Epilepsy is characterized by the hyperexcitability of individual neurons and hyper synchronization of groups of neurons (networks). The acquired changes that take place at molecular, cellular and network levels are important for the induction and maintenance of epileptic activity in the brain. Epileptic activity is known to alter the intrinsic properties and signaling of neurons. Understanding acquired changes that cause epilepsy may lead to innovative strategies to prevent or cure this neurological disorder. Advances in in vitro electrophysiological techniques together with experimental models of epilepsy are indispensible tools to understand molecular, cellular and network mechanisms that underlie epileptiform activity. The aim of the study was to investigate the epileptiform activity induced alterations in Ca2+ dynamics in apical dendrites of hippocampal subicular pyramidal neurons in slices and changes in network properties of cultured hippocampal neurons. We have also made attempts to develop an in vitro model of epilepsy using organotypic hippocampal slice cultures. In the first part of the present study, investigations on the basic properties of dendritic Ca2+ signaling in subicular pyramidal neurons during epileptiform activity are described. Subiculum, a part of the hippocampal formation is present, adjacent to the CA1 subfield. It acts as a transition zone between the hippocampus and entorhinal cortex. It receives inputs directly from the CA1 region, the entorhinal cortex, subcortical and other cortical areas. Several forms of evidences support the role of subiculum in temporal lobe epilepsy. Pronounced neuronal loss has been reported in various regions of the hippocampal formation (CA1 and CA3) leaving the subiculum generally intact in human epileptic tissue. It has been observed that epileptic activity is generated in subiculum in cases where the CA3 and CA1 regions are damaged or even absent. However, it is not clear how subicular neurons protect themselves from epileptic activity induced neuronal death. It is widely accepted that epileptiform activity induced neuronal damage is a result of an abnormally large influx of Ca2+ into neuronal compartments. In the present study, combined hippocampus / entorhinal cortical brain slices were exposed to zero Mg2+ + 4-amino pyridine artificial cerebrospinal fluid (ACSF) to generate spontaneous epileptiform discharges. Whole cell current-clamp recordings combined with Ca2+ imaging experiments (by incorporating Oregon green BAPTA-1 in the recording pipette) were performed on subicular pyramidal neurons to understand the changes in [Ca2+]i transients elicited in apical dendrites, in response to spontaneous epileptic discharges. To understand the changes occurring with respect to control, experiments were performed (in both control and in vitro epileptic conditions) where [Ca2+]i transients in dendrites were elicited by back propagating action potentials following somatic current injections. The results show clear distance-dependent changes in decay kinetics of [Ca2+]i transients (τdecay), without change in the amplitude of the [Ca2+]i transients, in distal parts (95–110 µm) compared to proximal segments (30–45 µm) of apical dendrites of subicular pyramidal neurons under in vitro epileptic condition, but not in control conditions. Pharmacological agents that block Ca2+ transporters viz. Na+/Ca2+ exchangers (Benzamil), plasma membrane Ca2+-ATPase pumps (Calmidazolium) and smooth endoplasmic reticulum Ca2+-ATPase pumps (Thapsigargin) were applied locally to the proximal and distal part of the apical dendrites in both experimental conditions to understand the molecular aspects of the Ca2+ extrusion mechanisms. The relative contribution of Na+/Ca2+ exchangers in Ca2+ extrusion was higher in the distal apical dendrite in in vitro epileptic condition. Using computer simulations with NEURON, biophysically realistic models were built to understand how faster decay of [Ca2+]i transients in the distal part of apical dendrite associated with [Ca2+]i extrusion mechanisms affect excitability of the neurons. With a linear increase in the density of Na+/Ca2+ exchangers along the apical dendrite, the decrease in τ decay values of [Ca2+]i transients in distal regions seen in experimental epileptic condition was reproduced in simulation. This linear increase in Na+/Ca2+ exchangers lowered the threshold for firing in response to consecutive synaptic inputs to the distal apical dendrite. Our results thus, show the existence of a novel neuroprotective mechanism in distal parts of the apical dendrite of subicular pyramidal neurons under in vitro epileptic condition with the Na+/Ca2+ exchangers being the major contributors to this mechanism. Although the enhanced contribution of Na+/Ca2+ exchangers helps the neuron in removing excess [Ca2+]i loads, it paradoxically makes the neuron