Biomedical subjects

L Maes

Publications and source records attributed to L Maes.

At least 19 recordsLinked to original sources

PubMed2007

Progression of astrocytomas and meningiomas: an evaluation in vitro.

OBJECTIVES/BACKGROUND: In biological terms, progression means that malignancy increases as genetic mutations accumulate leading to increased proliferation and invasion capacity. By verifying the proliferation capacity, human telomerase reverse transcriptase (hTERT) expression and in vitro invasion, in a group of highly malignant glioblastomas, benign meningiomas and astrocytomas, at the initial stage of progression, we have analysed putative progression in vitro for proliferation and telomerase expression. MATERIALS AND METHODS: The relative proliferation status (visualized with Ki-67 antibodies) and presence of hTERT protein was analysed in 27 intracranial tumours (6 astrocytomas, 8 glioblastomas and 13 meningiomas) by immunohistochemistry on paraffin-embedded biopsy tissue, as well as on primary tumour-derived cell cultures. A confrontation model was used to analyse invasiveness in vitro. RESULTS: The mean proliferation indices were 22.3 (SD = 18.1) for glioblastomas and 2.1 (SD = 1.9) for low-grade (LG) astrocytomas. The group of benign meningiomas had a labelling index of 2.2 (SD = 2.7). Mean percentages of staining for hTERT varied between 36.5 (SD = 28.4) for glioblastomas and 10.2 (SD = 8.6) for LG astrocytomas. The group of benign meningiomas had a labelling index of 12.4 (SD = 19.2) for hTERT. A significant difference was seen for Ki-67 (P < 0.05) and hTERT (P < 0.001) in vivo versus in vitro. No difference was seen between the group of invasive and non-invasive tumour-derived cell cultures for the histopathological markers Ki-67 and hTERT (P > 0.05) in vitro. CONCLUSIONS: The elevated expression of hTERT and Ki-67 in vitro provides a potential prognostic tool for early detection of the progression of brain tumours. As tumour cells require telomerase for continued proliferation, the expression of hTERT may mark immortality, leading to indefinite life span. On the other hand, hTERT expression and cell proliferation are not linked directly to invasion in vitro.

Adolescent↗

PubMed2006

Asthma and wheezing symptoms in young people in six Western countries.

BACKGROUND: Asthma diagnosed in children shows wide geographical variations. Large scale surveys identify children with diagnosed asthma, but neglect the group of youngsters with multiple asthmatic complaints. METHODS: A short validated asthma questionnaire was included in six national surveys of the Health Behaviour in School-Aged Children Study. Prevalence rates are presented by country, gender and age. Gender and age differences are analysed using binary and multinomial logistic regressions controlling for age and smoking. RESULTS: Large country differences are observed in the prevalence rates of diagnosed asthma (8.6%-20.9% in boys, 6.9%-18.5% in girls) and young people with "asthma-like symptoms" (9.6%-20.2% in boys, 9.2%-23.1% in girls). When controlling for age and smoking, significant gender differences are observed (more diagnosed asthma in boys, more asthmatic symptoms in girls). Age differences were observed in adolescents with "asthma-like symptoms", but not in diagnosed asthma. CONCLUSIONS: Using a short asthma questionnaire, large differences in diagnosed asthma and wheezing symptoms are observed between the countries. A considerable group of youngsters with "asthma-like symptoms" is detected in all countries, and may be an unrecognised risk group in health promotion.

Adolescent↗

PubMed2005

School food policy at primary and secondary schools in Belgium-Flanders: does it influence young people's food habits?

OBJECTIVE: To describe the availability of food items at primary and secondary schools in Belgium-Flanders and to examine the influence of school food policy (availability of food items, school food rules, nutrition education programmes) and aggregated school socioeconomical status (AGG SES) on the consumption of fruit, soft drinks, crisps and sweets, using multilevel modelling. DESIGN, SETTING AND SUBJECTS: In spring 2002, 360 schools were invited to participate in the Health Behaviour in School-aged Children survey. In January 2003, the same schools were asked to complete a short school policy questionnaire. Pupils of 197 schools participated in the pupil survey (n=16560); 247 school principals completed the school questionnaire; for 157 schools data were available for both (n=12 360). RESULTS: Mineral water, fruit juice, chocolate milk, and soup were available in most schools. Whole fat milk was available in most primary schools; soft drinks, diet soft drinks and biscuits were available in most secondary schools. Fruit was available in 14% of primary and 26% of secondary schools. Assessment of the variation in the outcome variables revealed no significant between-school variation in primary schools, but considerable variation between secondary schools in the consumption of soft drinks, sweets and crisps (but not fruit). School characteristics explaining some of this school variance independent of pupil level characteristics were: for soft drinks: availability at the school, rules regarding the consumption of sweets and AGG SES; for sweets: AGG SES; and for crisps: rules regarding the consumption of savoury snacks and AGG SES. CONCLUSION: The results indicate that school food policy can have an impact on adolescents' food habits.

