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Biomedical subjects

A Swann

Publications and source records attributed to A Swann.

At least 37 records · Page 2Linked to original sources
PubMed2000

Pharmacotherapy of depression and mixed states in bipolar disorder.

The treatment of bipolar depression requires the resolution of depression and the establishment of mood stability. A basic problem is that the treatments used in treating bipolar depression were developed and proven effective for other disease states: antidepressants for unipolar depression, and mood stabilizers for mania. The panel addressed four unresolved questions regarding depression in relation to bipolar disorder: (1) the relative effectiveness of different antidepressant treatments; (2) the relative likelihood of mood destabilization with different antidepressant treatments; (3) the effectiveness and role of mood-stabilizing medicines as antidepressants; and (4) the optimal approach to mixed states. The selection of an antidepressant depends both on its relative lack of mania- or hypomania-provoking potential and on its effectiveness against bipolar depression. There is little definitive evidence distinguishing effectiveness of the major groups of antidepressive agents, so side-effect profiles and pharmacokinetics are major considerations. The underlying bipolar disorder should be treated with mood stabilizers started simultaneously with any antidepressive treatments. Lithium, divalproex sodium and carbamazepine have all been found to be helpful, to some extent, in treating bipolar depressive episodes as well as for long-term mood stabilization. There is little evidence for long-term benefits of antidepressive agents in bipolar disorder, and some evidence that they may destabilize the disorder. Therefore, in contrast to the long-term use of mood-stabilizers, antidepressant use is recommended on a temporary basis. The duration of antidepressant treatment is determined by past history in terms of liability for mood destabilization, and by the ability of the patient to tolerate gradual antidepressant discontinuation without return of depression. Mixed states, where symptoms of depression and mania coexist, are regarded as a predictor of relatively poor response to lithium, and divalproex has been found to be more effective. Carbamazepine may too be useful in mixed states. Most patients with mixed states in actual practice require combinations of mood stabilizers, though there is little controlled data regarding such co-prescription, especially from a long-term perspective.

Antidepressive Agents↗
PubMed2000

MK-801 blocks the development of sensitization to the locomotor effects of methylphenidate.

Male Sprague-Dawley rats were divided to three groups (each n = 8) and were housed in test cages where motor activity was recorded continuously for 16 days using a computerized motor activity monitoring system to determine whether repeated administration of MK-801 could block the development and/or the expression of sensitization to the locomotor effects of methylphenidate (MPD). One group of rats received six daily injections (days 4-9) of 0.30 mg/kg MK-801, followed by 5 days without injection (days 10-14) and re-challenged (day 15) with 0.30 mg/kg MK-801. The second group received a challenge dose of 2.5 mg/kg MPD (day 4) followed by 5 days of co-treatment with MK-801 (0.30 mg/kg) given 1 h prior to MPD (days 5-9). This group was then re-challenged with MPD (2.5 mg/kg) on day 15. The last group received six daily injections of 2.5 mg/kg MPD (days 4-9). They were then split into two subgroups of rats which received either no treatment (control) or five daily injections of 0.30 mg/kg MK-801 (days 10-14) before being re-challenged on day 15 with 2.5 mg/kg MPD. MK-801 sensitized to its own locomotor effects. MK-801 given after sensitization had developed (i.e., days 10-14) was able to mask the expression of a sensitized response on day 15, but the effect was only transient since the sensitized response was present 3 weeks later. Moreover, MK-801, when coadministered during the repeated treatment phase was able to block the development of a sensitized response, which suggest that NMDA receptors involved in the process of MPD sensitization.

Animals↗
PubMed1999

Diurnal differences in amphetamine sensitization.

A computerized motor activity monitoring system was used to investigate the development and time dependence of sensitization to repeated exposure of amphetamine. Male Sprague-Dawley rats were acclimated for 7 days to light/dark cycle (0700 h:1900 h) in the testing room, and were then housed in the test cages for 16 days of continuous recording. The locomotor responses to s.c. administration of amphetamine (0.3, 0.6, or 1.2 mg/kg) were compared before and after five daily injections of 0.6 mg/kg of amphetamine. Different groups of rats were administered drug at either 0800 h, 1400 h, 2000 h, or 0200 h. The locomotor indices studied were total distance and vertical activity. Sensitization was more pronounced for total distance (i.e., forward ambulation) than for vertical activity (i.e., rearing), and its expression was dependent on the challenge dose. Sensitization was also time-dependent, with the strongest sensitized response occurring during the middle of the dark cycle (0200 h). Repeated administration of amphetamine (0.6 mg/kg) did not cause post-stimulant depression as has been seen at higher doses.

Amphetamine↗
PubMed1999

Prolactin response to buspirone was reduced in violent compared to nonviolent parolees.

