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J Gerlach

Publications and source records attributed to J Gerlach.

At least 91 records · Page 5Linked to original sources
PubMed1991

Zuclopenthixol, a combined dopamine D1/D2 antagonist, versus haloperidol, a dopamine D2 antagonist, in tardive dyskinesia.

Animal data suggest that a D1 antagonistic component in neuroleptic drugs counteracts development of dopamine supersensitivity and of tolerance to cataleptic effect. This has led to the hypothesis that neuroleptics with D1 antagonistic activity should cause a better suppression of tardive dyskinesia (TD) and less rebound aggravation after withdrawal than pure D2 antagonists. In this study the effect of zuclopenthixol (mixed D1/D2 antagonist) and haloperidol (D2 antagonist) was evaluated in chronic psychotic patients with TD. Fifteen patients completed a randomized crossover study with blind evaluation of TD and parkinsonism. The test medications, haloperidol and zuclopenthixol, caused a significant suppression of TD and a significant increase of parkinsonism. No significant differences between haloperidol and zuclopenthixol were observed. No TD aggravation was seen. The lack of differences between the mixed D1/D2 antagonist and a D2 antagonist suggest that tolerance and DA supersensitivity play no or a minor role for development of TD.

Adult↗
PubMed1991

New antipsychotics: classification, efficacy, and adverse effects.

Compared to traditional neuroleptics, most of the new antipsychotics are characterized by a low extrapyramidal side effect (EPS) liability and varying antipsychotic efficacy. This topic is reviewed for four principal classes of new, established, and potential antipsychotics: (1) Antipsychotics such as sulpiride and remoxipride that block a subgroup of dopamine (DA) D2/D3 receptors produce a relatively low level of side effects, including EPS, and have an antipsychotic effect equal to or slightly weaker than traditional neuroleptics. D1 antagonists demonstrate a low level of EPS in primates and may prove to be a valuable new type of antipsychotic drug. (2) Theoretically, partial D2 agonists have the advantage of producing few or no EPS and a specific beneficial effect in negative symptoms, but as yet the expectations have not been fulfilled. (3) Nondopamine drugs such as serotonin (5HT1) agonists, 5HT2 antagonists, 5HT3 antagonists, and gamma-amino-butyric-acid-A (GABA-A) benzodiazepine agonists have anxiolytic, antidepressant, antiaggressive, and maybe antiparkinsonian effects and may play an adjunctive role in the treatment of schizophrenia. 5HT3 antagonists (e.g., ondansetron), partial benzodiazepine agonists, and partial glutamate agonists may prove to be effective antipsychotics. (4) Antipsychotics such as clozapine and risperidone, which affect D2/D3 receptors as well as 5HT, alpha 1, and/or D1 receptors appear to have the most pronounced antipsychotic effect.

Antipsychotic Agents↗
PubMed1990

The effects of dopamine D1 and D2 receptor agonists and antagonists in monkeys withdrawn from long-term neuroleptic treatment.

The effects of dopamine D1 and D2 receptor agonists and antagonists were studied in eight Cebus apella monkeys previously treated with haloperidol for two years. SKF 81297 (specific D1 receptor agonist) induced oral hyperkinesia of variable intensity (P less than 0.01): some of the monkeys developed extreme lip smacking, tonque protrusions and licking movements while others developed only slight lip movements. A combined treatment of SKF 81297 with LY 171555 (full D2 receptor agonist) or SCH 23390 (D1 receptor antagonist) inhibited the oral hyperkinesia induced by SKF 81297 (P less than 0.01, P less than 0.02, respectively). Raclopride (D2 receptor antagonist) did not statistically change oral hyperkinesia (P less than 0.2), although five monkeys showed increased oral movements; most of these monkeys had pre-existing hyperkinesia. Treatment with SCH 23390 or raclopride resulted in an identical dystonic/cataleptic syndrome. SKF 81297 inhibited the dystonia induced by SCH 23390, while it did not significantly affect raclopride dystonia. The investigation indicates that oral dyskinesia may be related to an imbalance in D1 receptor and D2 receptor stimulation in favor of D1 receptors. The question now is whether D1 receptor antagonists, which may have antipsychotic potential, will produce tardive dyskinesia after long-term use.

