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Biomedical subjects

E Blanc

Publications and source records attributed to E Blanc.

At least 55 records · Page 3Linked to original sources

Cadmium rapidly and irreversibly blocks presynaptic phospholipase C-linked metabotropic glutamate receptors.

Calcium ions (Cd2+) inhibit inositol phosphate (IP) formation elicited by glutamate (GLU) or K+ ions, without affecting carbachol (Carb)-induced IP response in 8-day-old rat forebrain synaptoneurosomes and synaptosomes. On the contrary, Cd2+ was almost ineffective in blocking GLU- and K(+)-responses in hippocampal neurones in culture. The mechanism of Cd2+ inhibition was thus examined in synaptoneurosomes. Extensive washing of synaptoneurosomes pretreated for 1, 5, 15, or 30 min by 100 microM Cd2+ did not modify the inhibitory effect of Cd2+ on GLU-, K(+)- and A23187-evoked IP formation or its lack of effect on Carb response. The later addition of a high affinity Cd2+ chelator (100 microM), N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) also did not reverse the inhibitory effect. TPEN, however, penetrates into synaptoneurosomes and efficiently displaces Cd2+ from the Fura-2-Cd2+ complex as shown by Fura-2 fluorescence recordings. TPEN is not easily removed from the intracellular space, as demonstrated by its ability to still block Cd(2+)-induced Fura-2 fluorescence increase after extensive washing. Pretreatment of synaptoneurosomes by this chelator did not prevent Cd2+ inhibition of GLU-induced IP formation. These data indicate that Cd2+ ions rapidly, irreversibly and extracellularly inhibit GLU-elicited IP formation in synaptoneurosomes or synaptosomes, but not in hippocampal neurones in culture. It is speculated that Cd2+ ions could allow one to distinguish the activity of presynaptic metabotropic glutamate receptors (mGLURs) linked to phosphoinositide metabolism from that of mGLURs located postsynaptically.

Animals↗

A modulation of glutamate-induced phosphoinositide breakdown by intracellular pH changes.

The influence of intracellular pH (pHi) changes on the formation of inositol phosphate metabolites (IPs) produced by glutamatergic stimulation was studied in 8-day-old rat brain synaptoneurosomes. For this purpose pHi was measured using 2',7'-bis-(2-carboxyl)-5,6-carboxyfluorescein (BCECF) fluorimetric assay in parallel with the basal and receptor-mediated formations of inositol monophosphate (IP1) and inositol bisphosphate (IP2). We found that glutamate (1 mM), which induces a transient acidification (delta pH = -0.05), produces an identical accumulation of IP1 and IP2. K+ (30 mM), which provokes an alkalinization of the internal medium (delta pH = +0.22), mainly leads to the formation of IP1 metabolites. Paired combinations of glutamate with 1, 5 and 10 mM NH4+ finally result in an alkalinization of the intrasynaptoneurosomal medium. These combinations produce a strong decrease of the IP2 level concomitant with an increase of the IP1 formation, compared to the levels of IP1 and IP2 evoked by glutamate alone. The total amount of IPs (IP1 + IP2) produced by these combinations is not different from that obtained with glutamate alone. Paired combinations of carbachol with NH4+ produce an identical alkalinization to that produced by NH4+ alone. These combinations produce an increased IP1 accumulation, while the IP2 formation is slightly decreased. When the internal medium is acidified by diminishing the external concentration of Na+, the ratio IP1/IP2 produced after metabotropic glutamate receptor (mGluR) activation is shifted to lower values, while it is not affected for the muscarinic stimulation. These data suggest that the mGluR-associated pathway in synaptoneurosomes is sensitive to pHi shifts, while the muscarinic receptor-associated pathway is less altered when pHi is manipulated. It may be proposed that pH-sensitive inositol phosphate dephosphorylating systems, i.e. phosphatases, are associated with mGluRs in this preparation.

Animals↗

Stimulation of Ca(2+)-activated non-specific cationic channels by phospholipase C-linked glutamate receptors in synaptoneurosomes?

