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Biomedical subjects

E Morin

Publications and source records attributed to E Morin.

16 recordsLinked to original sources
PubMed2000

Stereoselective biotransformation of cicletanine in cultured rat and human hepatocytes.

Cicletanine [(+/-)-C] is a racemic furopyridine derivative used as an antihypertensive agent. Pharmacokinetic and metabolic studies have shown that cicletanine is rapidly and almost fully metabolized into sulfo- and glucuro-conjugated metabolites. However, the stereoselective metabolism of cicletanine is not well-known in humans. In the present study, the stereoselective aspect of cicletanine metabolism was investigated in cultured hepatocytes from humans and rats. The two enantiomers of cicletanine were both strongly metabolized in rat hepatocytes. So, after 24 h of incubation, very low amounts of free cicletanine were found [1.2% for (+)-C and 2.7% for (-)-C], respectively. In addition (+/-)-C was mainly biotransformed into conjugated metabolites: (-)-C mainly transformed into (-)-C-glucuronide (78.3+/-6.4%) and (+)-C mainly into (+)-C-sulfate (87.4+/-3.3%). In human hepatocytes, inter-individual variations were more marked than in rat hepatocytes. In addition (+/-)-C biotransformation in human was lower than the one observed in rat. (-)-C enantiomer was more metabolized than (+)-C. After a 24-h incubation the percentages of free (+)-C and (-)-C were 32.3+/-16.4 and 8.2+/-10.3, respectively. On the contrary to rat hepatocytes, both cicletanine enantiomers in humans were mainly metabolized into glucuroconjugated metabolites. These results clearly demonstrated that cicletanine underwent stereospecific metabolism in both rat and human hepatocytes.

Animals↗
PubMed1998

Effects of prostacyclin on the pulmonary vascular tone and cardiac contractility of patients with pulmonary hypertension secondary to end-stage heart failure.

Long-term administration of prostacyclin (PGI2) improves the hemodynamic state, symptoms, and survival in patients with primary pulmonary hypertension, but it increases mortality in patients with heart failure despite obvious hemodynamic benefits when it is given acutely. We evaluated the mechanisms of action of PGI2 in patients with heart failure and secondary pulmonary hypertension. Nineteen patients with end-stage heart failure and pulmonary hypertension, all candidates for heart transplantation, underwent right- and left sided cardiac catheterization with micromanometer-tipped catheters and were tested for PGI2 at incremental doses. PGI2 infusion significantly improved pulmonary hemodynamics with a 47% reduction in pulmonary vascular resistance (p=0.0003) and a doubling of pulmonary artery compliance (p <0.0001), reflecting improvement in pulmonary vascular tone. The dose of PGI2 necessary to reach this hemodynamic effect correlated significantly to the baseline severity of pulmonary artery compliance (r=0.54, p=0.01). Furthermore, PGI2 produced a significant positive inotropic effect (contractile element maximum velocity increased from 1.10+/-0.09 to 1.33+/-0.13 circ/s, p <0.009). The hemodynamic effects of PGI2 infusion were independent of the plasma and urinary levels of endogen prostaglandins. Thus, PGI2 at therapeutic doses exerts a positive inotropic effect in patients with heart failure, which may explain the increased mortality rate observed with the long-term use of PGI2 in this type of patient. The spectacular acute benefits on right ventricular afterload, however, may be useful in unstable patients with heart failure and secondary pulmonary hypertension or in transplanted patients with acute right ventricular failure of the donor heart.

Antihypertensive Agents↗
PubMed1998

Detection of Staphylococcus aureus in milk by use of polymerase chain reaction analysis.

OBJECTIVE: To evaluate polymerase chain reaction (PCR) analysis for detection of Staphylococcus aureus (nuc gene) in fresh and formalin-preserved milk. SAMPLE POPULATION: Samples from 80 lactating sheep and 100 lactating dairy cows. PROCEDURE: 4 lactating sheep were inoculated with S aureus by intramammary infusion. A set of primers specific for the nuc gene of S aureus was used to develop a PCR technique, and modification of the rapid boil method was used to isolate bacterial DNA. Milk was obtained from experimentally infected sheep before and after infusion with S aureus, and from the 100 cows and remaining 76 sheep. Samples were screened by bacteriologic culture and PCR. To validate the PCR assay, S aureus or other pathogens were added to distilled water and "normal" sheep milk samples, with and without formalin. RESULTS: The PCR assay was 100% specific for S aureus when known negative and positive samples were tested. Sensitivity was 100% for samples with added S aureus or other pathogens. Sensitivity was lower for samples obtained from experimentally infected sheep, but increased from 53% to 90% with increased washing of target DNA. CONCLUSIONS: The PCR technique based on the nuc gene is able to detect S aureus in sheep milk yields results faster than does traditional culturing, is highly specific, and is able to detect S aureus in formalin-fixed milk samples. CLINICAL RELEVANCE: The assay is particularly suitable for analysis of samples shipped or stored without refrigeration. Although antibiotics in milk may inhibit growth in culture, they should not affect the results of the PCR assay.

