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Biomedical subjects

A Durand

Publications and source records attributed to A Durand.

At least 91 records · Page 5Linked to original sources
PubMed1993

Solid state fermentation reactors: from lab scale to pilot plant.

Relatively many workers in the world are studying different aspects in SSF processes but few are working on reactor design and scale-up. From about 10 years, we are developing reactors from lab scale to pilot plant, based on the same technology, reactor design and flowsheet to allow fermentation with a deep layer (up to 1 m in the pilot plant). These reactors have all a forced aeration and the possibility or not to agitate. Regulations of temperature and water content of the culture are monitored by a special device.

Journal Article↗
PubMed1993

Use of chitin measurement to estimate fungal biomass in solid state fermentation.

Twenty-two strains of twelve species of Deuteromycotina: Hyphomycetes were studied. Most of them had a variable glucosamine amount (standard deviation higher than 5%). However, if we consider that the amount of glucosamine is constant, the accuracy of the method remains satisfactory (10% instead of 5%, which is the accuracy of the chitin hydrolysis and colorimetric glucosamine measurement). So, by means of this measurement, the fungal growth kinetics could be followed on different solid media (vegetable material such as sugar beet pulp and sponge or mineral like clay granules) used. It is important to note that this method should not be used to compare different media without calibration.

Journal Article↗
PubMed1993

Diminution of an acute cyclosporin-induced cholestasis by tauroursodeoxycholate in the rat.

CsA is a commonly used immunosuppressive drug known to possibly induce cholestatic side effects. Ursodeoxycholic acid (UDC), a nonhepatotoxic bile acid, has proved to be efficient for several types of cholestasis. The aim of this experiment was to evaluate the ability of tauroursodeoxycholate (TUDC) in preventing CsA-induced cholestasis on bile duct-cannulated rats. After bile flow stabilization, a bolus of 30 mg/kg CsA was given i.v. to one group (n = 7) and was associated with a 2 mumol/kg/min TUDC infusion in another group (n = 7). The control group was injected with CsA-solvent. CsA, as used here, had a rapid and marked cholestatic effect. However, both bile flow and bile salt secretion were significantly enhanced in the TUDC group when compared to the CsA alone-treated group and showed no difference with the solvent control group. In addition, TUDC significantly increased elimination of CsA and its metabolites in bile. In contrast to what was found for endogenous bile salts, TUDC uptake was not affected by CsA. The anticholestatic effect of TUDC probably resulted from preventing CsA-induced hepatocyte membrane damage and from easing biliary excretion of CsA. Such properties could be helpful for CsA-treated liver recipients who are especially exposed to cholestatic problems, and thus, to toxic CsA accumulation in the liver. Moreover, regulation of CsA elimination might prevent, in part, its general toxicity.

Animals↗
PubMed1993

Concentration of temarotene (Ro 15-0778) and its metabolite Ro 14-6113 in plasma and skin of hairless rat.

The aim of this preliminary report was to measure plasma and skin concentrations of Ro 15-0778 and its phenolic metabolite Ro 14-6113 in hairless rats receiving orally 10 mg/kg of Temarotene once daily during 10 days. Blood (2-3 ml) and skin (200-300 mg) samples were taken at different time points between 0.5 and 240 h after the last dose. We used a highly sensitive HPLC method for simultaneous determination of the two compounds with a quantification limit of 2 ng/ml in plasma and 10 ng/g in total skin (epidermis and dermis). After 10 h, plasma concentrations of Ro 14-6113 were 5-13 times higher than for Ro 15-0778. Ro 14-6113 concentrations in the skin were 4-10 times higher than for Ro 15-0778 within the initial 48 h. The concentrations of both compounds in the skin were higher than concentrations in plasma.

Administration, Oral↗
PubMed1993

Motor recovery after arthroscopic partial meniscectomy. Analyses of gait and the ascent and descent of stairs.

