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Biomedical subjects

A Alexandre

Publications and source records attributed to A Alexandre.

At least 19 recordsLinked to original sources

International code for phytolith nomenclature 1.0.

BACKGROUND: Phytoliths (microscopic opal silica particles produced in and between the cells of many plants) are a very resilient, often-preserved type of microfossil and today, phytolith analysis is widely used in palaeoenvironmental studies, botany, geology and archaeology. To date there has been little standardization in the way phytoliths are described and classified. SCOPE: This paper presents the first International Code for Phytolith Nomenclature (ICPN), proposing an easy to follow, internationally accepted protocol to describe and name phytoliths.

Crystallization↗

Wrist median nerve motor conduction after end range repeated flexion and extension passive movements in Carpal Tunnel Syndrome. Pilot study.

Carpal Tunnel Syndrome (CTS) can be due to a variety of different pathological conditions. These etiological and epidemiological differences may explain the non-homogeneous response to ordinary conservative therapeutical options observed in this syndrome. The aim of our study was to investigate on the possibility of identifying different sub-groups of patients among conservatively treatable CTS with different susceptibility to physiotherapeutic treatments. We decided to utilize an objective approach measuring some median motor nerve function parameters. Short term variations of Compound Motor Action Potential (CMAP) from the thenar eminence were compared in two groups of 55 hands (CTS patients and normal controls) after performance of two different types of end range passive movement. We found a different distribution of CMAP amplitude modifications within a sub-group of patients that suddenly improved more than the controls after two series of 10 end range passive flexions or after two series of ten end range passive extensions. Amplitude changes proved to be much more useful than latency variation studies in the provocative test neurophysiological approach. The method we propose appears to be useful for better surgical indication and/or for improvement of conservative therapeutic choice.

Action Potentials↗

Microsurgical treatment of lumbosacral plexus injuries.

Surgical treatment of lumbar and sacral plexus lesions is very rarely reported in the literature. The incidence of the involvement of these nervous structures in traumatic lesions of different etiology is probably much higher than believed, and surgical treatment should be taken into consideration more often. In this paper the experience derived from the surgical treatment of 15 cases is reported. Different surgical approaches have been employed according to ethiology, to level of nerve lesion and concomitant lesions of other organs. Patients who suffered a lesion in the lumbar or sacral plexus may have a very severe problem with deambulation since the leg may not be stable or may be unable to withstand the weight of the body. Pain syndrome in these patients may be a very severe obstacle to rehabilitation programs and to deambulation and everyday activity. Microsurgical nerve treatment in the retroperitoneal space is demanding both for the surgeon and for the patient but neurolysis and grafting procedures are possible also in this area. The resulting improvement of motor performance and the relief of pain are strong arguments in favor of this choice. Muscles benefitting most from surgery are the gluteal and femural muscles; more distant muscles, and particularly the anterior tibial nerve dependent muscles will gain minimal benefit from surgery. The relief from pain is relevant in all cases.

Adolescent↗

Femoral nerve entrapment.

We present 30 cases of femoral nerve entrapment (1999-2003, age range 35-65 yrs), in 13 patients with diagnosis of idiopathic compression and 7 patients of neurovascular conflict. The compression, in the other 10 patients, was iatrogenic: 3 patients following cardiac catheterization for balloon valvotomy, 2 patients following intra-abdominal vascular surgery and 5 patients following laparoscopic hernia treatment. Microsurgical nerve decompression, and the elimination of neurovascular conflict gave satisfactory results. The best result has been observed in neurovascular conflict cases.

Adult↗

Intradiscal injection of oxygen-ozone gas mixture for the treatment of cervical disc herniations.

