Calcium flux-independent NMDA receptor activity is required for Aß oligomer-induced synaptic loss.

Synaptic loss is one of the major features of Alzheimer's disease (AD) and correlates with the degree of dementia. N-methyl-D-aspartate receptors (NMDARs) have been shown to mediate downstream effects of the ß-amyloid peptide (Aß) in AD models. NMDARs can trigger intracellular cascades via Ca(2+) entry, however, also Ca(2+)-independent (metabotropic) functions of NMDARs have been described. We aimed to determine whether ionotropic or metabotropic NMDAR signaling is required for the induction of synaptic loss by Aß. We show that endogenous Aß as well as exogenously added synthetic Aß oligomers induced dendritic spine loss and reductions in pre- and postsynaptic protein levels in hippocampal slice cultures. Synaptic alterations were mitigated by blocking glutamate binding to NMDARs using NMDAR antagonist APV, but not by preventing ion flux with Ca(2+) chelator BAPTA or open-channel blockers MK-801 or memantine. Aß increased the activity of p38 MAPK, a kinase involved in long-term depression and inhibition of p38 MAPK abolished the loss of dendritic spines. Aß-induced increase of p38 MAPK activity was prevented by APV but not by BAPTA, MK-801 or memantine treatment highlighting the role of glutamate binding to NMDARs but not Ca(2+) flux for synaptic degeneration by Aß. We further show that treatment with the G protein inhibitor pertussis toxin (PTX) did not prevent dendritic spine loss in the presence of Aß oligomers. Our data suggest that Aß induces the activation of p38 MAPK and subsequent synaptic loss through Ca(2+) flux- and G protein-independent mechanisms.

The effects of water parameters on monthly seagrass percentage cover in Lawas, East Malaysia.

Seagrass is a valuable marine ecosystem engineer. However, seagrass population is declining worldwide. The lack of seagrass research in Malaysia raises questions about the status of seagrasses in the country. The seagrasses in Lawas, which is part of the coral-mangrove-seagrass complex, have never been studied in detail. In this study, we examine whether monthly changes of seagrass population in Lawas occurred. Data on estimates of seagrass percentage cover and water physicochemical parameters (pH, turbidity, salinity, temperature, and dissolved oxygen) were measured at 84 sampling stations established within the study area from June 2009 to May 2010. Meteorological data such as total rainfall, air temperature, and Southern Oscillation Index were also investigated. Our results showed that (i) the monthly changes of seagrass percentage cover are significant, (ii) the changes correlated significantly with turbidity measurements, and (iii) weather changes affected the seagrass populations. Our study indicates seagrass percentage increased during the El-Nino period. These results suggest that natural disturbances such as weather changes affect seagrass populations. Evaluation of land usage and measurements of other water physicochemical parameters (such as heavy metal, pesticides, and nutrients) should be considered to assess the health of seagrass ecosystem at the study area.

Active vaccination with ankyrin G reduces ß-amyloid pathology in APP transgenic mice.

Serum antibodies against amyloid-ß peptide (Aß) in humans with or without diagnosis of Alzheimer's disease (AD) indicate the possibility of immune responses against brain antigens. In an unbiased screening for antibodies directed against brain proteins, we found in AD patients high serum levels of antibodies against the neuronal cytoskeletal protein ankyrin G (ankG); these correlated with slower rates of cognitive decline. Neuronal expression of ankG was higher in AD brains than in nondemented age-matched healthy control subjects. AnkG was present in exosomal vesicles, and it accumulated in ß-amyloid plaques. Active immunization with ankG of arcAß transgenic mice reduced brain ß-amyloid pathology and increased brain levels of soluble Aß(42). AnkG immunization induced a reduction in ß-amyloid pathology, also in Swedish transgenic mice(.) Anti-ankG monoclonal antibodies reduced Aß-induced loss of dendritic spines in hippocampal ArcAß organotypic cultures. Together, these data established a role for ankG in the human adaptive immune response against resident brain proteins, and they show that ankG immunization reduces brain ß-amyloid and its related neuropathology.

Improvement of neurobehavioral disorders in children supplemented with magnesium-vitamin B6. I. Attention deficit hyperactivity disorders.

