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Biomedical subjects

F Fournier

Publications and source records attributed to F Fournier.

At least 37 records · Page 2Linked to original sources

Patient acceptability of transurethral incision of the prostate under local anaesthesia.

OBJECTIVE: To determine the acceptance by patients of transurethral incision of the prostate (TUIP) under local anaesthesia. PATIENTS AND METHODS: The study comprised 30 consecutive patients who elected to undergo local anaesthesia for TUIP and were treated between December 1994 and September 1995. Twenty-two were considered a high risk for general anaesthesia and eight patients chose local anaesthesia for personal reasons. Patients were premedicated (opioid and benzodiazepine) and 1% lidocaine was infiltrated transurethrally using an endoscopic needle. The level of acceptance was determined using an immediate post-operative questionnaire which included a linear visual analogue scale (VAS) to rate pain. RESULTS: No patient required conversion to another type of anaesthesia and there were no complications related to the local anaesthesia. The mean (SE) VAS score was 3.2 (1.7) and the questionnaire results showed that 83% of the patients did not consider that general anaesthesia was necessary for the operation and that 90% would agree to undergo the procedure again under local anaesthesia. CONCLUSION: TUIP under local anaesthesia was well tolerated in motivated patients. We recommend it as the operation of choice for the relief of obstruction in high-risk patients with a small benign prostatic hyperplasia.

Aged↗

Sensitization of InsP3-dependent calcium signalling through structural modification of voltage-dependent calcium channel: a physiological relevance of the calcium channel beta subunit.

The expression in Xenopus oocytes of the human voltage-dependent Ca2+ channel (VDCC) beta 2 subunit subtype (h beta 2) enhances the endogenous Ca2+ channel activity. By using the native Ca(2+)-dependent chloride conductance to monitor fast intracellular Ca2+ variations, we point out that the beta-enhanced Ca2+ entry (T1 component) is currently associated with a second delayed elevation of internal Ca2+ (T2 component). Further experiments show that this additional component absolutely requires Ca2+ entry through the beta-modulated channels although it directly derives from a Ca2+ release from intracellular inositol (1,4,5)-trisphosphate (InsP3)-sensitive stores. Finally, our study demonstrates that InsP3-evoked response in oocytes is dramatically modified since it gains a new shape of voltage dependency directly derived from the beta-modified Ca2+ influx. The main conclusion is that the spatiotemporal pattern of InsP3-dependent Ca2+ release may be closely influenced by the intrinsic characteristics of working VDCCs.

Animals↗

A voltage-dependent and pH-sensitive proton current in Rana esculenta oocytes.

Voltage clamp technique was used to study macroscopic ionic currents in Rana esculenta oocytes. Depolarization steps led to the activation of a single type of outward current (Iout) when contaminant potassium and calcium-dependent chloride currents were pharmacologically inhibited. The voltage threshold of Iout activation was 10 mV and this current, which did not inactivate, presented a deactivation the time constant of 73 +/- 21 msec (n = 26) corresponding to a membrane voltage of -60 mV. Its reversal potential (Erev) was dependent on the magnitude of the depolarization and also on pulse duration. These changes in Erev were thought to reflect intracellular ion depletion occurring during activation of the remaining outward current. Furthermore, the activation threshold of Iout was clearly affected by modifications in extracellular and intracellular H+ concentrations. Indeed, intracellular alkalinization (evoked by external application of ammonium chloride) or extracellular acidification induced a rightward shift in the activation threshold while intracellular acidification (evoked by external application of sodium acetate) or extracellular alkalinization shifted this threshold toward a more negative value. Lastly, Iout was dramatically reduced by divalent cations such as Cd2+, Ni2+ or Zn2+ and was strongly decreased by 4 Aminopyridine (4-AP), well-known H+ current antagonists already described in many cell types. Therefore, it was suggested that the outward current was prominently carried by H+ ions, which may play a key role in the regulation of intracellular pH and subsequent pH dependent processes in Rana oocyte.

4-Aminopyridine↗

Phospholipase C activates protein kinase C during induction of slow Na current in Xenopus oocytes.