For disc herniations the use of open surgical approaches is reduced since new percutaneous methods allowing shrinkage of the disc and improvement of the radicular function are gaining interest. Studies on the spontaneous disappearance of disc fragments have demonstrated autoimmune responses with a chronic inflammatory reaction. Also radicular pain has been shown to be mostly due to biochemical mechanisms. Researchers in different fields surprisingly noticed that a brief, calculated, oxidative stress by ozone administration may correct a persistent imbalance due to excessive, chronic oxidative injury. Oxygen-ozone gas injection in painful patients has a dramatic effect on clinical symptoms. On these bases the intradiscal injection of oxygen-ozone gas has been conceived. We report the treatment on a series of patients affected by cervical disc pathology, treated by intradiscal injection of oxygen-ozone gas mixture. The effects both on pain and on radicular dysfunction are impressive. The morphological effect of the treatment was also evaluated by pathological examination.

Adult↗

Percutaneous nucleoplasty for discoradicular conflict.

Minimally invasive techniques for the treatment of degenerative pathology of the spine have come to be preferred by surgeons since the destructive effect on bony structures is eliminated and scar formation is dramatically reduced. A critical review of the pathogenetic mechanisms for low back pain and sciatalgia has recently yielded that mechanical compression is one but non essential component of the matter. The importance of chemical irritative processes is stressed. Coblation nucleoplasty is one of these minimally invasive techniques. It provokes ablation of the nucleus of the disk by a controlled thermal effect produced by radiofrequency. By this procedure one to two ml of tissue are colliquated in a few minutes. From February 2001 to May 2003 we treated 1390 patients for of lumbosciatalgic pain caused by disc pathology. The alteration consisted of disc bulging or contained disc herniation. Exclusion criteria as provided by the protocol of the multicentric study conceived by Conor O'Neill have been respected. This technique has been conceived in order to obtain progressive results in cases of contained disc herniation which has scanty natural tendency to shrinkage, as demonstrated by several studies on the natural history of evolution of this pathology. Contained disc herniation is a pathology most difficult to manage by conservative procedures, physiotherapy and drugs, but we all agree that open surgery should be avoided. By this minimally invasive procedure the patient will not be compelled to abandon physiotherapy and his normal daily activities for more than a few days.

Adolescent↗

The different outcomes of patients with disc herniation treated either by microdiscectomy, or by intradiscal ozone injection.

Disc herniation with radiculopathy and chronic discogenic pain are the result of degenerative processes. Treatment approach in face of this problem has largely been debated in the last years. A number of reviews on surgical treatments in the '80s and '90s have been published and various new techniques have been introduced among which ozone discolysis is one non-invasive intradiscal treatment method. In a 3-year follow-up period we have investigated the different outcomes of 150 patients who received microdiscectomy and 150 patients who received intradiscal ozone injection. In this series results are in favour of discolysis for contained disc herniations and of microdiscectomy for large migrated fragments with pain so severe that open surgery was obligatory. Apart from this, our results with the two techniques are equivalent also concerning mild neurological motor deficits.

Back Pain↗

Thoracic outlet syndrome due to hyperextension-hyperflexion cervical injury.

Posttraumatic brachial plexus entrapment in fibrotic scarring tissue is taken into consideration as the cause of complaints for patients who suffered a hyperextension-hyperflexion cervical injury. All 54 patients included in this analysis where symptom-free before the accident and subsequently complained for pain, paresthesia and slight weakness in the arm. In 14 neurological signs of brachial plexus entrapment were observed. Electroneurophysiological, summary index testing was positive for a brachial plexus involvement in all cases. Conservative measures, comprising physical therapy and vasoactive drugs were applied for a period of 6 to 12 (mean 8.4) months; surgical procedure of neurolysis was then proposed in 39 cases to solve the problem. Thirty-two patients were operated on. Twenty of these had a neat improvement on a 6-month to 1-year follow-up. Seven patients had refused surgery; of these 6 patients had clinical worsening at the same follow-up period while 1 remained unchanged. All patients with clinical symptoms not reversed after some time post-injury should be investigated for a possible brachial plexus entrapment.

Adult↗

Suprascapular nerve entrapment.

It is important to be aware of neuropathy involving the suprascapular nerve. While direct trauma to the suprascapular nerve is the usual cause (direct blow to the base of the neck or posterior shoulder, shoulder dislocation or fracture), the problem may result from overuse injuries (such as repetitive tennis serving or spiking of a volley ball), excessive horizontal adduction, weight lifting, backpacking or no apparent reason. These last three years we have operated 8 cases of suprascapular nerve neurolysis at the level of suprascapular incision, and section of the transverse scapular ligament through the back supraspinal approach.