Some previous studies have reported the involvement of magnesium (Mg) deficiency in children with ADHD syndrome. In this work, 40 children with clinical symptoms of ADHD were followed clinically and biologically during a magnesium-vitamin B6 (Mg-B6) regimen (6 mg/kg/d Mg, 0.6 mg/kg/d vit-B6) which was set up for at least 8 weeks. Symptoms of ADHD (hyperactivity, hyperemotivity/ aggressiveness, lack of attention at school) were scored (0-4) at different times; in parallel, intraerythrocyte Mg2+ (Erc-Mg) and blood ionized Ca2+ (i-Ca) were measured. Children from the ADHD group showed significantly lower Erc-Mg values than control children (n = 36). In almost all cases of ADHD, Mg-B6 regimen for at least two months significantly modified the clinical symptoms of the disease: namely, hyperactivity and hyperemotivity/aggressiveness were reduced, school attention was improved. In parallel, the Mg-B6 regimen led to a significant increase in Erc-Mg values. When the Mg-B6 treatment was stopped, clinical symptoms of the disease reappeared in few weeks together with a decrease in Erc-Mg values. This study brings additional information about the therapeutic role of a Mg-B6 regimen in children with ADHD symptoms.

Improvement of neurobehavioral disorders in children supplemented with magnesium-vitamin B6. II. Pervasive developmental disorder-autism.

Previous studies reported positive results with the use of Mg-vitamin B6 in autism. Despite these reports, this intervention remains controversial. In order to study relationships between changes in clinical symtoms and biological parameters, 33 children (mean age: 4 [1-10] years old) with clinical symptoms of pervasive developmental disorder or autism (PDD, as defined in DSM-IV) were followed for at least 6 months; another group of 36 children (same age) devoided of any known pathology was used as control. All PDD children received a magnesium-vit B6 (Mg-B6) regimen (6 mg/kg/d Mg and 0.6 mg/kg/d vit B6). Intraerythrocyte Mg2+ (Erc-Mg), serum Mg2+ (s-Mg) and blood ionized Ca2+ (i-Ca) were measured before and after treatment. Clinical symptoms of PDD were scored (0 to 4). In contrast to s-Mg or i-Ca, PDD children exhibited significantly lower Erc-Mg values than controls (2.17 +/- 0.4 versus 2.73 +/- 0.23 mmol/L; 16/33). The Mg-B6 regimen led to an increase in Erc-Mg values (2.42 +/- 0.41 (after) versus 2.17 +/- 0.4 mmol/l (before), 11/17) and this supplementation improved PDD symptoms in 23/33 children (p < 0.0001) with no adverse effects: social interactions (23/33), communication (24/33), stereotyped restricted behavior (18/33), and abnormal/delayed functioning (17/33); 15/33 children were improved in the first three groups of symptoms. When the Mg-B6 treatment was stopped, PDD symtoms reappeared in few weeks. A statistically significant relationship was found in Erc-Mg values from children before treatment and their mothers. In conclusion, this study suggests that the behavioral improvement observed with the combination vitamin B6-magnesium in PDD/autism is associated with concomitant modifications of Erc-Mg values.

Poison as cure: a clinical review of botulinum toxin as an invaluable drug

Botulinum toxin is the most potent toxin known. It is readily absorbed from mucosal surfaces. If dispersed as an aerosol or mixed in the food or water it can lead to a large outbreak of botulism. The disease presents as a symmetric descending paralysis in an afebrile patient. Cranial nerve involvement with diplopia, dysarthria, dysphonia, dysphagia and respiratory paralysis is seen after a variable incubation period. The treatment is mainly supportive. The source of the toxin is Clostridium botulinum, an anaerobic gram-positive spore-forming organism. Some other species of Clostridium like C. butyricum and C. baratii also produce the toxin. The toxin is heat labile and can be inactivated by heating at 100°C for 10 minutes. The toxin acts at the peripheral cholinergic nerve terminals at the neuromuscular junctions, postganglionic parasympathetic ganglia, etc, and affects neurotransmitter release by inhibiting exocytosis. Clinical uses in various medical fields were found for it.(AU)

