"BUNANJE": XX CENTURY ABUSE OF ATROPA BELLADONNA HALUCINOGENIC BERRIES IN CONTINENTAL CROATIA

Background: Atropa belladonna (Engl. deadly nightshade, Cro. velebilje, bunika) is a plant containing pharmacologically active, potentially toxic alkaloids: atropine, hyocyamine and scopolamine. The risk of poisoning in children is important because of possible confusion of black/dark blue belladonna fruit berries with other edible berries. There are many reports in literature of accidental intoxication but no report on traditional intentional usage to achieve hallucinogenic effects. Subjects and methods: Here we report purposeful ingestion of Atropa belladonna berries for hallucinatory effects among adolescents in Bjelovar region in north part of Croatia. This has been happening among children/adolescents while they were grazing animals. We visited a dozen villages in the region and spoke to the oldest mostly to the elderly residents. Results: The existence of such abuse of Atropa belladonna berries in the first part of XX century was confirmed by eight narrators from five distinct places in the region. Interestingly this type of behavior had a specific name "bunanje", unknown in Croatian language, but clearly associated with local plant name bun or bunika. According to informants consumers of berries would develop delirium or hallucinations associated behavior, incoherent and meaningless speech. However nobody remembers any severe case of poisoning. At the regional hospital in Bjelovar in the Pediatric department, there is no record of poisoning with Atropa belladonna. To our knowledge this is the first report of intentional consumption of belladonna berries to achieve the hallucinogenic effect. Conclusions: The fact that the custom was observed in five distinct spots and it had its specific name "bunanje" suggest that those are not isolated random events but the type of practices; seasonal abuse of hallucinogenic berries of Atropa belladonna, among rural adolescents in the first part of XX century

Botulinum neurotoxin type A: actions beyond SNAP-25?

Botulinum neurotoxin type A (BoNT/A), the most potent toxin known in nature which causes botulism, is a commonly used therapeutic protein. It prevents synaptic vesicle neuroexocytosis by proteolytic cleavage of synaptosomal-associated protein of 25 kDa (SNAP-25). It is widely believed that BoNT/A therapeutic or toxic actions are exclusively mediated by SNAP-25 cleavage. On the other hand, in vitro and in vivo findings suggest that several BoNT/A actions related to neuroexocytosis, cell cycle and apoptosis, neuritogenesis and gene expression are not necessarily mediated by this widely accepted mechanism of action. In present review we summarize the literature evidence which point to the existence of unknown BoNT/A molecular target(s) and modulation of unknown signaling pathways. The effects of BoNT/A apparently independent of SNAP-25 occur at similar doses/concentrations known to induce SNAP-25 cleavage and prevention of neurotransmitter release. Accordingly, these effects might be pharmacologically significant. Potentially the most interesting are observations of antimitotic and antitumor activity of BoNT/A. However, the exact mechanisms require further studies

Botulinum toxin type A in motor nervous system: unexplained observations and new challenges

In the motor system, botulinum toxin type A (BoNT/A) actions were classically attributed to its well-known peripheral anticholinergic actions in neuromuscular junctions. However, the enzymatic activity of BoNT/A, assessed by the detection of cleaved synaptosomal-associated protein 25 (SNAP-25), was recently detected in motor and sensory regions of the brainstem and spinal cord after toxin peripheral injection in rodents. In sensory regions, the function of BoNT/A activity is associated with its antinociceptive effects, while in motor regions we only know that BoNT/A activity is present. Is it possible that BoNT/A presence in central motor nuclei is without any function? In this brief review, we analyze this question. Limited data available in the literature warrant further investigations of BoNT/A actions in motor nervous system

Antinociceptive action of botulinum toxin type A in carrageenan-induced mirror pain

