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Biomedical subjects

A Rolland

Publications and source records attributed to A Rolland.

At least 55 records · Page 3Linked to original sources

Modulation of cellular cholesterol and its effect on cornified envelope formation in cultured human epidermal keratinocytes.

When cultured human epidermal keratinocytes (NHK) reach confluence they start to differentiate and an increase in the total cellular cholesterol content is observed. This increase parallels the appearance of a characteristic feature of terminal keratinocyte differentiation, the spontaneous formation of cornified envelopes (CE). Synthesis of CE is catalyzed by the plasma membrane-associated transglutaminase (TGm). Supplementation of the medium with inhibitors of cholesterologenesis suppressed increase in cholesterol levels and CE formation but did not interfere with TGm expression or TGm activity. Modulation of the plasma membrane cholesterol-phospholipid ratio of confluent NHK cultures using either pure phospholipid liposomes or liposomes enriched in cholesterol strongly affected spontaneous CE formation. Pure phospholipid liposomes completely inhibited CE formation, whereas cholesterol-enriched liposomes ensured envelope formation, even in the presence of inhibitors of cholesterol synthesis. From these results we conclude that in differentiating NHK an increase in the cellular cholesterol level is part of the differentiation program and is essential for the spontaneous CE formation.

Cell Aggregation↗

Behavioral effects of Euphorbia hirta L.: sedative and anxiolytic properties.

Lyophilised aqueous extract of Euphorbia hirta L. (Euphorbiaceae) has been evaluated for behavioral effects in mice. The extract did not induce any toxic effect when it was administered i.p. and orally. Sedative properties could be confirmed with high doses (100 mg of dried plant/kg, and more), by a decrease of behavioral parameters measured in non-familiar environment tests (activitest and staircase test), whereas anticonflict effects appeared at lower doses (12.5 and 25 mg of dried plant/kg), by an enhancement of behavioral parameters measured in the staircase test and in the light/dark choice situation test. These findings validate the traditional use of E. hirta as a sedative and reveal original anxiolytic properties.

Animals↗

tert-Butyl hydroperoxide-induced injury in isolated rat hepatocytes: a model for studying anti-hepatotoxic crude drugs.

Tert-butyl hydroperoxide induces in freshly isolated rat hepatocytes malonaldehyde formation and lacticodehydrogenase and aspartate amino-transferase leakage. This model, when adapted to crude extracts, permits the demonstration of both anti-lipoperoxidant and antihepatotoxic activity of reference products like quercetin and silymarin and plant extracts like Rosmarinus officinalis and Eschscholzia californica.

Animals↗

Analgesic and behavioural effects of Morinda citrifolia.

The traditional therapeutic indications for the use of Morinda citrifolia L. (Rubiaceae) have been investigated. The lyophilised aqueous extract of roots of M. citrifolia was evaluated for analgesic and behavioural effects in mice. The extract did not exhibit any toxic effects but did show a significant, dose-related, central analgesic activity in the writhing and hotplate tests; this effect was confirmed by the antagonistic action of naloxone. Furthermore, administration of M. citrifolia extract at high dosages decreased all behavioural parameters in the two compartment test, the light/dark choice situation test, and the staircase test; together with the induced sleeping time, these results are suggestive of sedative properties.

Analgesics↗

Ocular onchocerciasis and intensity of infection in the community. III. West African rainforest foci of the vector Simulium sanctipauli.

The community pattern of ocular onchocerciasis is described for 11 villages from the forest area in Côte d'Ivoire where S. sanctipauli is the princial vector. An analytical method is applied which relates indices of ocular onchocerciasis with the Community Microfilarial Load (CMFL) and compares the results with the ocular onchocerciasis pattern found in the West African savanna. In spite of high transmission levels as estimated by entomological indices, the CMFLs were relatively low which complicated the characterization of the ocular disease pattern. Nevertheless, it could be shown that ocular onchocerciasis is less severe in the Sanctipauli forest than in the savanna, even after correction for differences in CMFL. The prevalence of onchocercal eye lesions and blindness were low and advanced sclerosing keratitis was completely absent. The differences are explained by presuming strain differences of the parasite Onchocerca volvulus. For given CMFLs the mean microfilarial loads in the eye were significantly lower than in the savanna which suggests that the parasite strain in the Sanctipauli forest is less invasive to the eye. Ocular microfilarial loads were too low to determine if the parasite is also less pathogenic to the eye, as has been concluded previously for foci of S. yahense, but this possibility cannot be excluded.

Animals↗

Blood clearance and organ distribution of intravenously administered polymethacrylic nanoparticles in mice.

