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Biomedical subjects

D Kirby

Publications and source records attributed to D Kirby.

At least 37 records · Page 2Linked to original sources
PubMed1997

Anxiolytic activity of NPY receptor agonists in the conflict test.

This investigation examined receptor subtype specificity and possible modulation by GABAa receptor ligands of NPY-induced behavioral responses to stressful stimuli. First, a series of NPY receptor agonists were examined for their potential effects on punished responding in a conflict test modified for incremental shock. NPY, peptide YY (PYY) and NPY Y1 receptor agonists [Leu31,Pro34]-NPY and [Gly6, Glu26,Lys26,Pro34]-NPY produced increases in punished responding in the conflict test. No significant effects on unpunished responding were noted. The pattern of responding was similar to that observed with the benzodiazepine agonist chlordiazepoxide. Neither pancreatic peptide (PP) nor the Y2 agonists NPY13-36 or [Glu2,32,Ala6,Dpr27,Lys28]-NPY significantly altered punished or unpunished responding. Of significance, the atypical Y1 agonist [Cys7,21,Pro34]-NPY produced negligible effects on punished responding, consistent with the presence of a subclass of Y1 receptors. Second, the anxiolytic effects of NPY were subjected to treatments that block actions at the GABAa receptor complex. The increase in punished responding produced by NPY was not altered by administration of the benzodiazepine antagonist flumazenil and only partially blocked by the picrotoxinin receptor ligand isopropylbicyclophosphate (10 and 15 microg/kg). These findings further support the hypothesis that the pharmacologic substrates for the anxiolytic-like actions of NPY may be mediated by the Y1 receptor subtype and suggest that these actions are independent of either the benzodiazepine or picrotoxinin binding sites of the GABA/benzodiazepine receptor complex.

Animals↗
PubMed1997

Electrophysiological actions of neuropeptide Y and its analogs: new measures for anxiolytic therapy?

Neuropeptide Y (NPY) has neuromodulatory actions on multiple brain functions including endocrine, behavioral, and circadian processes. Behavioral studies suggest that NPY is a potent anxiolytic; however, little is known about how NPY affects general arousal and/or attention states. The present study evaluated the effects of NPY on spontaneous brain activity as well as auditory processing by using electrophysiological measures. Electroencephalographic (EEG) and event-related potentials (ERPs) were obtained in awake animals after intracerebroventricular administration of NPY (1.0, 3.0 nmol) and two of its analogs, active at Y1 (1.0, 3.0 nmol) and Y2 (1.0, 3.0 nmol) receptor sites. NPY was found to produce dose-related effects on electrophysiological measures. Spectral analyses of the EEG revealed that NPY produced slowing of delta activity (1-2 Hz) in the frontal cortex and high frequency theta activities (6-8 Hz) concomitant with a speeding up of low frequency theta (4-6 Hz) in cortex, hippocampus, and amygdala. At higher doses (3.0 nmols) in addition to shifts in frequency, EEG power was also significantly reduced in all frequencies (0.5-50 Hz) in cortex, and in the higher frequencies (8-32 Hz) in the amygdala. The Y1 and Y2 agonists had a somewhat different profile of EEG effects than the parent compound. At the 1 nmol dose both agonists were found to produce selective depressions in power in the hippocampus. The 3.0 nmols dose of the Y1 agonist produced decreases in EEG stability, an effect commonly produced by anxiolytic drugs, whereas the Y2 agonist produced increases in EEG stability in cortex and amygdala. Auditory processing, as assessed by ERPs, was affected most significantly in the frontal cortex where dose-dependent decreases in the N1 component of the ERP, a finding also commonly seen after anxiolytics, was found. Y1 and Y2 agonists were also found to significantly reduce the amplitude of the N1 component of the ERP but less so than the parent compound. The electrophysiological and behavioral profiles of NPY and the Y1 agonist resembles those of anxiolytics such as ethanol and benzodiazepines. Taken together these data suggest that electrophysiological measures of the actions of this peptide system may represent a new potentially useful assay for the development of anxiolytic drugs.

Amygdala↗
PubMed1997

The safer choices project: methodological issues in school-based health promotion intervention research.

Randomized trials of school-based health promotion programs present unique design and analytical issues not widely discussed in the research literature. This article describes the Safer Choices study--a school-based program for prevention of HIV, other sexually transmitted diseases, and pregnancy--to illustrate critical methodological issues involved in large-scale, school-based intervention trials, particularly those evaluating interventions with a school-wide focus. The issues presented are: 1) comparability of the intervention and control groups even when few units are randomized; 2) factors that affect the decision to use a cohort or cross-sectional design; and 3) appropriate analysis strategy when the unit of randomization and intervention is at the school level, but observations are at the student level.

