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Biomedical subjects

P Franchimont

Publications and source records attributed to P Franchimont.

At least 19 recordsLinked to original sources
PubMed1992

Insulin-like growth factor II in two human colon-carcinoma cell lines: gene structure and expression, and protein secretion.

Abnormal expression and structural modification of the IGF-II gene in correlation with high IGF-II production have recently been described in human colorectal tumors in comparison with normal adjacent tissues. Here, we have studied IGF-II in 2 human colon-carcinoma cell lines, HT29 and COLO 320DM. RFLP analyses revealed no apparent alteration at the IGF-II locus in these 2 cell lines. HT29 cells weakly expressed IGF-II mRNA in comparison with the high over-expression previously observed in some colorectal tumors, and only the 4.8-kb mRNA species was present. In addition, the serum-free medium conditioned by HT29 cells contained high IGF-II levels (approx. 900 ng/10(8) cells), as measured in a specific IGF-II radioimmunoassay (RIA). After chromatography on Bio-Gel P-60, we observed that 64% of the total IGF-II secreted by HT29 cells were present as a high-molecular-weight form of about 17 kDa. In contrast, no detectable expression of the IGF-II gene was observed in COLO 320DM cells, and low IGF-II levels were secreted by these cells in the serum-free medium, with only 9% total IGF-II represented by the large species.

Carcinoma↗
PubMed1992

Active oxygen species, articular inflammation and cartilage damage.

Rheumatoid arthritis and osteoarthritis are age-related diseases, in which degenerative changes (arthrosis) and superimposed inflammatory reactions (arthritis) lead to progressive destruction of the joints. Active oxygen species derived from various sources play a role in this process, which may be influenced by appropriate treatment with antioxidants and free radical scavengers.

Aging↗
PubMed1992

Minimal levels of serum estradiol prevent postmenopausal bone loss.

Biochemical parameters reflecting bone resorption [urinary calcium/creatinine (Ca/Cr) and hydroxyproline/creatinine (OH/Cr)] were related to serum estrogens [estrone (E1) and estradiol (E2)] in 262 healthy women including 158 patients receiving estrogen replacement therapy (ERT) for at least 6 months, 49 eugonadal women, and 55 untreated postmenopausal women. A significant (P < 0.001) correlation exists between serum E2 and Ca/Cr: Ca/Cr (mg/dl) = -0.00044 E2 (pg/ml) + 0.129 (n = 262; r = -0.37), serum E2 and OH/Cr: (OH/Cr (mg/g) = -0.049 E2 (pg/ml) + 18.76 (n = 262; r = -0.36), serum E1 and Ca/Cr: Ca/Cr (mg/dl) = -0.0003 E1 (pg/ml) + 0.127 (n = 261; r = -0.28) but not between serum E1 and OH/Cr. Women with circulating levels of E2 between 60 and 90 pg/ml have a significant (P < 0.01) reduction of Ca/Cr and OH/Cr when compared with those with lower levels of E2. Higher values of E2 do not provide additional benefit. We conclude that in postmenopausal women receiving an estrogen replacement therapy (ERT), a significant reduction of bone resorption is achieved when circulating levels of estradiol reach a value (60 pg/ml) corresponding to the one measured, in eugonadal women, during the last days of the early follicular phase of the menstrual cycle. We suggest that oral or percutaneous ERT should induce a minimal value of 60 pg/ml to prevent postmenopausal bone loss.

Analysis of Variance↗
PubMed1992

Endogenous production of specific antibodies does not decrease hypocalcemic response to calcitonin in young rabbits.

In order to evaluate the potential inhibition of the acute anti-osteoclastic activity of salmon calcitonin (SCT) by specific antibodies (Ab), we compared the SCT-induced hypocalcemic effect in young male rabbits with significant titers of high affinity Ab and in matched animals without Ab. Immunization of rabbits was performed by repetitive s.c. injections of SCT and Freund adjuvant. Ab were present in four-fifths of SCT-treated rabbits (Ab+). Their titer varied from 0.8 x 10(-9) to 30 x 10(-9) M/liter and their constant of affinity from 0.97 x 10(9) to 4.2 x 10(9) L/M. Intravenous injection of 1 IU/kg SCT to Ab+ rabbits induced a significant decrease (P less than 0.01) of ionized serum calcium (Ca2+) after 30 minutes (mean +/- SD: -9 +/- 0.6%) and until the 240th minute of the test (-16.7 +/- 4.7%), with a maximum after 120 minutes (-22.6 +/- 2%). This was not significantly different from the hypocalcemic effect measured after the same procedure performed in matched animals without Ab (Ab-): significant decrease in Ca2+ (P less than 0.01) after 30 minutes (-8.2 +/- 2.2%), maximal after 150 minutes (-23.2 +/- 4.9%), and lasting until 210 minutes (-14.5 +/- 3.7%). We conclude that, in the particular model of the male young rabbit, specific anti-SCT Ab do not block or reduce the acute anti-osteoclastic activity of SCT.

