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Biomedical subjects

M Jeune

Publications and source records attributed to M Jeune.

At least 19 recordsLinked to original sources
PubMed2001

Diaminoindanes as microsomal triglyceride transfer protein inhibitors.

The synthesis and biological activities of biarylamide-substituted diaminoindanes as microsomal triglyceride transfer protein (MTP) inhibitors are described. One of the more potent compounds, 8aR, inhibited both the secretion of apoB from Hep G2 cells and the MTP-mediated transfer of triglycerides between synthetic acceptor and donor liposomes with IC(50) values of 0.7 and 70 nM, respectively. In normolipidemic rats and dogs, oral administration of 8aR dose-dependently reduced both plasma triglycerides and total cholesterol. Moreover, in rats and dogs, 8aR also prevented the postprandial rise in plasma triglycerides following a bolus administration of a fat load. Because MTP inhibitors decrease very low density lipoprotein assembly in the liver, the potential for hepatic lipid accumulation was evaluated. In normolipidemic rats, hepatic cholesterol and triglyceride contents were dose-dependently increased by 8aR. However, hepatic lipid accumulation resulted in negligible change in total liver weight and was reversible after withdrawal of the compound.

Animals↗
PubMed1999

Effect of matrix metalloproteinase inhibition on progression of atherosclerosis and aneurysm in LDL receptor-deficient mice overexpressing MMP-3, MMP-12, and MMP-13 and on restenosis in rats after balloon injury.

The broad-spectrum MMP inhibitor CGS 27023A was tested to determine its potential as a therapy for atherosclerosis, aneurysm, and restenosis. LDL receptor-deficient (LDLr -/-) mice fed a high-fat, cholic acid-enriched diet for 16 weeks developed advanced aortic atherosclerosis with destruction of elastic lamina and ectasia in the media underlying complex plaques. Lesion formation correlated with a 4.6- to 21.7-fold increase in MMP-3, -12, and -13 expression. Treatment with CGS 27023A (p.o., b.i.d. at 50 mg/kg) had no effect on the extent of aortic atherosclerosis (36 +/- 4% versus 30 +/- 2% in controls), but both aortic medial elastin destruction and ectasia grade were significantly reduced (38% and 36%, respectively, p < 0.05). In the rat ballooned-carotid-artery model, CGS 27023A (12.5 mg/kg/day via osmotic minipump) reduced smooth muscle cell migration at 4 days by 83% (p < 0.001). Intimal lesions were reduced by 85% at 7 days (p < 0.001), but intimal smooth muscle proliferation was unaffected, and inhibitory efficacy was lost with time. At 12 days, intimal lesion reduction was less potent (52%, p < 0.01). At 3 and 6 weeks, reductions of 11% and 4%, respectively, were not significant. This demonstrates that it is essential to include late time points when the ballooned-carotid-artery model is employed to ensure that lesion size does not "catch up" when a compound solely inhibits smooth muscle cell migration. In summary, MMP inhibitor therapy delayed but did not prevent intimal lesions, thereby demonstrating little promise to prevent restenosis. In contrast, MMP inhibitor therapy may prove useful to retard progression of aneurysm.

Animals↗
PubMed1999

The in vitro and ex vivo antioxidant properties, and hypolipidemic activity of CGP 2881.

