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Biomedical subjects

K Mueller

Publications and source records attributed to K Mueller.

At least 73 records · Page 4Linked to original sources

Time course of amphetamine-induced locomotor stereotypy in an open field.

Gamma (gamma) is a recently proposed statistic that quantifies and describes the repetitive patterns of locomotion (locomotor stereotypy) exhibited by amphetamine-treated rats in an open field. The time-course of locomotor stereotypy after 1, 2, 3, and 4 mg/kg amphetamine was investigated in this research. Locomotor stereotypy was often evident during the first observation period after amphetamine. Lower doses of amphetamine produced qualitatively different locomotor stereotypy than higher doses. Rats given higher doses of amphetamine exhibited locomotor stereotypy during the "hyperactivity" phase of the three-phase response produced by higher doses of amphetamine (hyperactivity; absence of locomotions, increased sniffing, biting etc.; hyperactivity). Contrary to expectations, rats injected with 2 mg/kg amphetamine exhibited the highest and most sustained increase in gamma. We conclude that locomotor stereotypy is an important component of the behavioral effects of amphetamine in rats. Whether locomotor stereotypy and focused stereotypy are similar phenomena is still unclear.

Amphetamine↗

Effects of caerulein + haloperidol on amphetamine-induced locomotor stereotypy in rats.

The combination of haloperidol + caerulein has been reported to produce a long-lasting reduction of amphetamine-induced hyperlocomotions in rats. This study was designed to replicate those findings and to determine whether haloperidol + caerulein produce any unique effect on amphetamine-induced locomotor stereotypy. In two experiments, haloperidol + caerulein failed to produce a long-lasting reduction in amphetamine-induced hyperlocomotions. Although haloperidol reduced the locomotor stereotypy produced by higher doses of amphetamine, caerulein had no effect, either alone or combined with haloperidol.

Amphetamine↗

Illness behavior and personality changes in patients with chronic prostatitis during a two-year follow-up period.

Illness behavior and personality changes during a 2-year follow-up period were studied in 40 patients with chronic prostatitis. In the first study, the existence of psychic problems among the subjects was high. Sexual problems were striking. During the follow-up period the personality of the patients did not change, but subjective well-being, both psychosocial and somatic, was impaired. Sexual problems and homosexual behavior also increased. In addition, the cooperation of the patients markedly decreased and their illness behavior became problematic. The results indicate a strong need for psychic support of these patients.

Adult↗

The pharmacological profile of CGP 28238, a novel highly potent anti-inflammatory compound.

CGP 28238 (6-(2,4-difluorophenoxy)-5-methylsulfonylamino-1-indanone ) exhibits very potent anti-inflammatory activity in rat adjuvant arthritis (ED40 = 0.05 mg/kg, p.o.) and pronounced analgesic and antipyretic activity in acute models in mice and rats (ED50 2-5 mg/kg, p.o.), but has clear advantages over reference NSAIDs with respect to gastro-intestinal tolerability. Threshold doses for gastro-intestinal ulcerogenicity in rats after single and repeated (10x) doses were found to be 30 mg/kg, p.o., and prostaglandin (PGE2) production in rat gastric and ileal mucosa was only marginally inhibited (ED50 greater than 30 mg/kg, p.o.). On the other hand, PGE2 production in rat inflammatory exudate and thromboxane synthesis in rat blood were inhibited with ED50 values of less than or equal to 2 mg/kg, p.o. Although CGP28238 does not inhibit cyclooxygenase in bovine seminal vesicle microsomal preparations (IC50 greater than 10(-3) mol/l), potent inhibition of prostaglandin synthesis was shown in various in vitro systems using human and animal cells with IC50 values of less than 10(-6) mol/l. IL-1-stimulated bone resorption and PGE2 production in murine calvarial cultures were inhibited with IC50 values of 3 x 10(-7) and 2 x 10(-8) mol/l, respectively. 5-Lipoxygenase (murine macrophages), phospholipase A2 (human PMN) and phospholipase C (human platelets) were not inhibited. CGP 28238 may represent a novel highly potent anti-inflammatory compound with improved gastro-intestinal safety.

Analgesics↗

Patterns of locomotor and stereotypic behavior during continuous amphetamine administration in rats.