Protein phosphorylation by protein kinase C (PKC) has recently been shown to be a key event in the induction of the slow inward Na current observed during sustained depolarization of the Xenopus oocyte membrane. The present work investigates the possible pathways leading to PKC activation. PKC is activated by a series of phospholipid metabolites, such as diacylglycerol (DAG) and arachidonic acid produced by phospholipases C (PLC) and A2 (PLA2) respectively. To test whether PKC activation was dependent upon the phospholipid metabolites produced either by PLC or by PLA2, enzyme activity was reduced using selective inhibitors. Results indicated that inhibition of PLA2 activity and inhibition of the enzymes involved in the arachidonic acid cascade failed to affect Na current amplitude. On the other hand, PLC inhibition caused a marked decrease of Na current amplitude. In another series of experiments, Na current was fully restored, in spite of PLC inhibition, by directly enhancing PKC activity with a powerful activator phorbol 12-myristate 13-acetate. These data strongly suggest that PLC is involved in PKC activation during Na channel induction.

Animals↗

Interaction between Ca2+ release from inositol trisphosphate sensitive stores and Ca2+ entry through neuronal Ca2+ channels expressed in Xenopus oocyte.

Rat cerebellar RNA injected into Xenopus oocytes leads to the expression of putative P-type voltage-dependent Ca2+ channels (VDCCs). The monitoring of intracellular Ca2+ variations by recording the Ca2+ dependent chloride current in voltage clamped oocytes indicates that activation of these Ca2+ channels by depolarization gives rise to two distinct components of cytosolic Ca2+ elevation. If the early component (T1) can be directly attributed to the Ca2+ entry through VDCCs, the second delayed one (T2) is related to a Ca2+ release from InsP3 sensitive stores activated following Ca2+ entry. Modifications of cytosolic Ca2+ by direct injection of Ca2+ into oocytes or by increasing the Ca2+ influx through VDCCs suggest that the Ca2+ release from intracellular InsP3 sensitive stores can be modulated in a differential manner. Namely, discrete elevations of cytosolic Ca2+ switch on the Ca2+ release whereas higher Ca2+ concentrations dampen the release. These results suggest a functional coupling between P-type VDCCs and InsP3 receptors.

Animals↗

Positive regulation by protein kinase C of slow Na current in Xenopus oocytes.

The slow inward Na current observed during sustained depolarization of the Xenopus oocyte membrane is due to a complex mechanism described as the induction of the channels. The present work investigates the role of protein phosphorylation in Na channel function. Injection of alkaline phosphatase in the oocytes decreased inward current. Therefore, the possible involvement of protein kinase in Na channel induction was explored. Treatment of oocytes with two activators of protein kinase C (PKC) resulted in enhanced Na current amplitude, whereas the treatment of oocytes with two potent PKC inhibitors decreased the inward current. These results imply that PKC phosphorylation is a fundamental step of Na channel induction. The possibility that the depolarization of the oocyte membrane may be the factor involved in PKC activation is discussed.

Alkaloids↗

Regulation by protein kinase-C of putative P-type Ca channels expressed in Xenopus oocytes from cerebellar mRNA.

Xenopus oocytes injected with rat cerebellar mRNA expressed functional voltage-dependent Ca channels detected as an inward Ba current (IBa). The pharmacological resistance to dihydropyridines and omega-conotoxin together with the blockade obtained with Agelenopsis aperta venom suggest that these channels could be somehow assimilated to P-type Ca channels. The precise nature of the transplanted Ca channels was assessed by hybrid-arrest experiments using a specific oligonucleotide antisense-derivated from the recently cloned alpha 1-subunit of P channels (BI-1 clone). In addition, we demonstrate that exogenous Ca channel activity was enhanced by two different PKC activators (a phorbol ester and a structural analog to diacylglycerol). The general electrophysiological and pharmacological properties of the stimulated Ca channels remain unchanged. This potentiation induced by PKC activators is antagonized by a PKC inhibitor (staurosporine) and by a monoclonal antibody directed against PKC. It is concluded that P-type Ca channels are potentially regulated by PKC phosphorylation and the functional relevance of this intracellular pathway is discussed.

Animals↗

Cyclic AMP-dependent regulation of P-type calcium channels expressed in Xenopus oocytes.