hyperexcitable to synaptic inputs in the distal parts of the apical dendrites. Thus, the Na+/Ca2+ exchangers may actually protect subicular pyramidal neurons and at the same time contribute to the maintenance of epileptiform activity. In the second part of the study, neuronal network topologies and connectivity patterns were explored in control and glutamate injury induced epileptogenic hippocampal neuronal networks, cultured on planar multielectrode array (8×8) probes. Hyper synchronization of neuronal networks is the hallmark of epilepsy. To understand hyper synchronization and connectivity patterns of neuronal networks, electrical activity from multiple neurons were monitored simultaneously. The electrical activity recorded from a single electrode mainly consisted of randomly fired single spikes and bursts of spikes. Simultaneous measurement of electrical activity from all the 64 electrodes revealed network bursts. A network burst represents the period (lasting for 0.1–0.2 s) of synchronized activity in the network and, during this transient period, maximum numbers of neurons interact with each other. The network bursts were observed in both control and in vitro epileptic networks, but the frequency of network bursts was more in the latter, compared to former condition. Time stamps of individual spikes (from all 64 electrodes) during such time-aligned network burst were collected and stored in a matrix and used to construct the network topology. Connectivity maps were obtained by analyzing the spike trains using cross-covariance analysis and graph theory methods. Analysis of degree distribution, which is a measure of direct connections between electrodes in a neuronal network, showed exponential and Gaussian distributions in control and in vitro epileptic networks, respectively. Quantification of number of direct connections per electrode revealed that the in vitro epileptic networks showed much higher number of direct connections per electrode compared to control networks. Our results suggest that functional two-dimensional neuronal networks in vitro are not scale-free (not a power law degree distribution). After brief exposure to glutamate, normal hippocampal neuronal networks became hyperexcitable and fired a larger number of network bursts with altered network topology. Quantification of clustering coefficient and path length in these two types of networks revealed that the small-world network property was lost once the networks become epileptic and this was accompanied by a change from an exponential to a Gaussian network. In the last part of the study, we have explored if an excitotoxic glutamate injury (20 µM for 10 min) that produces spontaneous, recurrent, epileptiform discharges in cultured hippocampal neurons can induce epileptogenesis in hippocampal neurons of organotypic brain slice cultures. In vitro models of epilepsy are necessary to understand the mechanisms underlying seizures, the changes in brain structure and function that underlie epilepsy and are the best methods for developing new antiseizure and antiepileptogenic strategies. Glutamate receptor over-activation has been strongly associated with epileptogenesis. Recent studies have shown that brief exposure of dissociated hippocampal neurons in culture to glutamate (20 µM for 10 min) induces epileptogenesis in surviving neurons. Our aim was to extend the in vitro model of glutamate injury induced epilepsy to the slice preparations with intact brain circuits. Patch clamp technique in current-clamp mode was employed to monitor the expression of spontaneous epileptiform discharges from CA1 and CA3 neurons using several combinations of glutamate injury protocols. The results presented here represent preliminary efforts to standardize the glutamate injury protocol for inducing epileptogenesis in organotypic slice preparations. Our results indicate that glutamate injury protocols that induced epileptogenesis in dissociated hippocampal neurons in culture failed to turn CA1 and CA3 neurons of organotypic brain slice cultures epileptic. We also found that the CA1 and CA3 neurons of organotypic brain slice cultures are resilient to induction of epileptogenesis by glutamate injury protocols with 10 times higher concentrations of glutamate (200µM) than that used for neuronal cultures and long exposure periods (upto 30 min). These results clearly show that the factors involved in induction of epileptiform activity after glutamate injury in neuronal cultures and those involved in making the neurons in organotypic slices resilient to such insults are different, and understanding them could give vital clues about epileptogenesis and its control. The resilience of CA1 and CA3 neurons seen could be due to differences in homeostatic plasticity that operate in both these experimental systems. However, further studies are required to corroborate this hypothesis.