Adolescent↗

PubMed2005

Young adolescents' nutrition assessment on computer (YANA-C).

OBJECTIVE: To assess the relative validity and acceptability of the computerised 24-h recall 'Young Adolescent's Nutrition Assessment on Computer (YANA-C)'. DESIGN: Food and nutrient intakes assessed with YANA-C were compared with food records (study 1) and 24-h dietary recall interviews (study 2). MAIN OUTCOME MEASURES: Intakes of food groups (fruit, fruit juice, vegetables, potatoes, bread, cereals, milk, cheese, other milk products, soft drinks, diet soft drinks, sugar/sweets, pastry/cookies, savoury snacks, butter/sauces, eggs, fish, meat) and nutrients (energy, carbohydrates, protein, fat, fiber, calcium, vitamin C and iron). SUBJECTS AND SETTING: A total of 237 pupils (11-14 y) from two primary and four secondary schools (study 1: n = 136; study 2: n = 101) in Belgium-Flanders. RESULTS: YANA-C proved to agree well with both standard methods in categorizing subjects in consumers and nonconsumers (kappa(study 1) = 0.48-0.92; kappa(study 2) = 0.38-0.90). Spearman's correlations for energy and nutrient intakes ranged between 0.44 and 0.79 for study 1 and between 0.44 and 0.86 for study 2. Nutrient and energy intakes were in general (excluding calcium) significantly higher in YANA-C in comparison with the food record, but not in comparison with the interview (only fiber). Statistics used to investigate whether YANA-C agreed with the other methods in ranking portions/amounts in consumers only were fair to moderate for most of the food groups (weighted kappa study 1 = 0.11-0.55; study 2 = 0.04-0.73); amounts in consumers only, were significantly lower in YANA-C against both standards for cereals; amounts were significantly higher in YANA-C against the food record for milk, soft drinks, sugar/sweets and savoury snacks and against the interview for potatoes. Only a few pupils evaluated the program negatively. CONCLUSION: YANA-C is a promising method to collect detailed dietary information from young adolescents with relatively low staff resources, useful in many nutrition research applications.

Adolescent↗

PubMed2005

The hTERT-protein and Ki-67 labelling index in recurrent and non-recurrent meningiomas.

Meningiomas are considered as benign neoplasms affecting the coverings of the central nervous system and compromise approximately 20% of all intracranial tumours. However, a number of these tumours recur even after total resection. The aim of this study is to evaluate the prognostic significance for recurrence of the human telomerase catalytic subunit (hTERT) in the cells of meningiomas. The expression of hTERT-protein can be evaluated by immunohistochemical staining using a monoclonal antibody against hTERT (clone 44F42, NCL-L-hTERT). The interdependence between tumour recurrence and cell proliferation in this study is analysed by Ki-67 immunoreactivity (clone MIB-1). Archival material from 29 non-recurrent and 32 recurrent tumours has been evaluated, including specimens from World Health Organization (WHO) stages I (n = 73), II (n = 2) and III (n = 12). Although the tumours were categorized as benign meningiomas following the WHO classification, recurrence in 22 of 50 cases did not correlate with the tumour stage. For hTERT staining, the following results were found for nucleolar and total nuclear staining, respectively: non-recurrent meningiomas, 2.9% (+/- 7.7) and 3.0% (+/- 8.0); recurrent meningiomas at first resection, 16.8% (+/- 19.7) and 31.6% (+/- 30.2). Concerning the Ki-67 labelling index (LI): for the group of non-recurrent meningiomas, results were 2.1% (+/- 1.7) and for the recurrent group at first resection, 1.7% (+/- 2.0). A significant difference was seen for the hTERT staining (P < 0.001) between the non-recurrent and recurrent meningiomas, whereas no statistical significance was found for Ki-67. In conclusion hTERT-positive meningiomas had a high incidence for recurrence. Ki-67 was a good marker of cell proliferation status of the tumours, but did not correlate with recurrence; thus, hTERT alone seemed to be a potential predictor for recurrence.

