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Biomedical subjects

G Soula

Publications and source records attributed to G Soula.

At least 55 records · Page 3Linked to original sources
PubMed1991

[A new combined vaccine against yellow fever and measles in infants aged 6 to 24 months in Mali].

In a rural area in Mali, 453 children were randomly enrolled in a study comparing the safety and the immunogenicity of a combined yellow-fever-measles freeze dried vaccine with each yellow-fever and measles separate administration. Children were divided in 2 populations 4-8 and 12-24 month old. 249 were controlled for measles (inhibition of hemagglutination) and yellow-fever (seroneutralization) antibodies. Seroconversion rates for measles were 82% when administrated before 9 months and 100% when given in 12-24 months period. Measles GMT is similar whatever the schedule or the age group; so, early vaccination does not impair the immunogenetic response. Moreover, 96% of the children vaccinated before 9 months still have detectable measles protective antibodies 8 months after. Among the initially seronegative children, the yellow-fever response is satisfactory with 92 to 96% seroconversion rate and post-immunization GMT ranging 16.5 to 29.5 without any statistical difference between the vaccine and age groups. The safety of the combined yellow-fever-measles vaccine is assessed by the rare number of reactions which are equivalent with the normally expected reactions with each vaccine administered separately. The results demonstrate the satisfactory immunogenicity and safety of the combined yellow-fever-measles vaccine. Combine yellow-fever-measles vaccination could help to improve the feasibility of EPI.

Age Factors↗
PubMed1991

Migration and death of skin-dwelling Onchocerca volvulus microfilariae after treatment with ivermectin.

The effects of a single dose of ivermectin (122-200 micrograms/kg) on Onchocerca volvulus microfilariae (mf) in skin and lymph nodes were studied histologically in a qualitative and quantitative manner over seven days after treatment. Ivermectin caused mf to move from the subepidermal layer into the deeper layers of the dermis, subcutaneous fat and connective tissue, and the regional lymph nodes. No mf were seen migrating upwards through the epidermis. Dead mf were not seen before 24 hr and the numbers found dead in the dermis were far fewer than the total numbers in the skin before treatment. Inflammatory cellular reaction around dead mf in the tissues was usually minimal. The results suggest that most of the mf which disappear from the skin may be destroyed in the lymph nodes and that the histological reaction excited by mf dying under ivermectin is less violent than that after diethylcarbamazine.

Adult↗
PubMed1990

Hyperphosphatasemia related to three intestinal alkaline phosphatase isoforms: biochemical study.

An unexplained hyperphosphatasemia was noted in a healthy 47-year-old woman. The electrophoretic pattern on agarose gel with and without wheat germ lectin of the serum of this patient showed the presence of three isoforms which have been characterised as being of intestinal origin: their biochemical (neuraminidase, phenylalanine) and thermodenaturation properties are similar to those of intestinal tissue extract. The pI and pH optima of these isoforms agree with an intestinal origin. Our results suggest the existence of different allelozymes of intestinal alkaline phosphatase.

Alkaline Phosphatase↗
PubMed1990

Comparative study of the incorporation of ellipticine-esters into low density lipoprotein (LDL) and selective cell uptake of drug--LDL complex via the LDL receptor pathway in vitro.

Esters of elliptinium with stearic (ST-NME), palmitic (PAL-NME) or oleic (OL-NME) acids, a series of lipophilic derivatives of ellipticine, were synthetized, in order to evaluate their incorporation into Low Density Lipoprotein (LDL). Among the three derivatives, OL-NME shows the most potent incorporation (83 micrograms/mg protein LDL) compared to ST-NME (37 micrograms/mg protein LDL) and PAL-NME (58 micrograms/mg protein LDL). The size of OL-NME-LDL was determined by size distribution particles, showing their homogeneity compared to native LDL. When culture normal human fibroblasts were incubated with [125I]LDL incorporated drug, they bound to the LDL receptor with the same affinity as native LDL and were internalized and degraded intracellularly. The presence of excess native LDL inhibited the cellular uptake and degradation of [125I]drug-LDL. We have used [125I]acetyl-LDL as a probe for a binding site on macrophages that mediated the uptake and degradation of chemically altered or denatured LDL. Mouse peritoneal macrophages were shown to take up and degrade [125I]acetyl-LDL at rates that were greater than those for the uptake and degradation of native [125I]LDL and [125I]drug-LDL. The in vitro cytotoxic test on L1210 murine leukemic cells demonstrated that the complex was cytotoxic and was more effective than the free drug. This cytotoxic activity of the drug-LDL complex depends on the LDL high affinity receptor since the addition of native LDL reduces the killing power. In contrast, methylated LDL, which does not bind to the LDL receptor, has no effect on it. We conclude that it is possible to incorporate a large amount of cytotoxic drug into LDL without modifying their cellular metabolism via the high affinity LDL receptor pathway. It indicates also that the delivery of lipophilic drugs using LDL might provide distinct advantages over the use of synthetic carriers.