Animals↗
PubMed1990

Remoxipride, a new selective D2 antagonist, and haloperidol in cebus monkeys.

1. Nine Cebus monkeys, 6 with mild spontaneous oral dyskinesia (tongue protrusions), were tested with two dopamine D2 antagonists, remoxipride (a new substituted benzamide) and haloperidol, and with two dopamine agonists, methylphenidate and apomorphine. 2. Remoxipride 4 and 8 mg/kg and haloperidol 0.01 and 0.02 mg/kg given alone induced identical dystonic-dyskinetic syndromes. 3. Methylphenidate 0.5 mg/kg caused increased arousal, but reduced oral dyskinesia, while apomorphine 0.25 mg/kg slightly increased arousal and induced/aggravated oral dyskinesia. 4. Remoxipride 2 and 4 mg/kg and haloperidol 0.005 and 0.01 mg/kg equally antagonized the methylphenidate- and apomorphine-induced arousal, but not oral dyskinesia. 5. Marked sedation was seen when apomorphine was given together with either D2 receptor antagonists. 6. It is concluded that remoxipride and haloperidol have a similar qualitative effect in motor behavior in Cebus monkeys, but the quantitative difference between the dystonia-inducing dose levels of the two drugs compared with the antipsychotic dose levels (estimated from clinical studies) suggests that remoxipride may cause relatively few extrapyramidal side-effects in human.

Animals↗
PubMed1990

Gas supply across membranes in bioreactors for hepatocyte culture.

The conditions required for hepatocyte cultures is a main topic in the development of bioreactors for hybrid liver support systems. The detoxification of ammonia and the synthesis of urea due to primary isolated hepatocytes was measured in order to compare two different models of gas supply in bioreactors: (a) indirect medium oxygenation and (b) direct membrane-contact oxygenation of the hepatocytes using polypropylene membranes. Increasing oxygen pressure promoted cell function. At day 6 of culture, urea synthesis was 0.8 +/- 0.3 mM in 21% of O2 cultures and 1.5 +/- 0.1 mM in oxygenated cultures. Alkalosis due to CO2 loss decreased ammonia metabolism. The direct membrane-contact oxygenation resulted in enhanced cell metabolism in comparison to medium oxygenation: urea synthesis at day six was 1.42 +/- 0.2 mM in 21% O2 cultures. Polypropylene oxygenation membranes proved to be sufficient for hepatocyte adhesion. Two functions can be integrated in one element in liver support systems using the investigated polypropylene membrane and the direct membrane-contact oxygenation: oxygenation with physiological oxygen pressure in bioreactors due to gas supply across the membrane and adhesion of hepatocytes in bioreactors on the membrane.

Animals↗
PubMed1990

[Not Available].

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History, Modern 1601-↗
PubMed1990

Computer aided time-lapse video analysis of hepatocyte morphology during adhesion to cellulose membranes.

An investigation was performed to demonstrate that time-lapse cinematography and computer aided video analysis of cell morphology is suitable to study and compare the characteristics of hepatocytes during the adhesion process to membranes. We chose to compare ordinary cellulose Cuprophan membranes and membranes coated with collagen or fibronectin. Striking differences between uncoated cellulose and fibronectin or collagen coating were seen in the cell count per square millimeter and adhesion behaviour. On the investigated uncoated Cuprophan the hepatocytes were found to attach but not to spread whilst on collagen coated Cuprophan most of the cells spread spherically, and on fibronectin coated membranes most of the cells flattened spherically or polygonally. Time-lapse video microscopy seems to be a valuable technique for assessing the morphologic behaviour of cells in a detailed and quantitative manner in order to improve the hepatocyte culture technique in bioreactors for hybrid systems.

Animals↗
PubMed1990

Membranes as substrates for hepatocyte adhesion in liver support bioreactors.