A neuroendocrine challenge procedure was carried out in male and female parolees. The parolees were divided into violent and non-violent groups based upon their criminal history. Buspirone (0.4 mg/kg), a 5-HT1a agonist, was used as the challenge agent and plasma prolactin levels were determined. The violent parolees had a blunted prolactin response compared to the non-violent parolees. While reduced serotonergic activity may account for this difference, the pharmacology of buspirone and control of prolactin release suggest a role for dopamine. A reduced serotonergic response would be consistent with a large body of data linking reduced serotonin function and aggressive behavior. While the mechanism is not definite, these data clearly provide evidence for an altered and blunted biological response in parolees with a history of violence.

Adult↗
PubMed1998

Dose-related effects of MK-801 on acute and chronic methylphenidate administration.

The non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist MK-801 has been shown to modulate both the effects of stimulants, such as amphetamine and cocaine, in producing locomotion and the chronic effects of stimulants in producing sensitization. In this study, we examine the interactions between MK-801 and the stimulant methylphenidate. Three different doses of MK-801 were administered 60 min prior to methylphenidate injection (2.5 mg/kg) and the acute response to MK-801 alone and the coadministration with methylphenidate were characterized. MK-801 alone was found to produce dose-dependent locomotor activation. The 0.15 mg/kg dose of MK-801 had no effect on the response to methylphenidate, while the 0. 3 and 0.6 mg/kg doses augmented the methylphenidate response. The effect of pretreatment with MK-801 on subsequent repeated methylphenidate administration was assessed. For all three doses tested, MK-801 pretreatment blocked the progressive locomotor sensitization expected during repeated methylphenidate administration. These findings suggest that MK-801 may exert a long-lasting effect on learning and memory process that result in a blocking of the development of sensitization.

Animals↗
PubMed1998

Diurnal differences in rat's motor response to amphetamine.

The dose-response characteristics and time-course of amphetamine's effect on motor activity after a single injection given to rats at four different times of the light/dark cycle was investigated using a computerized infrared motor activity recording system. After 7 days of acclimation and 2 days of baseline activity recording, rats received a single subcutaneous injection of vehicle (saline) or 0.6, 1.25 or 10 mg/kg amphetamine at 08.00, 14.00, 20.00 or 02.00. Recording was then resumed for an additional 36 to 48 h. The locomotor indices analyzed were horizontal activity, total distance, vertical activity, stereotypic activity and number of stereotypic movements. All doses (0.6. 1.25 and 10 mg/kg) significantly elevated (P < 0.01) locomotor activity compared to baseline at all times of administration. At all injection times, the maximum increase over baseline generally occurred following the 1.25 mg/kg dose of amphetamine (P < 0.001). The effect of the lower doses (0.6 and 1.25 mg/kg) on forward locomotion remained the same throughout the light/dark cycle regardless of the large difference in baseline motor activity between the light and dark phases. However, the effects of 10 mg/kg amphetamine on general stereotypic behavior, as well as the ability to cause subsequent depression of nocturnal forward ambulation, were dependent on the time of drug administration. These results showed that the circadian rhythms of locomotor and stereotypic effects of amphetamine are different.

Amphetamine↗
PubMed1998

Time-dependent differences in the rat's motor response to amphetamine.

The dose-related motor effects of d-amphetamine given at the beginning of the light and dark cycle of rats were investigated using a computerized activity-monitoring system that recorded five different motor behavior indices. After 7 days of acclimatization and 2 days of baseline monitoring, rats were randomized into either a no-treatment time control group (n = 12), or to receive 0 (vehicle), 0.6, 1.25, 2.5, or 10 mg/kg d-amphetamine (n = 8 each) either 1 h into the light phase (0800) or another five groups at 1 h into the dark phase (2000) of day 3. The time control group exhibited a stable baseline level of activity for the length of the experiment. All doses (0.6, 1.25, 2.5, and 10 mg/kg) significantly elevated (p < 0.01) locomotor activity compared to baseline at both times of administration, but not all motor indices followed the same pattern of response. At both injection times, the maximum increase over baseline generally occurred following the 1.25 mg/kg dose of amphetamine (p < 0.001). The duration of the drug effect also increased with each dose. The stereotypic effects produced by high doses of AMP (10 mg/kg) was different when applied at the light phase compared to the dark phase, but the amphetamine effect on locomotor behavior remained the same regardless of the difference in motor activity baseline between the activity phases.

Amphetamine↗
PubMed1997

Methylphenidate: diurnal effects on locomotor and stereotypic behavior in the rat.