Pre-hospital treatment of snake envenomation in patients presented AT a tertiary care hospital in Northwestern India

Snakebite is an important medical emergency. Anti-snake venom along with supportive care is the only specific treatment. However, many people put their faith in non-registered medical practitioners. Where medical aid is available, lack of trained health personnel jeopardizes the situation. This retrospective study, the first of its kind, was aimed at studying the pre-hospital treatment as well as the behavior of patients bitten by snakes and referred to the Postgraduate Institute of Medical Education and Research, Chandigarh, India. A total of 88 cases that occurred between January 1997 and December 2001 were studied. Seventy patients received treatment prior to admission (the majority was treated by non-registered medical practitioners, registered medical practitioners, and MBBS doctors). The various treatment modalities used were: anti-snake venom (ASV), tourniquet, incision and drainage (I&D), tetanus toxoid, injections, and tablets. Non-registered medical practitioners still preferred tourniquet and I&D. The patients who were referred within 24 hours stayed less time in the hospital and spent less money on the treatment compared to those who were referred after 24 hours. Non-registered medical practitioners and inadequately trained health staff are often the first contact of snakebite victims. Their traditional and unscientific methods of treatment lead to unnecessary morbidity and increased treatment cost. It is therefore necessary to train these people adequately so that proper treatment can be instituted at the earliest.

Contraction induced by glicentin on smooth muscle cells from the human colon is abolished by exendin (9-39).

UNLABELLED: Glicentin and glucagon-like peptide-1 (7-36) amide (GLP-1) are gut hormones released during digestion. Glicentin and GLP-1 slow down gastric emptying and glicentin can switch off the duodenojejunal fed motor pattern. The effect of glicentin on the motor activity of colon has never been reported in humans. Our aim was to determine if circular smooth muscle cells (SMC) from the human colon are target cells for glicentin or GLP-1, and if their motility is dependent upon these digestive hormones. METHODS: Twenty-two resections were performed on patients operated for colon adenocarcinoma. The SMC were isolated from colonic circular muscle layer and cell contraction was assessed. RESULTS: Glicentin caused a dose-related contraction of SMC, when GLP-1 determined a contraction of weak amplitude. Exendin-(9-39), described as a GLP-1 receptor antagonist, inhibited contraction due to glicentin or GLP-1. In contrast, on antral SMC from rabbit, GLP-1 exerts neither relaxation nor contraction; however, exendin-(9-39) dose dependently reduced the contractile activity of glicentin [glicentin EC(50) = 5 pM, exendin-(9-39) pA(2) = -9.36]. CONCLUSIONS: The circular muscle from the human colon is a target tissue for glicentin and GLP-1. Whereas glicentin is a long-life digestive hormone which would contribute to segmental contraction, the biological activity of GLP-1 remains unknown on this tissue. On the digestive smooth muscle, exendin-(9-39) behaved as an antagonist for two members of the glucagon-receptor family, GLP-1 and glicentin.

Evaluation of cardiac troponin I and T levels as markers of myocardial damage in doxorubicin-induced cardiomyopathy rats, and their relationship with echocardiographic and histological findings.