We studied motor recovery as shown by locomotor activities after arthroscopic partial medial meniscectomies in seventeen men who were twenty-five to forty-nine years old. The patients were evaluated before the operation and two, four, and eight weeks after the operation. Control values were obtained from twenty-two healthy men whose ages, weights, and heights were similar to those of the patients who had had a meniscectomy. Motion of the hip, knee, and ankle in the sagittal plane and the electromyographic activities (as measured with surface electrodes) in five muscles were recorded while each subject walked on a level walkway and then ascended and descended stairs at free speeds. The results showed that meniscal tears affect the motor-control mechanisms involved in the submaximum locomotor activities that were studied and that these abnormalities may persist for as long as eight weeks after a meniscectomy.

Adult↗
PubMed1993

[Modeling of feto-placental circulation. Clinical applications apropos of 21 patients having no or inverse diastolic umbilical flow].

The placental resistance index: (S-D)/S (S: represents the amplitude of the systolic peak and D: the amplitude of the telediastolic peak) is constantly inferior to one from the 14th-16th week of amenorrhea during a normal pregnancy. The diastolic umbilical arterial blood flow is continuous because of low placental vascular resistance. From a clinical study of 21 patients with an absent or reversed end diastolic flow in umbilical artery waveforms, an obliterative process in the placental vascular tree was observed. A computer model was used to stimulate the reversed end diastolic flow in umbilical artery waveforms when the placental resistance increased. This haemodynamic approach shows that the placental blood flow decreased, and that the arterial blood pressure, as well as the pulse wave velocity increased when the placental resistance increased. The increase in the difference between the umbilical resistance and the placental resistance caused a reduction of the diastolic flow owing to a progressive increase of the pulse wave velocity reflected. It was concluded that there is a relation between perturbations in placental vascular bed and the flow in umbilical artery waveforms.

Adult↗
PubMed1993

[Distribution of acitretin in human skin].

Acitretin has recently been introduced for the systemic treatment of dermatologic diseases such as psoriasis and congenital disorders of keratinization. At present, only an oral form of this drug is available. However results from recent studies have shown that considerable drug concentrations can be delivered to the skin by topical administration of acitretin. Based on this data we addressed the question whether the topical administration of acitretin can produce in humans a drug concentration in the skin which exceeds the drug concentration that is found in the skin after multiple oral acitretin dosing and is reported to be clinical effective. Drug concentrations in the skin were investigated under conditions in which the maximum dose that can be administered in a therapeutic situation was applied. Additionally, three different skin sampling techniques, the punch biopsy, the shave biopsy and the suction blister technique were validated to quantitate acitretin in the skin. The drug concentrations in skin after systemic application in a steady state situation were comparable with the drug concentration reached after a single 24 hours topical application of a saturated acitretin/isopropylmyristate formulation. However, no unequivocal effects in psoriasis and disorders of keratinization were observed up to now by the topical administration of acitretin. The inverse drug concentration gradients which are present in the skin, depending on the route of administration, may explain differences in activity. The skin samples in our and other studies were homogenized or dissolved and thus much of the anatomical information is lost. The latter may be most important for the understanding of the local events.

Acitretin↗
PubMed1993

Is there an interaction between low doses of corticosteroids and methotrexate in patients with rheumatoid arthritis? A pharmacokinetic study in 33 patients.

A study of methotrexate (MTX) pharmacokinetics with and without prednisolone was performed in 33 patients with rheumatoid arthritis. Ten mg im MTX were given on Day 0; patients were divided into 3 groups of 11 persons: Group 1: no corticosteroid; Group 2: prednisolone 15 mg/day per os from D -3 on; Group 3: patients continuing longterm prednisolone treatment (15 mg/day). Groups 1 and 2 were randomized. MTX plasma concentrations were measured at T 0, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12 and 24 h using fluorescence polarization immunoassay (TDx Abbott). There was no difference between MTX pharmacokinetics of Groups 1 and 2. Area under the curve (AUC), Cmax and residual concentration at 24th h were higher, while total body and renal MTX clearances were lower in Group 3 vs Groups 1 and 2. Only the differences in AUC and total clearance were significant (p < 0.01 and p < 0.05). Tmax and terminal half-life did not differ. Our data suggest a possible influence of prednisolone on MTX pharmacokinetics in longstanding steroid treated patients. The pharmacological processes that might be involved are discussed.