The dose-response relationship and time course of effect on motor activity after a single dose of methylphenidate given at different times of the light/dark cycle was investigated using a computerized infrared activity analysis system. After 5 to 7 days of acclimation and 2 days of baseline activity recording, rats received a single subcutaneous injection of vehicle (saline) or of 0.6, 2.5, 10 or 40 mg/kg methylphenidate at 08:00, 14:00, 20:00, or 02:00. Recording was then resumed for an additional 36 to 48 hours. The locomotor indices analyzed were horizontal activity, total distance, vertical activity, stereotypic activity, and number of stereotypic movements. Saline and 0.6 mg/kg did not alter motor activity, but 2.5, 10 and 40 mg/kg significantly increased (P < 0.01) motor activity. The time to the maximum effect and the duration of effect increased with dose. Ten mg/kg had the most robust effect on locomotor activity, while the largest dose, 40 mg/kg, elicited a more focused stereotyped activity that limited the amount of forward ambulation. A single injection of methylphenidate had only transient effects. The locomotor stimulating effects of the lower doses were similar whether given during the light or dark phase, despite the large diurnal variations in baseline activity between the activity phases. The stereotypic effects of the highest dose of methylphenidate, however, varied between the light and dark phase, with a smaller stereotypic effect during the dark phase when compared to administration during the light phase.

Animals↗
PubMed1997

Different treatment regimens to reduce microbial contamination of purified porcine islets of Langerhans.

BACKGROUND: Different treatment regimens for minimizing microbial contamination of purified porcine islets were analyzed. METHODS: Purified islets, prepared from abattoir-excised pancreata (n=26), were cultured in Hams F-12 with or without antibiotics after islet isolation. Aliquots of pancreas transport media were all contaminated with microbes (100%). Of those islets cultured with no antibiotics, 70% were contaminated, compared with 42% of the islets cultured in penicillin and streptomycin (P/S) (P>0.05). A further 20 consecutive pancreata were then randomized to saline washing (N=10) before islet isolation. Islets were then cultured in either Hams F-12 with P/S (groups C and E) or Hams F-12 with gentamicin, penicillin, and amphotericin B (G/P/A) (groups D and F). RESULTS: None of those purified islets prepared from washed pancreata and then undergoing culture in Hams F-12 with G/P/A (group F) were contaminated. This compared with 30% contamination when islets were cultured in P/S (group E). Neither antibiotic regimen compromised stimulated insulin release (P=0.13). CONCLUSIONS: In conclusion pancreas washing in saline and culture in G/P/A was shown to eradicate detectable microbial contamination of purified porcine islets isolated from abattoir-excised pancreata.

Animals↗
PubMed1997

Effect size of efficacy measures comparing divalproex, lithium and placebo in acute mania.

Effect size (ES) is a statistical concept that can be used to improve the interpretation of results from psychopharmacological studies. ES may aid interpretation of results when sample size is unbalanced or small or when units or levels of baseline measures differ across items. Usually, an investigator can define a threshold value for a clinically meaningful ES based on published data and clinical judgment or by resorting to conventions, e.g., a medium ES = 0.5 S.D., which can usually be discerned by the trained clinician. In the present study, we apply ES analysis to results from a study comparing the effectiveness of divalproex (DIVAL), lithium (LI), and placebo (PLA) in hospitalized, acutely manic patients. One hundred seventy-six patients were randomly assigned to DIVAL, LI, or PLA in a 2:1:2 ratio, with drug administered in a double-blind, parallel group design for 21 days. The primary efficacy measure was the Mania Rating Scale from the Schedule for Affective Disorders and Schizophrenia, composed of the Manic Syndrome Score (MSS) from items that are relatively specific to the manic state, and the Behavior and Ideation Score (BIS), which reflects severe but nonspecific psychopathology. Improvement of the MSS after 5 days of treatment was difficult to interpret based on percentage change (DIVAL = 19%, LI = 13.5%, PLA = 8.5%). However, the corresponding effect sizes of 0.79, 0.55, and 0.35 indicated a medium to marked ES for DIVAL, a medium ES for LI, and a small ES for PLA at this early point in treatment. Similarly, the ES for change on the MSS at the end of treatment indicated a large, readily observable improvement with both DIVAL (ES = 1.01) and LI (ES = 0.79) vs. an ES of 0.37 for PLA. ES analysis also indicated that the BIS is a less robust indicator of change to either drug. The ES at the end of treatment for the BIS was 0.67 for DIVAL-, 0.62 for LI-, and 0.25 for PLA-treated patients.

Adolescent↗
PubMed1997

Context-dependent cross-sensitization between cocaine and amphetamine.

