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Biomedical subjects

J J Legros

Publications and source records attributed to J J Legros.

At least 37 records · Page 2Linked to original sources

Inhibitory effect of oxytocin on corticotrope function in humans: are vasopressin and oxytocin ying-yang neurohormones?

Oxytocin (OT) and vasopressin (VP) are very similar neurohypophyseal peptides. While VP is known as an ACTH stimulating factor synergistic to CRF since two decades, the inhibiting activity of OT, first demonstrated in the human, is now confirmed in various species including mouse and rat!It is likely that endogenous oxytocinergic system which can be activated by physiological and/or pharmacological manipulation can "buffer" the stress activated vasopressin-ACTH-cortisol action. Since VP and OT share also opposite action on cognitive function, those two "sister" neuropeptides might be considered as "ago-antagonist" or "ying-yang" neurohormones!

Adrenal Cortex↗

[Interindividual variability of contingent negative variation].

The use of CNV in clinical practice requires the choice of a standardised protocol, the constitution of reference normative data and the consideration of intra- and interindividual variability. For this purpose, we recorded CNV in 86 control subjects (44 men and 42 women, 18 to 62 years old (mean age = 34 +/- 13 years) during a reaction time paradigm with a warning signal and a 1-second S1-S2 interval. Moreover, the role of inter-stimulation interval was analysed in a group of 12 subjects through the comparison of recordings made with 1- and 3-second intervals. The CNV amplitude, its morphology and topographic distribution as well as its resolution mode and evolution through the recording were studied. The subjects' performances and their interactions with electroencephalographic data were also included in the analyses. Our results underscore the contribution of age and gender and psychological factors to CNV variability. CNV amplitude (both M1 and M2) increased and changed topographic distribution toward more central sites in older. Men had faster reaction times than women and lower post-S1 P300. Moreover, the life events-related stress and the subject's current anxiety level were accompanied by a decreased CNV amplitude.

Adolescent↗

Daytime 50 Hz magnetic field exposure and plasma melatonin and urinary 6-sulfatoxymelatonin concentration profiles in humans.

Concern about the health effects of extremely low frequency (ELF) magnetic fields (MF) has been raised by epidemiological studies indicating an association between certain cancers and living near power lines or working in high electric field environments. Alterations in pineal function have been proposed as a mechanism through which power-frequency MFs may interact with living organisms. A double blind laboratory study was performed to evaluate daytime exposure effects of 100 microT root mean square (rms) 50 Hz MF. Three head exposure sessions of 30 min each were performed: sham, continuous, and intermittent (15 s on/off cycles) MFs were presented to each subject in early or late afternoon (13:30 or 16:30 hr). Twenty-one healthy male volunteers (20-27 yr old) participated in these 3-weekly experimental conditions. Blood samples were drawn for serum melatonin measurement, hourly at night (from 20:00 to 07:00 hr) under controlled environmental conditions. Urinary excretion of 6-sulfatoxymelatonin (aMT6s), the main melatonin metabolite, was measured for a 17 hr period, by means of urine samples taken at 19:00 hr (14:00-19:00 hr "afternoon period"), 23:00 hr (19:00-23:00 hr "evening period"), and 07:00 hr, day 2 (23:00-07:00 hr day 2 "night-time period"). There were no significant differences in either plasma melatonin or in aMT6s excretion profiles in the three experimental conditions. However, a tendency for a smaller increase of night-time urinary aMT6s after continuous MF exposure was found (P=0.08) particularly in men with the lower excretion rate of aMT6s ("Low Group") (P=0.07). We conclude that this study does not indicate that daytime acute MF exposure influences either melatonin secretion or aMT6s excretion. Inter-individual differences in pineal production of melatonin, however, have to be taken into account in further studies.

Adult↗

Novel plasma extraction procedure and development of a specific enzyme-immunoassay of oxytocin: application to clinical and biological investigations of small cell carcinoma of the lung.