Compartmentalization of cell membranes, in particular of the apical membrane of columnar epithelia, is the topic of this thesis. The first part characterizes the apical membrane and its specialized organization and morphology, whereas the second part focuses on the formation of this unique plasma membrane domain during epithelial polarization. The apical membrane of columnar epithelia is enriched in glycosphingolipids, a class of lipids that are known to interact with cholesterol to form liquid ordered domains, also termed "rafts", in cell membranes. Imaging the apical surface of untreated and raft lipid depleted MDCK cells with atomic force microscopy revealed that raft lipids are involved in the formation and/or maintenance of microvilli, actin based protrusions of the apical plasma membrane, indicating a regulatory link between membrane domains and the cytoskeleton. Furthermore, antibody patching and photobleaching experiments performed during the work of this thesis suggest that the organization into raft and non-raft domains is very different in the apical membrane of MDCK cells compared to the plasma membrane of a fibroblast. In fact, the data support the hypothesis that the apical membrane could be a percolating raft membrane in which rafts constitute the major phase and non-raft domains exist as isolated entities. The second part of this thesis analyses the segregation of apical and basolateral membrane domains during epithelial polarization. This segregation can either be achieved by generating scaffolded domains prior to junction formation or by polarized secretory and endocytic membrane traffic after the establishment of cell junctions. While most apical and basolateral marker proteins in MDCK cells follow the latter mechanism, this thesis reports that the apical marker gp135 is confined to the dorsal face already in single attached cells. The unknown antigen was purified and identified as podocalyxin. Analysis of a series of domain mutants revealed that the C-terminal PDZ-binding motif of podocalyxin is mainly responsible for its special localization, which it shares with the PDZ protein NHERF-2. Knocking down podocalyxin by RNA interference resulted in retardation of cell growth and epithelial polarization. Taken together, the data suggest that podocalyxin and NHERF-2 could be part of an early apical polarity scaffolding system based on PDZ-binding and PDZ-containing proteins.

The purpose of the thesis is to explore the role of BMP signaling in developing vertebrate midbrain. BMP signaling plays important roles in various tissues and stages of neural development to regulate cell fate, proliferation, differentiation, morphogenesis and more. We observed that several major BMPs are expressed not only at the roof plate but also the floor plate of the midbrain. This has led us to ask the role of BMP signaling in dorsal and ventral midbrain patterning. Despite ventral experiments, we found that BMP signaling does not regulate ventral cell fate specification in the midbrain. Instead BMPs profoundly influence the shape and early morphogenesis of the midbrain neural plate as it closes into a neural tube. During neural tube closure, one of the early events occurring at the ventral midline is median hinge point (MHP) formation. Failure to form MHP leads to neural tube closure defects, the 2nd most common birth defects in humans. However, the molecular mechanisms underlying MHP formation are not well known. We found that the lowest BMP signaling occurs at the MHP during early neurulation and BMP blockade is necessary and sufficient for MHP formation. Interestingly, we also demonstrated that BMP blockade directs MHP formation by regulating the apicobasal polarity pathway and this regulation may be mediated by biochemical interactions between pSMAD5 and the apical protein, PAR3. Additionally, our time-lapse data suggest that BMP blockade slows cell cycle progression by increasing duration of G1 to S transition and S phase which leads cell nuclei stay at the basal location longer. This mimics basal nuclear migration seen at the MHP where low BMP signaling occurs. Thus, we conclude that BMP signaling regulates neural tube closure via the apicobasal polarity pathway and in a cell cycle dependent manner at the ventral midline. We observed that BMP signaling is necessary and sufficient for the dorsal cell fate specification in a context-dependent manner and ventral BMP signaling affects dorsal cell fates. Taken together, we propose the idea that BMP signaling has distinct roles in different contexts. BMPs regulate tissue morphogenesis in the ventral midbrain and dorsally cell fate specification. / text

No description available.