Alkaloids↗
PubMed1990

The influence of food on the pharmacokinetics of CGP 6140 (amocarzine) after oral administration of a 1200 mg single dose to patients with onchocerciasis.

Eleven male patients from Mali with Onchocerca volvulus infections received in random order a 1200 mg single oral dose of CGP 6140 after an overnight fast and after food intake. The concentrations of CGP 6140 and of its N-oxide metabolite, CGP 13231, were measured in plasma and urine. Mean (+/- s.d.) AUC CGP 6140 values were 67.0 +/- 10.8 mumol l-1 h in fed and 22.0 +/- 17.2 mumol l-1 h in fasting patients. The mean maximum concentrations (Cmax) in plasma +/- s.d. were 12.7 +/- 2.8 mumol l-1 in fed and 4.7 +/- 4.1 mumol l-1 in fasting patients. The median time to Cmax was 3 h in fed and 2 h in fasting patients. Mean (+/- s.d.) AUC of the N-oxide metabolite was 59.9 +/- 10.7 mumol l-1 h in fed and 23.4 +/- 16.2 mumol l-1 h in fasting patients. The urinary recovery was less than 0.5% of dose for CGP 6140 in both fed and fasting conditions. It was 30.1 +/- 11.5 and 11.4 +/- 8.0% of the dose for the N-oxide metabolite in fed and fasting conditions, respectively. Variability in plasma concentrations and urinary recovery of CGP 6140 and of the N-oxide metabolite was greater in fasted patients. The low solubility of CGP 6140 in aqueous solutions at neutral pH and its higher solubility at acidic pH might explain the increase in bioavailability after food intake. The administration of CGP 6140 after food intake is therefore recommended for an optimal systemic effect.

Administration, Oral↗
PubMed1990

[Statement: alkaline phosphatases. Genetic aspects. Identification and clinical interpretation].

The human alkaline phosphatases constitute a family of several isoenzyme forms. They are coded by 3 different structural genes. The authors find respectively the placental isoenzymes, the intestinal isoenzymes, and the isoenzymes coded by a gene called aspecific tissular. These last isoenzymes coming from the liver and the bone tissue have very similar structures leading to a very difficult differentiation and quantification. In this study, a summary is made of the main procedures at the disposal of biologist, which allows to have a differentiation of liver and bone fractions. The selected technique proposes the reactivity by affinity with a lectin. Owing to its excellent resolution, this method must contribute to a better follow-up of bone and liver metastasis and to the detection of intestinal isoenzymes, allowing the research of a possible link with different pathologies.

Alkaline Phosphatase↗
PubMed1990

[Determination of cerebrospinal fluid proteins using the Cobas Fara centrifugal analyser. Adaptation of the turbidimetric technic to benzethonium chloride].

The authors have adapted a turbidimetric assay on centrifugal Cobas Fara analyser for cerebrospinal fluid proteins determinations. The later method is proposed by SFBC Protein Analysis Committee using benzethonium chloride as monoreagent. This adaptation is more sensitive than manual method. The linearity range is greater (0.08-1.85 g/l instead of 0.2-1.2 g/l). Sample assay and time of analysis were reduced by 90 p. cent.

Benzethonium↗
PubMed1989

Proliferative effect of high density lipoprotein (HDL) and HDL fractions (HDL1,2, HDL3) on virus transformed lymphoblastoid cells.

