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Biomedical subjects

J A Jansen

Publications and source records attributed to J A Jansen.

At least 163 records · Page 9Linked to original sources

Soft tissue response to different types of sintered metal fibre-web materials.

Recently, it has been demonstrated that the soft tissue response to polymeric filter implants was predominantly dependent on the implant surface topography and that variation in the implant material had little effect. The purpose of this study, therefore, was to compare histologically the soft tissue response to sintered fibre-web implants made from different materials and with varying web porosity. Three different fibre-web materials with two different weights and two different porosities were used. The implants were inserted subcutaneously in the dorsum of rabbits. The implants were left in situ for 4 and 12 wk. Histological and tissue compatibility evaluations were performed. It is found that all the tested fibre-web materials show a good biocompatible behaviour. In addition, the results appear to indicate a relation between flexibility of an implant material and tissue behaviour.

Adipose Tissue↗

Histologic evaluation of the osseous adaptation to titanium and hydroxyapatite-coated titanium implants.

The aim of this study was to obtain more information about the bone reaction to titanium and hydroxyapatite (HA)-coated titanium implants during the first 3 months after implantation. Therefore, uncoated and coated implants were inserted into the tibia of rabbits for various implantation periods. The histological results demonstrated that although there were no marked differences in bony reaction at the cortical level to the different implant materials, HA-coating appeared to induce more bone formation in the medullary cavity. It was also noted, that 3 months after insertion loss of coating thickness had occurred.

Animals↗

Development of a new percutaneous access device for implantation in soft tissues.

The objective of this study was to evaluate a new type of percutaneous device (PD) designed to be implanted in soft tissues. The new PD consisted out of: (1) a flange-shaped subcutaneous component, made from sintered titanium fiber-web, and (2) a percutaneous component, made from dense sintered hydroxyapatite. The PDs were inserted in the back of 15 rabbits. The surgical procedure was performed in two steps. In the first session the subcutaneous component was placed. In the second session, after 3-4 months the percutaneous component was fixed in the subcutaneous component. The implants were left in situ for 1 and 4 months after the second implantation session. Clinical and histological investigations were performed. It is found, that there was only a limited epidermal down-growth in the percutaneous area. No inflammatory reaction was observed in the dermal connective tissue. Histological analysis also demonstrated that titanium fiber mesh evokes minor adverse effects of the surrounding tissues. In conclusion, these experiments have shown that stabilization of the PD in the hypodermal area by using a sintered titanium fiber-web structure favors the longevity of PDs implanted in soft tissues.

Animals↗

Fibroblast and epithelial cell interactions with surface-treated implant materials.

The basic mechanisms underlying skin-implant interactions were investigated by means of in vitro experiments with fibroblast and epithelial cell cultures. Cells were cultured on various implant materials treated with radio frequency glow discharge. The possible influence of this treatment on the morphological mode of cell attachment, as well as cell behaviour in attachment and growth rate were investigated. The results demonstrate that there are significant behavioural differences between fibroblasts and epithelial cells.

Animals↗

Systemic and regional hemodynamic effects of the 5-hydroxytryptamine1A receptor agonists flesinoxan and 8-hydroxy-2(di-N-propylamino)tetralin in the conscious rat.

The systemic and regional hemodynamic effects of the centrally acting 5-Hydroxytryptamine1A (5-HT1A) receptor agonist flesinoxan (0.5 and 2.5 mg kg-1, intraarterially, i.a.) were investigated in conscious freely moving spontaneously hypertensive rats (SHR) and compared with those of 8-hydroxy-2(di-N-propylamino)tetralin (8-OH-DPAT) (0.1 and 0.5 mg kg-1, i.a.). In one group of animals, cardiac output (CO) was measured with a precalibrated electromagnetic flow probe around the ascending aorta. In another group, regional vascular conductances were measured using radioactive microspheres. Flesinoxan and 8-OH-DPAT dose dependently decreased blood pressure (BP) (22 +/- 5 and 13 +/- 4%, respectively, at the highest dose) mainly resulting from an increase in total peripheral vascular conductance (TPC) (34 +/- 12 and 16 +/- 3%, respectively) since there was no effect on CO. Both drugs reduced heart rate (HR) (17 +/- 4 and 20 +/- 4% for flesinoxan and 8-OH-DPAT, respectively, at the highest dose). Flesinoxan and 8-OH-DPAT showed a qualitatively similar pattern with regard to their effects on vascular conductances, causing increases in vascular conductances in the heart and skeletal muscles in contrast to results in a saline-treated group. Vascular conductances in the lungs were markedly increased by both flesinoxan and 8-OH-DPAT, which may indicate that the conductance in the arteriovenous shunt vessels was enhanced. These results demonstrate that flesinoxan and 8-OH-DPAT elicit a qualitatively similar systemic and regional hemodynamic profile in conscious SHR. Furthermore, the increase in TPC appears to be due mainly to vasodilatation in the skeletal muscles.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Dopamine receptor agonists: selectivity and dopamine D1 receptor efficacy.