Brachial Plexus Neuropathies↗

The adenosine inhibition of glutamate exocytosis in synaptosomes is removed by the collapse of the vesicle-cytosol deltapH plus the opening of farnesol-sensitive Ca(2+) channels.

Adenosine inhibits synaptosomal exocytosis of glutamate, triggered by KCl or by the K(+) channel inhibitor, 4-aminopyridine (4-AP), without affecting Ca(2+) influx. Its effect is removed by the activation of protein kinase C (PKC). We show that in the presence of the protein kinase inhibitor, staurosporine, the adenosine inhibition is removed also by collapsing deltapH between secretory vesicle and the cytosol with methylamine (MA), provided that exocytosis is triggered by KCl (which activates an initial transient spike of Ca(2+) influx) but not by 4-AP. If KCl is supplied prior to Ca(2+), the spike of Ca(2+) influx is absent and the adenosine inhibition is maintained. MA can remove the adenosine inhibition also with 4-AP, provided that tetraethylammonium (TEA), an inhibitor of a different class of K(+) channels, is supplied together with 4-AP. TEA promotes a further increase of cytosolic free Ca(2+) concentration ([Ca(2+)](i)), which adds to the 4-AP-induced Ca(2+) influx. Farnesol (5-10 microM), a physiological derivative of farnesyl pyrophosphate of the sterol biosynthetic pathway, specifically inhibits the Ca(2+) spike after KCl as well as the TEA-promoted Ca(2+) increase. At the same time, it prevents the removal of the adenosine inhibition by MA. We conclude that the adenosine inhibition is removed by the coincidence of two signals, the alkalinization of secretory vesicles and the opening of a particular class of Ca(2+) channels associated to the TEA-sensitive K(+) channels, equivalent to the Ca(2+) spike after KCl, and sensitive to farnesol.

4-Aminopyridine↗

Adenosine inhibits glutamate exocytosis largely without interfering with Ca2+ influx in rat cerebrocortical synaptosomes.

Adenosine is an inhibitor of glutamate release in synaptosomes. The inhibition is removed by the A(1) adenosine receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). We monitored the variations of cytoplasmic free Ca(2+) concentrations ([Ca(2+)](i)) in KCl or 4-aminopyridine-stimulated synaptosomes, in the presence of adenosine or adenosine plus DPCPX. The increment of [Ca(2+)](i) upon stimulation was unmodified by adenosine (up to 400-500 microM) while it was strongly decreased when exocytosis was decreased to a similar extent by lowering KCl or 4-aminopyridine. Adenosine also inhibited glutamate release induced by the Ca(2+) ionophore ionomycin. Increasing adenosine to 1.5 mM resulted in a decrease of the stimulus-induced increase of [Ca(2+)](i) and in the further potentiation of the adenosine inhibition of exocytosis from 41+/-3 to 51+/-4%. We conclude that adenosine affects glutamate exocytosis mostly in a Ca(2+) independent mode.

Adenosine↗

Involvement of nuclear factor-kappa B (NF-kappaB) activation in mitogen-induced lymphocyte proliferation: inhibitory effects of lymphoproliferation by salicylates acting as NF-kappaB inhibitors.

