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C Guillou

Publications and source records attributed to C Guillou.

12 recordsLinked to original sources

Potent acetylcholinesterase inhibitors: design, synthesis, and structure-activity relationships of bis-interacting ligands in the galanthamine series.

New galanthamine derivatives, especially bis-interacting ligands 3-5 and 7-9 were prepared in order to interact with the catalytic and the peripheral sites of acetylcholinesterase (AChE). The synthesis, the anticholinesterase activities, and the structure-activity relationships of bis-interacting ligands are reported. Compounds 4d-e were found to be more potent than galanthamine and tacrine in inhibiting AChE.

Acetylcholinesterase

Clinical implications of maximal respiratory pressure determinations for individuals with Duchenne muscular dystrophy.

OBJECTIVE: To analyze the relationship between disease progression, pulmonary volumes, respiratory muscle strength (maximum inspiratory [MIP] and expiratory [MEP] pressure), and arterial blood gases for patients with Duchenne muscular dystrophy (DMD). DESIGN: An inception cohort study of pulmonary volumes, MIPs, and MEPs, correlated with age and PaCO2 levels and with each other using linear and nonlinear regression analyses. SETTING: Outpatient clinic. PATIENTS: Fifty-two consecutive DMD patients who presented for regular evaluations at a regional DMD center. RESULTS: Maximum expiratory pressures were 47.7% +/- 10.9% of normal in the 167- to 14-year-old patients and decreased linearly thereafter (MEP% = -2.7 x age +73.8; p < .001). Declines in MEP also correlated linearly with expiratory reserve volume (p < .001) and inversely with residual volume (p < .001). By contrast, MIP was 66.3% +/- 19.0% in the 357- to 14-year-old patients and then declined to 30.2% +/- 19.5% after age 14. No linear relationships were found with age but declines did correlate linearly with inspiratory reserve volume (p < .001) and total lung capacity (p < .001). PaCO2 elevations correlated best with decreases in MIP (p < .0001) and appeared when MIP was below 30cmH2O. CONCLUSIONS: Lung volume changes in DMD patients correlate with respiratory muscle weakness, and although inspiratory muscle dysfunction plays a key role in the development of chronic ventilatory insufficiency, reductions in expiratory muscle strength are the first signs of dysfunction and lead to the first episodes of respiratory failure.

Adolescent

Hypoosmotic shocks induce elevation of resting calcium level in Duchenne muscular dystrophy myotubes contracting in vitro.

In Duchenne muscular dystrophy (DMD) muscle cells which lack dystrophin, contraction seems to be a dominant factor contributing to the abnormal elevated intracellular calcium level. Human normal and DMD contracting myotubes cocultured with nervous cells were exposed to a hypotonic medium to mimic contraction-induced mechanical stress on the membrane, and the cytoplasmic calcium activity was simultaneously monitored (Indo-1). Hypotonic shocks induced a reversible [Ca2+]i increase in 81% of the DMD cells vs. 54% of control. In addition, responses were qualitatively different: most of DMD myotubes displayed a fast increase of Ca2+ flowing from the edge of the myotube while the response in normal cells was slow and diffuse. The fact that these responses were not affected by ryanodine, was in favour of an external source of Ca2+ involved in the hypoosmotic shocks. The localized increase of Ca2+ in DMD myotubes, inhibited by Gd3+, could result from sites of high mechanosensitive channel activity or density which could constitute a pathway for Ca2+ entry provided these cells contract.

Calcium

Evidence for two domains of growth temperature for the psychrotrophic bacterium Pseudomonas fluorescens MF0.

The variations in the maximal specific growth rate of the psychrotrophic bacterium Pseudomonas fluorescens MF0 with respect to temperature were studied between 0 and 30 degrees C (optimal for growth). The Arrhenius plot showed a drastic change in slope at the intermediate temperature of 17 degrees C. Over the cold domain from 0 to 17 degrees C, the temperature characteristic was twofold higher than over the suboptimal domain from 17 to 30 degrees C. The macromolecular composition of exponentially growing cells was invariant over the entire range from 0 to 30 degrees C. Variations of temperature and growth rate were independently investigated through chemostat experiments in order to characterize their respective effects on cell macromolecular composition and size. The effect of growth rate in this psychrotrophic strain is identical to that of all other bacteria assayed so far. In contrast, an original biphasic variation of total protein concentration was demonstrated in strain MF0 with respect to temperature, with a maximum at 17 to 20 degrees C. Indeed, increasing the temperature in the chemostat resulted in a biphasic decrease in the net protein production rate: a very slight decrease below 17 degrees C and a much larger decrease from 17 to 28 degrees C. These results could signify an increase in the cellular protein degradation rate with increasing temperature, especially above 17 degrees C.