En se développant, les plantes produisent des organes le long des tiges suivant des organisations stéréotypées, appelées phyllotaxies. Ces structures se forment dans les méristèmes, qui abritent une niche de cellules souches : les organes y sont produits successivement et leur positionnement dépendrait d'interactions dynamiques avec les organes pré-existants. Ces interactions seraient notamment dues à des champs inhibiteurs générés par le transport polaire de l'hormone végétale auxine. Afin de rechercher si d'autres facteurs que l'auxine contrôlent la phyllotaxie chez Arabidopsis thaliana, nous nous sommes intéressés au rôle possible des cytokinines, une autre hormone végétale. Nous avons développé des nouvelles méthodes statistiques pour analyser la structure de la phyllotaxie. Cette approche nous a permis d'identifier des anomalies de phyllotaxie chez des plantes mutantes pour le gène AHP6 (ARABIDOPSIS HISTIDINE PHOSPHOTRANSFER protein 6), un inhibiteur de la signalisation des cytokinines. Notre analyse suggérait des possibles perturbations du plastochrone, la période de temps séparant l'initiation de deux organes, ce que nous avons alors confirmé par imagerie confocale en temps réel. Nos données montrent que AHP6 contrôle la régularité du plastochrone, et suggèrent que les perturbations de phyllotaxies sont dues à l'initiation simultanée de deux à trois organes dans le méristème. De plus, AHP6 est exprimé dans les organes et sa protéine établit des champs qui inhibent la signalisation des cytokinines au delà des organes. Pour mieux comprendre les rôles possibles de ces champs, nous avons généré un modèle numérique théorique de la phyllotaxie. Notre étude suggère que le plastochrone pourrait être déstabilisé par du bruit affectant le seuil d'activation nécessaire aux cellules méristématiques pour se différencier en organe. Des champs inhibiteurs pourraient filtrer les effets de ce bruit en influant sur la cinétique d'émergence des organes. Les propriétés observées des champs de AHP6 sont en accord avec ce modèle et nos données expérimentales suggèrent en effet que AHP6 et les cytokinines peuvent moduler la signalisation auxine lors de l'émergence des organes. Nous proposons comme modèle que le transport et la signalisation de l'auxine positionnent de manière robuste les organes mais génèrent un plastochrone irrégulier en présence de bruit. Des champs inhibiteurs de cytokinines stabiliseraient le plastochrone, assurant un couplage plus robuste entre le temps et l'espace lors de l'établissement de la phyllotaxie.

Experimental objective - the study was aimed to establish the developmental regularities of winter rape and its hybrids under the conditions of autumn-winter period becoming warmer and variable in length, to estimate the peculiarities of their biopotential formation and to optimize the measures of adaptation to changeable climate conditions. Statements to be defended: 1. Winter rape development until the end of autumn vegetation depends on sowing date and plant genotype. 2. The changes in nutrients in the rosette of winter rape ant its hybrids plants occurring after resumption of vegetation during the wintering period differ and depend not only on the genotype and sowing date but also on the year’s weather conditions. 3. Different sowing time influences over winter survival of winter rape and its hybrids plants. Rape hybrids respond less sensitively to the delay in sowing date. 4. Sowing time exerts a greater effect on the seed yield of winter rape compared with winter rape hybrids. / Tyrimų tikslas - nustatyti žieminių rapsų ir jų hibridų vystymosi dėsningumus skirtingos trukmės šiltėjančiu rudens – žiemos periodu, įvertinti jų biopotencialo formavimosi ypatumus bei optimizuoti prisitaikymo prie besikeičiančių klimato sąlygų adaptacines priemones (sėjos laiką). Disertacijos ginamieji teiginiai: 1. Žieminių rapsų vystymasis iki rudens vegetacijos pabaigos priklauso nuo sėjos laiko ir augalo genotipo. 2. Atsinaujinus vegetacijai žiemojimo metu, rapsų ir jų hibridų skrotelėje vykstantys maisto medžiagų pokyčiai skiriasi ir priklauso ne tik nuo genotipo ir sėjos laiko, bet ir nuo metų meteorologinių sąlygų. 3. Skirtingas sėjos laikas įtakojo žieminių rapsų ir jų hibridų peržiemojimą. Rapsų hibridai yra mažiau jautrūs sėjos laiko vėlinimui. 4. Sėjos laikas daro didesnę įtaką rapsų nei jų hibridų sėklų produktyvumui.

