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Biomedical subjects

C Brossard

Publications and source records attributed to C Brossard.

At least 19 recordsLinked to original sources

Rheological behaviour of saturated polyglycolysed glycerides.

Seven saturated polyglycolysed glycerides (Gelucires) of melting points varying from 42 to 53 degrees C and hydrophilic-lipophilic balance values from 2 to 14 were selected. Their rheological behaviour was determined by adjustment of the flow curves to the Ostwald power-law and by statistical assessment of the flow index. The flow of Gelucires was slightly shear thickening. This shear thickening rose when the temperature and the lipophilic specificity of the Gelucire increased. This behaviour accounted for a reorganization of the particles under the shear which became easier when the temperature increased and when the degree of condensation of the polyethylene glycol chains decreased with lipophilicity of the Gelucires.

Delayed-Action Preparations

[Optimization of liberation of theophylline derivatives from Gelucire matrix tablets].

Matrix tablets containing theophylline, etofylline, dyphylline and proxyphylline were prepared with saturated polyglycolysed glycerides whose melting point was 50 degrees C and HLB were 2 and 13 (Gelucires 50/02 and 50/13), in order to eliminate the melting point influence and to have extreme values of HLB. The influence of two parameters was studied: HLB of the mixtures of Gelucires and drug solubility. Drug release was found to increase as these two parameters rose, the main factor being HLB value. Multiple linear regression was used to evaluate their influence. The mathematical model obtained was employed to optimize the release of each active ingredient from the tablets made of mixtures of the two Gelucires with HLB ranging from 3 to 4 depending on drug solubility.

Chemistry, Pharmaceutical

[Osteocalcin in chronic alcoholism].

In order to investigate the mechanism by which the inorganic content of the bone is reduced in chronic alcoholism, the authors assayed osteocalcin in 60 chronic alcoholics. The level was significantly lower than in control subjects. There was no significant difference between levels in cirrhotics and in non-cirrhotic alcoholics. There was a negative correlation between osteocalcin and gamma GT levels. There was no correlation between osteocalcin and blood calcium, blood phosphorus, ALAT, ASAT, alkaline phosphatase, 5'-nucleotidase, albumin or bilirubin levels, or with the prothrombin time. These results suggest a direct impact of alcohol on the osteoblast.

Adult

A skin suction blister model in hairless rats: application to the study of anti-inflammatory and immunomodulatory drugs.

A suction blister model was developed in the hairless rat, in order to study the effects of various agents on the migration of polymorphonuclear leukocytes (PMN). A standardized abrasion, a suction blister, was formed by applying negative pressure to the skin and then separating the epidermis from the dermis. A migration chamber containing serum as the chemoattractant was placed over the wound. After 6 h of migration, the cells in the chamber were harvested, counted and identified. We evaluated PMN migration after treating the animals with active compounds: niflumic acid, and anti-inflammatory drug, and RU 41740, an immunomodulator. This in vivo model provided reproducible data and could be used to study further the functional properties of PMN. In addition, because this assay can also be used in man, a drug found to be effective in the animal system could then be tested for its activity in man.

Adjuvants, Immunologic

Studies on the human chromosome 3 centromere with a newly cloned alphoid DNA probe.

Starting from a chromosome-specific DNA library, we have isolated a human chromosome-specific satellite DNA sequence. This sequence of 635 base pairs (bp) consists of 3.7 alpha DNA monomers of 170-171 bp. Under high stringency it hybridizes to the centromere of chromosome 3 in a region composed of 2,750 bp tandem repeats characterized by the regular spacing of Hind III and TaqI restriction enzyme recognition sites. It has diverged and undergone amplification after the human speciation. The amplification allows an easy monitoring of the chromosome 3 centromere by in situ hybridization with a nonradioactive probe.

Animals

Hyaluronic acid-degrading enzymes in rat alveolar macrophages and in alveolar fluid: stimulation of enzyme activity after oral treatment with the immunomodulator RU 41740.