Xenopus oocytes injected with rat cerebellum mRNA, express voltage-dependent calcium channels (VDCC). These were identified as P-type Ca2+ channels by their insensitivity to dihydropyridines and omega-conotoxin and by their blockade by Agelenopsis aperta venom (containing the funnel-web spider toxins: FTX and omega-Aga-IV-A). Coinjection of cerebellar mRNA and antisense oligonucleotide complementary to the dihydropyridine-resistant brain Ca2+ channel, named BI [Mori Y. et al. (1991) Nature 350:398-402] or rbA [Starr T. V. B. et al. (1991) Proc Natl Acad Sci USA 88:5621-5625], strongly reduced the expressed Ba2+ current suggesting that these clones encode a P-type VDCC. The macroscopic Ca2+ channel activity was increased by direct intraoocyte injection of cAMP. This increase in current amplitude was concomitant with a slowing of current inactivation, and was attributed to activation of protein kinase A, since it could be antagonized by a peptidic inhibitor of this enzyme. Positive regulation of P-type VDCC could be of importance in Purkinje neurons and motor nerve terminals where this channel is predominant.

Animals↗

[Percutaneous nephrolithotomy after failure of extracorporeal shockwave lithotripsy. Indications, results, perspectives].

Eighty-one of the 579 extracorporeal lithotripsies (ECL) performed between 1987 and 1992 with an ultrasound-guided hydroelectric lithotriptor required the use of another treatment modality. 53 percutaneous nephrolithotomies (PCNL) were performed in these 81 patients after failure of ECL (21 for non-fragmentation, 32 for residual fragments). The authors analyse the factors responsible for failure in order to select the more appropriate type of treatment for different types of stones. The site of the stones, their size, their radiographic appearance, their chemical composition, the number of ECL sessions and the number of days spent in hospital were compared between the PCNL and ECL groups. Smooth, homogeneous stones denser than bone and larger than 15 mm in diameter were significantly more resistant to ECL, despite an increased number of shock waves. PCNL was successful in 92% of cases of non-fragmented stones (with no residual fragments). The success rate for multiple residual fragments was 64%. In view of the risk of complications associated with residual fragments, regardless of their size, the potential risks of ECL and cost imperatives, the authors recommend that these stones, considered to be resistant, should be treated immediately by PCNL, as the results of PCNL after ECL are less satisfactory.

Adult↗

Endogenous Xenopus-oocyte Ca-channels are regulated by protein kinases A and C.

Calcium entry into Xenopus oocyte occurs mainly through voltage-dependent calcium channels. These channels were characterized as belonging to a particular type of calcium channel insensitive to dihydropyridines, omega-conotoxin, and Agelenopsis aperta venom, but blocked by divalent cations (Co, Cd, Ni). Intracellular injection of cAMP, or bath application of phorbol ester, induced a marked increase in calcium current amplitude and a slowing of the inactivation time-course. Despite their different pharmacology, endogenous calcium channels, like cardiac or neuronal calcium channels, could be thus regulated by protein kinases A and C.

Animals↗

Protein kinase C regulation of cardiac calcium channels expressed in Xenopus oocytes.

L-Type cardiac Ca2+ channels expressed in Xenopus oocyte were studied following rat heart ribonucleic acid, messenger (mRNA) injection. We demonstrate that exogenous Ca2+ channels are sensitive to intracellular regulation by protein kinase C (PKC). This was performed by using two types of PKC activators [phorbol esters and a structural analogue of diacyl-glycerol (DAG)] and a specific peptidic inhibitor. Ca2+ channel modulation resulted in an initial increase of the inward current, without any modification of the voltage-dependent properties, and a second delayed phase, specifically observed with phorbol esters, characterized by a progressive decrease in current amplitude. Concomitantly, a reduction of membrane capacitance, reflecting a reduction of the total membrane surface area, was observed. We suggest that this phenomenon underlies the irreversible decrease of the expressed Ba2+ current via sequestration of Ca2+ channels and/or PKC. We also demonstrate that regulation of cardiac mRNA-directed Ca2+ channels by PKC activators was strictly dependent on intracellular Ca2+ concentration, and was partially additive with cyclic-adenosine-monophosphate-(cAMP) dependent regulation.

Animals↗

[Coma during a hip prosthesis under spinal anesthesia. Apropos of a case].

A case is reported of a postoperative coma in a ASA I 79 years old patient undergoing a spinal anaesthesia for hip prosthesis. The complication occurred three hours after the subarachnoidal puncture and 90 minutes after the completion of surgery. A complete recovery was observed in the following 48 hrs with the help of symptomatic treatments. Possible aetiologies and mechanisms of such accidents are discussed. However no definite cause could be ascertained in the case reported above, which is to add to similar ones observed during spinal anaesthesia in healthy patients. Anyhow, close surveillance is always mandatory.

Aged↗

Effect of ubiquitin on platelet functions: possible identity with platelet activity suppressive lymphokine (PASL).

