Thermodynamics of the structural transition in metal-organic frameworks.

A thermodynamic study of the structural large-pore (LP) to narrow pore (NP) transition in various Metal Organic Frameworks (MOFs) is presented. First, the pressure induced transition at a constant temperature is investigated using a Tian-Calvet microcalorimeter set-up equipped with a high pressure cell. This device permits simultaneous measurements of the mechanical work and heat associated with the LP → NP transition. It is shown that MIL-53(Al) and MIL-53(Cr) have similar thermodynamic and mechanical behaviour whilst the MIL-47(V) system is characterized by much higher transition energy and mechanical work. Second, the temperature induced transition at ambient pressure is studied by means of differential scanning calorimetry (DSC) combined with X-ray absorption spectroscopy. This set-up enables one to follow simultaneously the structural changes associated with the phase transition detected by DSC. The MIL-53(Cr)-Br functionalized MOF is chosen here as a case study where both energetics and structural changes are discussed.

Use of yeasts in affinity chromatography.

The use of the yeast Candida lipolytica as a support in affinity chromatography for the purification of lectins of Ricinus communis seeds has been studied. A comparison was made with columns of erythrocyte stromas and Sepharose 4B with respect to protein yields, the agglutinating activity yield, and the electrophoretic characteristics of the eluted substances. Even though the yield is less than with other supports, it does appear that the yeast columns represent an effective method for the purification of ricin lectins.

Purification and lectins from Ricinus communis by combination of affinity and ion-exchange chromatography and characterization of the isolated proteins.

Lectins in the seeds of Ricinus communis L. were separated by affinity chromatography using stromata, and 3 fractions obtained by ion-exchange chromatography. Polyacrylamide-gel electrophoresis showed that 2 fractions were homogeneous and that 1 fraction gave 2 bands. Immunoelectrophoresis with rabbit antisera and polyacrylamide-gel isoelectric focusing showed that the 3 fractions were separate and distinct entities consisting of many proteins with isoelectric points near the isoelectric point of the main protein. The molecular weights of the separated proteins and their subunits were studied by SDS polyacrylamide-gel electrophoresis.

Clinical isolates of Staphylococcus lugdunensis and S. schleiferi: bacteriological characteristics and susceptibility to antimicrobial agents.

The bacteriological characteristics and susceptibility to antimicrobial agents of 108 clinical isolates of Staphylococcus lugdunensis and Staphylococcus schleiferi are described. Fifty out of 108 isolates were considered to be responsible for 16 documented infections, including some severe infections (endocarditis, bacteraemia, osteitis). A number of bacteriological characteristics enabled the identification of these species in the clinical microbiology laboratory: the absence of coagulase and protein A, and the presence of a fibrinogen affinity factor and thermonuclease along with other biochemical characteristics (ornithine and arginine decarboxylases, carbohydrate acidification, novobiocin susceptibility) differentiated these new species from other staphylococci; however, they did not possess virulence markers such as toxins or haemagglutinin, but were haemolytic. In this series, almost all isolates were susceptible to 22 antibiotics and 4 antiseptics representative of the main groups of antimicrobial agents. More information is needed on the ecology and epidemiology of these new opportunistic pathogens.

Evaluation of erythropoietic/hematopoietic reconstitution after BMT by highly fluorescent reticulocyte counts compares favorably with traditional peripheral blood cell counting.

Highly fluorescent reticulocyte (HFR) counts and reticulocyte counts were analyzed daily using a Sysmex R-1000 automated reticulocyte counter after 42 BMT in children (median age 7 years, range 10 month-18.5 years). White blood cell levels were also analyzed daily using either traditional counting methods or, when levels were very low, cytocentrifuge preparations. Twenty-eight patients received autologous and 14 allogeneic BMT. After myeloablative therapy, HFR counts fell to zero and rose to 2% of the reticulocyte total after a median time of 10 days (range 6-23 days) post-autoBMT and 14 days (range 9-29 days) post-alloBMT. The appearance of HFR (at least 2% in two successive counts) preceded the attainment of 20 x 10(9)/l reticulocytes in 23 of 26 autoBMT by a median time of 3 days, and in 13 of 13 alloBMT with a median time of 4 days (p < 0.001). Two per cent HFR preceded the attainment of 0.5 x 10(9)/l neutrophils in the majority of BMT by a median time > 6 days (p < 0.001). The attainment of 0.05 x 10(9)/l monocytes was preceded by a rise in HFR in 12 of 26 autoBMT and in 7 of 13 alloBMT. Median times between 2% HFR and monocyte levels of 0.05 x 10(9)/l were respectively 2 (range 0- > 24) and 3 (range: 0- > 19) days after auto and alloBMT. These results show that the evaluation of erythropoiesis following BMT by means of HFR counting provides an early measure of hematopoietic reconstitution which is as precise and considerably more practical than monitoring the monocyte level.