Paraneoplastic secretion of the lactation-inducing hormone oxytocin (OT) has been reported in about 30% of cases of small cell carcinoma of the lung (SCCL). In order to investigate the role of OT in the biology of SCCL tumours, a specific enzyme-immunoassay (EIA) for OT, which can be applied to both human plasma and culture medium, has been developed. OT EIA is performed on 96-well microtiter plates coated with a rabbit polyclonal antibody (Ab) anti-OT (04). This antibody does not exhibit any significant cross-reactivity either with vasopressin (VP) or with vasotocin (VT). The immunological reaction involving Ab anti-OT is a competition between the tracer (biotinylated OT) and synthetic OT (standard curve) or OT present in biological samples. In order to limit interference induced by plasma proteins, plasma samples are filtrated by a one-step centrifugation on centricon YM-3 (cut-off 3000 Da). After plasma filtration, 90.7 +/- 5.1 (SD) % (n = 22) immunoreactive (IR) OT is recovered. The sensitivity of OT EIA is 1 pmol/L, while intra- and inter-assay coefficients of variation (CV) are around 3.41% and 2.84%, respectively. In healthy volunteers, plasma IR OT is 7.28 +/- 4.49 (SD) pmol/L (n = 32) with no gender difference. As shown by the data both from plasma of SCCL patients and from supernatants and cell contents of SCCL cell lines, this EIA procedure offers a novel, reproducible, specific and sensitive method for the measurement of IR OT.

Adult↗

A psycho-endocrinological overview of transsexualism.

The technical possibility of surgical sex change has opened up a debate concerning the legitimacy and utility of carrying out such an intervention at the request of the transsexual. Diagnostic, psychological, medical and ethical arguments have been brought forth, both for and against. Nonetheless, anatomical transformation by surgical means has currently become a practice as the frequency of serious gender identity disorders is constantly progressing. After a brief introduction, the present paper will consider typological, aetiological and epidemiological aspects of transsexualism. Treatment of the sex change applicant is then defined and discussed in terms of psychological, psychiatric, endocrinological and surgical aspects. Finally, the question of post-operation follow-up will be examined.

Endocrinology↗

[Is it reasonable to prescribe growth hormones in the elderly?].

During normal aging, there is a +/- 60% decrease of the endogenous GH secretion ("somatopause"). However it is safe to prescribe GH therapy only to those people who show a clear cut decrease of GH release as evidenced by low integrated 24 hr secretion and/or low plasma IGF-1. In our view, a complete clinical check up must also show, on the one hand, an abnormal decrease of the optimal quality of life and, on the other hand a willing to maintain a reasonable intellectual and physical activity in the absence of major clinical and biological abnormalities. The benefits are likely to be an increase of muscular strength and of exercise tolerance, a decrease of trabecular osteopenia, a decrease of abdominal obesity, an increase of immunocompetence and a general improvement of the "quality of life". A "pharmacological" prescription is contra-indicated whereas very low dose regimen could induce, through feed back mechanism, a putative decrease of endogenous GH-RH (and GHRPs?) function whose deleterious psychoneuroendocrine effects remain to be demonstrated.

Activities of Daily Living↗

[Autoimmune thyroiditis].

The continuum of clinical phenotype between different autoimmune thyroid diseases and mainly the common pathophysiological mechanisms have lead to a novel classification of these disorders into three types: (1) Type 1 autoimmune thyroiditis (euthyroidism associated with the presence of anti-thyroglobulin and anti-thyroperoxydase autoantibodies); (2) Type 2 autoimmune thyroiditis or Hashimoto's disease (hypothyroidism with anti-thyroglobulin and anti-thyroperoxydase autoantibodies). Postpartum thyroiditis falls into this category and is characterized by transient hyperthyroidism followed by hypothyroidism; and (3) Type 3 autoimmune thyroiditis or Graves-Basedow's disease (hyperthyroidism with anti-TSH receptor "stimulating" auto-antibodies, often associated with anti-thyroglobulin and anti-thyroperoxydase autoantibodies). Thyroid orbitopathy often complicates Type 3 autoimmune thyroiditis and is thought to result from an autoimmune response against an autoantigen common to thyroid and orbital fibroblasts/adipose cells. We present the actualized knowledge about the immunological parameters that can be detected and quantified in autoimmune thyroid diseases, about the pathophysiological mechanisms involved in these disorders, and about the options of their treatment that are currently offered to the medical community.