Dopamine receptor selectivity was investigated for a number of dopamine receptor agonists. In vitro, the benzazepine derivatives, e.g., SKF 38393 and SKF 75670 as well as the isoquinoline derivatives, SKF 89626 and SKF 89615, were D1 receptor-selective. All other compounds like apomorphine, CY 208-243, 6,7-ADTN and 3-PPP were either D2-selective or did not discriminate between subtypes. In general, the same receptor profile seen in vitro was observed in vivo. The exceptions to this pattern were: compounds which did not cross the blood-brain barrier, like 6,7-ADTN and SKF 89626, and compounds which appeared nonselective in vitro but demonstrated D2 selectivity in vivo like apomorphine, CI 201-678 and CY 208-243. A number of compounds were characterized in detail with respect to a GTP-induced affinity shift in inhibition of [3H]SCH 23390 binding, and potency and efficacy in stimulating adenylate cyclase from rat striatum. Inhibition of specific [3H]SCH 23390 binding by these agonists in the absence of GTP occurred with Hill slopes below unity and could best be explained by a two-site model with a high (KH)- and low-affinity (KL) component. Inhibition of [3H]SCH 23390 binding in the presence of 15 microM GTP occurred with Hill slopes of unity. The KI values obtained in the presence of 15 microM GTP were similar to the KL values, the low-affinity component observed in the absence of GTP. The capability of the agonists to stimulate the adenylate cyclase was analyzed in relation to dopamine (efficacy = 100%). The efficacy of the benzazepine derivatives varied from 24 (SKF 75670) to 100% (SKF 83189), dependent on the substituents on the benzazepine core. The isoquinolines, SKF 89626 and SKF 89615 had full efficacy, whereas most other agonists tested appeared to have only partial efficacy. In summary, the present paper presents data on dopamine receptor selectivity and efficacy in stimulating adenylate cyclase for a number of dopaminergic agonists. These data may create a basis for selection of agonists in future characterizations of dopaminergic-mediated events.

Adenosine Triphosphate↗

Tissue response to percutaneous implants in rabbits.

This study reports on certain aspects of wound-healing around percutaneous implants. Plasma-sprayed and dense hydroxylapatite, titanium, and carbon test implants were inserted into the tibia and the cranium of 12 rabbits. Four and 8 months after insertion, the animals were sacrificed and the implants with their surrounding tissues were processed histologically. Light- and transmission electron microscopic investigations were performed. It is found that direct and indirect bone-anchoring favors the longevity of percutaneous implants. No differences in tissue reaction between the various implant materials were observed.

Animals↗

(R)-N-[4,4-bis(3-methyl-2-thienyl)but-3-en-1-yl]nipecotic acid binds with high affinity to the brain gamma-aminobutyric acid uptake carrier.

(R)-N-[4,4-Bis(3-methyl-2-thienyl)but-3-en-1-yl]nipecotic acid (NO 328) has previously been shown to be a potent anticonvulsant in both mice and rats. Here, we report that NO 328 is a potent inhibitor of gamma-[3H]aminobutyric acid [( 3H]GABA) uptake in a rat forebrain synaptosomal preparation (IC50 = 67 nM) and in primary cultures of neurons and astrocytes. Inhibition of [3H]GABA uptake by NO 328 is apparently of a mixed type when NO 328 is preincubated before [3H]GABA uptake; the inhibition is apparently competitive without preincubation. NO 328 itself is not a substrate for the GABA uptake carrier, but NO 328 is a selective inhibitor of [3H]GABA uptake. Binding to benzodiazepine receptors, histamine H1 receptors, and 5-hydroxytryptamine1A receptors was inhibited by NO 328 at 5-30 microM, whereas several other receptors and uptake sites were unaffected. [3H]NO 328 showed saturable and reversible binding to rat brain membranes in the presence of NaCl. The specific binding of [3H]NO 328 was inhibited by known inhibitors of [3H]GABA uptake; GABA and the cyclic amino acid GABA uptake inhibitors were, however, less potent than expected. This indicates that the binding site is not identical to, but rather overlapping with, the GABA recognition site of the uptake carrier. The affinity constant for binding of [3H]NO 328 is 18 nM, and the Bmax is 669 pmol/g of original rat forebrain tissue. The regional distribution of NaCl-dependent [3H]NO 328 binding followed that of synaptosomal [3H]GABA uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of surface treatments on attachment and growth of epithelial cells.