Fourteen membranes out of cellulose (CuprophanR), polyamide and polypropylene were compared in a cytocompatibility test using the cytokinetics and cytomorphology of primary hepatatocytes as parameters. Additionally, the impact of coating the membranes with collagen or fibronectin was investigated. Hepatocytes were not able to attach in acceptable amounts on investigated cellulose membranes. On polyamide and polypropylene membranes a sufficient cell seeding was possible. Coating with collagen or fibronectin improves the attachment and spreading on all membranes. Differences between collagen and fibronectin were detected, observing the morphology of the cells: on collagen, most of the cells spread, whilst on fibronectin, most of the cells spread and flattened polygonally. If the adhesion of hepatocytes prolongs their metabolic function, a large adhesion surface in bioreactors is necessary. To reach a high surface area for cell adhesion in bioreactors one possibility is the use of polyamide and polypropylene membranes.

Animals↗
PubMed1989

Long-term experience with clozapine in Denmark: research and clinical practice.

In Denmark, the use of clozapine has increased markedly (15-25% per year) since 1983, when the drug was relaunched--after its withdrawal in 1975. Several factors have contributed to this development: 1) the interesting pharmacology of clozapine, especially the atypical influence on dopamine transmission, including a relatively high D-1/D-2 receptor affinity ratio, 2) the potent anti-anxiety and anti-psychotic effect in severe and otherwise therapy-resistant psychotic patients, and 3) the lack of extrapyramidal side effects. A special monitoring form (for registration of total and differential leucocyte counts, ECG, body weight, drugs, doses and reason for possible withdrawal of the clozapine) is used in most Danish psychiatric institutions. This form secures the regular control of vital parameters and serves as an instrument for surveys of the use of clozapine in Denmark. Also, more selective studies are being carried out, e.g., on the effect of clozapine monotherapy versus combined therapy, and on the influence of clozapine on cardiovascular functions, including left ventricular output (echocardiography).

Clozapine↗
PubMed1989

Endothelial cell seeding on different polyurethanes.

Six polyurethanes (PUs) were tested with respect to their cytocompatibility. Initial adhesion, initial spreading, and the proliferation of endothelial cells were investigated. All smooth PUs showed similar initial adhesion. Initial spreading was faster on rough PUs. Collagen coating resulted in faster initial adhesion but not better proliferation of endothelial cells.

Animals↗
PubMed1989

Isoelastic polyurethane prosthesis for segmental trachea replacement in beagle dogs.

Porous polyurethane (nonwoven) was used for the development of tracheal prosthesis, which--in a special testing design--was adapted to shape and biomechanic properties of the natural organ. This prosthesis was implanted into 19 beagle dogs using inverted, everted, and end-to-end anastomosis. Insufficiency of the anastomosis or infection was observed in the everted and end-to-end anastomosis, whereas the inverted anastomosis showed complete incorporation into surrounding tissue of the porous prosthesis but was complicated by airway obstruction due to anastomosis granuloma.

Anastomosis, Surgical↗
PubMed1989

Use of hepatocytes in adhesion and suspension cultures for liver support bioreactors.

Hepatocyte cultivation in bioreactors for hybrid liver support systems is possible under two conditions: attached to a substrate like membranes or microcarriers or in suspension culture. To compare the ammonia metabolism of hepatocytes cultivated under these two conditions, cultures of primary seeded rat hepatocytes were cultivated either attached to collagen coated tissue culture plastic or as a suspension culture. During the time course of culture, the ability of hepatocytes to reduce the ammonia content of the medium decreased in both adhesion and suspension cultures, though to different extents. In suspension cultures, ammonia content was reduced from 350 microM to about 100 microM (day 4) and to about 180 microM (day 6). No significant reduction was seen on day 8 of culture. In contrast, hepatocytes attached to collagen coated dishes remained viable and functional for at least 8 days after plating, reducing ammonia content from 350 microM to 70 microM (day 4), 90 microM (day 6) and 180 microM (day 8). The period of useful metabolism of hepatocytes in bioreactors for hybrid liver support systems appears to depend on the culture conditions.

Ammonia↗
PubMed1989

Isolation of vascular endothelial cells for investigations on hybrid prostheses.

