Recent animal experiments suggested that centrally transported botulinum toxin type A (BoNT-A) might reduce an abnormal muscle tone, though with an unknown contribution to the dominant peripheral ...muscular effect observed clinically. Herein, we examined if late BoNT-A antispastic actions persist due to possible central toxin actions in rats. The early effect of intramuscular (i.m.) BoNT-A (5, 2 and 1 U/kg) on a reversible tetanus toxin (TeNT)-induced calf muscle spasm was examined 7 d post-TeNT and later during recovery from flaccid paralysis (TeNT reinjected on day 49 post-BoNT-A). Lumbar intrathecal (i.t.) BoNT-A–neutralizing antiserum was used to discriminate the transcytosis-dependent central toxin action of 5 U/kg BoNT-A. BoNT-A-truncated synaptosomal-associated protein 25 immunoreactivity was examined in the muscles and spinal cord at day 71 post-BoNT-A. All doses (5, 2 and 1 U/kg) induced similar antispastic actions in the early period (days 1–14) post-BoNT-A. After repeated TeNT, only the higher two doses prevented the muscle spasm and associated locomotor deficit. Central trans-synaptic activity contributed to the late antispastic effect of 5 U/kg BoNT-A. Ongoing BoNT-A enzymatic activity was present in both injected muscle and the spinal cord. These observations suggest that the treatment duration in sustained or intermittent muscular hyperactivity might be maintained by higher doses and combined peripheral and central BoNT-A action.
Overt muscle activity and impaired spinal locomotor control hampering coordinated movement is a hallmark of spasticity and movement disorders like dystonia. While botulinum toxin A (BoNT-A) standard ...therapy alleviates mentioned symptoms presumably due to its peripheral neuromuscular actions alone, the aim of present study was to examine for the first time the toxin's trans-synaptic activity within central circuits that govern the skilled movement. The rat hindlimb motor pools were targeted by BoNT-A intrasciatic bilateral injection (2 U per nerve), while its trans-synaptic action on premotor inputs was blocked by intrathecal BoNT-A-neutralising antitoxin (5 i.u.). Effects of BoNT-A on coordinated and high intensity motor tasks (rotarod, beamwalk swimming), and localised muscle weakness (digit abduction, gait ability) were followed until their substantial recovery by day 56 post BoNT-A. Later, (day 62-77) the BoNT-A effects were examined in unilateral calf muscle spasm evoked by tetanus toxin (TeNT, 1.5 ng). In comparison to peripheral effect alone, combined peripheral and central trans-synaptic BoNT-A action induced a more prominent and longer impairment of different motor tasks, as well as the localised muscle weakness. After near-complete recovery of motor functions, the BoNT-A maintained the ability to reduce the experimental calf spasm evoked by tetanus toxin (TeNT 1.5 ng, day 62) without altering the monosynaptic reflex excitability. These results indicate that, in addition to muscle terminals, BoNT-A-mediated control of hyperactive muscle activity in movement disorders and spasticity may involve the spinal premotor inputs and central circuits participating in the skilled locomotor performance.
Tetanus and Botulinum type B neurotoxins are bacterial metalloproteases that specifically cleave the vesicle-associated membrane protein VAMP at an identical peptide bond, resulting in inhibition of ...neuroexocytosis. The minute amounts of these neurotoxins commonly used in experimental animals are not detectable, nor is detection of their VAMP substrate sensitive enough. The immune detection of the cleaved substrate is much more sensitive, as we have previously shown for botulinum neurotoxin type A. Here, we describe the production in rabbit of a polyclonal antibody raised versus a peptide encompassing the 13 residues C-terminal with respect to the neurotoxin cleavage site. The antibody was affinity purified and found to recognize, with high specificity and selectivity, the novel N-terminus of VAMP that becomes exposed after cleavage by tetanus toxin and botulinum toxin type B. This antibody recognizes the neoepitope not only in native and denatured VAMP but also in cultured neurons and in neurons in vivo in neurotoxin-treated mice or rats, suggesting the great potential of this novel tool to elucidate tetanus and botulinum B toxin activity in vivo.
Several negative factors contribute to a decline in the number of insect pollinators. As a novel approach in therapy, we hypothesize that the EM® for bees could potentially have an important ...therapeutic and immunomodulatory effect on honey bee colonies. The aim of our study was to evaluate its impact on honey bees at the individual and colony level. This is the first appliance of the commercial probiotic mix EM® PROBIOTIC FOR BEES in honey bees as economically important social insects. The sugar syrup with 10% of probiotic was administered by spraying or feeding the honey bee colonies in the field conditions, in order to evaluate the infection levels with spores of Nosema spp. and colonies’ strength. Moreover, in laboratory-controlled conditions, in the hoarding cages, adult workers have been fed with sugar syrup supplemented with 2.5, 5, and 10% of EM® for bees for biochemical and immunological analyses of hemolymph, and with 5 and 10% for measuring the size of hypopharyngeal glands. It was found that following the EM® for bees administration the Nosema spp. spore counts in colonies were significantly reduced, and colonies’ strength was increased. The results at the individual level showed significant positive physiological changes in treated groups of adult bees, revealing at the same time a higher mortality rate when feeding sugar syrup supplemented with the probiotic.