Identification and taxonomy of human and animal leishmanias by lectin-mediated agglutination.

The surface polysaccharides of two strains of lizard leishmanias, of the guinea pig parasite L. enrietti and of nine strains of human leishmanias belonging to the groups mexicana, donovani and tropica were studied by lectin-mediated agglutination. Twenty-three lectins prepared from seeds or from higher fungi carpophores were used. They revealed the presence of L-fucose, N-N'-diacetylchitobiose, alpha-D-glucose, alpha-D-mannose, beta-D-galactose, N-acetyl-D-galactosamine and lactose. We noted a range in the number and variety of lectin receptor sites detectable on the surface of the leishmanias, with the reptiles strains having the fewest sites and the tropica group having the most sites. We were unable to find specific group lectins, but it seems possible to identify a strain within each group by a lectin-binding pattern.

Identification of human and rabbit cytochromes P450 1A2 as major isoforms involved in thiabendazole 5-hydroxylation.

This report characterized one of the major cytochrome P450 isozyme involved in thiabendazole metabolism. This study was undertaken by using both cultured rabbit hepatocytes treated or not with drugs known to specifically induced various cytochromes P450 isoenzymes (i.e., P450 1A1/2 by beta-naphthoflavone, P450 2B4 by phenobarbital, P450 3A6 by rifampicine and P450 4A by clofibrate) and human liver (THLE-5) and bronchial (BEAS-2B) epithelial cells expressing or not the major constitutive human cytochromes P450 (i.e., CYP1A2, 2A6, 2B6, 2C9, 2D6, 2E1 or 3A4). Only hepatocytes exposed to beta-naphthoflavone and clofibrate significantly metabolized thiabendazole to 5-hydroxythiabendazole. Extensive biotransformation of this anthelmintic only occurred in human cells expressing CYP1A2. Moreover, experiments performed on rabbit preparations showed good correlations between thiabendazole 5-hydroxylase activity and both ethoxyresorufin and methoxyresorufin O-dealkylase activities. Thus, CYP1A2 is a major isoenzyme involved in thiabendazole 5-hydroxylation.

Evidence for cytochrome P4501A2-mediated protein covalent binding of thiabendazole and for its passive intestinal transport: use of human and rabbit derived cells.

Thiabendazole (TBZ), an anthelmintic and fungicide benzimidazole, was recently demonstrated to be extensively metabolized by cytochrome P450 (CYP) 1A2 in man and rabbit, yielding 5-hydroxythiabendazole (5OH-TBZ), the major metabolite furtherly conjugated, and two minor unidentified metabolites (M1 and M2). In this study, exposure of rabbit and human cells to 14C-TBZ was also shown to be associated with the appearance of radioactivity irreversibly bound to proteins. The nature of CYP isoforms involved in this covalent binding was investigated by using cultured rabbit hepatocytes treated or not with various CYP inducers (CYP1A1/2 by beta-naphthoflavone, CYP2B4 by phenobarbital, CYP3A6 by rifampicine, CYP4A by clofibrate) and human liver and bronchial CYP-expressing cells. The covalent binding to proteins was particularly increased in beta-naphthoflavone-treated rabbit cells (2- to 4-fold over control) and human cells expressing CYP1A2 (22- to 42-fold over control). Thus, CYP1A2 is a major isoenzyme involved in the formation of TBZ-derived residues bound to protein. Furthermore, according to the good correlation between covalent binding and M1 or 5OH-TBZ production, TBZ would be firstly metabolized to 5OH-TBZ and subsequently converted to a chemically reactive metabolic intermediate binding to proteins. This metabolic activation could take place preferentially in liver and lung, the main biotransformation organs, rather than in intestines where TBZ was shown to be not metabolized. Moreover, TBZ was rapidly transported by passive diffusion through the human intestinal cells by comparison with the protein-bound residues which were not able to cross the intestinal barrier. Consequently, the absence of toxicity measured in intestines could be related to the low degree of TBZ metabolism and the lack of absorption of protein adducts. Nevertheless, caution is necessary in the use of TBZ concurrently with other drugs able to regulate CYP1A2, particularly in respect to liver and lung tissues, recognised as sites of covalent-binding.