Animals↗
PubMed1992

Calcitonin metabolism in senile (type II) osteoporosis.

The exact role of calcitonin (CT) in the pathogenesis of senile (Type II) osteoporosis remains unknown. Whole plasma calcitonin (iCT) and extracted monomeric calcitonin (eCT) basal levels, metabolic clearance rate (MCR) and production rate (PR) of iCT and eCT were measured in 41 postmenopausal women, including 14 hip fractures (OP II) and 27 healthy controls. No significant difference appeared for basal iCT levels between OP II (mean +/- SEM: 41.9 +/- 3.4 pg/ml) and controls (mean +/- SEM: 46.2 +/- 5 pg/ml). eCT basal levels were similar in OP II (mean +/- SEM: 5.42 +/- 0.5 pg/ml) and in controls (mean +/- SEM: 7.3 +/- 0.7 pg/ml). MCR were similar in the two groups. iCT PR were similar in OP II (mean +/- SEM: 17.2 +/- 1.5 micrograms/24 h) and controls (mean +/- SEM: 18.6 +/- 1.1 micrograms/24 h). No difference appeared between eCT PR in OP II (mean +/- SEM: 2.3 +/- 0.2 micrograms/24 h) and controls (mean +/- SEM: 3.2 +/- 0.3 pg/ml). From these data, no evidence appears that calcitonin might be one of the determinant factors in the pathogenesis of senile osteoporosis.

Aged↗
PubMed1992

Effects of sodium naproxen on differentiated human chondrocytes cultivated in clusters.

The effects of different pharmacological concentrations of the non-steroidal anti-inflammatory drug (NSAID) sodium naproxen (NAP) were tested on several metabolic functions of differentiated human chondrocytes cultivated in clusters and compared with the action of acetylsalicylic acid (ASA). DNA synthesis was significantly inhibited by ASA but not by NAP. Proteoglycan production was also markedly decreased by ASA, while synthesis of type II collagen was not modified. By contrast, NAP did not affect these chondroformative processes. Both NSAIDs were potent inhibitors of prostaglandin E2 production. These results indicate that in terms of the parameters tested NAP does not lead to deleterious effects on human articular chondrocytes cultured in vitro.

Aspirin↗
PubMed1992

Physiological elevations of plasma beta-endorphin alter glucose metabolism in obese, but not normal-weight, subjects.

The present study was undertaken to evaluate the metabolic and hormonal responses to physiologic elevations of plasma beta-endorphin concentrations in both normal-weight and obese healthy subjects. The infusion of synthetic human beta-endorphin (4.5 ng/kg/min) produced the following: (1) in normal-weight subjects, no significant change of plasma glucose and pancreatic hormones (insulin, C-peptide, and glucagon), a significant plasma free fatty acids (FFA) increase, and a suppression of glycerol plasma levels; (2) in obese subjects, significant increases of glucose, insulin, C-peptide, and glucagon, a progressive decline of circulating FFA, and no change in glycerol plasma levels. In obese subjects, the intravenous administration of naloxone, given as a bolus (5 mg injected in 5 minutes) before the start of beta-endorphin infusion, reduced the plasma glucose response to the opioid by approximately half, annulled the pancreatic hormonal responses, and also reduced the FFA, but not glycerol, response. In normal-weight subjects, naloxone pretreatment did not induce any change of the flat glucose and hormonal responses to beta-endorphin, but reversed its effects on circulating FFA and glycerol. These data suggest that physiological elevations of plasma beta-endorphin concentrations produce metabolic and hormonal effects in obese subjects significantly different from those occurring in normal-weight subjects; these effects are partially naloxone-sensitive, suggesting the mediation of endogenous opioid receptors.

Adult↗
PubMed1992

Apomorphine stimulation of vasopressin- and oxytocin-neurophysins. Evidence for increased oxytocinergic and decreased vasopressinergic function in schizophrenics.