Antibodies, Monoclonal↗

PubMed2005

The hTERT protein as a marker for malignancy in meningiomas.

The meningioma evolution remains problematic as 6 to 19% relapse after total resection. We have no criterion or marker to predict with certainty the tumour behaviour, and the WHO grading system is to a certain degree controversial. Telomerase expression seems to play an active role in conferring to the tumour cell indefinite life span. Telomerase activity has been documented via TRAP protocol and telomerase messenger expression (hTERT mRNA). In meningiomas the protein hTERT itself has not been studied directly. Thirty tumour samples of meningiomas operated in our Neurosurgical Department are reviewed with a mean follow-up of 4 years. Specifically hTERT protein, resection type, proliferation markers (Ki-67), and recurrences are evaluated. MRI is used for recurrence controls. Seven samples appeared to be hTERT-positive and all seven showed recurrence. Four patients had undergone a subtotal resection (STR). Among them two were hTERT-positive; only these showed recurrence and malignancy. Of the five macroscopically total resections (MTR), two were initially histologically benign and progressed to malignancy. A strong correlation was found between hTERT and recurrences (coefficient=0.989; p=0,01) with the Spearman's rho test, and weaker one between the Ki-67 and hTER (coefficient=0.672; p<0.0001). The hTERT staining revealed the presence of the hTERT protein not only in their nucleoli but sometime outside as nuclear speckles. The presence of nucleolar or subnuclear hTERT is directly correlated to recurrence and progression towards malignancy. Relocalisation of this protein was confirmed. A distinction is proposed between regrowth, based on normal proliferation (Ki-67) which can accompany subtotal resection and recurrence. Recurrence appears to be pathologic proliferation linked to hTERT presence. The hTERT presence predicts a sombre clinical outcome at mid-term for the individual patient.

Adolescent↗

PubMed2003

World Association for the Advancement of Veterinary Parasitology (WAAVP) guidelines for evaluating the effectiveness of anthelmintics in chickens and turkeys.

These guidelines have been prepared to assist in the planning, operation and interpretation of studies designed to assess the effectiveness of drugs against helminth parasites of chickens and turkeys. They are the first to be compiled under the auspices of the World Association for the Advancement of Veterinary Parasitology (WAAVP) for these parasites. The advantages and disadvantages of the widely used critical and controlled tests are discussed. Information is provided on the selection of animals for experiments, animal housing, feed, dose determination studies, confirmatory and field trials, record keeping and necropsy procedures. This document should help investigators and those involved in product approval and registration in conducting and evaluating studies concerned with determining the effectiveness and safety of anthelmintic drugs.

Animal Husbandry↗

PubMed2003

Comparative study of eight well-known polyphenolic antioxidants.

Eight antioxidants from five different polyphenolic classes (cinnamic acids, benzoic acids, flavonoids, proanthocyanidins and stilbenes), and the water-soluble vitamin E derivative trolox were examined for their antioxidant activity in-vitro. In addition, the compounds were tested for their cytotoxicity on growing fibroblasts and their inhibition of the classical pathway of the complement system. Procyanidin C1 was shown to be a good scavenger of both DPPH(*) and HO(*), and a strong inhibitor of lipid peroxidation and the classical pathway of the complement system. Consequently, procyanidin C1 was classified as the most promising antioxidant in-vitro of all compounds tested. In contrast, genistein exhibited a very low antioxidant activity in both the lipid peroxidation and the DPPH(*) scavenging assay, a high cytotoxicity and a low complement-inhibiting activity.

Antioxidants↗

PubMed2001

A prodrug form of a Plasmodium falciparum glutathione reductase inhibitor conjugated with a 4-anilinoquinoline.