Adolescent↗
PubMed1997

An impact evaluation of project SNAPP: an AIDS and pregnancy prevention middle school program.

OBJECTIVES: A theory-based curriculum designed to delay the onset of intercourse and increase use of condoms was implemented in the classrooms of six Los Angeles middle schools. METHODS: The curriculum activities were very interactive, emphasized skill building, and were implemented by well trained peer educators, including young HIV-positive males and teen mothers. To evaluate the impact of the curriculum, 102 classrooms of students were randomly assigned to receive either the existing curriculum or the existing curriculum plus the intervention curriculum. Students completed confidential questionnaires before program implementation, five months later, and 17 months later. A total of 1,657 students completed both the baseline and 17-month follow-up questionnaires. RESULTS: Analyses of these data revealed that the curriculum significantly increased knowledge, significantly improved only two out of 21 attitudes or beliefs, and did not significantly change sexual or contraceptive behaviors. CONCLUSIONS: Well implemented programs that are based on upon theory, use interactive activities, and utilize well-trained peer educators do not always change important sexual attitudes and behaviors among middle school youth.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Safer Choices: a multicomponent school-based HIV/STD and pregnancy prevention program for adolescents.

Given the serious consequences of HIV infection, other STDs, and pregnancy among teens, professionals must develop and evaluate new approaches to reduce risks associated with adolescent sexual behavior. The Safer Choices intervention is a comprehensive, theoretically based program designed to reduce risk behaviors and increase protective behaviors to prevent HIV, other STDs, and pregnancy among high school adolescents. The program includes five components: a School Health Promotion Council involving administrators, school staff, students, parents, and community members; curriculum and staff development activities; school environment activities designed and implemented by a team of peer educators; parent education activities; and school-community linkage activities. The School Health Promotion Council is responsible for planning and overseeing program implementation. This article describes the theoretical framework, process for intervention development, and key intervention strategies used in Safer Choices.

Adolescent↗
PubMed1994

Incorporation of hydrophobic selectivity in capillary electrophoresis: analysis of recombinant insulin-like growth factor I variants.

A highly selective electrophoretic system employing differential hydrophobic interaction was evaluated for the quantitative determination of recombinant insulin-like growth factor I (IGF-I) variants. The system consisted of mixed aqueous-organic buffers containing suitable amounts of a zwitterionic detergent. In addition, a neutral hydrophilic coating was attached to the wall of the capillary to minimize analyte adsorption and electroosmotic flow. The zwitterionic detergent acted as a hydrophobic selector, allowing independent optimization of the electrophoretic and hydrophobic selectivities in the separation system. The extent of hydrophobic interaction was conveniently adjusted by varying the type and amount of organic modifier. Complete resolution of a mixture of IGF-I variants with closely related mass-to-charge ratios was achieved. Quantitative analysis of IGF-I process samples agreed well with HPLC results. Finally, the approach was found to be compatible with on-line capillary electrophoresis-mass spectrometry.

Amino Acid Sequence↗
PubMed1993

Increased blood levels of methyl tert-butyl ether but not of ethyl propionate during instillation with contact gallstone dissolution agents in the pig.

We performed experiments in anesthetized piglets with two cholesterol gallstone solvents, methyl tert-butyl ether and ethyl propionate, to determine whether blood levels of either solvent would increase during gallbladder instillation of these solvents under conditions simulating gallstone dissolution. The solvent was oscillated rapidly in and out of the gallbladder with a computer-controlled syringe pump; intraluminal pressure was set below the leakage pressure, and oscillating volume was set below the leakage volume to decrease loss of solvent into the intestine. Blood levels were measured with gas chromatography. Six piglets received methyl tert-butyl ether, and six piglets received ethyl propionate. During 2 hr of instillation with methyl tert-butyl ether, blood levels increased steadily to concentrations averaging 0.3 ml/L blood at 2 hr; during a 6-hr period of instillation, blood levels rose to above 0.4 ml/L blood. Replacement of methyl tert-butyl ether with saline solution in the gallbladder caused blood levels to decline gradually; plasma levels decreased by half in 90 min. In contrast, when ethyl propionate was infused for 2 or 6 hr, blood levels remained below the detection limit, probably because of high first-pass hepatic extraction. We conclude that, under conditions simulating those likely present in patients undergoing contact dissolution of gallbladder stones, the two solvents differ: Ethyl propionate is removed so rapidly from blood that its levels remain undetectable, whereas methyl tert-butyl ether levels in blood (and, presumably, peripheral tissues) increase continuously.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Structural requirements for neuropeptide Y18-36-evoked hypotension: a systematic study.