The regulation of intracellular Ca2+ concentration ([Ca2+]i) by glutamate metabotropic receptors (mGluR) was studied in 8-day-old rat forebrain synaptoneurosomes using spectrofluorimetric methods. Here we demonstrate that metabotropic glutamate agonists induce in rat brain synaptoneurosomes a Ca2+ influx largely dependent upon the presence of Ca2+ in the external medium. The pharmacological profile of this influx is strongly correlated with the pharmacological profile of the activation of phosphoinositide hydrolysis, i.e. quisqualic acid >> 1S,3R-amino-1-dicarboxylate-1,3 cyclopentane approximately equal to glutamate. This metabotropic glutamate receptor-induced Ca2+ influx is insensitive to voltage-dependent Ca2+ channel antagonists and occurs through a Mn2+ impermeant pathway. The study of the rapid kinetics shows that this influx is triggered after a 300 ms delay compared with that elicited by depolarizing agents and Ca2+ ionophore A23187. In order to assess further if mGluR stimulate this influx through the recruitment of inositol triphosphate (IP3)-sensitive intracellular Ca2+ stores, we have tested the effect of thapsigargin on membrane potential and intracellular Ca2+ simultaneously. Thapsigargin induces a depolarization of the synaptoneurosomal membrane followed by a massive Ca2+ influx, occurring via a Mn2+ nonpermeant route. This depolarizing effect is sensitive to the presence of the intracellular Ca2+ chelator [1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetoxymethyl ester], and partially sensitive to extracellular Na+, but insensitive to the presence of extracellular Ca2+. Taken together, our data suggest that mGluR stimulate self-maintained increases of [Ca2+]i in rat forebrain synaptoneurosomes via the activation of a multistep mechanism, sequenced in the following steps: (i) mGluR-induced IP3 synthesis; (ii) IP3-stimulated intracellular Ca2+ release; (iii) Ca(2+)-activated non-specific cation channel, leading to local depolarization and a Ca2+ influx; and (iv) activation of Ca(2+)-sensitive phospholipase C.

Animals↗

Protein kinase C differently regulates quisqualate- and 1S,3R-trans aminocyclopentane dicarboxylate-induced phosphoinositide hydrolysis during in vitro development of hippocampal neurons.

Transient peaks of quisqualate (QA)-, but not 1S,3R-1-amino-3-cyclopentane dicarboxylate (1S,3R-ACPD)- and carbachol-induced inositol phosphate formation occur between 2 and 5 days in vitro (DIV) in hippocampal neurons in culture. In order to elucidate the putative origin of such developmental activity differences, the effect of PKC on metabotropic glutamate receptor (mGluR) and muscarinic receptor responses was investigated at 3 and 10 DIV. (i) Stimulation of PKC by phorbol-12,13-dibutyrate inhibited QA, 1S,3R-ACPD and carbachol responses at 3 DIV. At 10 DIV, only 1S,3R-ACPD response was still inhibited by phorbol esters. (ii) Inhibition of PKC by staurosporine at 3 DIV potentiated 1S,3R-ACPD-induced inositol phosphate formation, but had no effect on QA and carbachol responses. At 10 DIV, all responses were potentiated by staurosporine. These data strongly suggest that PKC differently modulates 1S,3R-ACPD- and QA-induced inositol phosphate accumulations during in vitro development. The specific activity of mGluRs during development, vs that of muscarinic receptor, and the peculiar modes of regulation by PKC of these two mGluR activities further suggest their particular involvement in the maturation of neuronal culture.

Alkaloids↗

[Comparative study of the treatment of prostatic adenoma: laser photocoagulation versus endoscopic resection].

OBJECTIVE: Resection of the prostate using a Nd YAG laser is designed to destroy benign prostatic hyperplasia responsible for bladder neck obstruction. This technique is currently under investigation. PATIENTS AND TECHNIQUE: A total of 56 patients, with a minimal follow-up of 6 months and presenting indications for endoscopic resection of the prostate were treated by TULIP [22] or VLAP [34] laser coagulation. The objective and subjective results were compared to a group of patients [30] treated by endoscopic resection during the same period. Results are expressed as the percentage of patient responding to treatment in terms of objective (peak flow rate > 15 ml/s with improvement > 30% or between 12 and 15 ml, but improvement > 50%) and subjective parameters (IPSS < 7 and improvement > 30% or between 7 and 10, but improvement < 50%). RESULTS: With a minimal follow-up of 6 months, the objective response rates were 55.5% (TULIP), 84.6% (VLAP) and 83.2% (TURP), while the subjective response rates were 55.5% (TULIP), 92.3% (VLAP) and 83.3% (TURP). The hospital stay was significantly shorter in the laser group (2.1 VLAP and 3.3 TULIP; 4.93 TURP). In the TULIP group, 3 patients were incontinent and 4 developed chronic prostatitis. At 6 months, 4 patients in the VLAP group and 6 patients in the TULIP group had to undergo a complementary TURP. CONCLUSION: These results indicate that laser photocoagulation is effective in the treatment of benign prostatic hyperplasia. The VLAP technique appears to be better adapted to this indication. The benefit of VLAP will be more clearly demonstrated by the randomized study currently underway, provided the length of hospital stay, postoperative complications and cost-effectiveness ratio are taken into account. In contrast, the TULIP system is associated with numerous complications which appear to be unacceptable.

