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Biomedical subjects

M Juste

Publications and source records attributed to M Juste.

13 recordsLinked to original sources

Using a recombinant bispecific antibody to block Na+ -channel toxins protects against experimental scorpion envenoming.

In recent years, several molecular engineering methods of designing bispecific antibodies in various formats have been developed. Tandem-scFvs comprising two scFvs fused together via a peptide are 55-kDa molecules, and are one of the most promising and most straightforward approaches to bispecific antibody production. We report an attempt to design more effective antivenoms to the Androctonus australis scorpion using murine scFvs as building blocks to create a unique bispecific molecule that neutralizes the potent neurotoxins AahI and AahII. The tandem-scFv was produced in recombinant bacteria, purified by immobilized metal ion affinity chromatography, and analyzed by polyacrylamide gel electrophoresis, Western blot, gel filtration, mass spectrometry, and direct and competitive radioimmunoassay. In vivo, it neutralized the binding of the AahI and AahII toxins to their receptor, and protected mice against experimental envenomation. The findings reported here highlight the potential of recombinant antibody fragments for protecting against scorpion venom toxicity.

Animals↗

Population pharmacokinetics of high dose ibuprofen in cystic fibrosis.

AIMS: To evaluate ibuprofen population pharmacokinetics in a large series of data collected in children with cystic fibrosis (CF) treated with high doses of ibuprofen (59 patients; 2-18 years), and to identify the main causes responsible for the considerable interindividual variability in ibuprofen serum levels. METHODS: Blood samples were collected during routine clinical care; serum ibuprofen concentrations were determined by HPLC. Fitting of the concentration/time data to a one compartment kinetic population model was performed by a non-linear mixed effect regression method. RESULTS: Body weight, dose, and ibuprofen dosage form (lysinate salt or the free acid form), for elimination clearance (CL/F); and body weight, dose, and fasting status for the apparent distribution volume (Vd/F) proved to be the covariates with influence in the model. The four factors identified helped to explain part of the interindividual variability observed, but the remaining unexplained variability made therapeutic drug monitoring absolutely essential.

Administration, Oral↗

Fatty acid absorption in preterms on formulas with and without long-chain polyunsaturated fatty acids and in terms on formulas without these added.

BACKGROUND/OBJECTIVE: Long chain polyunsaturated fatty acids have beneficial effects in preterm neurophysiological development and are semi-essential. Their levels and variation in plasma and red cells in term and preterms are better known than their intestinal absorption. In this paper the absorption of supplemented arachidonic acid (AA) and docosahexaenoic acid (DHA) is evaluated in a preterm group. DESIGN: Four newborn randomized groups were studied. Group T comprised 11 terms on regular formula. Preterms: group P (n=9) was on a classic preterm formula. INTERVENTION: groups PA (n=9) and PB (n=13) were on the same formula but PB contained AA and DHA in similar proportion to breast milk. At 20 days a 3 day metabolic balance was taken for Ca, P(i), Mg, total fat and individual fatty acids (C8-C24, saturated unsaturated). RESULTS: Calcium absorption was (mean+/-s.d.) 51+/-13% in terms. In preterms it was respectively 45+/-18, 38+/-11 and 37+/-21%. Total fat absorption was 92.0+/-8.0% in terms, and from 95.0+/-2.0 to 91.0+/-8.0% in preterms. Absorption of 8:0, 10:0 and 12:0 showed a very high and constant rate despite significant intake differences (715-33 mg/kg/day). Linoleic acid and alpha-linolenic acid were absorbed in the three groups at around 94% regardless of a greater LA intake in group P. Details of absorption (mg/kg/day) were: for AA, intake 17+/-7, fecal excretion 5+/-4, net retention 12+/-5 (75.0+/-18%); for DHA, intake 10+/-3, fecal excretion 3+/-2, net retention 6+/-4 (62.3+/-30%). CONCLUSION: Intestinal absorption of fatty acids is high and is comparable in terms and preterms as regards the studied acids. Longer acids were less well absorbed. The supplemented amounts of AA and DHA were less well absorbed and probably not impairing calcium absorption. SPONSORSHIP: University of Alicante, University of Miguel Hernández.

Arachidonic Acid↗

[Absorptive pattern of individual fatty acids and total fat in full term babies. Its stability in the absence of lactose].