RU 41740 (Biostim) is an immunomodulator clinically used for the treatment of chronic bronchitis and recurrent pulmonary infections. In these diseases large amounts of mucus are produced which congest the bronchi. A major glycosaminoglycan constituent of this mucus is hyaluronic acid, one of the largest molecules in nature; its metabolic degradation is carried out by 3 acid hydrolases: hyaluronidase, beta-N-acetylglucosaminidase, and beta-glucuronidase. In the lung these enzymes are especially synthesized and active in alveolar macrophages. It was thus interesting to study the effect of RU 41740 administration on the hyaluronic acid-degrading activity of these cells. This compound was given by gastric gavage to rats and the activities of lung alveolar macrophage and alveolar fluid hyaluronidase, beta-N-acetylglucosaminidase, beta-glucuronidase, and acid phosphatase as a lysosomal marker were determined. The effect on macrophage proliferation was also examined. The results obtained showed that: (1) unstimulated alveolar macrophages display the remarkable property, compared with other cell types, that hyaluronidase activity is about equally distributed between the inside and the outside of the cell; (2) RU 41740 administration increases the total activity of the 4 enzymes studied in the alveolar macrophages without inducing any increase in the number of macrophages; (3) the intracellular activities of beta-N-acetylglucosaminidase and beta-glucuronidase are markedly increased, whereas intracellular hyaluronidase activity is not changed. However, in the extracellular fluid only hyaluronidase activity is highly increased; (4) even the lysosomal marker enzyme acid phosphatase has only its intracellular activity increased. This would suggest the possibility that other lysosomal enzymes may also be increased by this immunomodulator.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylglucosaminidase

Dissolution of a soluble drug substance from vinyl polymer matrices.

It was shown that vinyl polymers form good bases for in vitro sustained-release matrices, and that the character of the release curves is basically in line with their pH-solubility profiles. For a flow cell, the release curves may be approximated by the equation: In (m/m0) = - K(t -ti), where m is the amount not dissolved, m0 is the initial drug content, K is a dissolution constant, t is time, and ti is a lag time. Furthermore, it was shown that K is a function of tablet hardness (H) and polymer content (Q, percent). This functionality is well represented by the equation: In K = alpha H + gamma ln Q + epsilon, where alpha, gamma, and epsilon are polymer-dependent parameters. Matrix erosion is represented by an exponential decay: (p/p0) = exp(-Dt + a), where p is the amount not eroded, p0 is the initial weight, D is an erosion constant, and a is a soluble polymer-dependent parameter. In the case of these soluble polymers, K is not solely a function of D.

Chemistry, Pharmaceutical

In vitro immunological activities of the polysaccharide fraction from Haemophilus influenzae type a endotoxin.

Mild hydrolysis of Haemophilus influenzae type a lipopolysaccharide by ion exchangers in the presence of chloroform, to remove the lipid moiety, yielded a nontoxic and immunogenic polysaccharide fraction. This polysaccharide selectively triggered murine B lymphocytes in vitro: (i) it induced enhancement of thymidine incorporation and stimulated antibody secretion in cultures of normal and nude mouse spleen cells; (ii) it did not stimulate splenic T lymphocytes; (iii) the activation of B lymphocytes was not absolutely dependent on the presence of macrophages. Sepharose 4B gel filtration showed that this polysaccharide consisted at least of two fractions: PS I (molecular weight [MW] 10(6)) and PS II (MW 10(4)). Only PS I was found to act as a polyclonal B cell activator. EDTA treatment dissociated the polysaccharide into PS III (MW 10(6)) and PS IV (MW 10(4)), which was not reassembled after the addition of 0.02 M CaCl2. Both fractions PS III and PS IV were unable to stimulate B lymphocytes. The immunological active fraction of H. influenzae polysaccharide is PS I. This fraction consists of a high-molecular-weight group (10(6)) and an association of 10(4)-MW aggregated units.

B-Lymphocytes

In vivo and in vitro effect of the Haemophilus influenzae lipopolysaccharide on ciliated respiratory epithelium.

The lipopolysaccharide of Haemophilus influenzae is presumed to have a toxic effect on the tracheal epithelium, and then induce a bronchial obstruction. This activity of LPS was studied in vitro on the ciliary beat using a photo-oscillographic apparatus, and in vivo on the rabbit trachea. Neither modification of ciliary beat frequency, nor epithelial damage in the rabbit trachea was observed after a single administration of LPS. In contrast, histopathologic changes were observed in vivo when the intratracheal administration of H. influenzae LPS was followed 24 h later by an intravenous injection of the same LPS. These experimental models seem thus to implicate a Shwartzman type cellular necrosis in the trachea in vivo in the absence of a direct toxic effect of endotoxin itself on trachea in vivo or in vitro.

Animals

Characteristics of a lipid preparation (lipid A) from Haemophilus influenzae type a lipopolysaccharide.