Glutathione (GSH), which is known to guard Plasmodium falciparum from oxidative damage, may have an additional protective role by promoting heme catabolism. An elevation of GSH content in parasites leads to increased resistance to chloroquine (CQ), while GSH depletion in resistant P. falciparum strains is expected to restore the sensitivity to CQ. High intracellular GSH levels depend inter alia on the efficient reduction of GSSG by glutathione reductase (GR). On the basis of this hypothesis, we have developed a new strategy for overcoming glutathione-dependent 4-aminoquinoline resistance. To direct both a 4-aminoquinoline and a GR inhibitor to the parasite, double-drugs were designed and synthesized. Quinoline-based alcohols (with known antimalarial activity) were combined with a GR inhibitor via a metabolically labile ester bond to give double-headed prodrugs. The biochemically most active double-drug 7 of this series was then evaluated as a growth inhibitor against six Plasmodium falciparum strains that differed in their degree of resistance to CQ; the ED(50) values for CQ ranged from 14 to 183 nM. While the inhibitory activity of the original 4-aminoquinoline-based alcohol followed that of CQ in these tests, the double-drug exhibited similar efficiency against all strains, the ED(50) being as low as 28 nM. For the ester 7, a dose-dependent decrease in glutathione content and GR activity and an increase in glutathione-S-transferase activity were determined in treated parasites. The drug was subsequently tested for its antimalarial action in vivo using murine malaria models infected with P. berghei. A 178% excess mean survival time was determined for the animals treated with 40 mg/kg 7 for 4 days. No cytotoxicity due to this compound was observed. Work is in progress to extend and validate the strategy outlined here.

Aniline Compounds↗

PubMed2001

Synthesis and in vitro and in vivo antimalarial activity of new 4-anilinoquinolines.

A new series of 4-anilinoquinolines with two proton-accepting side chains has been synthesized. Antimalarial activity and levels of cytotoxicity upon both MRC-5 cells and macrophages were found to be highly dependent upon the features of these side chains. Several compounds were found to be active in the low nanomolar range, against both chloroquine-sensitive and -resistant strains of Plasmodium falciparum in vitro. From among them, a morpholino derivative cured mice infected by Plasmodium berghei and displayed a lower toxicity than amodiaquine upon mouse macrophages.

Aniline Compounds↗

PubMed2001

Antiplasmodial activity and cytotoxicity of bis-, tris-, and tetraquinolines with linear or cyclic amino linkers.

Bisquinoline heteroalkanediamines were structurally modified in order to study the effects of enhanced bulkiness and rigidity on both their activity on strains of Plasmodium falciparum expressing different degrees of chloroquine (CQ) resistance and their cytotoxicity toward mammalian cells. While cyclization yielded molecules of greater rigidity that were not more active than their linear counterparts, they were characterized by an absence of cytotoxicity. Alternatively, dimerization of these compounds led to tetraquinolines that are very potent for CQ-resistant strains and noncytotoxic.

Animals↗

PubMed2001

Novel inhibitors of Trypanosoma cruzi dihydrofolate reductase.

There is an urgent need for the development of new drugs to treat Chagas' disease, which is caused by the protozoan parasite Trypanosoma cruzi. The enzyme dihydrofolate reductase (DHFR) has been a very successful drug target in a number of diseases and we decided to investigate it as a potential drug target for Chagas' disease. A homology model of the enzyme was used to search the Cambridge Structural Database using the program DOCK 3.5. Compounds were then tested against the enzyme and the whole parasite. Compounds were also screened against the related parasite, Trypanosoma brucei.

Animals↗

PubMed2001

Potent and specific inhibitors of trypanothione reductase from Trypanosoma cruzi: bis(2-aminodiphenylsulfides) for fluorescent labeling studies.

In order to optimise the activity of bis(2-aminodiphenylsulfides) upon trypanothione reductase (TR) from Trypanosoma cruzi, a new series of bis(2-aminodiphenylsulfides) possessing three side chains was synthesized. Various moieties were introduced at the end of the third side chain, including acridinyl or biotinyl moieties for fluorescent labeling studies. TR inhibition was improved: the most potent inhibitor (IC50 = 200 nM) was selective towards TR versus human glutathione reductase and corresponded to a single myristyl group. Compounds were also tested in vitro upon Trypanosoma cruzi and Leishmania infantum amastigotes, upon-Trapanosoma brucei trypomastigotes, and for their cytotoxicity upon human MRC-5 cells. In the presence of serum, acridine derivative was no longer detectable in mass spectrometry and its antitrypanosomal activity no longer observed. This transformation might explain the absence of correlation between the potent TR inhibition and the in vitro and in vivo antiparasitic activity with both of the first generation of 2-aminodiphenylsulfides.

Aniline Compounds↗

PubMed2001

Antimalarial in-vivo activity of bis(9-amino-6-chloro-2-methoxyacridines).