Au vu de l'impact croissant du changement climatique global et en particulier de la sécheresse sur les forêts, il est nécessaire de comprendre les mécanismes de réponse des arbres face à des variations de disponibilité en eau. Ces dernières années, des études ont montré un contrôle épigénétique et notamment par la méthylation de l'ADN de la plasticité phénotypique des plantes en réponse aux variations environnementales. Dans ce contexte, cette thèse visait à évaluer le rôle de la méthylation de l'ADN des cellules du méristème apical caulinaire dans la plasticité développementale de la tige feuillée en réponse à des variations de disponibilité en eau chez le peuplier, un arbre modèle. A cette fin, le méthylome de la chromatine non condensée dans le méristème apical caulinaire de Populus trichocarpa a été caractérisé. Ensuite, l'impact de variations de disponibilité en eau sur la méthylation de l'ADN a été étudié dans l'apex caulinaire de différents hybrides (P. × euramericana). Les loci et les réseaux de gènes affectés pour leur expression et leur méthylation ont ainsi été identifiés. Ces travaux ont montré que dans le méristème apical caulinaire, la majorité des gènes étaient dans un état non condensé de la chromatine et méthylés dans leur corps. Ils ont également mis en évidence une forte variation de la méthylation globale de l'ADN selon les génotypes et en réponse à des variations de disponibilité en eau. De plus, des corrélations ont été établies entre les niveaux de croissance des arbres et de méthylation globale de l'ADN dans l'apex caulinaire. Enfin, les variations de la méthylation de l'ADN en réponse aux variations de la disponibilité en eau s'accompagnent de variations d'expression et ont ciblé particulièrement des gènes impliqués dans la signalisation par les phytohormones ou la morphogenèse. Ainsi, les travaux effectués lors de cette thèse suggèrent un rôle de la méthylation de l'ADN dans la plasticité phénotypique en réponse à des variations de disponibilité en eau chez le peuplier via le contrôle de l'expression de réseaux de gènes dans le méristème apical caulinaire.