Polymethacrylic nanospheres (mean diameter 0.25-0.30 microns), prepared by aqueous emulsion copolymerization, were developed as a new site-specific drug delivery system. The nanoparticles were labeled either with indium-111 or iodine-125, and after a single iv injection of labeled particles into mice, their blood clearance and organ distribution were analyzed. A rapid clearance of 111In-labeled nanoparticles from the blood circulation to the mononuclear phagocyte system (MPS) was visualized using external scintigraphic imaging. From 10 to 60 min, radioactivity measurements in blood and organs (liver, spleen, kidneys, lungs, heart) showed that the 125I-labeled nanospheres were rapidly removed from the bloodstream (distribution half-life approximately 3-5 min) and mainly deposited in the liver (60% of the administered dose, 10 min after administration). Up to 1 h, radioactivity in heart and lungs remained insignificant, while in the kidneys, radioactivity levels increased from 8 to 11%.

Animals↗

Ocular onchocerciasis and intensity of infection in the community. II. West African rainforest foci of the vector Simulium yahense.

A novel method of analysis was used to describe community patterns of ocular onchocerciasis in relation to the intensity of infection in West African forest villages where S. yahense is the sole vector. The pattern is completely different from that found in the savanna, even after correction for the intensity of infection as measured by the Community Microfilarial Load (CMFL). Lesions of the anterior segment of the eye as well as onchocercal blindness either do not occur or occur only sporadically with increasing CMFL in the Yahense forest whilst a steep linear relation exists between the prevalence of these lesions and the CMFL in the savanna. Lesions of the posterior segment of the eye are also less common in the Yahense forest. For a given skin microfilarial load, the ocular microfilarial load is lower in the Yahense forest. For a given ocular microfilarial load, a lower prevalence of eye lesions is found in the Yahense forest compared to the savanna. It is concluded that microfilariae of Onchocerca volvulus in the Yahense forest are less eye invasive than microfilariae from the savanna. Furthermore, they appear to be also less pathogenic to the eye. These findings explain why ocular onchocerciasis is relatively mild in the Yahense forest, in spite of the high intensities of O. volvulus infection in the community.

Animals↗

Ocular onchocerciasis and intensity of infection in the community. I. West African savanna.

A method is introduced for the analysis of community patterns of ocular onchocerciasis in relation to the intensity of infection as measured by the Community Microfilarial Load (CMFL). Specific features of this method are the clear definition of ocular lesions and their separation into early and advanced stages, and the estimation of the prevalence of onchocercal blindness after exclusion of other causes of blindness. The method is applied to the ophthalmological and parasitological data from 33 villages from the West African savanna in order to obtain a reference pattern for subsequent analyses of ocular onchocerciasis patterns from other bioclimatic zones. In the savanna, there exists a clear linear relationship between most indices of ocular onchocerciasis and the CMFL. Mean ocular microfilarial loads, prevalences of the advanced lesions of the anterior and posterior segment of the eye and prevalences of different classifications of blindness show a high degree of correlation with the CMFL, as does also early sclerosing keratitis. The correlation is poor for the other early ocular lesions. All relationships are similar for the two sexes with the exception of posterior segment lesions which remain more common in males after correction for intensity of infection. The CMFL is superior to the prevalence of microfilariae in the skin as an index of endemicity. It allows a good prediction of the severity of onchocercal ocular disease in savanna communities using parasitological information only.

Adolescent↗

Enhancement of adriamycin antitumor activity by its binding with an intracellular sustained-release form, polymethacrylate nanospheres, in U-937 cells.

We investigated the antitumor activity of Adriamycin on a monocytic-like cancer cell line U-937 after its binding on polymethacrylate nanospheres (diameter, 270-350 nm). Compared to free Adramycin (F-ADR), nanosphere-bound Adriamycin (B-ADR) exhibits a 3-fold enhancement of cytotoxicity, as determined by cell growth inhibition and DNA synthesis, after continuous exposure to 0.02 and 0.04 microgram/ml. The 90% growth inhibition concentration was 0.051 microgram/ml for F-ADR and was 0.018 microgram/ml for B-ADR (P less than 0.001). Furthermore, the nanosphere densities per cell play an important role since for the same drug concentration the higher the density increases, the better the activity is. Indeed, after 4 days of incubation in a medium containing 160 nanospheres at 0.5 fg/cell, the cell counts were 62.8 +/- 12.8% (SD) of the initial inoculum and they were only 16.1 +/- 0.1% after incubation in a medium containing 800 nanospheres at 0.1 fg/cell (P less than 0.001). A comparable enhancement of activity regarding the nanosphere densities was observed after a 24-h exposure to 0.02 and 0.05 microgram/ml. Short-term uptake studies showed that B-ADR accumulation was higher with B-ADR than with F-ADR. In addition, the efflux kinetics was modified. For cells exposed to F-ADR for 4 h, the efflux half-life was 23.7 +/- 7.7 h and the area to infinity under the efflux curve was 8.6 +/- 2.8 micrograms/mg protein x h-1. For cells exposed to B-ADR, the efflux half-life increased to 85.9 +/- 19.2 h and the area to infinity under the efflux curve to 29.6 +/- 6.6 micrograms/mg protein x h-1 (P less than 0.001). Electron transmission microscopy and previous findings have revealed that B-ADR was well internalized into cells. Our data support the hypothesis that B-ADR acts as an intracellular drug release complex after endocytosis. The findings regarding the number of nanospheres per cell and dose-effect relationships are consistent with mechanisms of drug actions extending to membrane domains.