BACKGROUND: Cardiac troponins I (cTnI) and T (cTnT) have been shown to be highly sensitive and specific markers of myocardial cell injury. We investigated the diagnostic value of cTnI and cTnT for the diagnosis of myocardial damage in a rat model of doxorubicin (DOX)-induced cardiomyopathy, and we examined the relationship between serial cTnI and cTnT with the development of cardiac disorders monitored by echocardiography and histological examinations in this model. METHODS: Thirty-five Wistar rats were given 1.5 mg/kg DOX, i.v., weekly for up to 8 weeks for a total cumulative dose of 12 mg/kg BW. Ten rats received saline as a control group. cTnI was measured with Access(R) (ng/ml) and a research immunoassay (pg/ml), and compared with cTnT, CK-MB mass and CK. By using transthoracic echocardiography, anterior and posterior wall thickness, LV diameters and LV fractional shortening (FS) were measured in all rats before DOX or saline, and at weeks 6 and 9 after treatment in all surviving rats. Histology was performed in DOX-rats at 6 and 9 weeks after the last DOX dose and in all controls. RESULTS: Eighteen of the DOX rats died prematurely of general toxicity during the 9-week period. End-diastolic (ED) and end-systolic (ES) LV diameters/BW significantly increased, whereas LV FS was decreased after 9 weeks in the DOX group (p<0.001). These parameters remained unchanged in controls. Histological evaluation of hearts from all rats given DOX revealed significant slight degrees of perivascular and interstitial fibrosis. In 7 of the 18 rats, degeneration and myocyte vacuolisation were found. Only five of the controls exhibited evidence of very slight perivascular fibrosis. A significant rise in cTnT was found in DOX rats after cumulative doses of 7.5 and 12 mg/kg in comparison with baseline (p<0.05). cTnT found in rats after 12 mg/kg were significantly greater than that found after 7.5 mg/kg DOX. Maximal cTnI (pg/ml) and cTnT levels were significantly increased in DOX rats compared with controls (p=0.006, 0.007). cTnI (ng/ml), CK-MB mass and CK remained unchanged in DOX rats compared with controls. All markers remained stable in controls. Analysis of data revealed a significant correlation between maximal cTnT and ED and ES LV diameters/BW (r=0.81 and 0.65; p<0.0001). A significant relationship was observed between maximal cTnT and the extent of myocardial morphological changes, and between LV diameters/BW and histological findings. CONCLUSIONS: Among markers of ischemic injury after DOX in rats, cTnT showed the greatest ability to detect myocardial damage assessed by echocardiographic detection and histological changes. Although there was a discrepancy between the amount of cTnI and cTnT after DOX, probably due to heterogeneity in cross-reactivities of mAbs to various cTnI and cTnT forms, it is likely that cTnT in rats after DOX indicates cell damage determined by the magnitude of injury induced and that cTnT should be a useful marker for the prediction of experimentally induced cardiotoxicity and possibly for cardioprotective experiments.

Biochemical basis of the pharmacologic action of chondroitin sulfates on the osteoarticular system.

BACKGROUND: Chondroitin sulfates (CS) are involved in articular metabolism and could be used as therapeutic agents in degenerative articular diseases. OBJECTIVES: To review the published reports describing both the metabolism of glycosaminoglycans (GAG) and their involvement in osteoarticular pathophysiology. METHODS: MEDLINE search for relevant articles and review of cited references. RESULTS: 1) CS are formed of disaccharide units; sulfated galactosamine residues in position 4 or 6 are found in various ratios, depending on the age and the type of tissue. Binding to the core protein through N- and O-linkages leads to aggregates of monomers with high molecular weights. The proteoglycan aggregate exhibits viscoelastic and hydration properties and an ability to interact with the surrounding tissue through electric charges leading to protection of the cartilaginous tissues. 2) CS are synthesized both in chondrocytes and in bone cells by the action of specific glycosyl-transferases; their catabolism occurs in the matrix and involves numerous matrix (metalloproteinases) and lysosomal enzymes. 3) CS are inhibitors of extracellular proteases involved in the metabolism of connective tissues. In addition to their anti-inflammatory effects, CS in vitro stimulate proteoglycan production by chondrocytes; they also inhibit cartilage cytokine production and induce apoptosis of articular chondrocytes. CS increase the intrinsic viscosity of the synovial liquid. 4) In vivo in experimental arthritis, the number and severity of articular symptoms decreases after CS administration. In bones, CS accelerate the mineralization process and bone repair. CONCLUSIONS: All these data suggest that CS play a role in articular and bone metabolism by controlling cartilaginous matrix integrity and bone mineralization.

Involvement of phosphatidylinositol 3-kinase and mitogen-activated protein kinases in glycine-extended gastrin-induced dissociation and migration of gastric epithelial cells.