Considerando-se a necessidade da obturação tridimensional e o adequado selamento marginal do sistema de canais radiculares, como fatores decisivos para o êxito da terapia endodôntica, este estudo objetivou avaliar as respostas inflamatórias periapicais resultantes da infiltração coronária em dentes de cães obturados com diferentes cimentos resinosos (AH Plus®, RealSeal® e RealSeal SE®) e técnicas obturadoras (condensação lateral e termoplástica). Para tanto, pré-molares e incisivos centrais e laterais de 5 cães tiveram o tratamento endodôntico realizado empregando-se limas de NiTi e creme de Endo PTC associado ao hipoclorito de sódio a 1%, estabelecendo-se como limite de instrumentação à distância de 1mm a 1.5mm aquém do vértice radiográfico. A seguir os condutos foram obturados de acordo com os grupos experimentais (n=12) e grupos controles (n=10): GI- AH Plus/condensação lateral, GII- AH Plus/termoplástificação, GIIIRealSeal/ condensação lateral, GIV- RealSeal/ termoplástificação, GV- RealSeal SE/condensação lateral, GVI- RealSeal SE/ termoplástificação, Grupo controle positivo e Grupo controle negativo. As cavidades coronárias ficaram expostas ao meio bucal por um período de 75 dias e, passado este período experimental, os cães foram eutanásiados por superdosagem de anestésico. Foi realizada a remoção cirúrgica das partes correspondentes aos pré-molares e incisivos da maxila e da mandíbula, fixação das mesmas em solução de formol a 10% por 72h e desmineralização em solução de ácido fórmico a 20% + citrato de sódio a 10% pelo período mínimo de 90 dias. Posteriormente, realizou-se a rotina histológica com cortes seriados com espessura de 6m e estes foram corados com hematoxilina e eosina (HE). Cada corte histológico foi digitalizado e analisado em relação à existência de patologia periapical por três avaliadores independentes. Os dados obtidos foram confrontados estatisticamente utilizando o teste de Kruskal-Wallis seguido do teste comparativo de Dunn, observando-se que em relação às técnicas, a termoplástificação por ondas contínuas de condensação associada à técnica de injeção mostrou melhores condições periapicais quando comparada à técnica de condensação lateral (p=0.0055), sendo que a utilização desta técnica resultou em reações inflamatórias mais intensas para o cimento RealSeal SE (p=0.002). Em relação aos cimentos avaliados, o RealSeal SE mostrou-se menos eficaz em evitar a percolação, produzindo maiores níveis de inflamação crônica independentemente do sistema de obturação (p=0.0088). / Considering the need for three-dimensional obturations and adequate marginal sealing of the radicular canal system as being decisive factors for successful endodontic therapy, this study had as its objective the evaluation of periapical inflammatory responses resulting from coronary infiltration in dog\'s teeth obturated using different resin sealers (AH Plus, RealSeal and RealSeal SE) and different obturation techniques (lateral condensation and thermoplastic). For this study, premolars, central and lateral incisors from five dogs had endodontic treatment employing NiTi files and Endo PTC cream associated with 1% sodium hypochlorite. The working length was established at a distance of 1.0 to 1.5mm short of the radiographic apex. After this, the teeth were obturated according to their experimental groups (n=12) and control groups (n=10). The groups were defined as follows: GI - AH Plus/lateral condensation, GII - AH Plus/thermoplastic, GIII - RealSeal/lateral condensation, GIV - RealSeal/thermoplastic, GV - RealSeal SE/lateral condensation, GVI - RealSeal SE/ thermoplastic, a positive control group and a negative control group. The coronal access were left exposed to the oral environment for a period of seventy-five days, and after this experimental period, the dogs were euthanized by anesthetic overdose. The parts corresponding to the premolars and the maxilar incisors were surgically removed. These were then submitted to a solution of 10% formol for 72 hours and then demineralized in a solution of 20% formic acid and 10% sodium citrate for a minimum period of ninety days. Before hand, a histological routine of serial cuts having a width of 6m was undertaken and these were colored with hematoxilin and eosin (HE). Each histological cut was digitalized and analyzed with respect to the existence of periapical inflammation by three independent evaluators. The data obtained was statistically compared, firstly using the Kruskal-Wallis test and then the comparative Dunn test, where it was noted that in relation to the techniques, thermoplastification by continuous wave of condensation associated with the injection technique showed better periapical conditions than what was seen for the lateral condensation technique (p=0.0055). On the other hand, for the sealers evaluated, the condensation technique resulted in more intense inflammatory reactions when the sealer RealSeal SE was used (p=0.002). In relation to the sealers evaluated, RealSeal SE was seen to be less effective against percolation, thus producing greater levels of chronic inflammation irrespective of the obturation system employed (p=0.0088).