Biomarkers↗

[Prolonged treatment with recombined growth hormone improves bone measures: study of body composition in 21 deficient adults on treatment].

Adult growth hormone deficiency is characterized by changes in body composition: increase in total fat, decrease in lean mass and osteopenia, with a fall in Bone Mineral Content (BMC) and in Bone Mineral density (BMD) leading to a rise in risk of fracture. We have analyzed the changes in body composition in 21 adults treated from 9 to 78 months, by dual X-RAY absorptiometry (DEXA). We've demonstrated a gain in bone mass and density, particularly of axial skeleton; a latence of minimum 12 months has been necessary to objective these changes. The balance of fat and lean mass has been poorly modified by treatment except for the lean mass of the trunk, which is significantly increased. We think that the usual doses of rGH, based on IGF-1 level, are perhaps underestimated.

Absorptiometry, Photon↗

Slow-release lanreotide in the treatment of acromegaly: a study in 66 patients.

OBJECTIVE: Slow-release (SR) lanreotide is a long-acting somatostatin analog that has been developed in order to overcome the inconvenience of multiple daily subcutaneous injections of octreotide, required for metabolic control in acromegaly. Lanreotide SR has been found to be well tolerated and effective in reducing GH and IGF-I levels but clinical data are still limited compared with those with subcutaneous octreotide treatment. DESIGN: Sixty-six unselected patients with active acromegaly were therefore evaluated in a multi-center, prospective, open label study. Lanreotide SR was given at a dose of 30mg intramuscular every 7-14 days. METHODS: At baseline and after 2, 4, 8, 12, 24, 36 and 48 weeks patients underwent a clinical examination with assessment of acromegaly related symptoms, and blood was sampled for serum GH, IGF-I, prolactin, glycosylated hemoglobin, fasting glucose, hematology, kidney function and liver function tests. Biliary ultrasonography and pituitary magnetic resonance imaging were performed at baseline and after one year. RESULTS: Treatment resulted in a significant improvement in the symptom score from 2.69+/-0.27 to 1.06+/-0.17 (P<0.0001). Serum IGF-I levels fell from 699+/-38microg/l at baseline to 399+/-26microg/l (P<0.0001, n=60) after one month, after which levels remained stable: 480+/-37microg/l after 6 months (n=54) and 363+/-32microg/l after one year (n=46). GH levels dropped from 13.8+/-3.2microg/l to 4.3+/-0.7microg/l after one month (P<0.0001, n=60) and remained stable thereafter: 3.9+/-0.4microg/l (n=54) after 6 months and 3.5+/-1.1microg/l after one year (n=46). Twenty-nine out of 66 patients (44%) attained a normal age-corrected IGF-I level and 30 patients (45%) attained a GH level below 2.5microg/l. Pituitary adenoma shrinkage of at least 25% was found in 5 of 14 patients (36%) after one year. Side effects were mainly transient gastrointestinal symptoms and pain at the injection site, resulting in drug discontinuation in only 6 patients (9%). Two patients developed new gall stones. No difference was found between subcutaneous octreotide and lanreotide SR in efficacy and almost all patients preferred the easier dose administration of lanreotide SR. CONCLUSIONS: Long-term treatment of acromegaly with SR-lanreotide is effective in controlling GH and IGF-I levels and symptoms and is well tolerated in the majority of patients. Compared with subcutaneous octreotide, lanreotide SR considerably improves patient's acceptance of therapy while having the same overall efficacy.

Acromegaly↗

Effect of nicotine on rat gingival fibroblasts in vitro.