The various molecular forms of gastrin can act as promoters of proliferation and differentiation in different regions of the gastrointestinal tract. We report a novel stimulatory effect of glycine-extended gastrin(17) only on cell/cell dissociation and cell migration in a non-tumorigenic mouse gastric epithelial cell line (IMGE-5). In contrast, both amidated and glycine-extended gastrin(17) stimulated proliferation of IMGE-5 cells via distinct receptors. Glycine-extended gastrin(17)-induced dissociation preceded migration and was blocked by selective inhibitors of phosphatidylinositol 3-kinase (PI3-kinase) but did not require mitogen-activated protein (MAP) kinase activation. Furthermore, glycine-extended gastrin(17) induced a PI3-kinase-mediated tyrosine phosphorylation of the adherens junction protein beta-catenin, partial dissociation of the complex between beta-catenin and the transmembrane protein E-cadherin, and delocalization of beta-catenin into the cytoplasm. Long lasting activation of MAP kinases by glycine-extended gastrin(17) was specifically required for the migratory response, in contrast to the involvement of a rapid and transient MAP kinase activation in the proliferative response to both amidated and glycine-extended gastrin(17). Therefore, the time course of MAP kinase activation appears to be a critical determinant of the biological effects mediated by this pathway. Together with the involvement of PI3-kinase in the dissociation of adherens junctions, long term activation of MAP kinases seems responsible for the selectivity of this novel effect of G(17)-Gly on the adhesion and migration of gastric epithelial cells.

Contraction of human colonic circular smooth muscle cells is inhibited by the calcium channel blocker pinaverium bromide.

UNLABELLED: The effects of L-type calcium channel blockers (CCBs) selective for the gastrointestinal tract (pinaverium) or non-selective (nicardipine and diltiazem), were investigated on CCK-, CCh- or KCl-induced contraction of smooth muscle cells (SMC) isolated from the circular muscle layer of normal or of inflamed human colons. In the normal tissue colon, whatever the contractile agent used, CCK-8 (1nM), CCh (1nM) or KCl (20mM), a micromolar concentration of pinaverium significantly inhibited contraction (88.36%, 93.10%, 93.92% inhibition respectively); this effect was concentration-dependent for CCh (IC50 = 0.73 +/- 0.08nM) and for CCK (IC50 = 0.92 +/- 0.12nM). In parallel, both nicardipine and diltiazem inhibit significantly contraction of isolated SMC. In inflamed colons, pinaverium (1 microM) display a significant higher efficacy than diltiazem or nicardipine to reduce cell contraction induced by CCK-8 or by KCl. In addition, RT-PCR experiments were performed to evidence tissue specificity of the L-type calcium channel. They revealed the expression of the messenger of the a-1 subunit L-type calcium channel (binding site of such CCBs), consistent with the expression of the rbC-2 splice variant of the alpha1-C gene. IN CONCLUSION: (i) the inhibition by calcium channel blockers of agonist-induced contractile activity suggest a modulation of SMC contraction upon extracellular calcium via 'L-type' voltage-dependent calcium channel; (ii) this study provides a rationale for the clinical use of pinaverium in colonic motor disoders affecting the contractility of SMC, since it appeared to decrease the contraction even in pathological situation; and (iii) RT-PCR experiments confirms the presence in human colon SMC of the alpha-1 subunit mRNA of calcium channel.

HGF regulates tight junctions in new nontumorigenic gastric epithelial cell line.

The regulation of intercellular adhesion by hepatocyte growth factor (HGF) was examined on a novel nontumorigenic gastric epithelial cell line (IMGE-5) derived from H-2Kb-tsA58 transgenic mice. IMGE-5 cells constitutively expressed cytokeratin 18 and HGF receptors. Under permissive conditions (33 degrees C + interferon-gamma), IMGE-5 cells proliferated rapidly but did not display membrane expression of adherens and tight junction proteins. Under nonpermissive conditions, their proliferation was decreased and they displayed a strong, localized membrane expression of E-cadherin/beta-catenin and occludin/ZO-1. HGF treatment largely prevented the targeting of ZO-1 to the tight junction and induced a significant decrease of the transepithelial resistance measured across a confluent IMGE-5 cell monolayer. HGF rapidly increased the tyrosine phosphorylation of ZO-1 and decreased its association with occludin in a phosphatidylinositol 3-kinase (PI 3-kinase)-dependent manner. PI 3-kinase was also involved in HGF-induced migration of IMGE-5 cells. Our results demonstrate that 1) HGF prevents the appearance of ZO-1 in the membrane during epithelial cell differentiation; 2) HGF causes partial relocalization of ZO-1 to the cytoplasm and nucleus and concomitantly stimulates cell dissociation and migration; and 3) IMGE-5 cells offer a useful model for the study of gastric epithelial cell differentiation.