Animals↗
PubMed1996

Reduction by (-)-cicletanine of the vascular reactivity to angiotensin II in rats.

Cicletanine [particularly the levorotatory (-)enantiomer] inhibits calcium/calmodulin cyclic GMP phosphodiesterase (PDE) in vascular smooth muscle (VSM) and potentiates the vasorelaxant actions of the guanylate cyclase activators sodium nitroprusside (SNP) and atriopeptin II, but the possible interference with vasopressor mechanisms remains to be determined. We tested racemic (+/-) cicletanine for its ability to modify the vascular responses to vasocontractant agents in pithed rats. The most significant results were obtained with angiotensin II (AII). Therefore, the dose of AII that increased the carotid artery blood pressure (BP) 50 mm Hg was twice as high in cicletanine-pretreated (50 mg/kg orally, p.o.) as that in vehicle-pretreated animals (ED50 = 0.48 +/- 0.012 vs. 0.25 +/- 0.007 microgram/kg, p < 0.05). The displacement by cicletanine represented 47.2% of that obtained with losartan (40 micrograms/kg, intravenously, i.v.). Similar results were obtained with (-)-cicletanine (p.o. or i.v.), but not with (+)-cicletanine. In isolated rat aorta, the contraction induced by AII was reduced by (-)-cicletanine in a noncompetitive manner (the percent reduction was independent of the AII concentration). (-)-Cicletanine reduces the vascular reactivity to AII, which plays a key role in several forms of hypertension. These findings are compatible with an action of (-)-cicletanine at any of the numerous steps that couple the occupation of AII receptors to the final contractile response, such as calcium/calmodulin cyclic GMP PDE.

Administration, Oral↗
PubMed1995

Evidence for (+)-cicletanine sulfate as an active natriuretic metabolite of cicletanine in the rat.

It was previously shown that the urinary sulfo-conjugate metabolite of cicletanine (cicletanine sulfate), and not free cicletanine, is salidiuretic in rats. Here we investigated potential differences between the resolved (+/-) enantiomers of cicletanine sulfate. Two groups of rats (n = 10) received either (+)- or (-)-cicletanine p.o. High performance capillary electrophoresis revealed that the 24-h urinary excretion of (+)-cicletanine sulfate was 5 times higher than that of (-)-cicletanine sulfate (18.9% vs. 3.8% of the oral dose). The same relative trend was observed after 5 and 10 days of oral administration. Following direct administration into the renal artery of anesthetized rats, (+)-cicletanine sulfate was 3-4 times more potent, in terms of active doses, than (-)-cicletanine sulfate to increase sodium excretion (ED50 = 1.86 +/- 0.28 mg/kg vs. 6.1 +/- 1.0 mg/kg, mean +/- S.E.M., n = 4). The maximal natriuretic potency of (+)-cicletanine sulfate was intermediate between that of furosemide and DIDS (4,4'-diisothiocyanostilbene-2,2'-disulfonate). In rat erythrocytes, (+)-cicletanine sulfate was between 2 and 3 times more potent to inhibit the Na(+)-dependent Cl-/HCO3- anion exchanger than (-)-cicletanine sulfate (IC50 = 61 +/- 3 microM vs. 142 +/- 31 microM, n = 4). In conclusion, (+)-cicletanine was more sulfo-conjugated and more potent natriuretic agent in rats than (-)-cicletanine. These results strongly suggest that (+)-cicletanine sulfate is the active natriuretic metabolite of racemic cicletanine in rats. This compound may probably act by inhibiting the Na(+)-dependent Cl-/HCO3- anion exchanger at the cortical diluting segment.

Acetates↗
PubMed1995

Urinary excretion of cicletanine in the rat. Stereochemical aspects.

The metabolism of (+)-cicletanine and (-)-cicletanine (10 mg kg-1) was studied in healthy male Wistar rats 24 hr after a single dose and following daily oral administration for 25 days. Urine, collected in 24-hr intervals on days 1, 5, 10, 15, 20, and 25, was analyzed by an HPLC method for parent drug and its sulfate/glucuronide conjugates. In urine, the sulfate and glucuronide conjugates of cicletanine were the only two major components quantitated; parent drug was a minor component. Within 24 hr after the first dose of (+)-cicletanine, the sulfate conjugate was the major urinary component; the ratio of sulfate to glucuronide conjugate was 3. After oral administration of (-)-cicletanine, the glucuronide and sulfate conjugates were present in similar amounts. For each enantiomer, the ratio of sulfate/glucuronide did not change upon multiple dosing, and inversion of the enantiomers did not occur. Although sulfate and glucuronide conjugates of each enantiomer are formed, the relative amounts of each conjugate depends on the enantiomer, indicating that there is stereospecificity in the disposition of cicletanine.