The present study examined the behavioral effects of continuous subcutaneous infusion of amphetamine (AMPH) to rats. Saline and 3 AMPH doses were infused for 96 hr (0.2 mg/kg/hr, 0.55 mg/kg/hr, 0.9 mg/kg/hr; n = 12). Locomotor behavior, grooming, gnawing and licking, sniffing, and head-bobbing were recorded for each animal for 1 hr in the light cycle and 1 hr in the dark cycle. The low dose AMPH animals exhibited increased locomotor activity. The medium and high dose groups developed similar behavioral patterns consisting of increased grooming and sniffing and changes in circadian rhythms of activity. Although most behaviors exhibited were similar to those discussed in previous literature describing the effects of chronic amphetamine, the pattern of the behaviors was not. Furthermore, continuous administration of AMPH seems to reliably increase the frequency of behaviors which are rarely observed after acute or chronic amphetamine. This finding has important implications since administration of AMPH to rats has been suggested to be an animal model of schizophrenia.

Amphetamine↗

Stroke rehabilitation outcome: impact of coronary artery disease.

The frequency of clinically significant coronary artery disease (CAD) among stroke patients and the impact of CAD on stroke rehabilitation were studied in 132 patients with first thrombotic or embolic stroke who participated in comprehensive rehabilitation. Sixty-one patients (46%) had a history of CAD, and 16 of the 61 also had congestive heart failure (CAD-CHF). Patients with CAD, and especially those with CAD-CHF, had significantly longer intervals from stroke onset to rehabilitation admission (p less than 0.001), and once in rehabilitation they experienced three times as many cardiac complications (p less than 0.001). While all patient groups improved function during rehabilitation, those with CAD and CAD-CHF improved significantly less than did those without CAD (p less than 0.01). Patients with CAD did least well with rolling, moving in bed, transferring from a wheelchair to bed, and walking. CHF not only adversely influenced overall function and mobility task performance but also affected the potential for achieving functional gains. These data suggest that specific measures of function and rehabilitation are affected by CAD and that the levels of achievement for patients with CAD-CHF are limited.

Aged↗

Voltammetric evidence in vivo of cholinergic modulation of extracellular ascorbic acid and uric acid in rat striatum.

The cholinergic agonist pilocarpine (2 and 4 mg/kg) produced a dose-related increase in striatal AA levels as measured by linear sweep voltammetry. The cholinergic antagonist scopolamine (0.5 and 0.6 mg/kg) blocked the pilocarpine-induced increase in AA levels, but methscopolamine (which does not cross the blood-brain barrier) reduced the pilocarpine effect only by about 20%. Pilocarpine alone had little effect on UA levels. Scopolamine (0.6 mg/kg) produced a dramatic increase in UA levels that was reduced by pilocarpine. Methscopolamine had little effect (less than 10%) on extracellular UA levels. Thus cholinergic drugs modulate striatal extracellular AA levels by predominantly central rather than peripheral effects.

Animals↗

The effects of serotonin depletion on the voltammetric response to amphetamine.

In vivo voltammetry with carbon paste electrodes reliably produces two oxidation peaks. Previous research suggests that in caudate peak 1 (P1) monitors ascorbic acid and peak 2 (P2) monitors uric acid. To provide additional evidence that P2 monitors uric acid rather than indoles, the effects of the serotonin synthesis inhibitor p-chlorophenylalanine (PCPA) were studied in caudate (serotonin-poor) and globus pallidus (serotonin-rich). In both caudate and globus pallidus PCPA had little effect on P2 and pretreatment with PCPA failed to inhibit the amphetamine-induced increase in P2. In general, P2 recorded from globus pallidus was always very similar to P2 recorded from caudate. These data are consistent with the hypothesis that P2 represents uric acid even in serotonin-rich areas of the brain. Pretreatment with PCPA dramatically enhanced the amphetamine-induced increase in P1 in caudate but not in globus pallidus. This finding is interesting in light of reports that PCPA enhances certain behavioral effects of amphetamine.

Amphetamine↗

Effects of haloperidol on amphetamine-induced increases in ascorbic acid and uric acid as determined by voltammetry in vivo.

Amphetamine produces dramatic changes in extracellular ascorbic acid (AA) and uric acid (UA) in rat caudate; the origin of extracellular AA and UA is being widely investigated. In this study, linear sweep voltammetry with carbon paste electrodes was used to monitor extracellular AA and UA levels in conscious behaving rats. Amphetamine (2 and 4 mg/kg) produced a dose-related increase in UA; the increase in AA was very similar at both doses. Haloperidol (0.2 mg/kg) blocked the amphetamine-induced increase in UA but reduced the AA increase only by about 20%. Thus the amphetamine-induced increase in AA is only partly dependent on dopamine (DA) receptor stimulation whereas the amphetamine-induced increase in UA is completely dependent upon DA receptor stimulation.

Animals↗

In vivo voltammetric recording with nafion-coated carbon paste electrodes: additional evidence that ascorbic acid release is monitored.

