy of the KD in intractable epilepsy.

Acetone↗
PubMed2003

The effect of kindled seizures on the locomotory behavior of Long-Evans rats.

The incidence of attention deficit hyperactivity disorder (ADHD) is higher in children with epilepsy than in the general childhood population. The origin of the symptoms of ADHD seen in children with epilepsy is unknown. This experiment used an animal model to investigate whether seizures could be a cause of the hyperactivity sometimes associated with epilepsy. Sixteen male Long-Evans rats were implanted with electrodes, and 8 of them were kindled until generalized stage 5 seizures were elicited. Eight subjects were handled, but not kindled. The behavior of the rats in the two groups was compared in an open field test. The time spent in four behaviors was measured: exploratory behavior, immobility, eating, and grooming. Rats were tested after 5 stage 5 seizures, after 10 stage 5 seizures, after 15 stage 5 seizures, after a 2-week rest period, and after 5 more stage 5 seizures. Data were analyzed using the Mann-Whitney rank sum test. Twenty-four hours after a seizure, the kindled rats displayed a greater level of exploratory behavior than did the controls. They were not found to differ on any other measure. After a 2-week rest period, the group difference in behavior disappeared. When kindling was reinitiated, the kindled rats again showed increased exploratory behavior. The findings suggest that the increased exploratory behavior found in the kindled rats resulted from recent seizure activity. It may be that the hyperactivity seen in some children with epilepsy also results from recent seizure activity.

Animals↗