Management of maternal Amanita phalloïdes poisoning during the first trimester of pregnancy: a case report and review of the literature.

BACKGROUND: Amanita phalloïdes poisoning produces acute liver failure and often death. Maternal poisonings are rare, and medical decisions of abortion or liver transplantation in this critical situation frequently are based on laboratory data. We report here the case of a 22-year-old-woman in the 11th week of pregnancy, who ingested mushrooms. CASE REPORT: The patient's clinical symptoms (e.g., vomiting and diarrhea) and blood chemistry data (persistent increases of aspartate aminotransferase and alanine aminotransferase and severe decreases in prothrombin, factor V, factor II, factor VII, and factor X) indicated poisoning of medium severity. The management consisted of intravenous hydration, and administration of silymarine and N-acetylcysteine. No fetal damage was observed, and birth and development of the infant (now 2 years of age) proceeded without incident. CONCLUSION: Abortion is not necessarily indicated in maternal poisoning by A. phalloïdes, even in the first trimester of pregnancy.

The COOH-terminal Src kinase Csk is a tumor antigen in human carcinoma.

The cytoplasmic tyrosine kinase cSrc is involved in the regulation of many important cellular functions including cell growth and transformation, and its activity is down-regulated by phosphorylation of the Tyr530 residue by the COOH-terminal Src tyrosine kinase, Csk. Because cSrc was previously found overexpressed, activated, and in some cases mutated in carcinoma, we investigated whether it could act as a tumor antigen. We show that whereas no autoantibodies were found against cSrc or its relative Fyn, up to 20% of patients with carcinoma had high-affinity autoantibodies against Csk. Immunity mainly resulted from a secondary response, as indicated by the presence of IgG1 in the sera. Antibodies were linked to the cancer because they were not detected in healthy subjects nor in patients with unrelated diseases, and their levels decreased in the sera of patients after surgical resection. Furthermore, they behaved as early markers of epithelial transformation because they were present in sera of patients with early-stage tumors and precancerous lesions such as colorectal polyps and in sera of patients that were scored negative for other cancer serological markers (CEA, CA15-3, CA19-9, p53 antibodies). Finally the presence of these antibodies was attributed, at least in part, to a substantial elevation of Csk protein levels in the corresponding tumors. However a strong increase in Src activity was also observed in these tissues, which suggested that Csk cannot regulate Src-like activity in carcinoma. Taken together, these data demonstrate that Csk acts as an autoantigen, and the detection of anti-Csk antibodies may have potential diagnostic usefulness in the early detection and postoperative follow-up of patients with carcinoma.

Deregulation of the cytoplasmic tyrosine kinase cSrc in the absence of a truncating mutation at codon 531 in human bladder carcinoma.

The involvement of the cytoplasmic tyrosine kinase cSrc was investigated in human bladder carcinogenesis. Kinase activity was determined in tissue lysates from bladder transitional cell carcinoma (TCC) relative to normal epithelia. Strong kinase activation was observed at all stages of carcinogenesis with a peak at the stage pT1, where tumor cells disrupt the basement membrane and invade the submucosa. In agreement with a role for cSrc in cell invasion, immunocytochemistry analysis showed a strong staining of invading cells. An increase in cSrc protein level were also found in most tumor samples, however, it did not correlate with an increase in activity (r = 0.44) suggesting that cSrc is deregulated in these tumors. Indeed, high Src activity was affinity-purified from a column (IRSVSSDGHE(p)YIYVDP-Affigel 10) that specifically retains active Src. Enzymatic regulation involves the C-terminus, recently found mutated at codon 531 in a subset of advanced human colon cancers. However, no such mutations were detected in TCC, suggesting the existence of other mechanisms for kinase activation.

CK-MB mass test in ischemic myocardial injury. Comparison of two tests: BioMerieux Vidas and sanofi access immunoassays.