In an attempt to clone a suppressive lymphokine of platelet function (PASL), we have obtained a cDNA clone coding for the previously described human ubiquitin-80 amino acid fusion protein. Our clone differs from the described sequence in that it contains the complete amino acid sequence of ubiquitin as well as a short (25 bp) 5' noncoding region. In addition the 3' untranslated region is slightly longer than that previously shown. Like PASL, purified ubiquitin can inhibit the cytotoxic properties of platelets and the production of oxygen metabolites by these cells. Moreover, this molecule is able to act as a proaggregating factor and seems of a great interest in pathologies involving defects in platelet aggregation. Ubiquitin could also have a potential use in the regulation of immunological disorders in which platelets seem to be implicated such as hymenoptera venom hypersensitivity and aspirin-sensitive asthma, since in both situations, ubiquitin is able, as is PASL, to inhibit the cytotoxic function of platelets. Indeed ubiquitin possesses important pharmacological potentialities which have not been previously described. This molecule and PASL share several similarities in their functional and physicochemical properties. PASL could therefore belong to the family of ubiquitins.

Adenosine Diphosphate↗

Functional expression of P2Y purinoceptor in Xenopus oocyte injected with brain mRNA.

Xenopus oocytes injected with embryonic guinea-pig brain mRNA expressed functional P2Y purinoceptors. Extracellular ATP stimulated in a dose-dependent manner a delayed Ca(2+)-dependent Cl- current component. Analysis of the interactions of ATP with compounds that affect Ca2+ fluxes through the plasma membrane or Ca2+ release from internal stores indicates that ATP raises [Ca2+]i by a mechanism that involves activation of voltage-dependent Ca2+ channels, which leads to influx of extracellular Ca2+ into the cells, as well as release of Ca2+ from intracellular stores. Since this phenomenon was not found in control oocytes, it is suggested that brain mRNA encoded for a newly synthesized Ca(2+)-release process stimulated by purinoceptor activation. This mechanism could be largely involved in the short-term regulation of intracellular Ca2+ level involved in ATP neuromodulation functions.

Adenosine Triphosphate↗

Ins(1,4,5)P3 formation and fluctuating chloride current response induced by external ATP in Xenopus oocytes injected with embryonic guinea pig brain mRNA.

In voltage-clamped Xenopus oocytes injected with embryonic guinea pig mRNA, effective concentrations of extracellular ATP elicited an inward fluctuating current. This current, carried by Cl-ions, was mainly dependent upon liberation of Ca2+ ions from stores as demonstrated by experiments using intracellular EGTA loading and TMB-8 superfusion. Neomycin inhibited these fluctuating currents indicating that the transplanted purinoceptor is linked to phospholipase C activity and triggers Ins(1,4,5)P3 formation. Ins(1,4,5)P3 production evoked by external ATP was clearly demonstrated by directly measuring the water-soluble Ins(1,4,5)P3 level in injected oocytes. Finally, it is suggested that the ATP effect was mediated by a Ca2+ release from Ins(1,4,5)P3 sensitive pools since heparin blocked the ATP responsiveness. The acquired purinoceptor may be made apparent to a P2 subtype since ATP and ADP were equipotent in eliciting Cl- current while AMP and Adenosine were ineffective in injected oocytes.

Adenosine↗

Expression of calcium channels in Xenopus oocyte injected with crab skeletal muscle fibre mRNA.

Using the whole cell voltage-clamp technique and a C1 free and Na free Ba methane sulfonate solution, stage V and VI Xenopus oocytes demonstrated a Ba current (endogenous component) with a peak amplitude average of 6 nA (6 +/- 2 nA). When oocytes were injected with crustacean skeletal muscle mRNA, an additional component of IBa could be detected (exogenous IBa). The latter current could be distinguished from the native one by several electrophysiological means: a peak amplitude average of 90 nA (90 +/- 4 nA), activation potential threshold, steady state inactivation properties and sensitivity to Ca blockers. As shown by Jdaïâa and Guilbault in crustacean skeletal muscle fibres, exogenous IBa could be divided into two components: a "fast component" and a "slow component" probably passing through two types of Ca channels (fast and slow) since the peak Ba current voltage relationship was biphasic and the fast component of exogenous IBa was less sensitive than the slow to nifedipine. The features of the newly synthesized channels incorporated in the Xenopus oocyte membrane suggest that they may be associated with fast and slow channels, previously described in many preparations, particularly in crustacean skeletal muscle fibres.

Animals↗