"Mirror pain" or mirror-image pain (MP) is pain opposite to the side of injury. Mechanism and frequency in humans are not known. There is no consent on therapy. Here we report that unilaterally injected botulinum toxin type A (BT-A) has bilateral effect in experimental MP, thus deserves to be investigated as therapy for this condition. We examined the localization of BT-A's bilateral antinociceptive action in MP induced by 3 % carrageenan intramuscular injection in Wistar rats. BT-A was applied peripherally (5 U/kg), into ipsilateral or contralateral hind paw pad (i.pl.) and centrally (1 U/kg), at spinal (intrathecally, i.t.) or supraspinal (intracisternally, i.c.) level. Additionally, we examined the involvement of central opioid and GABAergic systems, as well as the contribution of peripheral capsaicin-sensitive neurons to BT-A's bilateral antinociceptive effect. Ipsilateral i.pl. and i.t. BT-A reduced the bilateral mechanical sensitivity to von Frey filaments, while contralateral i.pl. and i.c. treatments had no effect on either tested side. Bilateral antinociceptive effect of ipsilateral i.pl. BT-A was prevented by μ-opioid antagonist naloxonazine (1.5 μg/10 μl) and GABAA antagonist bicuculline (1 μg/10 μl) if applied at the spinal level, in contrast to supraspinal application of the same doses. Local treatment of sciatic nerve with 2 % capsaicin 5 days following BT-A i.pl. injection caused desensitization of sciatic capsaicin-sensitive fibers, but did not affect bilateral antinociceptive effect of BT-A and the presence of cleaved SNAP-25 at the spinal cord slices. Present experiments suggest segmental actions of peripheral BT-A at spinal level, which are probably not solely dependent on capsaicin-sensitive neurons

Indendiary weapons

Ratna primjena zapaljivih sredstava u svrhu ubijanja i ranjavanja ljudi i uništenja materijalnih dobara bila je poznata još u drevnoj Kini. Tijekom I. svjetskog rata započeo je posebno intenzivan razvitak novog zapaljivog oružja i sredstava njihove primjene. Tvari poput napalma i bijelog fosfora imaju fizikalno-kemijske osobine koje im omogućuju spontanu zapaljivost (bijeli fosfor), dugo gorenje, oslobađanje velikih količina topline i otrovnih plinova pri sagorijevanju i si. Izazivaju teške opekline, visok rizik otrovanja i nastanak šoka. Specifičnosti u njezi ranjenika proizlaze iz potrebe prevencije i liječenja intoksikacije, te iz teškog općeg stanja ozlijeđenih. Intenzivnija uporaba zapaljivih ratnih sredstava redovito izaziva i masovna stradanja civilnog pučanstva. U tekstu su iznesena i neka iskustva iz rada Medicinskog centra u Vukovaru vezana za ozljede nanesene zapaljivim oružjem.Incendiary weapons have been known and used since the ancient China, and their intensive development began during World War I. The new substances, such as napalm and white phosphorus, have physical and chemical properties phosphorus), allow prolonged burning and release of great amounts of heat and toxic gases. They cause severe burns with a high risk of intoxication and circulatory collappse (shock). The particularities of tending the wounded arise, therefore, from the need to prevent and cure such complications. Incendiary weapons, especially when used as tactical weapons cause mass casulties in the civilian population. In this article we present some of the experiences from Medical center Vukovar concerning injuries inflicted by incendiary weapons

Effects of botulinum toxin type A facial injection on monoamines and their metabolites in sensory, limbic and motor brain regions in rats

Despite its toxicity, botulinum neurotoxin type A (BTX-A) is a valuable therapeutic agent for several motor, autonomic and pain disorders. Numerous studies have described its peripheral as well as central effects. Using reversed-phase High Performance Liquid Chromatography with Electrochemical Detection (HPLC-ED) and gradient elution, we quantified the concentrations of dopamine (DA), noradrenaline (NA), serotonin (5-HT) and their metabolites in 10 brain regions, ipsilateral and contralateral from the site of unilateral BTX-A administration (5 U/kg) into the rat whisker pad. In regions associated with nociception and pain processing we also examined possible BTX-A effects in combination with formalin-induced inflammatory orofacial pain. The dominant BTX-A effects on the monoamines and their metabolites were insignificant. The only significant increase caused by BTX-A alone was that of NA in striatum and serotonin in hypothalamus. While antinociceptive effects of BTX-A are most probably not related to central monoamine concentrations, the localized increased NA and 5-HT concentrations might play a role in reported BTX-A efficacy for the treatment of depression

Destruction of medical services in Slavonia and Baranja during the war against Croatia (till the end of 1991)