The analytical and clinical performances of the new fluorescent immunoassay (CK-MB mass Vidas-BioMerieux) were examined and compared to the chemiluminescent test (CK-MB mass Access-Sanofi-Pasteur). Assay precisions of the CK-MB Vidas test within-assay or between-assay were less than 5.4 and 5.3%, respectively. Linearity was tested up to 214 microg/L. The CK-MB Vidas test was free of interference with CK-BB, CK-MM, and macro-CK. One hundred nineteen blood samples from patients with ischemic myocardial injury (IMI): acute myocardial infarction (AMI), suspected myocardial contusion (SMC), and unstable angina pectoris (UA), were tested using both immunoassays. In AMI, a good correlation was found (Y [CK-MB Access] = 1.1372 x [CK-MB Vidas] - 6.3902; r(2) = 0.96). In UA and SMC, low values were observed and both methods were well correlated (Y [CK-MB Access] = 1.3662 x [CK-MB Vidas] + 0.0671; r(2) = 0.97). Clinical data were in good agreement with both immunoassays. ROC analysis performed in AMI demonstrated that the clinical performances of the two assays were similar.

Time-course of cardiac troponin I release from isolated perfused rat hearts during hypoxia/reoxygenation and ischemia/reperfusion.

The study was designed to determine the time-course of cardiac troponin I (cTn-I) release in isolated and Langendorff-perfused rat hearts during hypoxia and reoxygenation (H/Reox), and after various durations of total ischemia and subsequent reperfusion (I/R). For this purpose, in H/Reox, cTn-I was measured with the conventional Access immunoassay (ng/ml) and a new immunoassay which operates at pg/ml, and compared with creatine kinase (CK), lactate dehydrogenase (LD) and cardiac troponin T (cTn-T). In I/R, cTn-I was compared with CK and LD. The anti-Tn-I mAbs used in cTn-I assays cross-react with cTn-I of the rat. A clear difference between time-courses and concentration levels of cTn-I in I/R and H/Reox models was found. In I/R, maximum release of cTn-I, CK and LD similarly occurred within minutes following reperfusion; however cTn-I did not return to baseline values. cTn-I levels were not linked to the duration of ischemia. In I/R, we were only able to detect small cTn-I concentrations. In H/Reox experiments, cTn-I, CK and LD increased time-dependently. We found higher cTn-I maximal peak levels detected with the Access immunoassay than with the new assay (median, 0.346 ng/ml per min/g dry wt vs 132 pg/ml per min/g dry wt). cTn-T maximal concentrations were lower than maximal cTn-I levels (median, 0.117 ng/ml per min/g dry wt). Time-courses of cTn-I release were roughly similar with both assays in the H/Reox model (r = 0.90). These data indicate that the cTn-I time-course is related to experimental model (I/R or H/Reox), but also likely depends on the sensitivity of cTn-I assays in such experimental conditions.

[Autonomic nervous system and prostatic physiology. Specific features of the alpha-adrenergic system]. / Système nerveux végétatif et physiologie prostatique. Particularités du système alpha adrénergique.

A better understanding of the rich autonomic innervation of the prostate allows more effective treatment of voiding disorders secondary to benign prostatic hyperplasia. The glandular contingent possesses mainly cholinergic innervation (M2 muscarinic receptors). Smooth muscle cells are richly supplied with alpha and beta catecholaminergic receptors, involved in muscle contraction and muscle relaxation, respectively, but they may also be involved in growth. These alpha receptors, divided into 2 families (alpha 1 and alpha 2), belong to the family of G protein-coupled seven membrane-spanning helix receptors. The genes, followed by the recombinant proteins of 3 subtypes of alpha 1 receptors have been described: alpha 1-a, -b, -d. In the prostate, these receptors are predominantly located in the stroma, mainly in the centroprostatic region. The mRNA present mainly code for the alpha 1a subtype. The use of specific agonists and antagonists shows that these receptors control smooth muscle contraction according to a mechanism initially considered to be of the alpha 1a type. However, their low affinity for prazosin and the development of new alpha 1 blocking agents is in favour of the involvement of a different functional subtype: alpha 1L. This difference could be explained by a different conformation of the receptor or by different coupling mechanisms. The subtype involved in prostatic smooth muscle contraction has yet to be characterized.