The growth-promoting activities of plasma lipoproteins (LDL, HDL, HDL1,2, HDL3) and total HDL apolipoproteins on a virus transformed lymphoblastoid cell line in vitro, has been compared. When maintained in lipoprotein-deficient serum-supplemented medium, these cells do not proliferate optimally. The addition of either HDL, HDL1,2 or HDL3 induced optimal cell proliferation as compared to the result observed in fetal calf serum-supplemented medium. The HDL1,2 subfraction was found to be more potent than the HDL3 subfraction in supporting cell growth. Total HDL apolipoproteins were able to support significant cell proliferation. In contrast, LDL did not promote cell growth. In serum-free conditions and in the presence of transferrin, only HDL and HDL subfractions induced cell proliferation. These results suggest that HDL and HDL subfractions could initiate B lymphoblastoid cell growth and that total HDL apolipoproteins could support a part of cell proliferation.

B-Lymphocytes↗
PubMed1989

Preparation of low density lipoprotein-9-methoxy-ellipticin complex and its cytotoxic effect against L1210 and P 388 leukemic cells in vitro.

Previous studies have suggested that low density lipoprotein (LDL) may be used as a drug targeting carrier for chemotherapeutic agents to neoplastic cells. In this study the cytotoxic agent 9-methoxy-ellipticin (MeOE) was incorporated into dimirystoyl phosphatidylcholine, cholesteryl oleate stabilized microemulsion and the latter fused with human LDL. Both agarose electrophoresis migration and the electron microscopic shape of the drug-LDL complexes were similar to those of native LDL. The in vitro cytotoxic tests on L1210 and P388 leukemic cells demonstrated that the complex was able to kill cells and was more effective than the free drug. This cytotoxic activity of the drug-LDL complex depends on the LDL high affinity receptor: the native LDL reduces the killing power. In contrast, methylated LDL, which does not bind to the LDL receptor, has no effect on it. On the other hand, heparin, which prevents binding on the cell surface receptors, partially reduced the cytotoxic activity of the drug-lipoprotein complex. These results suggest that it is possible to incorporate lipophilic cytotoxic drugs into LDL, using a technique of fusion with the microemulsion which contains the drug. This technique allows us to obtain a drug-LDL complex which is able to kill cells via the LDL receptor pathway.

Alkaloids↗
PubMed1989

Pharmacokinetics of Ro 03-8799 in mice bearing melanosarcoma: comparison with tumors without melanin.

The pharmacokinetics of Ro 03-8799 has been studied in melanic and non-melanic tumor bearing mice after iv administration of 150 mg/kg. The peak concentration in B16 melanosarcoma tumor reached 152 micrograms/g, that is 7.6-fold higher than the plasma concentration at the same time. This concentration is 3-times greater than that obtained in the tumor of mice bearing non melanic sarcoma (DB16) or Lewis lung carcinoma (3LL). The exposure of B16 tumor (AUC) is respectively 15-times and 11-times higher than the 3LL and the DB16 ones. These experimental data confirm that this 2-nitro-imidazol compound has an important affinity for melanin and suggest that it might be used as a radiosensitizer for the treatment of malignant melanoma.

Animals↗
PubMed1989

[Prognostic value of prostatic acid phosphatase in stage B and C prostatic cancer. Apropos of 84 cases].

The authors have studied the prognostic interest of evaluating the prostatic acid phosphatase level before any treatment in 84 cases of stage B and C prostatic cancer. An abnormal PAP level did not significantly modify the 5-year life expectancy of patients, but was significantly correlated with a shorter period of disease-free survival. An abnormal PAP level increased the risk of recurrence; the higher the PAP level, the shorter the disease-free interval was. The disease stage (i.e., B or C) did not modify the 5-year survival period or the length of the remission. The prognosis is worse for a stage B prostatic cancer with a pathological PAP level than for a stage C cancer with a normal PAP level. A pathological PAP level seems to indicate the presence of occult metastases and should incite the clinician to actively investigate the matter.

Acid Phosphatase↗
PubMed1988

Evidence for qualitative abnormalities in high-density lipoproteins from myeloma patients: the presence of amyloid A protein could explain HDL modifications.