This report describes the in vitro and ex vivo antioxidant properties of a new antioxidant, CGP 2881. This compound is structurally similar to probucol, in that both compounds contain bis-tertiary butyl phenyl groups. However, CGP 2881 consistently inhibited CuSO4 (Cu2+)- and macrophage (MO)-induced oxidation of human low density lipoproteins (LDL) more potently than equimolar concentrations of probucol. CGP 2881 (1 mumol/l) prolonged the lag phase of diene formation during Cu(2+)-induced LDL oxidation by 3.4 versus 1.5-fold prolongation with 1 mumol/l probucol (P < 0.05 vs CGP 2881). The IC50 for inhibiting the formation of Cu(2+)-induced thiobarbituric acid-reactive substances (TBARS) was 0.15 mumol/l for CGP 2881, versus approximately 10 mumol/l for probucol. The IC50 for MO-induced oxidation of LDL (TBARS) was 0.64 mumol/l. In contrast, 1 mumol/l probucol failed to inhibit MO-induced oxidation of LDL. Treatment of cholic acid/cholesterol-fed rats with CGP 2881 (50 mg/kg per day, orally for 5 days) inhibited ex vivo Cu(2+)-induced oxidation (TBARS) of the very low density lipoproteins (VLDL) + LDL lipoprotein fraction by 93% versus vehicle controls (P < 0.0001), and prolonged the lag phase for Cu(2+)-induced diene formation by 3.4-fold over vehicle-treated controls. Five days of orally administered CGP 2881 reduced plasma total cholesterol and LDL cholesterol levels to 55 and 54% of vehicle-treated controls, respectively (P < 0.05). In contrast, probucol had no appreciable effect on plasma total cholesterol or LDL cholesterol levels, unless administered for longer than 5 days. Treatment of hypercholesterolemic rabbits with 50 mg/kg per day orally for 5-12 days delayed the lag phase of diene formation during LDL oxidation by 4.3-fold over controls. However, the relative antioxidant potencies of CGP 2881 and probucol seen with oral administration to hypercholesterolemic rabbits were reversed when the compounds were given intravenously. In addition, the effects of these antioxidants were potentiated when given to normocholesterolemic rabbits compared to hypercholesterolemic animals. These data establish that CGP 2881 demonstrates hypolipidemic activity and is a substantially more potent antioxidant than probucol (in vitro and ex vivo). CGP 2881 may be useful as a new antioxidant tool in the effort to better understand the atherogenicity of oxidized LDL (oxLDL).

Animals↗
PubMed1997

HIV risk perception, risk behavior, and seroprevalence among female commercial sex workers in Georgetown, Guyana.

A study of 108 female sex workers engaged in prostitution in Georgetown, Guyana, was made in April 1993. Based on interviews and procurement of blood samples, the study investigated relationships between HIV seroprevalences and AIDS knowledge, risk behaviors, client characteristics, and condom use. Street-walkers-as distinct from sex workers in bars, hotels, and Port Georgetown-tended to charge less, be worse off socioeconomically, and have clients who were similarly disadvantaged; they were therefore classified as belonging to a "lower" socio-economic stratum, while the other workers were classified as belonging to a "higher" stratum. The overall HIV seroprevalence found among the sex workers was 25% (95% CI: 17%-33%). But the 50 subjects in the lower stratum had a relatively high seroprevalence (42%, as compared to 10% among those in the higher stratum), accounting for 21 of the 27 HIV-seropositive subjects. Reported patterns of client origins (Guyanese or foreign), worker willingness to have sex without a condom, and condom use by clients differed by stratum. Participants in the higher stratum were more disposed to having sex without a condom. The workers' knowledge of what causes AIDS and how HIV is transmitted was low in both strata; substantial numbers of workers said they had contracted a sexually transmitted disease within the past two years or were users of illicit drugs. Condom use is reportedly less common among Guyanese than foreign clients, suggesting a greater risk of contracting HIV from Guyanese clients or infecting Guyanese clients with it. The HIV seroprevalence among workers who said they had only Guyanese clients was statistically greater than the rate among those who said they had only foreign clients. The HIV seroprevalence among those reporting more than five clients per week was statistically greater than among those reporting fewer. HIV seropositivity was relatively high among the 12 workers who said they used cocaine. Overall, the findings supported the view that interventions targeted at female sex workers and their clients should be strengthened-more specifically, that concerted efforts should be made to intensity condom promotion, distribution, and social marketing; to improve STD services that provide treatment and counseling for female sex workers; and to increase educational activities among the workers' Guyanese clients.