The transcription factor nuclear factor-kappa B (NF-kappaB) is involved in the production of inflammatory cytokines and in the control of the inflammatory response. Some nonsteroidal anti-inflammatory drugs such as acetylsalicylic acid (ASA) or salicylate are known to exert some of their anti-inflammatory pharmacological properties independently of cyclooxygenase inhibition. For ASA and salicylate, an NF-kappaB inhibitory effect at mM concentrations (pharmacological plasma concentrations reached in vivo) has been shown. We studied the action of ASA, salicylate, and several NF-kappaB inhibitors on the mitogen-induced activation of peripheral blood lymphocytes (PBL) and purified T cells. We showed that ASA and salicylate (1-3 mM) (but not indomethacin, a specific cyclooxygenase inhibitor) as well as a group of chemically unrelated inhibitors of NF-kappaB (including the sesquiterpene lactone parthenolide, Bay 11-7082, sulfasalazine, the proteasome inhibitor MG-132 and the peptide SN-50, an inhibitor of the nuclear transfer of the p50 subunit of NF-kappaB), were potent inhibitors of phytohemoagglutinin-activated PBL and T cell proliferation. At the same concentrations, they inhibited NF-kappaB binding to DNA in nuclear extracts. The inhibition of proliferation was not relieved by exogenous interleukin (IL)-2. We concluded that NF-kappaB activation has a fundamental role in T cell proliferation independently of IL-2 production. Some pharmacological actions of ASA may be ascribed to the inhibition of immune cell proliferation via the inhibition of the transcription factor NF-kappaB.

Cell Division↗

Oral N-acetyl-cysteome increases the production of anti HIV chemokines in peripheral blood mononuclear cells.

The C-C chemokines MIP-1alpha, MIP-1beta and RANTES are specific and powerful inhibitors of HIV infectivity. They appear to work by blocking the interaction of the virus with the receptor (CCR5). The latter is utilized as a coreceptor for cell penetration by macrophage-tropic (R5) HIV strains responsible for the majority of HIV transmissions. A natural high capability to release such chemokines has been proposed as a protection factor against HIV infection in exposed uninfected individuals. We report that oral administration of N-acetyl-cysteine (NAC) to healthy volunteers increases the capability of their peripheral blood mononuclear cells (PBMC) to release such anti HIV chemokines upon stimulation. The data reported may explain at least in part the mechanism of action of NAC as an anti HIV therapeutic agent: By potentiating chemokine production NAC may decrease susceptibility to infection.

Acetylcysteine↗

Modulation of glutamate exocytosis by redox changes of superficial thiol groups in rat cerebrocortical synaptosomes.

The treatment of cerebral cortex synaptosomes with the membrane impermeable thiol reagent 5,5'-dithio-bis-(2-nitrobenzoic acid) (DTNB) induces a long-lasting partial inhibition (about 40%) of the KCl-stimulated Ca2+-dependent exocytosis of glutamate. Synaptosomes are not damaged by the treatment. The increase of cytoplasmic free Ca2+ concentration ([Ca2+]i) upon depolarization is not affected by DTNB. The inhibition is observed also if exocytosis is induced with the Ca2+-ionophore ionomycin. In all cases the inhibition is reversed by the impermeable reductant glutathione (GSH). Similarly the inhibition of exocytosis by H2O2 (Zoccarato, F., Valente, M. and Alexandre, A., Hydrogen peroxide induces a long-lasting inhibition of the Ca2+-dependent glutamate release in cerebrocortical synaptosomes without interfering with cytosolic Ca2+. J. Neurochem., 64 (1995) 2552-2558.) is reversed by GSH. It is concluded that redox changes (possibly thiol-disulfide transitions) of superficial groups modulate the exocytotic apparatus directly. In an attempt to identify the protein(s) involved in this novel type of control, we evidenced DTNB (H2O2) reactive bands at 35 and at 85-150 kDa which can be labeled with a monobromotrimethylammoniobimane bromide (qBBr) derivatization.

Animals↗

Ganglioside GM1 protection from apoptosis of rat heart fibroblasts.

Ceramide is involved as a mediator of apoptosis induced by a variety of signaling molecules or stressful events. Ceramide-derived sphingosine 1-phosphate behaves as an antiapoptotic agent. The ganglioside GM1 is known to protect neuronal cell lines from apoptosis induced by serum/growth factor withdrawal and its effect is mediated in part by the direct activation of the trkA NGF receptor [G. Ferrari et al. (1995) J. Biol. Chem. 270, 3074-3080]. We show that GM1, similarly to sphingosine 1-phosphate, protects rat heart fibroblasts from apoptosis induced by the protein kinase C inhibitor staurosporine and by C2-ceramide. Furthermore, we show that GM1 induces the synthesis of sphingosine 1-phosphate and that this effect is partially prevented by the sphingosine kinase inhibitor N,N-dimethylsphingosine. We conclude that the antiapoptotic action of GM1 is largely to be ascribed to an increased sphingosine kinase activity.

