Pathophysiological mechanisms of animal and plant toxins actions

Povećanje incidencije otrovanja biljnim i životinjskim toksinima tijekom proteklih godina ukazuje na važnost poznavanja otrovnih vrsta na području Republike Hrvatske. Od otrovnih biljnih vrsta u Republici Hrvatskoj raste velebilje, kranjski bijeli bun, duhan, bunovina, crna bunika, bijeli kužnjak, crni kukurijek i jesenski mrazovac. Većina otrovnih biljaka pripada porodici pomoćnica (Solanaceae). To su biljke bogate tropanskim alkaloidima koji djeluju kao antikolinergične tvari. Imaju antagonističko djelovanje na muskarinske acetilkolinske receptore. S obzirom na široku rasprostranjenost navedenih receptora u ljudskom organizmu, pri intoksikaciji tim biljkama dolazi do poremećaja rada srca, inhibicije ili stimulacije lučenja pojedinih žlijezda, kao i poremećaja intestinalnog motiliteta. Jedan je od najpoznatijih učinaka pojava delirija i halucinacija koji nastaju zbog inhibicije muskarinskih acetilkolinskih receptora u mozgu. Opisane su i otrovne gljive, iako one pripadaju zasebnome carstvu. U našem području najvažnije su zelena pupavka i muhara. Ove gljive pripadaju rodu Amanita u kojima nalazimo dvije grupe toksina, falotoksine i amatoksine koji inhibiraju RNA polimerazu II i time onemogućuju sintezu vitalno važnih bjelančevina. Od životinjskih toksina opisani su toksini zmija, paukova i riba. Većina zmija otrovnica u Republici Hrvatskoj pripada porodici Viperidae. Naše su najpoznatije otrovnice poskok i riđovka. Njihov otrov sadrži hijaluronidaze, fosfolipazu A2 i metaloproteinaze. Od paukova opisani su crna udovica i smeđi primorski riječni pauk. Otrov pauka smjesa je monoamina, koji djeluju proalgetski, peptida s ekscitatornim učincima koji izazivaju nociceptivni odgovor. Završni dio osvrće se na ribe otrovnice, škrpinu i morskog pauka.The increasing incidence of plant and animal toxins poisoning during recent years has shown the importance of knowing poisonous species in the territory of the Republic of Croatia. In the Republic of Croatia, one can find belladonna or deadly nightshade (Atropa belladonna), European scopolia or henbane bell (Scopolia carniolica), nicotiana (Nicotiana alata), mandrake (Mandragora officinarum), jimson weed (Datura stramonium), Christmas rose or black hellebore, (Helleborus niger) and autumn crocus or meadow saffron (Colchicum autumnale) as poisonous plant species. The majority of dangerous plants are a part of the family of nightshades (Solanaceae). They are rich in tropane alkaloids, which serve as anticholinergic substances. They have an antagonistic effect on the muscarinic acetylcholine receptors. Considering the fact that the muscarinic acetylcholine receptors are widespread in the human body, during the intoxication with these plants the following symptoms occur: disturbance in the heart rate and rhythm, inhibition or stimulation of secretion of glands and disorders of intestinal motility. One of the most well-known effects is the occurrence of delirium and hallucinations due to the inhibition of the muscarinic acetylcholine receptors in the brain. Poisonous mushrooms are described as well. In Croatia, the most significant ones are death cap (Amanita phalloides) and fly agaric (Amanita muscaria). They belong to the Amanita genus, in which we can find two different toxin groups: phallotoxins and amatoxins, which inhibit RNA polymerase II and thus disable the synthesis of vitally important proteins. From animal toxins, snake, spider and fish toxins have been described. In the Republic of Croatia, the majority of venomous snakes belong to the Viperidae family. Our best known poisonous snakes are the horned viper (Vipera ammodytes) and the common European adder (Vipera berus). Their venom contains hyaluronidases, phospholipase A2, and metalloproteinases. Among the spiders, the black widow and the brown coastal river spider are described. Spider venom is a mixture of monoamines, with aproalgesic effect, peptides with excitatory effects that cause a nociceptive response. Our most famous poisonous fish are the scorpionfish (Scorpanea scrofa) and the greater weever (Trachinus draco)