Adolescent↗
PubMed1980

Kinetics of the HCG-induced steroidogenic response of the human testis. III. Studies in children of the plasma levels of testosterone and HCG: rationale for testicular stimulation test.

Little information is available regarding the time, rhythm, number, and appropriate dosage of human chorionic gonadotropin (HCG) for adequate testing of testicular function in human. The time course of the effect of two, three, or seven HCG injections at intervals of one, five, and two days, respectively, on the plasma levels of testosterone was studied in 11 boys. The first injection induced a progressive and modest rise of T. The second given one day later had little additive effect, maximal values being seen 72 to 120 hr later. In the prepubertal boys to whom several HCG injections were given, testosterone levels reached comparable levels after four injections every five days or seven injections every other day. Although the number of subjects studied was relatively small, these results give some rational basis for the following HCG test: two or four injections at four-day intervals.

Child↗
PubMed1980

[XY pure gonadal dysgenesis. Two cases report (author's transl)].

Two cases of XY dysgenesis are reported. In one case, that of a 13 year-old girl presenting with impuberism, a gonadoblastoma was detected by histologic examination of the streak. In the second case, that of a 6 month-old girl, short stature and dysplasia of the nails suggested the diagnosis.

Adolescent↗
PubMed1980

[Puberty in congenital hypothyroidism (author's transl)].

Puberty was studied in 95 patients with congenital hypothyroidism treated between 1953 and 1977 from the first months or first year of life. Pubertal abnormalities were observed in 13 cases: 1. Delayed puberty in 11 cases (late diagnosis in 6 cases, insufficient treatment in 2 cases, delayed puberty in the family in 1 case). 2. An amenorrhea-galactorrhea syndrome was observed in two cases with insufficient treatment. In the other cases, the outcome of puberty seemed within the normal range. However a careful study showed: 1st. A delay of every stage of puberty, 2nd. The absence of the peak of high velocity in some cases. 3rd. The age of menarche was 13 years 8 months (9 years 1 month-16 years 6 months) (normal girls: 13 years). Final height was dependent upon an early and efficient treatment, and upon a fast catch up of growth and bone maturation.

Adolescent↗
PubMed1979

[Oculocraniosomatic neuromuscular disease].

A child with a myopathy that started in the pelvic girdle, non-obstructive cardiomyopathy and retinitis pigmentosa is described. There was a progressive neurological deterioration with external ophthalmoplegia and ptosis. The clinical course could be predicted from the appearance of the muscle biopsy.

Adolescent↗
PubMed1978

[Septo-optic dysplasia with antidiuretic hormone deficiency and central adrenocortical insufficiency. Three cases report in infants (author's transl)].

Three cases of septo-optic dysplasia are related in infants. A neurogenic diabetes insipidus and an central adrenocortical insufficiency is proved. An growth hormone deficiency is founded in one case. The other anterior pituitary functions are normal. The pneumo-encephalography with congenital absence of septum lucidum and the ophtalmologic anomalies are typical. The treatment is envisaged. In one case an autopsy sustains the radiologic aspect.

Adrenal Insufficiency↗
PubMed1978

Combined immunodeficiency disease associated with absence of cell-surface HLA-A and -B antigens.

An infant with a family history suggestive of immunodeficiency presented with combined immunodeficiency. No HLA-A and -B antigens were present on lymphocyte and platelet surfaces, but they were found in the serum. HLA-D determinants were present on lymphocytes. In spite of a fetal thymus transplantation, the infant died of infections associated with the immunodeficiency. The thymus and lymphoid organs were present but hypoplastic and contained few lymphocytes at postmortem examination. The finding of an immodeficiency associated with an absence of cell-surface HLA-A and -B antigens may be regarded as the consequence of the lack of cellular histocompatibility antigens on immune development. Alternatively, other membrane components may have also been defective and partly responsible for the observed abnormalities.

Cell Membrane↗