Bacterial Proteins

Abnormal calcium homeostasis in Duchenne muscular dystrophy myotubes contracting in vitro.

Resting intracellular calcium activity was recorded in three kinds of human muscle cells in culture: normal (control) and dystrophic (DMD and FSH), by means of a ratiometric fluorescence method using the calcium probe Indo-1 under laser illumination. DMD cells are characterized by a lack of dystrophin whereas FSH cells express normal dystrophin. The aim of this study was to determine whether, in dystrophin-deficient muscle cells (DMD), contraction destabilized internal calcium homeostasis. Muscle cells were cocultured with rat spinal cord explants to improve the maturation of human myotubes up to the stage where contraction appears. The resting intracellular calcium level was significantly higher in contracting DMD cells (107 +/- 8 nM; n = 44) compared to control cells (66 +/- 6 nM; n = 43) or in FSH cells (56 +/- 6 nM; n = 35). DMD myotubes cocultured in the presence of TTX which inhibited contractile activity, did not develop an increase in free cytosolic Ca2+ concentration. The amplitudes of calcium transients elicited by exposure to acetylcholine (ACh) or high K+ medium (100K) were significantly higher in contracting DMD myotubes than in control ones. The extra-responses were not observed in DMD myotubes cocultured with TTX. This study strongly suggest that: (i) contraction is a dominant factor contributing to Ca2+ abnormalities in DMD cells; and (ii) contracting dystrophin-deficient cells have defective calcium handling mechanisms during electrical events which involve sarcolemma.

Acetylcholine

Treatment of respiratory insufficiency in Duchenne's muscular dystrophy: nasal ventilation in the initial stages.

Fourteen patients with Duchenne's muscular dystrophy (DMD) received nasal ventilation at the beginning of the declining phase of their vital capacity (VC). At that point, the mean value (SD) of their vital capacity was 1,756 (363) mL notably inferior to the predicted values. Nasal ventilation was performed according to a precise protocol, with an average nocturnal duration of 8 h. The annual decline of vital capacity was about 70 ml, showing a significant reduction compared with the value of 200 mL.yr-1 of untreated patients. Follow-up of treated patients (3.8 yrs; SD 1.9 yrs) has enabled us to distinguish different groups of results with useful practical consequences. In 29% of cases, the initial progression of decline of vital capacity was poorly modified by the treatment. In 71% of patients, the decline of VC was significantly decreased. In 35% of cases tracheal ventilation followed nasal ventilation. The normal mortality rate of DMD has greatly changed as a result of this method.

Adolescent

Effect of growth temperature on several exported enzyme activities in the psychrotrophic bacterium Pseudomonas fluorescens.

In accordance with previous results, the activity of extracellular proteases from Pseudomonas fluorescens MF0 is maximal at a growth temperature of 17.5 degrees C, well below the optimal growth temperature. In addition, the activities of three periplasmic phosphatases display the same growth temperature optimum. Chemostat experiments have shown that it is the growth temperature itself and not the value of the growth rate that regulates these activities. In contrast, a foreign periplasmic phosphatase, expressed under the control of its own promoter, displays a different sensitivity toward temperature. We conclude that in the psychrotrophic strain P. fluorescens MF0, growth temperature exerts a specific control upon the activity of certain enzymes. The critical temperature (17.5 degrees C) is within the range of normal growth, suggesting that this control is probably different from a cold shock or heat shock response.

Acid Phosphatase

[Role of a hygiene department in the control of respirator disinfection].

Different methods of disinfection of ventilators are used in hospitals. They are chosen according to the type of apparatus, the configuration of its internal circuit, the system of disinfection available and the degree of contamination. There are three types of disinfection: a) partial disinfection, b) partial internal disinfection by connection to an apparatus of disinfection with liquid formaldehyde, c) total automatic internal and external disinfection with formaldehyde powder. The hospital public health team controls the different disinfection procedures. Samples were taken from 13 places on four ventilators (Engström, Bennett, Servo 900, RPR). They were taken on polyvalent and on three selective culture media (gram positive, gram negative and Pseudomonas aeruginosa). Three criteria were defined: absence of contamination, limited contamination and widespread contamination. After disinfection, satisfactory results were always observed. However, these results were observed only immediately after disinfection and before stocking and transport. The results of these controls, communicated within 48 h to the doctors, allow us to check the reliability of the method used.

Disinfection