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Biomedical subjects

J van Dijk

Publications and source records attributed to J van Dijk.

35 records · Page 2Linked to original sources

In vitro biochemical and in vivo biological studies of the uridine 'rescue' of 5-fluorouracil.

The effect of delayed uridine administration on the in vitro growth inhibitory effects of 5-fluorouracil (5FU) and on the in vivo antitumour activity and toxicity was studied. In vitro growth inhibition of the human intestinal cell lines WiDr and Intestine 407 by 3 microM 5FU could be reversed by 1.0 mM uridine; the effect was more pronounced with WiDr cells. At 0.1 mM uridine an intermediate effect was observed. Inhibition of colony formation in both cell lines could also be reversed by delayed administration of uridine at 0.1 and 1 mM. Incorporation of 5FU into RNA of WiDr cells did not proceed after addition of uridine, in contrast to Intestine 407 cells. In these cells only a partial inhibition was observed. In vivo we studied the effect of uridine on two colon carcinoma tumour lines, the 5FU sensitive Colon 38 and the relatively resistant Colon 26. 5FU was administered i.p. in a weekly schedule. With Colon 26 delayed administration of uridine (3500 mg kg-1) at 2 and 20 h after 5FU enabled us to increase the 5FU dose from 100 to 250 300mg kg-1. The combination of high-dose 5FU and uridine resulted both in a superior antitumour effect and an increase in life span. In the 5FU sensitive Colon 38 we determined whether the sensitivity to 5FU was affected by uridine. Mice were treated at the non-lethal dose of 100 mg kg-1 which inhibited tumour growth almost completely. Delayed administration of uridine did not significantly affect the antitumour effect. In non-tumour bearing mice we studied the time course of the reversal of the haematological toxicity of 5FU. The effective dose of 100 mg kg-1 induced a significant decrease in leukocytes; in combination with delayed uridine the leukopenia was less severe and recovered more rapidly. 5FU also induced a decrease in haematocrit, which could be prevented by delayed administration of uridine. In conclusion, in cell culture the reversal of 5FU cytotoxicity could be achieved at a low concentration of 0.1 mM uridine, the extent of the reversal might be related to the 5FU incorporation into RNA. In vivo the relatively resistant tumour Colon 26 could be treated with a higher dose of 5FU in the presence of uridine. The sensitivity to 5FU of the sensitive Colon 38 was not affected by delayed administration of uridine, while the haematological toxicity of 5FU was less. So, delayed administration of uridine after 5FU resulted in an improved therapeutic effect in both a relatively resistant and sensitive tumour.

Animals↗

Perfusion of tumor-bearing kidneys as a model for scintigraphic screening of monoclonal antibodies.

Tumor-bearing human kidneys were used in an ex vivo perfusion model to screen monoclonal antibodies, recognizing renal cell carcinoma-associated antigens for diagnostic potential in vivo. Perfusion of tumor-bearing kidneys with 99mTc-labeled G250 and RC38 antibody resulted in visualization of the tumor, whereas perfusion with two other monoclonal antibodies, RC2 and RC4, did not lead to tumor visualization. Uptake of radiolabel in normal kidney tissue was low for G250 and RC38 antibody. Tumor-to-kidney tissue ratios after perfusion with G250 and RC38 antibody were 2.7 and 2.2, respectively. After rinsing for 3 hr with unlabeled perfusion fluid the tumor-to-kidney tissue ratios increased to 8.6 for G250 antibody and to 2.7 for RC38 antibody. We conclude that perfusion of tumor-bearing human kidneys with radiolabeled monoclonal antibodies is a relatively simple way to evaluate renal cell carcinoma associated monoclonal antibodies as diagnostic agents in vivo.

Antibodies, Monoclonal↗

Surface-free energy and bacterial adhesion. An in vivo study in beagle dogs.

Conflicting reports have been presented on the rôle of substratum surface free energy (s.f.e.) on bacterial adherence. It is the aim of the present study to evaluate the effect of the s.f.e. of substrata on bacterial adherence in vivo. The following substrata with s.f.e. varying from 23.3-124.9 erg X cm-2 were cut into facings of 5 by 6 mm, polished and cleaned: polytetrafluorethylene (PTFE), Parafilm, polyvinylchloride (PVC), polymethylmethacrylate (PMMA), bovine dentin, bovine enamel and glass. In 5 beagle dogs, 7-9 years old, part of the buccal periodontium of the upper cuspids was excised and crowns were made and cemented with a non-fluoridated cement. The facings were placed in the crowns and placed in the oral cavity for 2 h. After removal, the facings were rinsed in saline. S.f.e. was assessed from contact angles with water, water/n-propanol mixtures and a-bromonaphthalene, according to the concept of dispersion and polar components, firstly on clean air dried facings and later on facings exposed to the oral cavity for 2 h. Immediately after rinsing, the water contact angle was measured as a function of time, to monitor the evaporation of free water from the protein layer adsorbed on the substrate which had been exposed to the oral cavity. It appeared that after a rapid increase in contact angle, a stable maximum value was obtained after 40-120 min depending on the substratum. S.f.e.'s of the protein-coated substrata were subsequently determined after a 120 min drying period. Following the contact angle determinations, the exposed facings were stained with ethidium bromide, enabling fluorescence microscopical counting of the adhered microorganisms.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Experimental gingivitis in a Down's syndrome child and sibling.

Biopsies were taken from a child with Down's syndrome and her sibling under experimental gingivitis conditions and analyzed with monoclonal antibodies. At first, plaque caused a shift from a predominance of T cells to a predominance of B cells. Later, a gradual increase of T cells and a looser arrangement of B cells were observed.

B-Lymphocytes↗

Periodontal disease in Down's syndrome: a review.