Animals↗
PubMed1993

Operator error in a level coded myoelectric control channel.

Two forms of error exist in the level coded myoelectric control channel: system error and operator error. Currently in level coded (3-state) myoelectric prosthesis, target and switching level settings are optimized for the presence of system error only. In this study, system error was minimized in order to examine operator error. The magnitude of the operator error was found to exceed the magnitude of the experimental system error as well as the system error associated with a typical prosthesis control unit. These findings suggest that operator error should be considered when optimizing target levels and decision boundaries for level coded myoelectric prosthesis controllers. Since the operator response was estimated to be normally distributed, it is described by its mean and standard deviation. This information can be used to determine the desired optimal settings.

Arm↗
PubMed1988

Coliphages and enteric viruses in the particulate phase of river water.

The present study was undertaken to determine if indigenous enteric viruses and coliphages are free or associated with suspended particulate matter in natural waters. River water was filtered on filters of decreasing porosities (100-0.25 micron) that were pretreated with detergent to eliminate viral adsorption while retaining particulates. This filtered water was refiltered in virus-adsorbing conditions to retain free viruses. The virus-adsorbing filter retained most of the enteric viruses (77.4%) and coliphages (65.8%), which indicated that these viruses were probably free or associated with particles with a diameter of less than 0.25 micron. These observations are important because in water treatment plants small particulates are often the most difficult to eliminate.

Adsorption↗
PubMed1987

Characterization and processing of surface recorded spinal somatosensory evoked potentials.

Somatosensory evoked potentials were recorded from the skin surface overlying the spinal cord, from the lower lumbar to the lower cervical regions. The recorded responses did not vary over time in any one individual and at each level a consistent wave shape was obtained across all individuals tested. Since the initial signal-to-noise ratio (SNR) for the evoked response recorded at any cord level is very low, the signal data must be processed. In this study, bandpass filtering or matched filtering was used together with ensemble averaging to obtain a usable signal in a reasonable processing time. SNR was improved approximately 1.5 X with bandpass filtering and 2 X with matched filtering. Although the output of the matched filter is a distorted version of the input signal, detection of information is enhanced and processing time using the matched filter and ensemble averaging can be reduced to 1/4 that required for ensemble averaging alone.

Evoked Potentials, Somatosensory↗
PubMedDate not supplied

Induction and inhibition of cicletanine metabolism in cultured hepatocytes and liver microsomes from rats.

Cicletanine, a racemic furopyridine derivative synthesized as racemate, is used as an antihypertensive agent. Its two enantiomers are involved in the pharmacological effects of the drug. Cicletanine is metabolized by conjugation enzyme systems (phase II) into sulfoconjugated or glucuroconjugated enantiomers. This study reports on the use of both the induction with 3-methylcholanthrene (3-MC) or phenobarbital (PB) and inhibition with selective compounds to determine and identify UGT isoenzymes involved in the metabolism of cicletanine enantiomers. PB and 3-MC both enhanced the cicletanine enantiomer glucuronidation. These two compounds being known as inducing agents of UGT2B1 and UGTIA6 isoforms, respectively, this suggests an implication of UGT2B1 and UGT1A6 isoforms in the metabolism of the two cicletanine enantiomers: ( + )-cicletanine and ( - )-cicletanine. The use of selective compounds for inhibition study evidenced, in addition to UGT2B1 and UGT1A6 isoforms, the involvement of other UGT isoforms such as UGT1A1, UGT2B7 and UGT2B15 in cicletanine metabolism.

Animals↗
PubMedDate not supplied

[Intracellular changes induced by the canine infectious laryngotracheitis virus (CAV-2)].

Canine infectious laryngotracheitis virus, an adenovirus designated CAV-2, induces numerous changes in the nucleus and cytoplasm of canine kidney cells (MDCK). The following features could be observed on ultrathin sections examined in the electron microscope: a shift of the nucleolus towards the nuclear membrane and a compression of the latter by the virus particles; the release of virions into the cytoplasm following the tearing or evagination of the nuclear membrane; the attachment of virus particles onto the numerous microtubules of the infected cell. Microfilaments appear to be involved into the vectorial movement of virus particles towards the cytoplasmic membrane in the final phase of infection.

Adenoviridae↗