Tobacco smoking is considered a major risk factor for the development and progression of periodontal diseases (Haber, J. and Wattles, J. (1994). J. Periodontol., 64, 16-23). The purpose of this study was to determine the effects of nicotine on rat gingival fibroblasts (RGF) cultured in vitro. After ether anesthesia, rat gingival tissues were obtained from the attached gingiva of a Wistar rat. Small fragments of gingiva were maintained in culture in Petri dishes. Fibroblasts developing from these explants were collected to obtain monolayer cultures. After the fourth passage (T4), cells were supplemented with nicotine at various concentrations. Control and treated cells were examined under phase contrast or transmission electron microscopy. They were compared as regards their DNA content, mitochondrial activity, collagen and protein synthesis, and cell death by apoptosis or necrosis. Nicotine from 0.05 microM to 1 mM did not affect the DNA content or protein and collagen synthesis. At concentrations between 3 and 5 mM, growth was significantly diminished and the survival rate reduced. Ultrastructural analysis revealed dilated mitochondria and vacuolization in treated cells, suggestive of necrosis, but increased apoptosis was also revealed by cytometry. On the basis of this in vitro study, it appears that tobacco, through its component nicotine, may directly affect various functions of RGF.

Animals↗

[Towards a consensus regarding androgen substitution therapy for andropause].

"Andropause" or "male climateric" refer to the term "menopause" in the women. The parallelism between both entities is however only partial since the decrease of gonadal function in the male is very different from one individual to the other. Some men present a gonadal deficiency together with an increase gonadotropin function as early as in the 40s while others show normal testicular function at 80 or later! It appears that besides genetic factors many life events (stress, obesity, sedentarity...) can "precipitate" testicular failure. Besides the major symptoms of sexual impotency and loss of libido, testosterone deficiency also induces reversible modification in lipid profile, muscle strength, bone density ... and on some cognitive and psychological parameters. It is therefore reasonable to treat androgen deficiency in early or late aging provided a cautious urological check-up has been realized before treatment. The mode of administration (i.m., p.o., or transdermal) will depend on the principal goal of the treatment and on the wish of the patient! An annual clinical and biological urological assessment is mandatory.

Aged↗

[Melatonin. I. Physiology of its secretion].

Melatonin is a hormone mainly secreted by the pineal gland during the dark phase of the light-dark cycle. The best known function of melatonin in mammals is to transmit information concerning light-dark cycles playing the role of an active neuroendocrine transducer of environmental information. Although melatonin circadian rhythm is endogenous, based on 25 hour cycles, it is modulated by light-dark cycle. During the day, the light signal is sent to the pineal gland through a special neuronal pathway and inhibits melatonin secretion. During the night, the last neuron of this pathway which is coming from the cervical ganglion superior releases nonadrenalin in the interstitium. Nonadrenalin stimulates melatonin synthesis through cAMP accumulation. Some factors other than light can also influence melatonin levels. Electromagnetic fields, age, male sex, Cushing syndrome, hypogonadotrophic hypogonadism, alcoholism seem to be associated with lower melatonin secretion. Female sex, hypergonadotrophic hypogonadism, sport and fasting seem to be linked to higher melatonin secretion. Some pathologies and drugs can modulate some steps of the neuroanatomic pathway of melatonin synthesis. Stress has no effect. The influence of weight and height is still investigated. Once released, melatonin can act on different organs through specific receptors (retina, supra-chiasmatic nucleus, hypophysis, brain, blood vessels, digestive tract, ovaries).

Alcoholism↗

[Melatonin. II. Physiological and therapeutic effects].

Melatonin is a hormone mainly secreted by the pineal gland during the dark phase of the light-dark cycle. The most known function of melatonin in mammals is to transmit information concerning light-dark cycles playing the role of an active neuroendocrine transducer of environmental information. Given this chronobiologic role of pineal melatonin, it seems to be useful in the management of shift work, jet lag and some sleep disorders. In vitro like in vivo melatonin seems to be effective as an antioxidant and oncostatic agent. Melatonin may provide protection against aging process, degenerative diseases, cancer and play a role also in sexual maturation, reproduction, immune function and psychiatric illness. The administration of melatonin in the jet-lag syndrome is well codified. Further clinical research is needed for a better understanding and definition of other indications, treatment regimens and safety of the hormone. The aim of this paper is to review the current knowledge on its clinical implications.