The objective of this study was to enlarge the understanding of the basic mechanisms underlying epithelial tissue implant reaction by means of in vitro experiments with epithelial cell cultures. For the experiments, rat palatal epithelial cells were cultured on various implant materials. The implant surfaces were treated by different procedures. The possible influence of these treatments on the attachment percentage and growth rate of the cells was studied. The results of the experiments demonstrate no significant relation between surface treatment and the behaviour of rat palatal epithelial cells cultured on the various kinds of substrates relevant for implants.

Animals↗

Epithelial reaction to percutaneous implant materials: in vitro and in vivo experiments.

The major fact in determining percutaneous implant success is the formation of a stable skin-implant junction. However, the characteristics an implant material must meet to secure a durable percutaneous seal are still unknown. The objective of this study, therefore, is to gain more insight into the mechanisms underlying implant-skin reactions by means of in vitro cell culture and in vivo animal experiments. For the in vitro experiments rat palatal epithelial cells were cultured on various implant materials and the possible influence of the initial surface free energy and state of cleanliness of these materials on the growth rate of cells was studied. The results of these experiments demonstrate no significant relation between these parameters and cellular growth. In the in vivo experiments, plasma-sprayed and dense hydroxylapatite percutaneous implants were inserted into the tibia and dorsum of guinea pigs and into the tibia and onto the cranium of rabbits. The implants were left in situ for 3 weeks to 8 months. Clinical and histological investigations were performed. The results show, that stabilization of a percutaneous implant by bony skeletal tissue is effective in the maintenance of a permanent percutaneous passage.

Animals↗

Guinea pig and rabbit model for the histological evaluation of permanent percutaneous implants.

The object of this study was to develop a small experimental animal model for a systematic study of the interfacial phenomena between percutaneous implants and skin. Plasma-sprayed and dense hydroxyapatite test implants were inserted into the tibia and dorsum of guinea pigs and into the tibia and on the cranium of rabbits. At preselected periods, the animals were killed and the implants with their surrounding tissues were processed histologically. The results revealed that the tibia and cranial implants had healed uneventfully. The epidermis showed no tendency to grow down into the dermis, but appeared to form a stable junction with the implant surface. Around the dorsal implants, the epidermis migrated downwards and most of these implants were lost 6 weeks after insertion. It was concluded that the guinea pig and the rabbit were a suitable model for studying the pathophysiology of percutaneous wound healing and that the implant location is an important factor for percutaneous implant success.

Animals↗

Combined boric acid and cinchocaine chloride poisoning in a 12-month-old infant: evaluation of haemodialysis.

A mixture containing 3 g of boric acid and 300 mg of cinchocaine chloride prescribed due to painful dental protrusion was accidentally ingested by a 12-month-old girl. She developed violent vomiting and coughing. Irritability, tremor, seizures and a delirious reaction. She was treated with diazepam, intubated, sedated and ventilated. Her diuresis was stimulated with furosemide and fluid. Within the first 24 h she was treated with haemodialysis twice on femoral catheters. Her renal function was unaffected. In two days she fully recovered. The maximum measured levels of boric acid and cinchocaine chloride approximately 6 h after ingestion were 26 micrograms/ml and 71 ng/ml respectively. The plasma half-life of boric acid was 7.0 h and decreased to 3.6 and 4.4 h during the two haemodialyses. The total body clearance of boric acid increased correspondingly from 21 ml/min to 41 and 34 ml/min. The in vitro clearance of boric acid of the dialyser was later determined to be 18 ml/min. It is concluded that haemodialysis is valuable in the treatment of boric acid intoxication because it increases the elimination of the drug even in patients without any sign of renal toxicity.

Boric Acids↗

[3H]GBR 12935 binding in vivo in mouse brain: labelling of a piperazine acceptor site.