Expression Profiles of Metallothionein I/II and Megalin in Cuprizone Model of De- and Remyelination

Abstract—Copper chelator cuprizone (CPZ) is neurotoxicant, which selectively disrupts oligodendroglial respiratory chain, leading to oxidative stress and subsequent apoptosis. Demyelination is, however, followed by spontaneous remyelination owing to the activation of intrinsic CNS repair mechanisms. To explore the participation of metallothioneins (MTs) in these processes, in this study we analyzed the expression profiles of MT-I/II and their receptor megalin (low-density lipoprotein receptor related protein-2) in the brain of mice subjected to different protocols of CPZ feeding. Experiments were performed in female C57BL/6 mice fed with 0.25% CPZ during 1, 3 and 5 weeks. They were sacrificed immediately after feeding with CPZ or 2 weeks after the withdrawal of CPZ. The data showed that CPZ-induced demyelination was followed by high astrogliosis and enhanced expression of MTs and megalin in white (corpus callosum and internal capsule) and gray matter of the brain (cortex, hippocampus, and cerebellum). Moreover, in numerous cortical neurons and progenitor cells the signs of MT/megalin interactions and Akt1 phosphorylation was found supporting the hypothesis that MTs secreted from the astrocytes might directly affect the neuronal differentiation and survival. Furthermore, in mice treated with CPZ for 5 weeks the prominent MTs and megalin immunoreactivities were found on several neural stem cells and oligodendrocyte progenitors in subgranular zone of dentate gyrus and subventricular zone of lateral ventricles pointing to high modulatory effect of MTs on adult neuro- and oligodendrogenesis. The data show that MT I/II perform important cytoprotective and growth-regulating functions in remyelinating processes activated after toxic demyelinating insults

Prevalence of Metabolic Syndrome among Patients with Major Depressive Disorder – Differences Between Newly Diagnosed First Episode and Recurrent Disease

The objective of the present study was to assess differences in prevalence of the metabolic syndrome among depressed patients in regard to the duration of the illness (first episode versus recurrent episodes). A total of 190 patients suffering from major depressive disorder were included in the study, diagnosed according to International classification of disor- ders, 10th revision 1 . The same criteria were used to divide participants into two groups: first episode major depressive disorder and major depressive disorder with recurrent episodes. The metabolic syndrome was defined according to the criteria of the American National Cholesterol Education Program-Treatment Panel III 2 . Results showed that metabolic syndrome is significantly more prevalent in patients with recurrent major depressive disorder (45.2%) compared to pa- tients with first episode of major depressive disorder (27.3%), mainly due to differences in plasma glucose, triglycerides and HDL-cholesterol levels. These findings indicate the importance of the duration of depression and the number of re- curring episodes as factors involved in etiopathogenesis of the associated metabolic syndrome

Expression of metallothioneins in placental and fetal tissues in undisturbed and PGM-Zn treated syngeneic pregnancy

Metallothioneins (MTs) are cysteine-rich proteins, which have been implicated in regulation of physiological processes, such as cell growth, repair, differentiation, apoptosis and immunoregulation, as well as in the protection against heavy metals, oxidant damages, inflammation and other stressful conditions. To investigate their roles in physiological and detoxification processes at the maternal-fetal interface and in fetal organogenesis we examined the tissue expression of MT I/II isoforms in undisturbed syngeneic pregnancy and after the treatment with peptidoglycan monomer linked with zinc (PGM-Zn). The data showed that in undisturbed pregnancy the MTs were highly expressed at junctional zone of placenta, on endovascular trophoblast giant cells, glycogen cells and spongiotrophoblast cells, as well as on villous trophoblast cells. In the fetus they were found predominantly in the liver and in epithelial tissues, such as intestine, pancreas and kidney. Treatment with PGM-Zn markedly enhanced the intensity of MT staining both at the maternal-fetal interface and in fetal organs. The data imply that MTs are involved in the protection of trophoblast cells against the pregnancy-induced deregulation of redox and neuro-immuno-endocrine homeostasis, in transport and storage of essential metals required for fetal organogenesis, as well as in the protection of fetus against bacterial toxins