Aged↗

Prostatic tissue destruction by high-intensity focused ultrasound: experimentation on canine prostate.

High-intensity focused ultrasound (HIFU) has been used transrectally to induce intraprostatic coagulation necrosis lesion in the canine prostate. The device combines a firing system (power amplifier and therapy transducer) and a localization system (ultrasound scanner). Thirty-seven dogs have been treated with ultrasound intensity ranging from 720 W/cm2 to 2300 W/cm2 and shot durations ranging from 1 to 4 seconds. The threshold for focal ultrasonic lesions was determined to be 1000 W/cm2 with a 1-second shot duration. Intraprostatic lesions were obtained without any damage to the rectal wall. These lesions were homogeneous coagulation necroses and progressed first to an inflammatory fibrosis and then to sclerosis with cavity formation. Intraprostatic lesions also occurred with a combination of moderate acoustic intensity (720 W/cm2) and longer shot duration (4 seconds). The temperature reached at the focal point of the transducer was 85 degrees C. The study confirms the possibility of creating irreversible lesions in the prostatic tissue through the rectal wall. The destruction of localized prostatic cancer seems to be possible in the near future using HIFU delivered by the transrectal route.

Animals↗

Effects of high-energy focused ultrasound on kidney tissue in the rat and the dog.

In vivo tissue destruction was performed on 124 rat and 16 canine kidneys by focusing high-intensity ultrasound with a 1- and 2.25-MHz transducer. A precise tissue lesion was obtained in both models which varied in size according to the number of firings and the acoustic intensity. In the rat experiments, which were used to define the constants necessary to produce a localized tissue lesion at the focus of the transducer, the lesions obtained were either coagulating necrosis or a 'punched out' cavity which represented the threshold of tissue ablation. In the canine experiments, a kidney lesion was achieved in 10 animals (63%) extracorporally. These lesions were also histologically determined to be coagulation necrosis. These lesions are created by highly focused ultrasound and are caused most likely by a combination of cavitation and thermal effects, depending on the duration and frequency of the ultrasound bursts. Exact mechanism of this effect is explored as well as potential clinical applications in treating kidney, liver, and prostate tumors in humans.

Animals↗

[The diagnosis of Lyme borreliosis. Apropos of a neurological case].

The clinical diagnosis of Lyme borreliosis is easily established in the initial phase of the illness. Erythema chronicum migrans is pathognomonic of this infection. However, during further complications (neurological, cardiac or articular) the diagnosis is chiefly based on laboratory results. The detection of specific antibodies to B. burgdorferi is one of the effective means of confirming the diagnosis. Culture or isolation of this bacteria is not routinely performed due to its very low yield. In this article a case of serologically proved neuro-borreliosis is described and the methods of diagnosis are discussed. Intrathecal synthesis of antibodies observed in the cerebrospinal fluid of this patient and the specificity of serologic tests confirmed by Western-blot provide the diagnosis. However, the absence of locally synthesized antibodies in the cerebrospinal fluid is not sufficient to rule out neuro-borreliosis.

Aged↗

Partial lipodystrophy, meningococcal meningitis and nephritis.

Partial lipodystrophy (PLD) started in a 12-year-old girl after measles. Aged 17 she had meningococcal meningitis. Nephritis, hypocomplementemia and nephritic factor were found some years later at the time of her first pregnancy. Only few patients with PLD and meningococcal infections have been described and all were hypocomplementemic. Like other patients with complement deficiency, patients with PLD should be aware of this life-threatening complication.

Adult↗

Unusual aspects of the dialysis disequilibrium syndrome.

In five patients with chronic renal failure, rapid correction by dialysis of hypertension and/or high blood urea levels provoked acute neurological disorders, followed by slowly reversible neuropsychiatric disturbances. Focal EEG alterations were noted in three patients with normal carotid angiograms. Our cases differed from those usually described as suffering from the dialysis disequilibrium syndrome because of their duration, the severity of mental disturbances, and the asymmetrical pattern of EEG abnormalities. We propose that the symptoms observed could be due to cerebral ischemia. This possibility emphasizes the importance of limiting the duration and efficiency of the first dialyses in patients with severe hypertension and high nitrogen retention, especially if high performance dialyzers are used.

Adult↗