It has been shown that NPY and select C-terminal fragments of NPY that evoke a hypotensive response upon intraarterial administration in the rat also cause mast cell degranulation and histamine release in vitro. Additionally, elevation of plasma histamine levels has been observed concomitant with the hypotensive effect of NPY and various C-terminal fragments. In order to investigate whether the hypotensive response to NPY18-36 is correlated to this observed elevation of histamine in vivo, we sought to characterize the structural requirements for each activity. We conducted a systematic replacement of each amino acid in NPY18-36 by its D-isomer. Additionally, various modifications were made to the N- or C-terminii of NPY18-36. The following rank order of potency was obtained for the hypotensive action of these analogues of NPY18-36 relative to NPY18-36. Only one analogue ([D-Tyr21]NPY18-36) exhibited significantly enhanced potency. Eleven analogues of NPY18-36, ([D-Thr32]-, [D-Arg35]-, [D-Ile31]-, [D-Leu30]-, [D-Tyr27]-, [D-Ser22]-, [D-Tyr36]-, [D-Gln34]-, [D-Asn29]-, [D-Ala23]-, and [D-Arg33]NPY18-36) were equipotent with NPY18-36. Four analogues ([D-His26]-, [D-Ile28]-, and [D-Ala18]NPY18-36 and -NPY18-27) had reduced potency (10-80%) while eight analogues ([D-Arg19]-, [D-Tyr20], [D-Leu24]-, [D-Arg25]-, [Ac-Ala18]-, [Me-Ala18]-, [desamino-Ala18]NPY18-36 and NPY18-36 free acid) failed to produce a significant hypotensive response (less than 10%) at the doses tested. The sensitivity of NPY18-36 to chiral inversion of single residues or other modifications at the N-terminus suggested the presence of a conformationally well defined N-terminal pharmacophore. Additionally, five NPY18-36 analogues were tested for elevation of plasma histamine levels. The rank order of potency ([D-Thr32]NPY18-36 = [D-Tyr21]NPY18-36 much greater than NPY18-36 greater than [D-Ala18]NPY18-36 greater than [Ac-Ala18]NPY18-36) was correlated with each analogue's potency at evoking a hypotensive response. In contrast, NPY1-36 failed to evoke an elevation in plasma histamine levels despite its hypotensive effects. Hence, we conclude that the magnitude of the hypotensive response evoked by an NPY18-36 analogue is primarily a function of its ability to elevate plasma histamine levels. However, the mechanism underlying NPY1-36-evoked hypotension appears to be different.

Animals↗
PubMed1992

School-based programs to reduce sexual risk-taking behaviors.

This article reviews the major approaches implemented during the last two decades to reduce sexual risk-taking behaviors, examines their evidence for success, and provides several recommendations for effective programs and program evaluations. This article does not discuss more broad-based sexuality education programs which address sexuality in a broader context. Instead, this article focuses primarily on programs that educators believed would reduce unprotected sexual intercourse.

Adolescent↗
PubMed1987

D-xylose absorption and disposition in patients with moderately impaired renal function.

D-Xylose kinetics were studied after oral and intravenous administration to 10 patients with impaired renal function, three of whom were being evaluated for intestinal malabsorption. The 0.32 +/- 0.06 L/kg (mean +/- SD) distribution volume of D-xylose in patients with uncomplicated renal impairment was larger than the value of 0.23 +/- 0.04 L/kg that we reported previously for normal subjects (P less than 0.01). Renal clearance was also reduced, averaging 87% of glomerular filtration rate estimated from creatinine clearance, so that the elimination-phase half-life was prolonged to 138 +/- 39 minutes from 75 +/- 11 minutes in normal individuals (P less than 0.01). The 25 gm oral D-xylose dose was 77.4% +/- 14.8% absorbed in the patients with uncomplicated renal impairment, similar to the 69.4% +/- 13.6% absorption reported in normal individuals. However, the absorption half-life was prolonged from 31 +/- 12 minutes in normal subjects to a value of 62 +/- 23 minutes (P less than 0.02). Of the usual clinical indexes of D-xylose absorption, the serum concentration measured 1 hour after the oral dose was best correlated with the extent of D-xylose absorption (r = 0.76; P less than 0.01), and the standard lower normal limit of 0.2 mg/ml was satisfactory.

Adult↗