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New findings on degradation of famotidine under basic conditions: identification of a hitherto unknown degradation product and the condition for obtaining the propionamide intermediate in pure form.

The degradation behavior of famotidine (1) was investigated in 25% ammonia solution and in 2 M NaOH. The hydrolysis of the drug in ammonia resulted in separation of [3-[[2-[(diaminomethylene)amino]-4-thiazolyl]methyl]thio]propionamide (3), an impurity listed in British Pharmacopoeia. The treatment with 2 M NaOH resulted in formation of [3-[[[2-[(diaminomethylene)amino]-4-thiazolyl]methyl]thio]propionyl]sulfamide (2) and 3. These products further decomposed to [3-[[2-[(diaminomethylene)amino]-4-thiazolyl]methyl]thio]propionic acid (4) and a heretofore unknown product, 5. The latter separated out in the reaction mixture as brown shiny crystals. Proton and carbon-13 nuclear magnetic resonance spectroscopy, mass spectrometry, and elemental analysis of the charcoal-treated product established the structure. The formation of 5 is postulated to involve abstraction of a proton from the alpha-carbon of intermediates 2 and 3 followed by elimination of the thiol moiety.

Amides↗

Selective hypergravity stimulation: its effects on the human balance and gait functions. A model to assess, in normal gravity conditions, some aspects of the perturbations induced on human body by microgravity conditions.

To assess on Earth some reactions of the muscle mechanoreceptors to transitions from normogravity to microgravity, we studied the effects of transitions from hypergravity to normogravity. Hypergravity was selectively applied to the extensor muscles by increasing their activity during half an hour by means of 2 rubber extensible springs stretched from shoulders to feet. Immediate effects and post effects of such a stimulation were measured on quantifying dynamic balance (angular or linear displacement) and gait functions (spatio-temporal parameters and inferior limb length variations). The main results are: (1) a post effect on the balance function, appearing 3 minutes after the end of the selective hypergravity stimulus and improving the efficiency of balance function compared with the basal one, (2) a post effect on the gait function, appearing immediately after the end of the selective stimulation. It concerns the measures which quantify the gait phases during which flexor muscles are active (swing phases). It decreases the efficiency of the gait function compared with the basal one, It disappears 3 minutes after the end of the selective hypergravity stimulation. According to these results, if the effects on the muscle mechanoreceptors of the transitions from normogravity, to microgravity looks like those of transitions from hypergravity to normogravity, post effects could be a mechanism of the motor perturbations at the beginning of the orbital flights.

Adult↗

The adsorption of 99mTc(Sn)-diphosphonate complexes on tri-calciumphosphate: the influence of preparation conditions, ligand-type, incubation media and adsorption conditions. The reversibility of the adsorption.

The influence of several variables on the adsorption of 99mTc(Sn)-diphosphonate complexes on tri-calciumphosphate was determined. The composition of the incubation medium influenced the percentage adsorption: with Hank's balanced salt solution (a medium frequently used for bone cell cultures) and Tris buffer lower percentage adsorption was obtained than with physiological saline as the incubation medium. The influence of addition to the incubation medium of some ions and neutral species, some of which occur in bone fluid, is very specific. Addition of Sn(II) or Mg(II) (a component of HBSS) reduces the amount of adsorption. Addition of Ca(II) and Al(III) had no effect. Addition of sodium-citrate and MDP to the medium and an increase of the pH of the medium decreased the percentage adsorption. The ligand that was used in the preparation of the complex mixture influences the percentage adsorption considerably. The Sn(II) concentration used during the preparation of the 99mTc(Sn)-MDP and 99mTc(Sn)-MHDP complexes showed no definite influence on the percentage adsorption. The pH and ligand concentration, used in the preparation, however, did effect the percentage adsorption. It was concluded that the 99mTc(Sn)-disphosphonate mixtures are part reversibly and part irreversibly bound to tri-calcium-phosphate.

Adsorption↗

Evaluation of culture conditions for cellulase production by two Trichoderma reesei mutants under solid-state fermentation conditions.

Response surface methodology (RSM) was used to evaluate the effects of fermentation parameters for cellulase production by Trichoderma reesei QM9414 and T. reesei MCG77 in solid-state fermentation using rice bran as substrate. Initial pH, moisture content and temperature were optimized using filter paper activity (FPA) as response. Statistical analysis of the results for T. reesei QM9414 showed that only moisture content had significant effect on cellulase activity and had a linear effect on enzyme activity (maximum enzyme activities were obtained at 70% moisture content). The results for T. reesei MCG77 showed that temperature and moisture content were the most significant parameters for cellulase activity. The optimum cellulase production was in the temperature range of 25-30 degrees C and moisture content between 55% and 70%. After the optimization, the FPA in T. reesei MCG77 was increased by 2.5 folds compared to that of T. reesei QM9414.

Bioreactors↗

Critical study of common conditions of storage of glucocorticoids and catecholamines in 24-h urine collected during resting and exercising conditions.

BACKGROUND: Except immediate freezing of the samples, no practical method has been validated for preservation of glucocorticoids and catecholamines in 24-h urine collection. Furthermore, the influence of urine storage at bladder temperature during periods of different lengths and the effect of prior exercise on preservation of these hormones in the bladder have not been investigated until now. METHODS: Ten healthy volunteers collected their urine both after a resting and after an exercise session. Urine was aliquoted into tubes which were stored during 24 h in the presence or in the absence of preservatives and at different temperatures. Two samples were stored either 3 or 9 h at 37 degrees C (bladder temperature) without additive. RESULTS AND CONCLUSIONS: When collecting 24-h urine samples for glucocorticoids determination, sample can be stored at room temperature during the 24-h collection period without compromising glucocorticoids preservation. When collecting 24-h urine samples for catecholamines determination, samples have to be chilled without preservative during the whole of the collection period. If the samples have to be stored at room temperature, HCl should be used. Moreover, we report for the first time that catecholamines can be degraded in the bladder and therefore that subjects should urinate every 3 h during either a resting or an exercising day.

Adolescent↗

An investigation of DNA mismatch repair capacity under normal culture conditions and under conditions of supra-physiological challenge in human CD4+T cell clones from donors of different ages.

T cells undergo rapid clonal expansion upon antigenic stimulation to produce an effective immune response. Any defect in the DNA mismatch repair (MMR) system may have a detrimental effect on T cell proliferation. This study employed an in vitro model of human CD4+T cell ageing to investigate MMR capacity at various stages of T cell lifespan. A novel modification of the alkaline comet assay, which utilised T4 endonuclease VII to detect single base DNA mismatches, was used to assess DNA mismatch frequency. No clear pattern in DNA mismatch frequency with increasing culture age was observed. However, the ability to repair induced DNA mismatches (following treatment with acridine mutagen ICR-191) revealed an age-related decline in the efficiency of the MMR system in clones derived from a 26 and a 45-year-old donor, but not from an 80-year-old very healthy SENIEUR donor. This study suggests that unchallenged, dividing human T cell clones have variable levels of DNA mismatches throughout their lifespan, not affecting proliferation. However, when challenged with supra-physiological levels of DNA mismatches, deficiencies were found in ageing T cell clones in MMR capacity, with the exception of T cell clones from a SENIEUR donor previously shown to maintain effective DNA excision repair.

Adult↗