Mild hydrolysis of Haemophilus influenzae type a lipopolysaccharide by ion exchangers yielded a lipid A extracted by chloroform. It contained phosphorus, glucosamine, and fatty acids. Myristic, palmitic, 3-hydroxymyristic, and oleic acids and two other unidentified long-chain fatty acids were found. The free lipid A was not toxic for mice at doses of up to 50 mg/kg and did not provoke a Shwartzman reaction. The Limulus test activity was positive up to 10(-12) g/ml, but the pyrogenicity in rabbits was lower than with the original lipopolysaccharide. However, the lipid A did induced a mitogenic response and polyclonal B-cell activation in mouse spleen cell cultures. Complexing lipid A with bovine serum albumin gave a nontoxic preparation which lost these immunological activities. Immunochemical studies showed that the major reactive determinants of this lipid-protein complex were altered after such a linkage. Consequently, the nontoxic and mitogenic lipid A isolated from H. influenzae type a did not exhibit all of the classical activities of lipid A preparations.

Animals

Comparative study of biological activities and mitogenic effect of extracts from Haemophilus influenzae type a.

Two preparations designated as PWE and NCE were obtained from H, influenzae type a by treatment with either phenol water or hypertonic NaCl citrate respectively. The protein content of NCE was three fold higher than for PWE. Electroimmunodiffusion against H. influenzae antiserum disclosed an immunological relationship between NCE and PWE. The toxicity for mice was lower for both antigenic extracts (LD50 PWE: 47 +/- 7 mg/kg; LD50 NCE: 943 +/- 5 mg/kg) than for E. coli LPS. Limulus assay showed that both H. influenzae extracts had a weaker potency (100 to 1000 times less) than E. coli LPS. Sanarelli and Shwartzman reactions failed for PWE and NCE. The blast transformation of DBA/2 and nude mouse spleen cells were strikingly different for the three preparations: PWE, NCE, and E. coli LPS. Neither extract from H. influenzae cells showed the biological properties of a classical endotoxin. We suggest that they are endotoxin-like substances.

Animals

Preparation of a nontoxic and immunogenic polysaccharide fraction from a Haemophilus influenzae phenol-water extract.

A phenol-water extract from Haemophilus influenzae type a was hydrolyzed to decrease the toxicity without affecting the antigenicity of the preparation. We used partial hydrolysis for 15 h with ion exchangers in the presence of chloroform. The lipid fraction was collected into the organic solvent. The preparation obtained from the aqueous solution was designated the polysaccharide fraction. Rhamnose, glucose, galactose, mannose, and glucosamine were the major components of the polysaccharide fraction, and their molar ratios were determined by gas-liquid chromatography; 2.5% myristic acid was also found in the polysaccharide fraction. The mild hydrolysis of the polysaccharide fraction for 15 h caused a marked reduction in toxicity (50% lethal dose, 183 +/- 9 microgram/kg) and pyrogenicity. The generalized Sanarelli reaction was negative. The local Shwartzman phenomenon was not observed if chloroform and Dowex were exchanged three times during hydrolysis. Most of the antigenic components remained active after the hydrolytic process. The polysaccharide fraction could also induce the formation of circulating antibodies in rabbits and also increase the phagocytic process against H. influenzae from month 2 to 6.

Animals

[Studies on an extract from Haemophilus influenzae type a. I.--Antigenic and immunogenic studies (author's transl)].

Haemophilus influenzae is the bacteria most commonly found in chronical bronchitis not treated by antibiotic therapy. Experimental studies have suggested that the destruction of the ciliated respiratory epithelium is in conjunction with the toxic product of the cell-wall of this bacteria. Endotoxin is extracted by phenol-water procedure. Toxicity is reduced by mild hydrolysis. Antigenicity of the preparation is controlled by gel diffusion in a parallel sides-tank diffusion and electroimmunodiffusion. These methods show that common antigenicity is not affected by hydrolysis. After immunisation by that preparation, circulating antibodies are detected by passive hemagglutination and immuno-precipitation. The immunized rabbits have agglutinin titer of 1 : 256th. Antigenicity of this bacterial extract is preserved and the preparation is still immunogenic.

Animals

[Studies on an extract from Haemophilus influenzae type a. II.--Phagocytic capacity of sera obtained from rabbits immunized by this bacterial extract (author's transl)].

Opsonins may protect against infections. In this study, the different parameters of opsonization assay are strictly standardized. Results are expressed as percentage of opsonization. 0% and 100% opsonization must be established. The experiment without immunserum is used as the 0% opsonization. To determine the 100% opsonization an excess of reducing capacity is required. This is provided by crushed leukocytes. Rabbits are immunised by bacterial extract from Haemophilus influenzae type a. The hemagglutinins are detected in sera earlier (D + 30) and longer than the opsonic activity. Phagocytosis increases from the second month following the immunization. Percentage of opsonization is maintained at about 50% up to the sixth month. Alternatively, the percentage of phagocytosis is decreasing when heterologous bacteria are used. The serum thermolabile factors are necessary for the response. The phagocytic capacity is not modified whether leukocytes are obtained from immunized rabbits or not.

Animals