Adrenal Cortex Hormones↗
PubMed1992

Glutamic acid decarboxylase (GAD) autoantibodies are additional predictive markers of type 1 (insulin-dependent) diabetes mellitus in high risk individuals.

The prevalence of glutamic acid decarboxylase autoantibodies was determined with an immunotrapping enzyme activity assay in newly-diagnosed Type 1 (insulin-dependent) diabetic patients as well as in first-degree relatives using rat brain homogenate as a source of glutamate decarboxylase. Twenty-six out of 86 islet-cell cytoplasmic auto-antibody positive and one out of 24 islet cell autoantibody negative patients of recent onset, had autoantibodies to glutamate decarboxylase above the upper 99% confidence limit obtained from 89 control sera. Among 27 islet cell autoantibody positive relatives including 19 siblings and 8 parents, antibodies to glutamate decarboxylase were found in 8 of 9 (89%) relatives and 7 of 8 (87.5%) siblings with islet cell auto-antibody titres above 20 JDF units, in 1 of 19 (5.2%) relatives with islet cell autoantibody titres between 2 and 5 JDF units, in 2 of 263 (0.7%) siblings and 1 of 139 parents without islet cell autoantibodies. In first-degree relatives, high titre islet cell autoantibodies and autoantibodies to glutamate decarboxylase were tightly associated (X2 = 182, p = 0.0001). None of the relatives with low genetic risk (n = 64), i.e. HLA-different to the diabetic proband, was found to be antibody positive. Antibodies to glutamate decarboxylase were present only in those relatives sharing at least one haplotype with the diabetic proband, including two islet cell autoantibody negative but HLA-identical siblings. Autoantibodies to glutamate decarboxylase were present in 7 of 9 (77%) relatives who developed the disease, including one islet cell autoantibody negative sibling.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Evaluation of Bayesian estimation in comparison to NONMEM for population pharmacokinetic data analysis: application to pefloxacin in intensive care unit patients.

The pharmacokinetics of pefloxacin (PF) were investigated in a population of 74 intensive care unit patients receiving 400 mg bid as 1-hr infusion using (i) Bayesian estimation (BE) of individual patient parameters followed by multiple linear regression (MLR) analysis and (ii) NONMEM analysis. The data consisted of 3 to 9 PF plasma levels per patient measured over 1 to 3 dosage intervals (total 113) according to four different limited (suboptimal) sampling 3-point protocols. Twenty-nine covariates (including 15 comedications) were considered to explain the interpatient variability. Predicted PF CL for a patient with median covariates values was similar in both BE/MLR and NONMEM analysis (4.02 and 3.92 L/hr, respectively). Bilirubin level and age were identified as the major determinants of PF CL by both approaches with similar predicted magnitude of effects (about 40 and 30% decrease of median CL, respectively). Confounding effects were observed between creatinine clearance (26% decrease of PF CL in the BE/MLR model), simplified acute physiology score (a global score based on 14 biological and clinical variables) (18% decrease of median CL in the NONMEM model) and age (entered in both models) which were highly correlated in our data base. However, both models predicted similar PF CL for actual subpopulations by using actual covariate values. Finally, the NONMEM analysis allowed identification of an effect of weight on CL (decrease of CL for weight < 65 kg) whereas the BE/MLR analysis predicted an increase of CL in patients treated with phenobarbital. In conclusion, both approaches allowed identification of the major risk factors of PF pharmacokinetics in ICU patients. Their potential use at different stages of drug development is discussed.

Adolescent↗
PubMed1992

Influence of food on the tyramine pressor effect during chronic moclobemide treatment of healthy volunteers.