Anticarcinogenic Agents↗

Mutation analysis of the MEN1 gene in Belgian patients with multiple endocrine neoplasia type 1 and related diseases.

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by tumors in parathyroids, enteropancreatic endocrine tissues, anterior pituitary, and other tissues. The gene for MEN1 has recently been cloned and shown to code for a 610-amino acid protein of enigmatic function which probably acts as a tumor suppressor. Several mutations causing the MEN1 phenotype have been recently identified. In order to determine the spectrum of MEN1 gene mutations in a sample of 25 Belgian patients, we have systematically screened the 10 exons and adjacent sequences of the MEN1 gene by means of an automatic sequencing protocol. Twelve different mutations were identified including nonsense, frameshift, splicing, and missense mutations. Two of these mutations (D172Y and 357del4) occurred more than once. A missense mutation was also found in a kindred with familial hyperparathyroidism. We observed no significant correlation between the nature or position of mutation and the clinical status. We have also detected 6 intragenic polymorphisms and DNA sequence variants and have analyzed their frequencies in our population.

Belgium↗

50 Hz magnetic field exposure influence on human performance and psychophysiological parameters: two double-blind experimental studies.

Two double-blind studies were performed to examine magnetic field (MF) exposure effects and to determine the impact of temporal variation (continuous vs. intermittent exposure) of 100 mu T(rms) 50 Hz MF diurnal exposure on psychological and psychophysiological parameters in healthy humans. Three cephalic exposure sessions of 30-min, i.e., sham, continuous, and intermittent (15 s ON/OFF cycles) MF conditions, were involved. Each subject participated in all sessions, which were spaced at 1-wk intervals. In each session, mood ratings and performance measures were obtained before, during, or after exposure and several electrophysiological data (event-related brain potentials [ERP]) were recorded after each exposure session. These criteria were chosen to evaluate sensory functions as well as automatic and voluntary attentional processes. In experiment 1, 21 healthy male volunteers (20 to 27 years of age) were studied. Ten subjects were exposed at 13:30 h, and 11 subjects were exposed at 16:30 h. Statistically significant changes in the amplitude of ERP were observed after MF exposure in the dichotic listening task, indexing selective attention processes. Eighteen of the 21 original male volunteers took part in experiment 2, undertaken to better understand the results related to information processing involved in selective attention and control for ultradian rhythmicity. Exposure time for all the subjects was at 13:30 h. The analysis of the data again revealed significant amplitude changes of the ERP recorded in the dichotic listening task. Moreover, they demonstrated ERP latency and reaction time slowing in the oddball paradigm, a visual discrimination task after real MF exposure. These results also indicate that a low level 50 Hz MF may have a slight influence on event-related potentials and reaction time under specific circumstances of sustained attention.

Activity Cycles↗

Graft of autologous fibroblasts in gingival tissue in vivo after culture in vitro. Preliminary study on rats.

Several grafting techniques and guided tissue regeneration techniques (GTR) have been well-developed in periodontal surgery. However, these techniques could induce pain and side effects, such as a gingival recession during the healing period following the therapy. The graft of a small autologous connective tissue, using non-invasive surgical techniques could yield several benefits for the patients. Our preliminary study explores the feasibility of collecting healthy gingival tissues, culturing them in vitro to amplify rat gingival fibroblasts (RGF) and inoculating the obtained cells into autologous rat gingival tissues in vivo. Gingival tissues samples were cultured as explants as described by Freshney et al. and Adolphe. Confluent cells surrounding explants were detached after 7 d of culture from Petri dishes using 0.05% trypsin and designated "first transferred cells" (T1). At the third passage (T3), cells cultured as monolayer were either examined under microscopy--phase contrast, scanning, or transmission electron--or numerated after trypan blue exclusion test. Autologous RGF labelled with fluorochrome were inoculated at the vestibular and palatine site of gingival tissue close to the superior incisors. In this preliminary study, 12 Wistar rats were used; for each, 2 biopsies were dissected and fixed for phase contrast or fluorescence microscopy. On d 1, 3 and 7 after injection in rat gingival tissues, fluorochrome-labelled cells could be detected in all these.

Animals↗