In the fight against malaria, chemotherapy using bisacridines may represent an alternative method to overcoming chloroquine-resistance. Eight bis(9-amino-6-chloro-2-methoxyacridines), in which acridine moieties were linked by polyamines substituted with a side chain, were tested for their in-vivo activity upon mice infected by Plasmodium berghei. Three of the compounds revealed antimalarial activity but no relationship could be deduced from a comparison of in-vitro and in-vivo activities. N-alkylation of the central amino group generated toxicity and, therefore, only compounds N-acylated in this position can be selected as leads.

Aminoacridines↗

PubMed2001

"One-pot" synthesis and antimalarial activity of formamidine derivatives of 4-anilinoquinoline.

Amodiaquine (AQ) is an antimalarial which is effective against chloroquino-resistant strains of Plasmodium falciparum but whose clinical use is severely restricted because of associated hepatotoxicity and agranulocytosis. "One-pot" synthesis of formamidines likely to be transformed into AQ derivatives is reported. Compared with AQ, the new compounds were devoid of in vitro cytotoxicity upon human embryonic lung cells and mouse peritoneal macrophages. One showed a potent in vivo activity in mice infected with P berghei. Transformation of this compound by reductive amination led to a new type of AQ derivatives that displayed an in vitro activity similar to that of AQ but did not lead to toxic quinone-imines.

Amidines↗

PubMed2000

Antimalarial, antitrypanosomal, and antileishmanial activities and cytotoxicity of bis(9-amino-6-chloro-2-methoxyacridines): influence of the linker.

Forty bis(9-amino-6-chloro-2-methoxyacridines), in which acridine moieties are joined by alkanediamines, polyamines, or polyamines substituted by a side chain, were synthesized and tested for their in vitro activity upon the erythrocytic stage of Plasmodium falciparum, trypomastigote stage of Trypanosoma brucei, and amastigote stage of Trypanosoma cruzi and Leishmania infantum as well as for their cytotoxic effects upon MRC-5 cells. Results clearly showed the importance of the nature of the linker and of its side chain for antiparasitic activity, cytotoxicity, and cellular localization. Among several compounds devoid of cytotoxic effects at 25 microM upon MRC-5 cells, one displayed IC(50) values ranging from 8 to 18 nM against different P. falciparum strains while three others totally inhibited T. brucei at 1.56 microM.

Acridines↗

PubMed2000

Drug-abbreviated infections of Trichostrongylus colubriformis and development of immunity in jirds (Meriones unguiculatus).

The objective of this study was to examine the development and the duration of immunity achieved with drug-abbreviated infections of Trichostrongylus colubriformis in jirds (Meriones unguiculatus). Jirds were primarily infected either by trickle infection with 6 x 100 infective larvae (L3) of T. colubriformis at 3-day intervals or by a single infection with 600 L3. On day 35 post-infection, one batch of jirds from each group was autopsied; the others were treated with oxfendazole at a dose of 5 mg/kg and were challenged with 1,000 L3 on either day 7 or day 42 post-treatment. All jirds were autopsied at 17 days post-challenge. Trickle infection resulted in lower levels of egg production during the primary infection period. The systemic IgM and IgG antibody response was significantly stronger in trickle- and single-infected groups as compared with the negative control group (P < 0.01-P < 0.05). Significantly higher levels of intestinal IgA were demonstrated in trickle- and single-infected groups than in the negative control group (P < 0.01). Numbers of mucosal mast cells increased following infection, but this was not dependent on the type of immunisation. After challenge the extent of worm reduction was greater in trickle-infected than in single-infected subgroups. The IgM and IgG response was significantly stronger in challenged subgroups as compared with negative control subgroups (P < 0.01). However, the IgG response was weaker in control challenged subgroups than in challenged subgroups (P < 0.01). There was a negative correlation between the IgG response and the worm burden after the second challenge (r = -0.73). The acquired immunity to T. colubriformis infection in jirds developed within 5 weeks of primary infection. The level of immunity was higher after trickle infection than after single infection. Furthermore, the immunity persisted for at least 6 weeks after oxfendazole treatment in the absence of a worm burden and larval intake, which is very similar to the situation in domestic ruminant hosts.

Animals↗

PubMed2000

Trypanothione reductase inhibition/trypanocidal activity relationships in a 1,4-bis(3-aminopropyl)piperazine series.

A series of symmetrically substituted 1,4-bis(3-aminopropyl)piperazines was synthesized and tested towards trypanothione reductase and for its in vitro trypanocidal potency. The most trypanocidal amongst them was found to be totally inactive towards the enzyme and thus constitutes a lead structure for the identification of new potential Trypanosoma cruzi target(s).

Animals↗