Cross-sectional as well as longitudinal studies indicate that the prevalence of periodontal disease in persons with Down's syndrome (DS) under the age of 30 years is extremely high. It is even noted in the deciduous dentition. The progression of the disease is rapid, especially in the younger age groups. Severe periodontal breakdown with horizontal bone loss is often present in the lower anteriors. The large amount of plaque and calculus alone cannot explain the severity of periodontal disease in DS persons. Many contributing factors are reported. Abnormal capillary morphology, disorders in connective tissue and anatomical aspects of teeth are some of those considered to be of influence. Alteration in immunological response may also play a role in the progression of the disease process. Disorders in the polymorphonuclear leucocyte function and monocyte function have been reported in persons with DS. T-cell functioning declines after the first 10 years of life. T-cell lymphocyte counts are low and an immature subset of T-lymphocytes is present. This latter effect occurs especially in institutions where the immunological system is under stress. The altered immune response together with higher calculus scores may explain the difference in severity of periodontal disease between institutionalized DS children and those living at home.

Adolescent↗

Experimental gingivitis around deciduous teeth in children with Down's syndrome.

Epidemiological studies have shown that there is a high prevalence and rapid progression of periodontal disease in children with Down's Syndrome (DS). In this respect, DS children exhibit a markedly different response compared with healthy children. In order to understand the reasons for this difference, a controlled study was set up to determine the extent and the quality of the differences in the early periodontal tissue response towards dental plaque in the deciduous dentition of DS children and matched control children. In a preliminary investigation, the gingival health was estimated by determining the bleeding tendency. 9 healthy children were selected from a group of 14 and matched with 9 DS children with respect to plaque development, sulcus depth and age. The DS children had a higher bleeding tendency than the matched controls. In the DS children, moreover, a correlation was found between bleeding tendency and age. No such correlation was found in the controls. After a period of intensive oral hygiene, all cleaning of teeth was discontinued for 21 days. The amount of plaque according to the plaque index, the gingival health according to the gingival index, and the amount of crevicular leucocytes and gingival exudate were assessed at days 0, 7, 14 and 21. During the experimental phase of the study, the amount of plaque increased at a similar rate in both groups. In the DS children, the development of gingival inflammation started earlier and was more extensive. It increased after day 14, whereas in the control children, the gingival inflammation seemed to stabilize at this time. The results of the present experimental study thus confirm earlier results from epidemiological studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗

Effect of vision on development of multiply handicapped children.

The effect of vision on (abnormal) development was studied in a group of 81 visually and/or hearing impaired rubella children, 18 of whom had bi-lateral cataracts operated between 2-18 months, 3 children had uni-lateral cataract, and 60 children had clear media. In this group of children the effect of visual impairment on (abnormal) behaviour is enormous. Vision has in these children a greater impact on their development than hearing impairment or prenatal variables such as low birthweight. This justifies the conclusion of cataract surgery as early as possible. After surgery the environment should be manipulated in such a way, that it becomes visually attractive for the child. This might prevent strong light-gazing and/or exhibiting the phenomenon of HBE (Hand Before the Eyes). The desire for rocking and jumping should be seen in connection with stimulus deprivation, especially social ones. It is therefore recommended that these children should be offered ample experience and interaction with the environment, such as giving the child proprioceptive stimuli, rocking him in the crib or on the lap. The interest in the world outside his own body should be encouraged by manipulating the children's special interest (such as changing the objects for light gazing). The purpose for this kind of management is to develop orientation reflex, in other words to stimulate the child to give attention to the world around him and therefore learn from it. When this sort of early stimulation is provided the child's development may be not so retarded as without appropriate intervention.

Animals↗

The effect of 4-aminopyridine on acetylcholine release.

The effect of 2-, and 4-aminopyridine (4-APYR) on the release mechanism of acetylcholine (ACh) from the nerve terminals of the Auerbach plexus-longitudinal muscle preparation of the guinea-pig ileum, suspended in eserinized Krebs' solution, was investigated. 2- and 4-APYR increased the release of ACh from the nerve terminals at rest and at both low and high frequency stimulation. The enhanced ACh release was found to be due to increased volley output. At lower frequency of stimulation, potentiation of ACh release was much higher than at higher rate of stimulation. 4-APYR was able to increase ACh release in the absence of [Ca2+]o. However, when a Ca-chelating agent, EDTA, was also added to the Ca-free Krebs' solution, 4-APYR was entirely ineffective. The depression of ACh release induced by Mg-excess was completely antagonized by 4-APYR. Tetrodotoxin (TTX) prevented augmentation of ACh release by 4-APYR. It is suggested that 4-APYR lowers the demand of nerve terminals for [Ca2+]o required for the excitation-secretion coupling process. The presence of a low concentration [Ca2+]o, however, is essential for the action of 4-APYR.

Acetylcholine↗

Oxime ether derivatives, a new class of nonsteroidal antiinflammatory compounds.

A series of new 2-hydroxyethyl and carboxyalkyl ethers of aromatic oximes was found to possess pronounced antiinflammatory activity in the carrageenan-induced edema test in the rat. The activity was limited mainly to derivatives of p-haloacetophenone oxime and of p-halobenzaldehyde oxime. Nevertheless, the hydroxyethyl and carboxyalkyl groups may be converted into many derivatives with maintenance of activity. Some structure-activity relationships are in contrast to those of the well-known antiinflammatory arylacetic acids. The activity is limited to the E stereoisomers. The hydrochloride of 2-(dimethylamino)ethyl (E)-[[(p-chloro-alpha-methylbenzylidene)-amino[oxy]acetate (36, INN name Cloximate) was chosen for clinical evaluation. The first results agree with the pharmacological prospects.

Animals↗