An open study was carried out to examine the effect of moclobemide, a new antidepressant reversible inhibitor of MAO-A, on the pressor response induced by oral tyramine added to meals of different lipid and protein composition, and to correlate the blood pressure increase in the tyramine test with that obtained during an exercise test. Eight healthy volunteers of both sexes participated in the study. A tyramine sensitivity and an exercise test were performed beforehand. Subjects were included if, under fasting condition, their systolic blood pressure (SBP) increased by more than 30 mmHg after administration of 400 or 600 mg tyramine. Exercise tests were performed to determine the grade of effort that corresponded to a rise in SBP of 30 mmHg. Subjects received moclobemide 600 mg/d. Starting on Day 7, each subject consumed a standardized meal (52 g lipids, 43 g proteins, 86 g carbohydrates) just before taking moclobemide. Tyramine was added to these meals in daily increasing doses of 50, 100, 150...mg until an increase in SBP > or = 30 mmHg was obtained. On moclobemide treatment, an average dose of 250 mg tyramine (range 150-400 mg) increased SBP by 36.6 mmHg. The time to reach peak SBP was longer (175 min) than in the fasting condition before the trial (40.6 min).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1992

Measurement of lymphatic flow variation by noninvasive method cases of lymphedema.

The purpose of this study was to measure the variations of lymphatic flow. A noninvasive isotopic method was used to achieve a functional exploration of lymphatic circulation. Fifteen subjects were used in the study: 10 healthy subjects and 5 patients with lower extremity lymphedema. A first subcutaneous injection of technetium 99m rhenium sulfate (99mTc) was performed in the first interdigital space of both feet. The radioactivity was recorded in two places: the first one on the inguinal site by a gamma camera; the second, below the first, on the precordial site by a multichannel analyzer. With the two types of recording procedures, it was possible to obtain a curve that showed the amount of radioactivity in relation to time. In order to obtain a muscular activity fifty-five minutes after the injection, each subject or patient spent ten minutes on an ergometric bike. A second subcutaneous injection was performed one week later, but prior to the injection, the subject or patient took orally 1800 mg of heptaminol adenosine phosphate (HAP) per day for three days. The radioactivity recording was made under the same conditions as with the muscular activity. The statistical results of the experiment without treatment on the two types of recording show that in the healthy subjects the amount of radioactivity increased during muscular activity. Moreover, the treatment indicated higher radioactivity values, which remained at a higher level. However, the muscular activity performed by a patient was unable to increase the radioactivity. On the other hand, the drug gave radioactivity values that were higher than the previous values of the first curve.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Monophosphate↗
PubMed1992

Comparative in vivo and in vitro regional selectivity of central omega (benzodiazepine) site ligands in inhibiting [3H]flumazenil binding in the rat central nervous system.

The in vivo selectivity for central omega (benzodiazepine) modulatory site subtypes of ligands from several chemical classes has been evaluated by measuring the displacement of the in vivo binding of [3H]flumazenil to several rat central nervous system structures differentially enriched in omega 1 and omega 2 sites. This labeling was prevented in a dose-related manner by the i.p. administration, 30 min before the radioligand, of several benzodiazepine derivatives, the cyclopyrrolone derivatives suriclone and zopiclone, the triazolopyridazine derivative CL 218,872 and the imidazopyridine derivative zolpidem. Most of the benzodiazepine derivatives studied displayed in vivo some selectivity for omega 2-enriched structures. In contrast, oxoquazepam and CL 218,872 were 2- to 3-fold more potent at preventing [3H]flumazenil binding in omega 1-enriched (cerebellum) than in omega 2-enriched structures. Maximal inhibitions by zolpidem of in vivo [3H]flumazenil binding [cerebellum (100%) > cerebral cortex (79%) > or = striatum (74%) > hippocampus (52%) > spinal cord (37%)] were related to the relative omega 1/omega 2 distribution ratio in each structure. These differences did not result from an uneven distribution of this compound in the central nervous system. Quantitative autoradiographic studies performed on 30 central nervous system regions showed a strong correlation between the in vitro and in vivo regional selectivity of zolpidem. For all the drugs studied there was a significant global correlation between their potency at inhibiting [3H]flumazenil binding in vitro and in vivo either in the cerebellum (P < .001) or in the spinal cord (P < .01) and between the in vitro and in vivo cerebellum/spinal cord selectivity. The differential in vivo selectivity of zolpidem may account for the reported hypnoselective profile of this imidazopyridine in the rodent.