Cell Compartmentation↗

A new immunoreagent for cell labeling. CD3 monoclonal antibody covalently coupled to fluorescent polymethacrylic nanoparticles.

The preparation and application of immunonanospheres are described. CD3 monoclonal antibodies were covalently coupled to fluorescent polymethacrylic nanoparticles by the glutaraldehyde reaction and the resultant conjugate purified by gel filtration on a Sepharose 4B column. Peripheral blood mononuclear cells labeled with this immunoreagent were observed by both fluorescence microscopy and scanning electron microscopy in order to evaluate the technique.

Antigens, Differentiation, T-Lymphocyte↗

[Long-term fate of pituitary dwarfs treated with growth hormone].

A questionnaire having been mailed to 50 hypopituitary patients aged 18 to 36 years (m 21.7 +/- 3.4) previously treated with human growth hormone for at least 3 years, 44 answers have been received. The final height is 2.1 +/- 0.9 standard deviations below the average. However 57% of the patients consider it is sufficient. The smallness is felt as a handicap by 20% only of these adults, though 88% had suffered for it during their adolescence. The treatment is retrospectively considered as useful and acceptable by 68%, heavy but useful by 25%, heavy and useless by 7%, without correlation with the results. Only 41% are satisfied with their school achievements. However, more than two thirds of patients had severe school difficulties at the time of onset of the treatment. Actually 75% of the patients are professionally qualified, among whom 36% have achieved high school, and most have an educational level similar to that of their parents or even higher. But 41% only have an employment, 27% are still students and 32% are unemployed. The way of life of the young hypopituitary adults is severely affected: 6 only are married or living with a mate, 11 only write they have occasional sexual experiences, 16 remain completely alone. In contrast, leisure activities are good in more than 90%. A score taking all these data into consideration to evaluate their way of life shows, among the 43 complete answers to the questionnaire, 16% with excellent results, 49% with a rather good social status and 35% with poor final result.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Flow cytometric quantitative evaluation of phagocytosis by human mononuclear and polymorphonuclear cells using fluorescent nanoparticles.

The use of fluorescent polymethacrylic nanoparticles (0.3 micron) as a flow cytometric reagent in the quantitative evaluation of phagocytosis by human mononuclear and polymorphonuclear cells is described. The preparation of the nanoparticles, by emulsion copolymerization of methacrylic monomers, and their physicochemical properties are briefly summarized. Nanoparticles coupled with a fluorescent agent (ethidium bromide) were used in a flow cytometric assay to study opsonin-independent phagocytosis by human polymorphonuclear cells and by human monocytes. The phagocytosis of nanospheres by monocytes was determined by flow cytometry from the fluorescence distribution and ingestion was visualized by scanning and transmission electron microscopy. One possible application of the fluorescent nanoparticles is the simultaneous analysis of cell surface antigens and cell phagocytic activity.

Acrylates↗

Dose-response relationship in the treatment of hypopituitary children with human growth hormone: a retrospective survey.