Apomorphine challenge tests (0.5 mg SC) were performed in 14 normal male volunteers and in 9 male schizophrenic inpatients, drug-free for at least 2 wk. In the normal volunteers, apomorphine induced an increase of serum growth hormone (GH) (maximum at 40 min), of vasopressin-neurophysin (hNpI) (maximum at 20 min), and oxytocin-neurophysin (hNpII) (maximum at 20 min). The release of neurophysins was independent of digestive side effects. In the schizophrenics, the GH level and release pattern were similar to those in the controls. The basal level of hNpI was reduced (t0: 0.42 +/- 0.1 ng/ml in the schizophrenics and 0.66 +/- 0.05 ng/ml in the controls, p < 0.02). In contrast, the basal level of hNpII was increased (3.34 +/- 0.04 ng/ml in the schizophrenics to 0.92 +/- 0.21 ng/ml in the controls, p = 0.001). The response to apomorphine was blunted, with no significant release of hNpI or of hNpII. Although the hNpII data are consistent with an increased dopaminergic tone, the psychopathological meaning of the increased basal oxytocinergic and decreased vasopressinergic functions remains to be defined.

Adult↗
PubMed1992

Direct stimulation of cytokines (IL-1 beta, TNF-alpha, IL-6, IL-2, IFN-gamma and GM-CSF) in whole blood: II. Application to rheumatoid arthritis and osteoarthritis.

Rheumatoid arthritis (RA) is an immune disease in which the pathological immune reaction is thought to be initiated by the presentation of an (auto) antigen or superantigen by MHC class II positive cells to CD4 T cells. These successive immunological events can be studied by the cytokines produced at the different stages. Cytokine secretion by stimulated cells in autologous diluted whole blood has allowed the study of the immune profile characteristic of rheumatoid arthritis. The pattern of RA patient whole blood cells cultured in autologous blood is characterized by hyperactivity of the mononuclear cells with high secretion of IL-1 beta, TNF-alpha and IL-6 and low production of IFN-gamma, in comparison with the normal (N) and osteoarthrosis (OA) populations. The IL-2 secretion pattern is unique, arising from production followed by consumption. This production-consumption turnover is the most elevated in the RA group. The T cells are indeed activated in rheumatoid arthritis but regulatory events suppress some of their functions. A correlation was found between the inflammatory proteins and mediators of cellular immunity and macrophagic function: IL-1 beta and the sedimentation rate; IL-6 and fibrinogen; TNF-alpha and the number of blood monocytes. The secretion of OA-stimulated whole blood cells was similar to RA for two monokines (overproduction of TNF-alpha and IL-6) and different for IL-1 beta, not different from normal in OA. Stimulated whole blood cell cytokine secretion profile from RA and OA groups, was the same as previously observed in synovial fluid.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Metabolic and respiratory changes after cholecystectomy performed via laparotomy or laparoscopy.

We have compared metabolic and respiratory changes after laparoscopic cholecystectomy (n = 15) with those after open cholecystectomy (n = 15). The durations of postoperative i.v. therapy, fasting and hospital stay were significantly shorter in the laparoscopy group. During the first and second days after operation, analgesic consumption but not pain scores (visual analogue scale) were significantly smaller after laparoscopy, while vital capacity, forced expiratory volume in 1 s, and PaO2 were significantly greater. The metabolic and acute phase responses (glucose, leucocytosis, C-reactive protein) were less after laparoscopy compared with laparotomy. Although plasma cortisol and catecholamine concentrations were not significantly different between the two groups, after surgery interleukin-6 concentrations were less in the laparoscopy group.

Acute-Phase Reaction↗
PubMed1992

The effect of nasal hCT on bone turnover in Paget's disease of bone--implications for the treatment of other metabolic bone diseases.

Thirty pagetic patients were treated for 6 months with a daily nasal application of 2 mg of synthetic human calcitonin (hCT). Serum alkaline phosphatases (SAP) and urinary hydroxyproline/creatinine ratio (OH/Cr), reflecting bone turnover, were significantly reduced from the first month of treatment (mean +/- SEM: SAP, -13.9 +/- 2.2%; OH/Cr, -22.2 +/- 5.8%; both P less than 0.01) and until the end of the 6-month course (mean +/- SEM: SAP, -29.7 +/- 4.6%; OH/Cr, -22.5 +/- 5.9%; both P less than 0.01). Nasal hCT was perfectly tolerated both locally and systemically. These results allow us to consider nasal hCT for long-term trials in metabolic bone diseases characterized by a relative increase of bone resorption.