Hybrid vascular prostheses are coated with vascular endothelial cells (EC) in an attempt to reduce thrombogenicity through the metabolic activities of living cells. The present studies were planned to develop a standardized method of isolating bovine aortic EC with high yield for studies of endothelial coating of vascular prostheses. The best results were achieved using a combination of incubation with collagenase and mechanically scraping the mobilised cells from the donor vessel. Isolated adult male bovine endothelial cells were identified by the typical "cobble stone" morphology in culture and characterized by factor VIII related antigen immunofluorescence microscopy. The cells were seeded successfully on PTFE vascular prostheses.

Animals↗
PubMed1989

Endothelial cell seeding on PTFE vascular prostheses using a standardized seeding technique.

A standardized method was developed for seeding endothelial cells (EC) in tubular vascular grafts. A rotational cell seeding device for tubular prostheses is presented and parameters influencing the kinetics of cell adhesion (rotation speed, graft diameter, cell suspension level, inoculated cell number) are reported. Seeding EC in 14 mm ID PTFE vascular grafts with rotation rate of 10 rph gave an adhesion rate of 80% in a homogeneous monolayer.

Blood Vessel Prosthesis↗
PubMed1988

Arginine is a physiological precursor of endothelium-derived nitric oxide.

ATP dose dependently stimulated the formation and release of nitric oxide (NO) from perfused rabbit aorta. L-Canavanine, an inhibitor of various L-arginine-utilizing enzymes, abolished basal and ATP-induced NO formation and release. ATP increased the accumulation of presumably NO-derived NO2- in the medium of primary cultures of bovine aortic endothelial cells. 15NO, 15NO2- and 15NO3- formation was found when L-[guanido-15N2]arginine was added to the culture medium. We conclude that the terminal guanidino nitrogens of L-arginine are the physiological precursors of endothelium-derived NO.

Animals↗
PubMed1988

Behavioural effects of dopamine D-1 and D-2 receptor agonists in monkeys previously treated with haloperidol.

The effects of dopamine D-1 and D-2 receptor agonists were evaluated in five Cebus apella monkeys. During a previous haloperidol treatment (2 years), three of the monkeys had developed oral tardive dyskinesia (tongue protrusion and/or chewing). The partial D-1 agonist, SKF 38393, induced/aggravated oral dyskinesia and slight sedation, but no non-oral repetitive movements. Conversely, the selective D-2 agonist, LY 171555, produced non-oral repetitive movements and increased reactivity (arousal), but no significant change in the oral movements. Apomorphine (a mixed D-1/D-2 agonist) induced non-oral repetitive movements, increased reactivity, and increased oral dyskinesia. Pretreatment with SKF 38393 inhibited the LY 171555-induced non-oral repetitive movements, while in four monkeys the SKF 38393-induced oral movements were inhibited by LY 171555. The results suggest that oral dyskinesia (tardive dyskinesia) is more related to D-1 receptor stimulation than to D-2 receptor supersensitivity.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1988

Future treatment of schizophrenia.

In spite of 35 years of experience with antipsychotic drugs, the psychiatrists are still faced with the limitations of these drugs: no or minimal therapeutic effect in hallucinations and delusions in about 25% of schizophrenic patients; persisting anergia and emotional withdrawal in otherwise successfully treated patients; a great spectrum of side effects, some irreversible. Quo vadis? An incidental discovery of a completely new drug, a new "chlorpromazine" would be the ideal solution, but for the present, one has to continue with the small pragmatic steps, especially within the following areas: (a) the selective antidopaminergic drugs, especially the substituted benzamides, may be further developed in the direction of antipsychotic selectivity with fewer and fewer extrapyramidal side effects; (b) the atypical clozapine ought soon to have successors, hopefully without the risk of bone marrow depression and cardiovascular side effects; (c) the D1 antagonists as well as the D1 agonists may imply therapeutically valuable effects; (d) the dopamine autoreceptor has long been in focus, but until now, no pure agonist has been found, and the drugs available, including (-)3-PPP, appear to have many side effects; (e) serotonin antagonists may be an interesting possibility; and (f) when it may be possible to influence brain peptides more efficiently than up to now, this area will probably provide us with several psychotropic drugs. Furthermore, during the search for new antipsychotic drugs, one must not forget to improve the practical use of available neuroleptics and of nonpharmacological, psychosocial treatment modalities.

Antipsychotic Agents↗