Animals↗
PubMed1991

Insulin prevents adoptive cell transfer of diabetes in the autoimmune non-obese diabetic mouse.

Early intensive insulin treatment is thought to improve subsequent Beta-cell function in Type 1 (insulin-dependent) diabetic patients. Prophylactic insulin administration also reduced diabetes incidence in diabetes-prone animals. To study the mechanisms by which these effects occur, we tested the ability of insulin therapy in the model of non-obese-diabetic mice, to prevent the penetration of committed T cells into the islets and subsequent Beta-cell destruction. Sublethally irradiated non-obese-diabetic males of 8 weeks of age were adoptively transferred with splenocytes from diabetic donors and treated with the maximum tolerable dosage of fast-acting insulin (0.5 U, twice daily) until 30 days after cell transfer. Diabetes incidence was compared to control animals injected with the same concentration of insulin diluent. After one month of treatment, the cumulative diabetes frequency was significantly less within the insulin-treated group (4 of 15, 26.6%) than in the control group (15 of 18, 83.3%; p less than 0.01). Pancreatic histological analysis of insulin-treated animals revealed a lower severity of insulitis and Beta-cell necrosis and a higher percentage of normal islets (46.6 +/- 10% vs 2.3 +/- 2%, p less than 0.01), including five (33%) mice with no lesions. Immunoperoxydase staining of pancreatic sections indicated similar insulin and ganglioside staining of Beta cells from insulin-treated mice and control animals. Insulin-treated mice had comparable pancreatic insulin content to normal mice. Flow cytometry analysis of spleen cell populations indicated that insulin increased the number of Thy1,2+ and Lyt-2+ T cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Pharmacokinetics of navelbine after oral administration in cancer patients.

The pharmacokinetic behavior of navelbine was investigated in 19 patients presenting with advanced cancers (mainly women with breast cancer). Navelbine was given orally at seven dose levels of up to 200 mg/week. For a given dose, patients received four successive weekly treatments. Five subjects also received two different doses. After drug administration, plasma was collected for 48 or 72 h and monitored for navelbine concentration by radioimmunoassay. Absorption of navelbine was very rapid after oral administration: maximal drug concentrations were reached within the first 1 or 2 h (Tmax, 0.9-1.75 h; cmax, 70.9-832.6 ng/ml), with absorption constants ranging from 0.85 to 2.42 l/h. A comparison of dose-normalised plasma concentration profiles revealed significant time dependence in six evaluable patients (P less than 0.001). Only four subjects who received low doses (less than or equal to 100 mg/week) exhibited time-independent kinetics. All of the five patients who were treated at different doses displayed apparent dose dependence (P less than 0.001). No individual profile was characterised by both time- and dose-independent pharmacokinetics. In all, 18 patients presented biphasic plasma concentration-decay patterns, and only 1 subject exhibited monophasic decay kinetics. The navelbine pharmacokinetic parameters obtained following oral administration were similar to those observed after i.v. bolus injection and were characterised by high oral clearance (0.43-1.45 1 h-1 kg-1), a large apparent volume of distribution (27.4-45.9 1/kg), and a long terminal half-life (24.2-56.5 h). Large intra- and inter-individual variations in pharmacokinetic parameters were observed. Moreover, after a high dose of 200 mg, an enterohepatic cycle and/or a delay in navelbine's absorption at a distal intestinal site as evidenced by a marked plasma level rebound was observed.

Administration, Oral↗