Administration, Intranasal↗
PubMed1992

Cytokine serum level during severe sepsis in human IL-6 as a marker of severity.

Forty critically ill surgical patients with documented infections were studied during their stay in an intensive care unit. Among these patients, 19 developed septic shock and 16 died, 9 of them from septic shock. Interleukin 1 beta (IL-1 beta), tumor necrosis factor (TNF alpha), and interleukin 6 (IL-6) were measured each day and every 1 or 2 hours when septic shock occurred. Although IL-1 beta was never found, TNF alpha was most often observed in the serum at a level under 100 pg/mL except during septic shock. During these acute episodes TNF alpha level reached several hundred pg/mL, but only for a few hours. In contrast, IL-6 was always increased in the serum of acutely ill patients (peak to 500,000 pg/mL). There was a direct correlation between IL-6 peak serum level and TNF alpha peak serum level during septic shock and between IL-6 serum level and temperature or C-reactive protein serum level. Moreover, IL-6 correlated well with APACHE II score, and the mortality rate increased significantly in the group of patients who presented with IL-6 serum level above 1000 pg/mL. Thus, IL-6 appears to be a good marker of severity during bacterial infection.

Adult↗
PubMed1992

Gonadal-independent developmental changes in activation of N-methyl-D-aspartate receptors involved in gonadotropin-releasing hormone secretion.

Using hypothalamic explants of male rats, we have shown that the N-methyl-D-aspartate (NMDA) receptors involved in a stimulatory control of gonadotropin-releasing hormone (GnRH) secretion were transiently activated at 25 days around the time of onset of puberty. This was evidenced by studying the dose-related inhibition of veratridine-induced GnRH secretion by MK-801, a use dependent antagonist of NMDA receptors. An increase in sensitivity of GnRH secretion to the inhibitory effect of MK-801 was used as a marker of increased activation of NMDA receptors involved in stimulation of GnRH secretion. Here, we report on data obtained in intact and castrated rats at different ages. The aim was to determine whether the absence of gonads would affect the developmental changes in activation of NMDA receptors that we described recently. In pubertal (50-day-old) rats, orchidectomy resulted in an activation of NMDA receptors which was nonsignificant after 4 days but significant after 13 days. In prepubertal rats orchidectomized at 5 or 10 days and studied 10 days later, the NMDA receptors involved in GnRH secretion were also more activated than in intact animals. Using explants of intact and castrated animals, a similar increase in activation of NMDA receptors was observed between 15 and 25 days of age, a period preceding onset of puberty. Subsequently, between 25 and 50 days, a reduction in NMDA receptor activation was seen. This decrease was observed in intact rats showing normal sexual development and in castrated rats as well.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Effects of changes in nutritional conditions on timing of puberty: clinical evidence from adopted children and experimental studies in the male rat.

Among 32 patients with idiopathic central precocious puberty seen during a 3-year period, 1/4 were adopted children from developing countries who showed early sexual maturation during the catch-up process following their arrival in Belgium. To study the possible mechanism accounting for such clinical observations, we used the male rat as a model, and evaluated the effect of variations in early nutritional conditions, by manipulating litter size, on hypothalamic and testicular maturation. We had shown previously that, in the male rat, onset of puberty was preceded, between 15 and 25 days of age, by a transiently increased activation of N-methyl-D-aspartate receptors involved in a facilitatory control of pulsatile secretion of gonadotropin-releasing hormone. We also showed that the proportion of elongated spermatids in testicular cell homogenates increased between 25 and 45 days of age. When compared to pups of a small litter (6/dam), those of a large litter (14/dam) showed a reduced growth rate (1.9 vs. 3.5 g/day) before weaning (21 days), whereas they grew at a similar rate (5.6 vs. 4.7 g/day) after weaning. At 35 days of age, the animals raised in the large litter showed evidence of delayed hypothalamic and testicular maturation when compared to animals from the small litter. Reduction of litter size at 17 days allowed food-restricted pups of a large litter to resume a normal growth rate before weaning.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Neuroendocrine mechanism of onset of puberty. Sequential reduction in activity of inhibitory and facilitatory N-methyl-D-aspartate receptors.