HDL apolipoproteins (apo) from normal subjects and patients with multiple myeloma were studied by isoelectric focusing (IEF) and by two-dimensional gel electrophoresis. Qualitative abnormalities were detected in myeloma HDL apolipoproteins. We observed two new bands not previously described in this disease. As determined by IEF and two-dimensional gel electrophoresis, the relative molecular weight of these two proteins was 12,600, with pI = 6.04 and 6.36, respectively. They correspond to two isoforms of serum amyloid A protein (SAA), as confirmed by western blot assay against specific antiserum to SAA. The high sensitivity of this assay revealed also other SAA isoforms. Our data are consistent with the hypothesis that major apolipoproteins of normal HDL, apo A-I and apo A-II, could be displaced by SAA isoproteins in myeloma HDL. This could lead structural changes in HDL.

Aged↗
PubMed1988

Hypohaptoglobinaemia as an epidemiological and clinical indicator for malaria. Results of two studies in a hyperendemic region in West Africa.

Hypohaptoglobinaemia is a common phenomenon in tropical countries, where it is probably due to malaria-induced haemolysis. Two studies were carried out in a hyperendemic zone of West Africa to test its specificity and usefulness as an epidemiological indicator for measuring malaria endemicity. The first study evaluated the prevalence of hypohaptoglobinaemia before and after courses of antimalarial chemotherapy of varying duration. The second monitored haptoglobin levels in an untreated population during a whole year to compare its seasonal variations with those of several classic indicators of malaria. These studies suggest that in regions where malaria is endemic the prevalence of hypohaptoglobinaemia could be as useful an indicator as the parasitic index but would be much easier to establish and to monitor.

Adolescent↗
PubMed1988

Autoradiographic distribution of [14C]-labelled pimonidazole in rhabdomyosarcoma-bearing rats and pigmented mice.

The hypoxic cell radiosensitizer [2-14C] pimonidazole (2-nitro-alpha-(piperidinomethyl)-l-imidazole ethanol) was injected i.p. into pigmented mice and rats bearing transplanted rhabdomyosarcoma. The injected dose level was 200 mg/kg, and the delivered activity was 96 microCi/kg. Whole-body autoradiography was carried out on all animals. We noted an extensive whole-body distribution of radioactivity. At short intervals, the autoradiograms were characterized by an accumulation of radioactivity in the metabolic and excretory organs (liver, kidney, urinary tract, and intestinal content) as well as in lymphomyeloid tissues (thyroid gland, suprarenal gland, and hypophysis) and salivary glands. In pigmented mice, the uveal and biliary tracts were the highest labelled. The liver and particularly the renal medulla were identified as sites of retention of radioactivity. In the tumor the radioactivity was detected only in peripheral regions, with higher uptake in viable zones than in necrotic islets.

Animals↗
PubMed1987

Uptake and binding of teniposide (VM26) in Krebs II ascites cells.

With [3H] VM26 as marker, the uptake and binding of teniposide have been made in cells of Krebs II ascitic tumors. The intracellular accumulation of drug displayed a passive diffusion and a saturation kinetics with an apparent Michaelis-Menten constant of 37.54 10(-6) M and a flux of 13.4 nM/min/mg of protein. VM26 was rapidly taken and an equilibrium was established with the extracellular drug in about 30 min. The steady-state accumulation was diminished by Na+ and Ca2+ absence and VP16-213, whereas, K+ and Mg2+ have no effect. Energy dependence of the system was characterized by a Q10 of 1.75 +/- 0.2 and the uptake was reduced by ouabain and iodoacetamide, when 2-4-dinitrophenol and glucose absence were without appreciable change. The study of the efflux showed that about 87% of the uptaken drug was removed, the residual amount being probably irreversibly bound. The intracellular accumulation of the drug was associated with various cell organelles, however, only the nuclear fraction demonstrated a high affinity binding.

Animals↗
PubMed1987

Pharmacokinetics of high-dose i.v. alizapride in prevention of cisplatin-induced emesis.

Alizapride is a new antidopaminergic-related benzamide with specific antiemetic properties. Pharmacokinetics at a high repetitive dose (16 mg/kg) shows a biexponential plasma decay with T1/2 alpha of 8.33 +/- 2.47 min and T1/2 beta 2.8 +/- 0.7 hr. Large Vdss and high total body clearance are apparent. We demonstrate an increase in drug exposure during the first 6 hr after CDDP infusion by shortening the interval between injections. We conclude that the rate of infusion of alizapride could be important in the efficacy of the drug.

Antiemetics↗