Evaluation of infectious episodes in neonates using a new procedure for the nitroblue tetrazolium test.

A new procedure for the NBT slide test for peripheral blood neutrophils has been tested. 255 neonates were studied of which 63 served as control cases. Among the 114 term infants, 37 were patently infected, 30 suspicious and 47 non-infected. The latter did not significantly differ from control cases, whereas suspicious and infected infants were credited with significantly higher NBT scores. 78 infants were preterm, 31 of which were patently infected, 22 suspicious and 25 non-infected. NBT scores of infected and suspicious infants were significantly higher than those of non-infected infants, but, as previously reported, scores of preterm infants were systematically and significantly lower than those of full-term infants of the same bacteriological class. Threshold values are suggested; they could represent an accurate diagnostic aid in the early differentiation of healthy infants from high-risk infants regarding bacterial infections.

Poisoning by Gyromitra : a possible mechanism.

"Gyromitra" are considered to be edible mushrooms although their potential toxicity has been long known. They have caused numerous accidents, sometimes lethal. Historical accounts of poisoning are reported and the authors describe the main characteristics : inconstant toxicity, influence of repetitive ingestions and variable individual sensitivity. Knowing the "gyromitrin" (N-methyl-N-formyl-acetyl-hydrazone) can be converted into methyl-hydrazine, the authors suggest a relation between individual sensitivity to the mushrooms and variation of every body's ability to carry out such a conversion. Several metabolites of gyromitrin can produce enzyme activation ith subsequent synthesis of methylhydrazine. The cumulative activating role of consecutive ingestions is emphasized.

Cerebrospinal fluid cytomorphology in neonates.

A prospective cytologic study of cerebrospinal fluids from 57 full-term neonates confirmed the previously reported cellular polymorphism. The cells were classified as (1) exogenous cells, (2) blood and bone-marrow cells, (3) histiomonocytes, (4) cell aggregates and (5) "free" cells. Histiomonocytes were a constant feature in these fluids and were the cause of neonatal pleiocytosis. Various degrees of activation could be recognized. The so-called inactive forms were closely related to brain damage. Identification of erythrophages and siderophages had diagnostic significance. The presence of fat in macrophages (lipophages) suggested a serious developmental disorder. The free cells were incompletely identified, as were the cell aggregates, which probably originate in the meningeal lining. Both require further study.

[Rapid screening for neonatal infection by employing new techniques for the use of the nitroblue tetrazolium test (NBT) (author's transl)]. / Dépistage rapide de l'infection néonatale par le test au nitrobleu de tétrazolium réalisé selon des modalités nouvelles.

A new method for carrying out the nitroblue tetrazolium test (NBT) has been used on micro-specimens taken from 116 newborn infants for the purpose of carrying out a prospective enquiry into neonatal infection. 44 children aged from 1 to 6 days were selected at random from a population that was said to be normal in the maternity unit and were the control group. 72 children of less than 48 hours of age were made to object of a prospective study of neonatal infection, an enquiry that allowed them to be divided into 3 groups: non-infected, infected and suspect. The study showed a very strong correlation between raised scores (higher than 100) and the presence of an infection, whereas scores in the controls and the non-infected infants were low. This test, which is hardly invasive and easy to introduce as a routine when carried out early is a good screening test for infection and can be best used on the newborn population in a maternity unit.

[Nitroblue tetrazolium test. Neonatal infections and antibiotic therapy]. / Test au nitrobleu de tétrazolium. Infections néonatales et antibiothérapie.