In humans and in several animal species, puberty results from changes in pulsatile gonadotropin-releasing hormone (GnRH) secretion in the hypothalamus. In particular, the frequency of pulsatile GnRH secretion increases at the onset of puberty, as can be shown by using hypothalamic explants of male rats of 15 and 25 d. Previous observations from us and others suggested that the initiation of puberty could involve a facilitatory effect of excitatory amino acids mediated through N-methyl-D-aspartate (NMDA) receptors. We found that GnRH secretion could be activated through NMDA receptors only around the time of onset of puberty (25 d). The aim of this study was to clarify why this activation did not occur earlier (at 15 d) and could no longer be observed by the end of puberty (at 50 d). We studied GnRH secretion in the presence of MK-801, a noncompetitive antagonist of NMDA receptors or AP-5, a competitive antagonist. We showed that, in the hypothalamus of immature male rats (15 d), a highly potent inhibitory control of pulsatile GnRH secretion in vitro was mediated through NMDA receptors. These data were confirmed in vivo because administration of the antagonist MK-801 (0.001 mg/kg) to immature male rats resulted in early pubertal development. Onset of puberty (25 d) was characterized by the disappearance of that NMDA receptor-mediated inhibition, thus unmasking a facilitatory effect also mediated through NMDA receptors. During puberty, there was a reduction in activity of this facilitatory control which was no longer opposed by its inhibitory counterpart. We conclude that a sequential reduction in activity of inhibitory and facilitatory NMDA receptors provides a developmental basis for the neuroendocrine mechanism of onset of puberty.

Animals↗
PubMed1992

Sites of interaction between epidermal growth factor and transforming growth factor-beta 1 in the control of steroidogenesis in cultured porcine Leydig cells.

The present study examines how the hormonal action of gonadotropin is modulated by transforming growth factor-beta 1 (TGF beta 1) and epidermal growth factor (EGF) in primary cultures of purified porcine Leydig cells. Although TGF beta 1 (1 ng/ml; 48 h) and EGF (10 ng/ml; 72 h) individually enhanced hCG-stimulated testosterone formation, the effects of EGF were more pronounced than those of TGF beta 1. When studied in combination, the effects of maximal concentrations of TGF beta 1 and EGF were additive on gonadotropin hormonal action. In the present study we demonstrate that their additive effects resulted from a complex interaction occurring at the levels of cholesterol substrate availability in the mitochondria and of 3 beta-hydroxysteroid dehydrogenase/isomerase activity (3 beta HSDI). First, TGF beta 1 (1 ng/ml; 48 h) and EGF (10 ng/ml; 72 h) were, respectively, shown to reduce and enhance dehydroepiandrosterone (DHEA) formation (evaluated in the presence of 10(-5) M WIN 24540, an inhibitor of 3 beta HSDI) in Leydig cells when acutely (3 h) stimulated with hCG (0.01-1 ng/ml), but not when incubated with 22R-hydroxycholesterol (3 micrograms/ml). Such findings indicate that TGF beta 1 and EGF did not affect cholesterol side-chain cleavage cytochrome P450 activity, but, respectively, decreased and increased cholesterol substrate availability for this enzyme in the mitochondria. Furthermore, when Leydig cells were treated with the combined factors, the formation of delta 5-steroid intermediates (such as DHEA) in untreated (control) and EGF-plus TGF beta 1-treated cells was not significantly different whether the cells were acutely stimulated with the gonadotropin or incubated with 22R-hydroxycholesterol. Such findings indicate that the effects of EGF and TGF beta 1 on cholesterol substrate availability in the mitochondria are antagonistic. Second, EGF, TGF beta 1, and EGF plus TGF beta 1 significantly (P less than 0.001) increased delta 5-steroid intermediate (i.e. pregnenolone and DHEA), but not delta 4-steroid intermediate (i.e. progesterone and androstenedione), conversion into testosterone, indicating that the growth factors increased, individually or in combination in an additive manner, 3 beta HSDI activity (respectively, 90.7 +/- 0.6%, 80.6 +/- 2.6%, and 164 +/- 4.5% increase in the presence of EGF, TGF beta 1, and EGF plus TGF beta 1). Together, the reciprocal suppression of the effects of TGF beta 1 and EGF on the mitochondrial cholesterol substrate availability coupled to their stimulatory additive actions on 3 beta HSDI activity provide an explanation of the additive actions of the two growth factors on gonadotropin-induced testicular androgen formation.

Androstenedione↗