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Biomedical subjects

H Fisher

Publications and source records attributed to H Fisher.

At least 73 records · Page 4Linked to original sources
PubMed1989

Increased incidence and severity of neuroleptic-induced movement disorder in pinealectomized rats.

The effects of prior pinealectomy on neuroleptic-induced perioral movements were examined in male Sprague-Dawley rats. Treatment with haloperidol resulted in significantly more severe movement disorder in pinealectomized rats than in unoperated control rats. Subsequent administration of melatonin (4 mg, i.p.) was associated with a nonsignificant reduction of the severity of movements in the pinealectomized rats within one hour. We conclude that pinealectomy facilitates the onset of neuroleptic-induced perioral movements, and suggest that impaired melatonin secretion may be implicated in the pathophysiology of tardive dyskinesia in humans.

Animals↗
PubMed1989

Effects of compound 48/80 and exogenous histamine on wound healing in mice.

Compound 48/80 has previously been shown to improve wound healing in rats, presumably through stimulation of histidine decarboxylase activity and mobilization of histamine from mast cells. In the present study, C57Bl/6 mice were wounded by dorsal skin incision followed by treatment with compound 48/80, exogenous histamine, or the combination of 48/80 plus histamine. Skin-breaking strength was significantly increased over saline-injected controls by the combined treatment with 48/80 and histamine. Neither 48/80 or histamine alone had any influence on wound healing. Histamine content of skin at the wound site was significantly reduced by 48/80 treatment, but was unaffected by 48/80 plus histamine or histamine given alone. In contrast, stomach and leg muscle histamine levels were significantly increased beyond those of unwounded, wounded saline- or 48/80-injected mice. These results were also confirmed in CD mice, and are in contrast to findings in rats in which treatment with 48/80 alone significantly improved wound healing of similarly injured animals.

Animals↗
PubMed1989

Improved survival from compound 48/80-induced lethal stress and inhibition of myocardial histamine and carnosine mobilization by lodoxamide.

The precise roles of carnosine and histamine in the physiologic response of the cardiovascular system to stress are unknown. We have previously shown in skeletal and cardiac muscle that carnosine serves as a histidine reservoir available for subsequent histamine synthesis following trauma and sepsis. This study was designed to quantify the effect of histamine-releasing and blocking agents on the myocardial carnosine-histamine pathway as well as on survival during severe stress. Four groups of mature (9-month-old) Sprague-Dawley rats were treated with either (1) saline, (2) lodoxamide (L, mast cell degranulation inhibitor), (3) compound 48/80 (a mast cell degranulator which causes stress), or (4) L followed by 48/80, and observed until agonal or the end of 30 min. When either endpoint was reached the animals were sacrificed and their hearts were removed for tissue analyses of histidine, histamine, 3-methylhistamine, and carnosine via high-pressure liquid chromatography. All five L-pretreated animals survived challenge with 48/80 while all five animals given 48/80 alone died (P less than .005). This mortality correlated well with the increase in the myocardial levels of histidine (P less than or equal to .0005), histamine (P less than or equal to .0077), and 3-methylhistamine (P less than or equal to .0004) and the decrease in carnosine (P less than or equal to .009) experienced by the animals treated with 48/80 alone in comparison to the control, L-only- and L + 48/80-treated groups. A protective effect of L was shown against the deleterious effects of 48/80 which is associated with prevention of myocardial carnosine mobilization to histidine and histamine. These data support the role of carnosine as a nontoxic myocardial histidine reservoir which is mobilized in response to stress-induced increases in histamine requirements.

Amino Acids↗
PubMed1988

Dietary pyridoxine interaction with tryptophan or histidine on brain serotonin and histamine metabolism.