The authors report the results of a prospective test of NBT carried out by an original method already described, and now used for seventy newborn babies. Eleven of them (group I) were tested by simultaneously taken samples from the cord and the heel in the labour ward. The levels obtained according to the position from which the samples were taken showen no significant difference. In 59 other infants (group 2) three successive tests were carried out in the first two weeks of life. These results were classified according to whether the children were: infected, perhaps infected and non-infected. The results confirm correlations between raised levels and infections. Giving antibiotic therapy does not alter significantly the levels in non-infected babies, nor the high positive scores in infected babies that were revealed in the four days after the start of treatment. Following this delay, levels of infected babies' blood did drop significantly, which was a probable indication of the efficacy of the antibiotic therapy.

Pharmacodynamics of ibafloxacin in micro-organisms isolated from cats.

The pharmacodynamic properties of ibafloxacin were investigated in micro-organisms isolated from cats. Minimal inhibitory concentrations (MIC) of ibafloxacin (racemate, R- and S-enantiomers) and its metabolites (7-hydroxy- and 8-hydroxy-ibafloxacin) and time-kill kinetics were determined against Gram-negative and Gram-positive bacteria isolated from dermal and respiratory and urinary tract infections in cats. Racemic ibafloxacin has a broad spectrum of bactericidal activity against Gram-negative and some Gram-positive bacteria. Escherichia coli and Pasteurella, Klebsiella and Staphylococcus spp. are commonly isolated from feline infections and all are susceptible to ibafloxacin (MIC90 < or = 0.5 microg/mL), whereas Pseudomonas aeruginosa, Proteus mirabilis and Streptococcus spp. are considered intrinsic resistant. Microbiological activity resides primarily in the S-enantiomer of ibafloxacin whereas the R-enantiomer is less active. Killing curves using concentrations of racemic ibafloxacin and 8-hydroxy-ibafloxacin, which are representative of the in vivo situation observed in cats, showed at least 99.9% reduction in viable bacterial isolates from feline clinical samples over 24 h. Bacterial eradication was achieved in cats with Cmax/MIC and AUC/MIC values much lower than the target values previously established in man and laboratory animals. Additional studies in dogs and cats are necessary to define more clearly the surrogate markers of antibacterial activity (i.e. Cmax/MIC, AUC/MIC ratios), which are associated with a good clinical response.

Pharmacokinetics of ibafloxacin in healthy cats.

The pharmacokinetics of ibafloxacin following single and repeated administration of an oral gel formulation and the effect of food intake were investigated in cats. Ibafloxacin is a chiral fluoroquinolone available for clinical use as a racemic mixture of the R- and S-enantiomers. Plasma concentrations of ibafloxacin and its metabolites were determined using microbiological, LC-MS-MS and enantioselective capillary zone electrophoresis assays. Ibafloxacin was absorbed rapidly [time of maximum concentration (tmax) 2-3 h], reaching a mean maximum concentration (Cmax) of approximately 2.1 and 1.6 microg/mL for R- and S-ibafloxacin, respectively, following a single oral administration of the racemate at 15 mg/kg. Once absorbed, ibafloxacin was metabolized to 7-hydroxy-ibafloxacin and mainly to 8-hydroxy-ibafloxacin. Following repeated oral administration, significant increases in Cmax and AUC of ibafloxacin and its less active metabolites (racemic or enantiomers) were observed between the first and the tenth day of treatment. This twofold exposure increase in concentrations of ibafloxacin and its metabolites may contribute additionally to the efficacy of this drug in the treatment of feline bacterial infections. Single and repeated doses of ibafloxacin were well tolerated by cats. Food promoted the absorption of ibafloxacin, doubling Cmax and increasing AUC and slightly delaying tmax. High concentrations of the metabolites, mainly 8-hydroxy- and 7-hydroxy-ibafloxacin were excreted in urine, either unchanged or as glucurono-conjugates.

RU 486: a new method for early abortion.

PIP: At the end of September 1988, Mifepristone or RU-486, was put on the market in France, to be used in association with prostaglandins to terminate pregnancy during the 1st 7 weeks. Mifepristone stops the pregnancy, and the prostaglandins facilitate the expulsion of the egg. At the initial visit the woman is examined and told about Mifepristone. A week later, she returns and takes 3 tablets of RU-486 in the presence of the physician. 48 hours later she returns to hospital and is given an intramuscular injection of prostaglandin. Bleeding starts within 48 hours and is sometimes heavy and protracted. A week later the woman is given a check-up and an interview. Women find the experience extremely stressful, especially since they themselves carry out the act that terminates the pregnancy.^ieng