U tijeku rata protiv Republike Hrvatske na području Slavonije i Baranje posebno su stradale zdravstvene ustanove. Praktično su porušeni medicinski centri i bolnice u Vukovaru, Vinkovcima, Pakracu i Novoj Gradišci te lječilišta u Lipiku i Daruvaru, dok su Opća bolnica u Osijeku i Dom zdravlja u Daruvaru teško oštećeni tako da je linija agresije na Hrvatsku zacrtana upravo oštećenim i uništenim zdravstvenim ustanovama. Pri tim napadima na bolnice Istočne Hrvatske poginula su četiri zdravstvena djelatnika, 12 ih je ranjeno, a sudbina 2 liječnika je nepoznata. Poginulo je i pet bolesnika. Ukupna materijalna šteta na navedenim objektima iznosi oko 360 milijuna DEM. Dok je to god bilo moguće, do zauzimanja pojedinih ustanova od strane agresora, te su ustanove radile. Najvećim dijelom u podrumima i skloništima ošte­ ćenih i razorenih civilnih bolnica, često pod udarima neprijateljske artiljerije i zrakoplovstva, do kraja 1991. liječeno je oko 7 000 ranjenika, medju njima i oko 50 pripadnika federalne armije. Sve zdravstvene ustanove bile su propisno obilježene oznakama Crvenoga križa. Sam njihov broj i činjenica da su pojedine ustanove (npr. Opća bolnica Osijek) gađane iz neposredne blizine, daje korišteno precizno artiljerijsko i avionsko oružje, te da su pojedine bolnice gadjane prije drugih, vojno značajnijih objekata, ukazuje na to da u ratu protiv Hrvatske neregularne srpske trupe ali i federalna armija namjerno razaraju zdravstvene ustanove koje su zaštićene brojnim međunarodnim humanitarnim konvencijama.During the war against Croatia health services in the Slavonia and Baranya region suffered the greatest damage. Medical centers and hospitals in Vukovar, Vinkovci, Pakrac and Nova Gradiška and the rehabilitation centers in Lipik and Daruvar were practically levelled to the ground; the General Hospital in Osijek and the Health Centre in Daruvar were both heavily demaged. The line of aggression against Croatia can be precisely recognised by the damaged and demolished hospitals. Casualties of enemy attacks on hospitals in Estern Slavonia among the medical staff are: 4 killed, 12 injured, two doctors missing; 5 patients were killed too. Total damage is estimated at 360 mill. DEM. Hospitals were working as long as it was possible, until the very moment of ocuppation. Till the end of 1991 about 7000 wounded (among them 50 YFA soldiers) were treated in the damaged and demolished hospital basements and shelters, often under permenent enemy artillery and aircraft attacks. All health services were properly marked by the Red Cross sign. Their number itself, the fact that some hospitals (General Hospital in Osijek, for instance) were attached from thir very neighbourhood; the use of precise artillery and aircraft weapons; attaching civilian hospitals rather than millitary targets - all this proves that in the war against Croatia irregular Serbian troops, even the Federal Army, deliberatly destroyed hospitals in spite of the protection provided by a series of international humanitarian conventions

Central Action of Peripherally Applied Botulinum Toxin Type A on Pain and Dural Protein Extravasation in Rat Model of Trigeminal Neuropathy

BACKGROUND: Infraorbital nerve constriction (IoNC) is an experimental model of trigeminal neuropathy. We investigated if IoNC is accompanied by dural extravasation and if botulinum toxin type A (BoNT/A) can reduce pain and dural extravasation in this model. ----- METHODOLOGY/PRINCIPAL FINDINGS: Rats which developed mechanical allodynia 14 days after the IoNC were injected with BoNT/A (3.5 U/kg) into vibrissal pad. Allodynia was tested by von Frey filaments and dural extravasation was measured as colorimetric absorbance of Evans blue - plasma protein complexes. Presence of dural extravasation was also examined in orofacial formalin-induced pain. Unilateral IoNC, as well as formalin injection, produced bilateral dural extravasation. Single unilateral BoNT/A injection bilaterally reduced IoNC induced dural extravasation, as well as allodynia (lasting more than 2 weeks). Similarly, BoNT/A reduced formalin-induced pain and dural extravasation. Effects of BoNT/A on pain and dural extravasation in IoNC model were dependent on axonal transport through sensory neurons, as evidenced by colchicine injections (5 mM, 2 µl) into the trigeminal ganglion completely preventing BoNT/A effects. ----- CONCLUSIONS/SIGNIFICANCE: Two different types of pain, IoNC and formalin, are accompanied by dural extravasation. The lasting effect of a unilateral injection of BoNT/A in experimental animals suggests that BoNT/A might have a long-term beneficial effect in craniofacial pain associated with dural neurogenic inflammation. Bilateral effects of BoNT/A and dependence on retrograde axonal transport suggest a central site of its action