The binding of the selective dopamine uptake inhibitor [3H]GBR 12935 was studied in vivo in mouse brain. The binding was reversible with t1/2 = 80 min. The localisation of [3H]GBR 12935 binding and of dopaminergic receptors did not overlap. The binding of [3H]GBR 12935 was distributed almost uniformly throughout the brain. Also, the in vitro inhibition of dopamine uptake and the inhibition of in vivo [3H]GBR 12935 binding did not correlate when a series of relevant reference compounds was used. The potencies of various dopamine uptake inhibitors to induce stereotyped behavior did not correspond to the inhibitory potencies in the [3H]GBR 12935 binding assay. In conclusion, [3H]GBR 12935 labels in vivo a site which is different from the dopamine uptake complex. We have recently obtained results for the in vitro binding of [3H]GBR 12935 that indicate that this site could be a piperazine acceptor site.

Animals↗

Pharmacokinetics of intravenous, intrathecal and epidural morphine and fentanyl in the goat.

Intrathecal and epidural catheters and an intravenous cannula were inserted in 10 goats. After administration of either morphine 4 mg, intravenously, 1 mg intrathecally or 4 and 8 mg epidurally, or fentanyl 0.1 mg intravenously, 0.05 mg intrathecally or 0.1 and 0.2 mg epidurally, venous blood and CSF were sampled at 2, 5, 10, 15, 30 min and 1, 2, 4, 6, 8 and 24 h. The concentrations of the drugs were measured by radioimmunoassay. After administration of intravenous morphine the plasma concentration-time curve fitted a 3-compartment model (body clearance = 84 +/- 23 ml/min/kg, mean +/- s.d., N = 5), while after fentanyl the plasma concentration-time curve was best described by a 2-compartment model (body clearance = 3.9-5.8 ml/min/kg, N = 3]. After intrathecal injection the elimination rates of the opioids from CSF were 0.3 to 2.0 and 0.6 to 2.4 ml/h/kg for morphine and fentanyl, respectively (N = 3). The time to reach maximum CSF concentration after epidural administration was 0.22 +/- 0.14 h for morphine (N = 6) and 0.22 +/- 0.13 h for fentanyl (N = 8). In the same goat the CSF availability was 2.3 and 11.3% for morphine and 0.8 and 3.3% for fentanyl following epidural administration of the low and high doses, respectively. After epidural administration, morphine and fentanyl are absorbed into CSF at the same rate but the relative amount of drug absorbed may be higher for morphine than fentanyl. Bulk flow is supposed to be the principal mechanism of opioid elimination from CSF.

Animals↗

A comparison between dopamine-stimulated adenylate cyclase and 3H-SCH 23390 binding in rat striatum.

Methods for measuring 3H-SCH 23390 binding and dopamine (DA) stimulated adenylate cyclase (AC) were established in identical tissue preparations and under similar experimental conditions. Pharmacological characterization revealed that both assays involved interaction with the D1 receptor or closely associated sites. In order to investigate whether the binding sites for 3H-SCH 23390 and DA in fact are identical, the antagonistic effects of a variety of pharmacologically active compounds were examined. Surprisingly, the Ki-values obtained from Schild-plot analysis of the antagonism of DA-stimulated AC, were 80-240 times higher than the Ki-values obtained from competition curves of 3H-SCH 23390 binding. Since both assays were performed under identical conditions, the differences in Ki-values indicate the possibility of different binding sites for DA and 3H-SCH 23390 or, that DA and 3H-SCH 23390 label different states of the same receptor.

Adenylyl Cyclases↗

Increased thiopental sensitivity in cardiac patients.

The average dose of thiopental necessary for induction was 3.4 mg/kg body weight in seven patients on long-term therapy with digoxin and a diuretic and 4.7 mg/kg body weight in seven matched control patients (P less than 0.05). The initial volumes of distribution (V1) did not differ significantly. The amounts of thiopental redistributed (removed from V1) during the induction were calculated as V1 X k12 X ct and V1 X k13 X ct, where k12 and k13 are the rate constants describing the drug transfer from V1 to V2 and V3 and ct the computer-calculated average thiopental concentration in V1 during the initial 40 s of the induction period. There was no evidence of a lower amount being removed during the induction in the cardiac patients. The intravascular drug concentration at the time of sleep was expressed as the average of the arterial and the venous sleep concentrations. In the cardiac patients the average of that value was 20.1 micrograms/ml and in the control patients 30.2 micrograms/ml (P less than 0.05). It is concluded that the lower dose requirement in the cardiac patients was caused at least in part by a higher cerebral sensitivity to the drug.

Aged↗