OBJECTIVE: Lactose absence implies a decrease in calcium absorption. If not absorbed, calcium soaps can be produced with the intestinal fatty acids. Absorption and retention of total fat, individual fatty acids, calcium, magnesium and phosphate have been compared between two groups of children, one fed with lactose free formula and higher levels of calcium (FSL) and the other with standard starting formula (FI). None of them had additional arachidonic or docosahexaenoic acids. PATIENTS AND METHODS: A randomized prospective study was made on 19 term newborn babies by means of metabolic balance measurement during an 8 day period (four days of a stabilization period on the formula, 3 days of the balance period and the final day for feces collection). Both groups were selected following the same criteria for gestational age, balance age, and weight and length at both time periods. Aliquos from the formula were collected daily, as well as all feces and urine during the balance period. Calcium and magnesium quantification of the corresponding ashed products was performed by means of atomic absorption, while Pi was with a colorimetric assay. Total fat was extracted by organic solvents and quantified by gravimetry. Lipid phase fatty acids were methylated, extracted and quantified by means of gas chromatography with a detector of flame ionization. RESULTS: Total fat content and the percentages of each fatty acid did not differ, only calcium concentration in FSL was slightly higher (64.9 +/- 6.9 vs 58.9 +/- 7.0 mg/100 g). No differences were found between groups in relation to ingestion, excretion and retention. The percentages of calcium and total fat retention, however, were slightly superior in the FI in relation to the FSL group. Ca: 68 +/- 22 mg/kg/d, 49 +/- 14% vs 56 +/- 23 mg/kg/d, 48 +/- 17% and total fat: 6.6 +/- 1.2 g/kg/d, 92 +/- 8% vs 6.8 +/- 1.5 g/kg/d, 90 +/- 9%. Absorption of MC fatty acids was 99% for C8. Linoleic and alfalinolenic acid showed an absorption of around 90% despite the big differences in their intake (10/1). Net retention of linoleic acid was 933 +/- 168 mg/kg/d (FI) and 963 +/- 190 mg/kg/d (FSL) and the amount of alpha-linolenic acid was 95 +/- 16 (FI) and 100 +/- 22 mg/kg/d (FSL). No correlation could be found between the amount of excreted calcium and the total amount of fat in feces or with any of the fatty acids studied. This was true for each group studied separately or when considered as a single group. CONCLUSIONS: The absorptive pattern of fatty acids in full term babies, when quantified did not show any conspicous alterations in relation to the accepted values of other ages. The absence of lactose (FSL) in a formula does not make any change in the absorption of total fat and the individual fatty acids when compared to lactose containing formula (FI), when these are present in the same proportions. Supplemented calcium in the formula without lactose could compensate for its lower absorbtion. The absorptive pattern of fatty acid in full term babies did not show any conspicuos alterations in relationship to the accepted values of other ages.

Absorption↗

Short-term polycose substitution for lactose reduces calcium absorption in healthy term babies.

A vitamin D-independent paracellular and not saturable mechanism important for intestinal calcium absorption turned out to be less effective in lactose-free diets. Twelve normal term babies with identical repletion levels of 25-hydroxyvitamin D (25D) were fed sequentially with starting formulas that differed only in their carbohydrate sources: lactose (control) and polycose. A 3-day test was performed after a 1-week adjustment to the new diet. Fecal excretion of calcium was significantly higher in the lactose-free formula period compared to the control one: 56.6 (13.9) versus 39.6 (12.8) mg/kg/day (p less than 0.02); subsequently, the net retention was considerably higher and statistically significant (p less than 0.01) for the control period versus the lactose-free formula period: 99.4 (15.3) versus 78.1 (14.3). Plasma 25D values were 21.8 (9.1) and 23.7 (7.1) ng/ml at the beginning of the lactose and polycose periods, respectively, and 1,25-dihydroxyvitamin-D values were 64 (62) and 75 (45) pg/ml, not significant. Results suggest that formulas containing polycose as the sole carbohydrate source may reduce the intestinal absorption of calcium in term newborns, but determining long-term biological significance requires further observation.

Calcium↗

Hyperimmunoglobulinemia E syndrome of neonatal onset.

A case of hyperimmunoglobulinemia IgE with recurrent infections of neonatal onset and unfavourable evolution is described. The first clinical finding was the appearance of maculopapular rash in the skin when the child was fifteen days old. From this period onwards, respiratory and cutaneous infections were continuous, leading to a progressive deterioration of the general condition, and malnutrition, which ended fatally at the age of three years. IgE levels were measured on several occasions, this being 17 IU/ml at the onset of the symptoms; afterwards, the mean value was 17.680 IU/ml (Range: 14.9-32.710 IU/ml).

Disease Susceptibility↗