Abstract Microbial infection in dental root canal induces an inflammatory reaction called apical periodontitis. In post-treament disease, Enterococcus faecalis is the most commonly found organism, which may survive well in root canal despite calcium hydroxide paste medication. In these cases, effective irrigation or repeated chlorhexidine medication are recommended. New medications with long-lasting antimicrobial activity are needed for the treatment of persistent root canal infections. 2-hydroxyisocaproic acid (HICA) is a protein fermentation product of lactobacilli and few other bacterial or fungal species express enzymes required for its metabolism. However, mammalian cells can metabolise it and use it for protein production. It is known to be well-tolerated by humans and have anti-inflammatory properties as well. Therefore, the hypothesis was that it affects microbe-specific metabolic pathways and have potential as a novel antimicrobial agent. The aim of this study was to evaluate the antibacterial and antifungal spectrum of HICA using in vitro microdilution methods for susceptibility testing and an ex vivo extracted tooth root canal infection-model. The impact of dentine on the antimicrobial activity of HICA was also evaluated. The results showed that HICA has broad-spectrum bactericidal activity for gram-positive and gram-negative organisms. It is also fungicidal for several fungal species and it is only marginally inactivated by clinically-relevant concentrations of dentine. It is at least as active against E. faecalis as presently-used interappointment medications in infected root canals after a seven-day incubation ex vivo. Since HICA has a broad-spectrum and long-term antimicrobial activity as well as an anti-inflammatory effect, it may be a useful new agent for clinical endodontology. However, controlled clinical studies are needed for evaluation of the efficacy of HICA in clinical conditions. / Tiivistelmä Hampaan juurikanavan mikrobi-infektio aiheuttaa apikaalisen parodontiitin eli tulehdusreaktion juuren kärjen läheisyydessä oleviin kudoksiin. Silloin, kun infektio ei parane hoidon jälkeen, Enterococcus faecalis on yleisin löydös. Jos kalsiumhydroksidilääkitys ei ole tehokas, hoitoon suositellaan huolellista desinfektiohuuhtelua ja uusittavaa lyhytkestoista klooriheksidiinilääkitystä. Juurikanavainfektioiden hoitoon tarvitaan uusia antimikrobiaineita, joilla on pitkäaikainen vaikutus. Lactobacillus-bakteerit tuottavat proteiiniaineenvaihdunnassa 2-hydroksi-isokapronihappoa eli HICAa, jonka metaboloimiseen tarvittavia entsyymejä tunnetaan vain muutamilla muilla bakteereilla. Ihmissolut metaboloivat ja käyttävät sitä proteiinituotantoon. Se on hyvin siedetty aine ja se lieventää tulehdusreaktiota. Tutkimuksen hypoteesina oli, että HICA vaikuttaa mikrobien aineenvaihduntaan ja se voisi olla mahdollinen uusi antimikrobiaine. Tässä tutkimuksessa HICAn antimikrobitehoa tutkittiin bakteereita ja sienilajeja vastaan pienerälaimennusmenetelmällä tehdyissä herkkyystesteissä. Sen soveltuvuutta hampaiden juurikanavainfektioiden hoitoon arvioitiin dentiinin läsnäollessa sekä potilailta poistetuissa ja kokeellisesti infektoiduissa hampaissa. Tulokset osoittavat, että HICA tappaa laajakirjoisesti gram-positiivisia ja gram-negatiivisia bakteereita sekä hiivoja ja muita sienilajeja. Dentiinin vaikutus HICAn antimikrobitehoon on vähäinen. Sen vaikutus E. faecalista vastaan poistettujen hampaiden juurikanavissa on viikon jälkeen yhtä hyvä tai parempi kuin nykyisten lääkeaineiden vaikutus. Laajakirjoisen, pitkäkestoisen antimikrobitehon ja anti-inflammatorisuuden vuoksi HICA voisi olla uusi vaihtoehto juurikanavainfektioiden hoitoon. HICAn kliinisen tehokkuuden arviointiin tarvitaan kontrolloituja kliinisiä tutkimuksia.

No description available.