We investigated the effect of amphetamine pretreatment on the locomotor response to subsequent cocaine challenge. Rats were administered either 0.75 mg/kg amphetamine in a testing environment and saline in their home cage, saline in the testing environment and 0.75 mg/kg amphetamine in their home cage, or saline in both the testing environment and home cage. After 5 pairings of drug to environment, conditioning was tested by administration of a saline injection. Both amphetamine treated groups exhibited increased locomotion in response to saline injection. After the eighth session of the pairing regimen, all animals were administered 5 mg/kg cocaine in the test environment and their behavior measured for 30 min. Sensitization to cocaine was observed only in rats with previous amphetamine exposure in the testing environment. There was no difference between groups in whole brain, striatal, or plasma levels of cocaine. The data support the hypothesis that sensitization is independent of brain cocaine levels.

Amphetamine↗
PubMed1997

Sensitization to locomotor effects of methylphenidate in the rat.

A computerized activity monitoring system was used to investigate whether repeated exposure to methylphenidate (MPD) could produce sensitization to its locomotor effects in the rat. Male Sprague-Dawley rats were housed in test cages and activity was recorded continuously for 16 days as follows: Baseline activity (Day 1-2), recording following saline injection (Day 3), MPD Challenge Doses--either 0.6, 2.5, or 10 mg/kg of MPD (Day 4); five days of a repeated dose of 2.5 mg/kg (Day 5-9), five additional recording days of no treatment (Days 10-14), and MPD Re-Challenge (Day 15). Each group was re-challenged with the same doses as on day 4. Recording was resumed for an additional post-treatment day (Day 16). All injections were at 14:00. Horizontal activity, total distance, vertical activity, stereotypic activity, and number of stereotypic movements were recorded and analyzed. An augmented response (i.e., sensitization) was observed only to the lower MPD doses of 0.6 and 2.5 mg/kg. The sensitized response was more pronounced for forward ambulation than for rearing, with a complete lack of sensitization to the stereotypic effects of MPD.

Animals↗
PubMed1997

Behavioral sensitization to cocaine in the absence of altered brain cocaine levels.

We conducted experiments investigating the role of altered cocaine distribution in behavioral sensitization. The first was designed to determine whether carry-over from one injection to the next occurs after acute cocaine administration. Female, Sprague-Dawley rats were administered 5 mg/kg 3H-cocaine and 24 h later were challenged with either 5 mg/kg unlabeled cocaine or saline. Animals were sacrificed 15 min after drug administration. There was no difference between groups in cocaine levels in brain, liver, or plasma, thus indicating that carry-over did not occur following acute cocaine administration. The second experiment was designed to determine whether bound cocaine could be released following acute or multiple dose cocaine administration. In the acute dose study, animals were administered either 20 mg/kg cocaine or saline, challenged 24 h later with 5 mg/kg 3H-cocaine, and sacrificed 5 min after drug administration. Animals with previous cocaine experience exhibited a significant increase in the number of rearings. The groups did not differ in brain or plasma cocaine levels. In the multiple dose study, animals were injected daily for 4 days with 20 mg/kg cocaine or saline, challenged with 5 mg/kg 3H-cocaine on day 5, and sacrificed 10 min after drug administration. Animals with previous cocaine experience exhibited significantly greater locomotor activity and number of rearings. There was no difference between groups in cocaine levels in various brain regions, plasma, or liver. Brain cocaine content in various regions was significantly correlated, though heterogeneously distributed within the various regions. The highest cocaine levels were found in hippocampus, striatum, thalamus/hypothalamus, and cortex. These results provide further evidence that behavioral sensitization is not the result of cocaine redistribution following repeated administration.

Animals↗
PubMed1997

Does hippocampal atrophy on MRI predict cognitive decline? A prospective follow-up study.

OBJECTIVES: To investigate whether the presence of hippocampal atrophy (HCA) on MRI in Alzheimer's disease (AD) leads to a more rapid decline in cognitive function. To investigate whether cognitively unimpaired controls and depressed subjects with HCA are at higher risk than those without HCA of developing dementia. DESIGN: A prospective follow-up of subjects from a previously reported MRI study. SETTING: Melbourne, Australia. PARTICIPANTS: Five controls with HCA and five age-matched controls without HCA, seven depressed subjects with HCA and seven without HCA, and 12 subjects with clinically diagnosed probable AD with HCA and 12 without HCA were studied. They were followed up at approximately 2 years with repeat cognitive testing, blind to initial diagnosis and MRI result. MEASURES: HCA was rated by two radiologists blind to cognitive test score results. Cognitive assessment was by the Cambridge Cognitive Examination (CAMCOG). RESULTS: No significant differences in rate of cognitive decline, mortality or progression to dementia were found between subjects with or without HCA. CONCLUSIONS: HCA was not found to be a predictor of subsequent cognitive decline in this series.

Aged↗