During the past 15 years, dose-response studies of hGH have been limited to prepubertal patients with complete somatotrophic deficiency, who have usually been treated with hGH three times/week within a dose range of 10-40 IU/kg/year. In such studies a weak positive correlation has been found (r = 0.429, p less than 0.001) with marked important individual variations. Very few or no data have been published regarding the dose-response relationship after the first year of hGH treatment, or when the dose is increased because the growth rate is waning, or during puberty. The present paper reports some data on these issues. A group of 32 young hGH deficient children, whose bone age was 0-4 years, was followed up for at least 3 years with hGH given intramuscularly three times weekly at doses of 12-48 IU/kg/year (mean, 25 +/- 9 IU/kg/year - i.e. approximately 0.15 IU/kg/injection). A dose-response relationship existed during the first year but not during the following 2 years nor for the height gain obtained at the end of the third year of treatment. The results of an increase of the dose of hGH by 33-66% in 13 prepubertal hGH deficient children whose growth rate had decreased after 2-5 years of treatment were fair in 6, limited in 4 and absent in 3, and did not relate to the extent of dose increase. However, this series is too small to allow definite conclusions. The growth rate of 67 adolescents with complete hGH deficiency and normal spontaneous puberty was close to the normal mean in the 45 males but much less in the 22 females. Although the least favourable results came from cases with post-radiotherapy hypopituitarism, the mean total pubertal growth spurt in patients with idiopathic hGH deficiency was also below the average, mainly in the girls, and with a large range of individual variation. An important fact was that bone age increased more than height age or chronological age in these hypopituitary pubertal patients. No dose-response relationship was found in this group, within a limited range of doses (40 patients receiving 16-20 IU/kg/year injected three times weekly, 19 receiving less than 16 IU/kg/year and 8 receiving more than 20 IU/kg/year). It may be concluded that in prepubertal hypopituitary children, hGH at a dose of approximately 20 IU/kg/year at the onset of treatment is probably appropriate. The lack of a dose-response relationship after the first year of treatment suggests that higher initial doses should be avoided.(ABSTRACT TRUNCATED AT 400 WORDS)

Body Height↗

[Natural history of intrauterine growth retardation: pubertal growth and adult height].

The evolution of height and bone age up to complete or near complete achievement of growth has been followed in 13 children born at term with a length of 42 to 46 cm, who after age 2 years had still a growth delay of -2.1 to -4.9 SD. Their mean annual growth velocity has been slightly below the average, excepted in the years preceding and following immediately the onset of puberty. The bone age, largely delayed and close to height age up to approximatively 8 years, afterwards has increased more than growth, so that the final height has always been less than the adult height predicted at age 8 years. The main factor in this difference between final and predicted height has been the fact that puberty has not been delayed. Starting at the usual age, in children whose height deficiency was still important, the pubertal growth spurt has not allowed full catch-up. Thus, in spite of delayed bone age during childhood, the mean adult height in the 13 patients of this series has been -3.43 SD versus -3.16 SD at age 2-5 years, these mean values involving different individual growth curves with absolute deterioration in 6 only of the 13 cases. These data will have to be considered when discussing the final results of therapeutic trials in children with severe and persisting intra-uterine growth retardation.

Adolescent↗

The effect of 7-8 years of vector control on the evolution of ocular onchocerciasis in West African savanna.

The evolution of ocular onchocerciasis was studied in a cohort of 1170 persons over 5 years of age who were examined before the start of and after 7-8 years of effective vector control in 12 originally hyperendemic villages in the central part of the OCP area. The proportion of the cohort which at the outset of vector control was free from ocular onchocerciasis or had an early or recent infection in the form of punctate keratitis only, remained largely free of or lost their signs of ocular infection respectively and only a very insignificant proportion acquired microfilariae in the eyes or developed a severe onchocercal eye lesion at the initial stage. The proportion of the cohort with a heavy ocular microfilarial load had a reduced risk of developing severe eye lesions and no risk of going blind. The proportion of the cohort with already existing severe eye lesions at the advanced stage remained largely unchanged and some lesions at the initial stage disappeared. Blindness occurred only in those who had severe eye lesions at the outset and was comparatively less than in areas of on-going transmission.

Adolescent↗

[Effects of human growth hormone on very short children with intermediate responses to somatotropic stimulation tests].

The effects of treatment with human growth hormone (hGH) were studied in 29 patients aged 2 to 16 years with growth retardation between 2.2 and 6 standard deviations and insufficient growth velocity in whom repeated pharmacologic somatotropic stimulation tests had shown discordant responses either above 7 ng/ml, or lower than 6 ng/ml. An important acceleration of growth was obtained in 10 of 16 patients before puberty and in all the 13 cases treated at the beginning of puberty. No correlation was observed between the GH levels observed during the stimulation tests and the clinical results of treatment. These data lead to discuss partial GH deficiency and to propose a trial of treatment in very short children with low and/or dissociated responses to repeated tests of pituitary somatotropic secretion.

Adolescent↗

[Ototoxic potential of erythromycin].

On the basis of a personal case and a review of the literature, the authors raise the problem of the potential ototoxicity of erythromycin in patients with renal failure. The cochlear toxicity of this antibiotic is very different from that of the aminoglycosides, as in all of the reported cases, hypoacusis appears very early and always resolved once the antibiotic was stopped. The actual mechanism of the cochlear damage has not been studied. Although this iatrogenic reaction is uncommon, the authors recommend caution when prescribing erythromycin to patients with renal failure.

Adolescent↗