The response of nafion-coated carbon paste electrodes was studied in vitro and in vivo with linear sweep semidifferential voltammetry. In vitro nafion-coated electrodes were insensitive to ascorbic acid (AA) but were equally sensitive to dopamine (DA) as were the uncoated electrodes. In vivo (anterior caudate) nafion-coated electrodes recorded small, poorly defined peaks. However, nafion-coated electrodes were equally responsive to microinfusion of DA as observed with the uncoated electrodes. Nafion-coated electrodes were insensitive to micro-infusion of AA while uncoated electrodes showed a large response to AA. These data suggest that endogenous DA levels are below the sensitivity of carbon paste electrodes in caudate and that the endogenous peaks recorded with uncoated carbon paste electrodes reflect AA.

3,4-Dihydroxyphenylacetic Acid↗

Repeated pemoline produces self-injurious behavior in adult and weanling rats.

Self-injurious behavior (SIB) is a serious problem among the mentally handicapped and is often accompanied by other repetitive or stereotyped behaviors. Acute administration of high doses of amphetamine or pemoline to rats produces transient SIB which is accompanied by severe deterioration of the behavioral repertoire. Repeated subcutaneous (SC) administration of pemoline to rats produces a high incidence of SIB without the dramatic behavioral changes produced by high doses of oral pemoline. Repeated pemoline increased locomotions and rears and produced intermittent stereotyped sniffing and licking/biting. However, the animals were still able to eat, drink, sleep and groom. Hotplate tests provided no evidence for analgesia. Because SIB is often associated with human developmental disorders, the effects of repeated SC administration of pemoline to weanling rats was also investigated. SC injections every 12 hours produced a high rate of SIB in weanling rats.

Animals↗

In vivo voltammetric evidence of production of uric acid by rat caudate.

Linear sweep in vivo voltammetry with carbon paste electrodes records a prominent peak at about 340 mV in the anterior caudate of rat brain. This peak is increased by microinfusion of uric acid or xanthine oxidase (which enhances conversion of hypoxanthine and xanthine to uric acid) and is decreased or eliminated by microinfusion of uricase. Allopurinol (a specific xanthine oxidase inhibitor) also decreases this peak when given either intracranially or intraperitoneally. Co-administration of uricase and allopurinol reliably eliminate the peak in question. These data suggest that uric acid, a purine metabolite that has been thought to be absent in brain, is formed locally in rat caudate and that uric acid is the sole component of the peak at 340 mV. In vivo voltammetry may be a useful new tool for studying brain purine metabolism.

Allopurinol↗

Progressive cardiac involvement by Fabry's disease despite successful renal allotransplantation.

Enzyme replacement by renal allotransplantation has been suggested as a specific mode of therapy for Fabry's disease. We report a case of Fabry's disease who developed symptoms and signs of heart failure despite successful renal transplantation 14 years ago. Echo- and angiocardiographic features resembled findings in patients with hypertrophic non-obstructive cardiomyopathy. Endomyocardial biopsy specimens demonstrated cardiac manifestation of Fabry's disease.

Biopsy↗

Isolation and characterization of DNA-dependent RNA polymerase I of Tetrahymena pyriformis.

A procedure for the separation and purification of DNA-dependent RNA polymerases [EC 2.7.7.6] from macronuclei of Tetrahymena pyriformis is described. We have used it to isolate and characterize the class I enzyme. RNA polymerase I was identified by its resistance against alpha-amanitin and its location in nucleoli. The purified enzyme consists of at least 12 major subunits with approximate molecular weights of 180,000, 118,000, 37,500, 36,000, 29,000, 27,500, 20,000, 18,500, 15,600, 14,500, 13,500, and 12,600. Chromatography on DEAE-Sephadex separated two forms of RNA polymerase I which differed in the presence of an additional polypeptide of 25 kDa. Independently of this polypeptide, the enzyme was found to segregate on DNA cellulose into a binding and a non-binding fraction. This type of heterogeneity was found to be unrelated to differences in molar ratios or molecular weights of the enzyme subunits. The catalytic properties of all enzyme subfractions were very similar and complied with the general characteristics of RNA polymerase I [cf. Roeder, R.G. (1976) in RNA Polymerase (Losick, R. & Chamberlin, M., eds.) pp. 285-329, Cold Spring Harbor Publ. Co., New York].

Animals↗

Effect of DNA gyrase inactivation on RNA synthesis in Escherichia coli.

The average chain growth rates of rRNA and of total RNA were not affected by a thermal inactivation of DNA gyrase in a temperature-sensitive gyrB mutant of Escherichia coli. The fact that total RNA synthesis decreased under these conditions suggests that transcription is primarily affected at the step of chain initiation. The fraction of rRNA in total pulse-labeled RNA was not altered by inactivation of the enzyme, indicating that the latter is not required to actively maintain a high rate of synthesis of this RNA species.

Escherichia coli↗