We studied the metabolic effects of high dietary intakes of pyridoxine and of the substrate-cofactor interaction between dietary histidine or tryptophan and pyridoxine in rat brain. In the substrate-cofactor interaction study, histamine and serotonin levels were determined in rats fed elevated or requirement levels of substrate (histidine: 0.3% and 0.8%, tryptophan: 0.15% and 0.6%) and excess or requirement levels of pyridoxine HCl (7 mg vs. 3,000 mg/kg). Excess pyridoxine intake caused a differential effect on brain histamine concentration--inhibitory with the requirement level of histidine (-29%), and stimulatory (+21%) with the elevated level of histidine. When dietary tryptophan was fed at the requirement level, excess pyridoxine caused essentially no changes in hypothalamic serotonin and 5HIAA (-2%, -2%). With elevated tryptophan intake, excess pyridoxine significantly increased serotonin and 5HIAA (+32%, +20%) in the hypothalamus. These results indicate a clear interaction between substrate and coenzyme precursor which influences brain metabolism of histamine and serotonin.

Animals↗
PubMed1988

Fenfluramine-induced behavior changes in rats prefed serotonin-altering amounts of tryptophan and pyridoxine.

It has been well established that elevated dietary tryptophan (TRP) levels can increase brain serotonin concentrations, thereby influencing serotonergic transmission. We previously examined interaction between dietary substrate (TRP: 0.15 and 0.6%) and the cofactor precursor (pyridoxine HCl: 3 and 3,000 mg/kg) on brain serotonin metabolism, observing significant increases in serotonin concentrations from such dietary interaction. The present experiments were designed to explore possible behavioral consequences of the substrate-cofactor interaction. After the IP injection of fenfluramine (FA: at 5, 10, 15, and 20 mg/kg), serotonin-mediated behavior traits and the appearance of flushing were observed in rats fed experimental diets as stated above. With a 5 mg/kg dose of FA, a differential dietary effect was most visible. However, at higher FA levels (15 and 20 mg/kg), such dietary effects were no longer discernible. The appearance of flushing was also dependent on dietary TRP intake and the dosage of FA. These results indicate a clear substrate-cofactor interaction on certain serotonin-mediated behavior traits in the rat.

Animals↗
PubMed1988

L-tryptophan in neuroleptic-induced tardive dyskinesia.

Administration of the serotonin precursor L-tryptophan in a patient with neuroleptic-induced tardive dyskinesia, produced a dramatic reduction in the severity of the abnormal movements within 24 hours. This report supports our hypothesis that alterations in the function of serotoninergic neurotransmission are implicated in the pathophysiology of neuroleptic-induced tardive dyskinesia.

Antipsychotic Agents↗
PubMed1988

Serotonin in involuntary movement disorders.

Several recent studies have emphasized that serotonergic pathways in the CNS are intimately involved in the modulation of motor behavior, and in the pathophysiology of human involuntary movement disorders. These observations are supported by recent reports demonstrating large serotonergic innervation of the striatum and substantia nigra, and a close interaction between the activity of serotonergic neurons with the dopamine system in the striatum and nigra. In the following communication we summarize evidence demonstrating defective serotonergic functions in a number of human movement disorders and discuss their management with serotonergic drugs.

Basal Ganglia↗
PubMed1987

The effects of L-tryptophan on haloperidol-induced movement disorder in the rat.

An animal model of haloperidol-induced tardive dyskinesia was studied in relation to the dietary manipulation of tryptophan and its effect on the movement disorder. This study showed a significant negative behavioral response to the neuroleptic drug, haloperidol. Increased dietary tryptophan (1.0 vs. 0.3%) significantly reduced the frequency of drug-induced head movements. Brain serotonin levels were elevated by the drug treatment. Brain serotonin levels correlated significantly with the behavioral response. Contrary to expectation, brain dopamine levels did not correlate with the behavioral response. These findings suggest a possible serotonergic involvement in neuroleptic-induced tardive dyskinesia and an amelioration of the disorder through tryptophan supplementation.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1987

Pressure-dependent vasoactive effects of histamine in the coronary circulation.