Animals↗

Dose-dependent effects of IL-12 treatment to immune response induced after immunization with a recombinant respiratory syncytial virus (RSV) fusion protein fragment.

The amino acid (aa) sequence 190-289 of the RSV fusion (F) glycoprotein expressed in insect cells (bF(190-289)) has been shown to partially protect BALB/c mice and to prime for a Th2 cell response. We evaluated the effects of IL-12 treatment during antigen priming of bF(190-289) on immune response and protective efficacy. Low doses of IL-12 (10 ng) reduced IL-4 and IL-5 secretion (but did not affect IL-10 production) and decreased inflammatory signs whereas high doses of IL-12 had no effects. In addition, IL-12 treatment did not improve resistance to RSV replication. These results suggest that IL-12 treatment attenuates Th2 response and Th2 associated pulmonary inflammatory response in a dose-dependent manner, without improving protective efficacy.

Animals↗

The pH-sensitive dye acridine orange as a tool to monitor exocytosis/endocytosis in synaptosomes.

We introduce the use of the pH-sensitive dye acridine orange (AO) to monitor exo/endocytosis of acidic neurotransmitter-containing vesicles in synaptosomes. AO is accumulated exclusively in acidic v-ATPase-dependent bafilomycin (Baf)-sensitive compartments. A fraction of the accumulated AO is rapidly released (fluorescence increase) upon depolarization with KCl in the presence of Ca2+. The release (completed in 5-6 s) is followed by reuptake to values below the predepolarization baseline. The reuptake, but not the release, is inhibited by Baf added 5 s prior to KCl. In a similar protocol, Baf does not affect the initial fast phase of glutamate release measured enzymatically, but it abolishes the subsequent slow phase. Thus, the fast AO release corresponds to the rapid phase of glutamate release and the slow phase depends on vesicle cycling. AO reuptake depends in part on the progressive accumulation of acid-loaded vesicles during cycling. Stopping exocytosis at selected times after KCl by Ca2+ removal with EGTA evidences endocytosis: Its T(1/2) was 12 +/- 0.6 s. The K(A)+, channel inhibitors 4-aminopyridine (100 microM) and alpha-dendrotoxin (10-100 nM) are known to induce glutamate release by inducing the firing of Na+ channels; their action is potentiated by the activation of protein kinase C. Also these agents promote a Ca2+-dependent AO release, which is prevented by the Na+ channel inhibitor tetrodotoxin and potentiated by 4beta-phorbol 12-myristate 13-acetate (PMA). With alpha-dendrotoxin, endocytosis was monitored by stopping exocytosis at selected times with EGTA or alternatively with Cd2+ or tetrodotoxin. The T(1/2) of endocytosis, which was unaffected by PMA, was 12 +/- 0.4 s with EGTA and Cd2+ and 9.5 +/- 0.5 s with tetrodotoxin. Protein kinase C activation appeared to facilitate vesicle turnover.

4-Aminopyridine↗

Immune response to baculovirus expressed protein fragment amino acids 190-289 of respiratory syncytial virus (RSV) fusion protein.

At least two neutralizing epitopes have been identified in the amino acid (aa) sequence 190-289 of the RSV fusion protein. The authors expressed this region in insect cells (bF190-289) and compared the immune response to bF190-289 with that induced by baculovirus expressed full-length fusion protein (bF). As with bF, mice primed with bF190-289 produced exclusively antibodies of IgG1 isotype, generated neutralizing antibodies, reduced significantly the virus titer (about a half log10 reduction) after RSV challenge and induced a Helper T (Th) 2 cell response in mediastinal lymph node cells (MLNC) restimulated in vitro. Thus, the aa sequence 190-289 represents a major immunogenic region of the RSV fusion protein.

Amino Acid Sequence↗