Rijeka/Fiume war im 19. Jahrhundert eine der führenden Industriestädte Europas. Damals entwickelte sie sich, sowohl im Bereich der Politik als auch der Wirtschaft und Kultur. Der bekannte ...Industrielle aus England beispielsweise, Robert Whitehead, erweitert seine Produktion und entwirft Skizzen für die ersten Torpedoraketen. Es werden die ersten Banken und Handelskammern in Rijeka gegründet. Wohltätigkeitsbälle werden organisiert und Bibliotheken ausgestattet. Wissenschaftler (Naturwissenschaftler), Künstler, Großindustrielle, Politiker nehmen an Debatten teil, um den Ausbau der Stadt zu planen und um die Lebensqualität aller Bürger zu verbessern. Eine direkte Zugverbindung von Wien über Opatija (Abbazia) nach Rijeka (Fiume), mehrere überozeanische direkte Schiffsverbindungen aus Rijeka nach Amerika, Neuseeland und Australien ermöglichen die Erkundung neuer Welten, anderer Sprachen und den Import dergleichen während der Rückkehr eigener Bewohner/Seefahrer oder der Ankunft von Fremdlingen/Migranten als neuen Bewohnern der Stadt. Rijeka/Fiume war und ist es bis heute geblieben: ein europäisches transkulturelles und mehrsprachiges Zentrum. Aus diesem Grund soll die Transkulturalität in diesem Beitrag anhand bekannter Persönlichkeiten deutschsprachiger Herkunft in dieser Stadt veranschaulicht werden. Dieser Beitrag stützt sich und ergänzt die bisherigen Forschungsergebnisse von Ervin Dubrović, Gerhard Dienes und Irvin Lukežić. Dabei stehen Aspekte der Mehrsprachigkeit/Translation als auch Multikulturalität im Vordergrund dieser Untersuchung.
Cephalic tetanus (CT) is a severe form of tetanus that follows head wounds and the intoxication of cranial nerves by tetanus neurotoxin (TeNT). Hallmarks of CT are cerebral palsy, which anticipates ...the spastic paralysis of tetanus, and rapid evolution of cardiorespiratory deficit even without generalized tetanus. How TeNT causes this unexpected flaccid paralysis, and how the canonical spasticity then rapidly evolves into cardiorespiratory defects, remain unresolved aspects of CT pathophysiology. Using electrophysiology and immunohistochemistry, we demonstrate that TeNT cleaves its substrate vesicle-associated membrane protein within facial neuromuscular junctions and causes a botulism-like paralysis overshadowing tetanus spasticity. Meanwhile, TeNT spreads among brainstem neuronal nuclei and, as shown by an assay measuring the ventilation ability of CT mice, harms essential functions like respiration. A partial axotomy of the facial nerve revealed a potentially new ability of TeNT to undergo intra-brainstem diffusion, which allows the toxin to spread to brainstem nuclei devoid of direct peripheral efferents. This mechanism is likely to be involved in the transition from local to generalized tetanus. Overall, the present findings suggest that patients with idiopathic facial nerve palsy should be immediately considered for CT and treated with antisera to block the potential progression to a life-threatening form of tetanus.
U radu se obrađuje ogled
pod naslovom
De Thucydidis historia
iudicium
. Riječ je o latinskom prijevodu djelomično sačuvane rasprave
O Tukididovu značaju
(Περὶ Θουκυδίδου
χαρακτῆρος), koja se ...pripisuje Dioniziju iz Halikarnasa (1. st. pr. Kr. – 1.
st. po Kr.). Prijevod je načinio humanist Andrija Dudić (1533. – 1589.), a
otisnut je 1560. u Manuzijevoj tiskari u Veneciji. Grčko-rimski povjesničar i retoričar
ondje je prikazao Tukididovu
Povijest
Peloponeskog rata
kao ogledan primjer atičkog jezičnog izraza. Dionizije je
i sâm uspješno oponašao slavnog Atenjanina i time poticajno djelovao na kasnije
pisce. Iako ga je hvalio zbog obračuna s mitologiziranjem povijesnih djela,
Halikarnašanin nije skrivao kritički ton spram nekih Tukididovih postupaka. Na
tragu čitanja Tukidida i Dionizija, u radu se najprije skicira kulturno-povijesna uloga originalnog djela. Zatim se obrađuje
recepcijska sudbina obojice pisaca. Nudi se filološka
obrada Dudićeva latinskog prijevoda. Cilj članka
jest prikazati Dudićev rad u okviru recepcije obojice antičkih pisaca i u
kontekstu renesansnog prevođenja s grčkog na latinski te analizirati Dudićeve
prevodilačke postupke
Thucydides,
one of the greatest Greek historians, has been admired for centuries after
writing his account of the Peloponnesian war. His critics were fewer than his
admirers, but he was not exempt from critique. Dionysius of Halicarnassus wrote
the treatise Περὶ Θουκυδίδου χαρακτῆρος, judging harshly the Athenian
historian. Andreas Dudithius, a Renaissance scholar and diplomat, translated
the treatise into Latin, encouraged by his friend Paolo Manuzio who published
the translation in 1560. Dudithius dedicated the translation to his sponsor
Nicolaus Olahus, bishop of Estergom and a historian. In the preface, Dudithius
states that his translation will not be
ad
verbum
. In his use of Latin he
emulates classical models. In the context of humanist translation Dudithius is
closer to the learned and influential Leonardo Bruni than to the adherents of
the
ad verbum
style such as Andreas
Divus and Alonso of Cartagena.
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