Twenty-one isolated, perfused, spontaneously rhythmic guinea pig hearts (Langendorff preparation) were used to investigate the effects of coronary perfusion pressure (CPP) on the coronary vasoactive response to a continuous infusion of histamine. Heart rate (HR), coronary perfusate flow (CPF), left ventricular pressure, dp/dtmax, oxygen extraction, and myocardial oxygen consumption (MVO2) were measured at constant CPP of 40 (n = 9), 53 (n = 6), and 65 cm H2O (n = 6) in the absence and presence of continuous intracoronary infusion of histamine [0.9 +/- 0.2 microgram/(min X g)]. At 40 cm H2O histamine caused significant coronary vasodilation. At 65 cm H2O histamine caused significant coronary vasoconstriction. At an intermediate pressure of 53 cm H2O histamine had no effect on CPF. At all three pressures HR, left ventricular pressure, dp/dtmax, and oxygen extraction increased significantly in response to histamine. MVO2 was unchanged by histamine at 65 cm H2O (flow was reduced but extraction increased. MVO2 increased modestly but significantly at 53 cm H2O (12% increase; flow unchanged but extraction increased), and increased prominently at 40 cm H2O (50% increase; flow and extraction increased). We conclude that the coronary vascular effects of continuously infused histamine are dependent on the preexisting, steady-state level of CPP in the isolated perfused guinea pig heart.

Animals↗
PubMed1987

Histamine-induced changes in coronary circulation and myocardial oxygen consumption: influences of histamine receptor antagonists.

The effects of histamine and selected H1 and H2 histamine receptor antagonists on cardiac inotropic and chronotropic activity, coronary perfusate flow (CPF), and myocardial oxygen consumption (MVO2) were studied in isolated guinea pig hearts perfused at constant pressure. Data were collected at the end of a 3-min infusion period at steady state. Cardiac performance increased significantly whereas CPF decreased during histamine infusion. MVO2 remained constant owing to a significant increase in myocardial oxygen extraction. Diphenhydramine attenuated the coronary vasoconstriction but potentiated the positive inotropic response. Cimetidine attenuated the inotropic and chronotropic responses but had no effect on coronary vasoconstriction. In combination, the histamine antagonists attenuated the changes in heart rate, contractility, and CPF. The histamine-induced increase in myocardial oxygen extraction was accompanied by a significant increase in MVO2 in the presence of diphenhydramine. The ratio of the change in oxygen extraction to the change in oxygen consumption caused by histamine was significantly increased by diphenhydramine. This compensated for a histamine-induced decrement in the ratio of the change of CPF to the change in oxygen consumption. Cimetidine had no effect on the changes in coronary flow, oxygen consumption, or the above ratios. Thus, histamine causes direct coronary vasoconstriction via an H1 receptor mechanism, cardiac positive inotropy by an H2 receptor mechanism, and cardiac positive chronotropy by combined H1 and H2 mechanisms. In the presence of a histamine-induced decrease in myocardial oxygen supply, increments in oxygen demand are met by increased oxygen extraction.

Animals↗
PubMed1986

Comparative effects of polymyxin B and compound 48/80 on histamine metabolism in rat muscle and gastric tissue.

Polymyxin B, administered in vivo, increased histidine decarboxylase (HDC) activity and histamine (HM) concentrations in muscle tissue homogenates and supernatants. When administered in vitro it increased HDC activity and HM concentrations in both muscle and gastric tissue. The stimulatory effect on muscle was similar to that obtained with compound 48/80, but 48/80, unlike polymyxin B, did not affect gastric tissue. In vitro additions of alpha-fluoromethylhistidine inhibited both in vivo and in vitro stimulatory effects of polymyxin B. The results of these studies show that the action of compound 48/80 and of polymyxin B are similar, and that both affect HM synthesis in a manner that requires further elucidation.

Animals↗