Radiography and ultrasonography of common prostatic diseases in dogs

Rendgenska pretraga prostate temeljna je slikovna dijagnostička metoda koja omogućuje prikaz oblika, veličine, položaja i intenziteta sjene prostate kod pasa. Rendgenografski vidljive promjene često nisu dovoljno specifične. Stoga ultrazvučnom pretragom znatno bolje vizualiziramo i razlikujemo bolesti prostate. Patološke promjene prostate koje diferenciramo uključuju benignu hipertrofiju prostate, ciste, prostatitis, apsces ili neoplazije. U modernoj se praksi rendgenski prikazi prostate vrlo često nadopunjuju ultrazvučnim ili kontrastnim radiografskim pretragama.Radiography is a basic diagnostic imaging procedure that permits presentation of the appearance of the shape, size, position and intensity of prostatic shadows in dogs. X-ray imaging findings are not sufficiently specific for certain diagnosis. Ultrasonography has considerably improved the visibility of prostatic diseases. It has made it possible to show the inner structure of the prostatic gland using a simple and non-invasive approach. Diagnoses which should be differentiated during diagnostic imaging include: benign prostatic hyperplasia, cyst, prostatitis, abscess or neoplasia. In practice, x-ray imaging is supplementary to ultrasonography and contrast media imaging. The purpose of the diagnostics is to show the changes clearly and to make a correct diagnosis for the sake of proper treatment

Osteopontin–metallothionein I/II interactions in experimental autoimmunune encephalomyelitis

Osteopontin (OPN), an extracellular matrix (ECM) glyco-phosphoprotein, plays an important role in autoimmune-mediated demyelinating diseases, including multiple sclerosis and experimental autoimmune encephalomyelitis (EAE). As an integrin and CD44 binding protein it participates in bidirectional communication between the ECM and target cells and affects transduction pathways that maintain neuronal and immune cell homeostasis. Its biological activity is also heavily influenced by microenvironment, which stimulates the cleavage of OPN and changes its functions. In this study we estimated the expression profile of OPN in neural tissues of DA rats during the first relapse of chronic relapsing EAE and investigated the relationship of OPN to metallothionein I+II (MTs), which play pivotal role in zinc-related cell homeostasis and in protection of CNS against cytokine-induced injury. The data showed that in EAE rats OPN mRNA and protein levels increased concurrently with the transcription of MTs and that within the spinal cord (SC) lysates EAE-afflicted rats had a higher content of OPN fragments of low molecular weight than untreated and CFA-treated rats. The expression of OPN and MTs was upregulated on ependymal, lymphoid and astroglial cells and on multiple αvβ3+ neurons in SC and in the brain (cortex, white matter, hippocampus, and cerebellum). Besides, multiple cells co-expressed OPN and MTs. Granular OPN signals were detected in secretory vesicles of Golgy (αvβ3 neurons) and in patches adjacent to the plasma membrane (subventricular zone). The findings imply that in demyelinating lesions are generated proteolytic OPN fragments and that OPN/MT interactions contribute to tissue remodeling during an autoimmune attac

Hepatic Expression of Metallothionein I/II, Glycoprotein 96, IL-6, and TGF-β in Rat Strains with Different Susceptibilities to Experimental Autoimmune Encephalomyelitis

In a search of peripheral factors that could be responsible for the discrepancy in susceptibility to EAE in Albino Oxford (AO) and Dark Agouti (DA) rats, we estimated the expression of metallothioneins I/II (MT), heat shock protein-gp96, interleukin (IL)- 6, and transforming growth factor (TGF)- in the livers of these animals. Rats were immunized with bovine brain homogenate (BBH) emulsified in complete Freund adjuvant (CFA) or only with CFA. Western blot and immunohistochemical analyses were done on day 12 after the immunization, as well as in intact rats.The data have shown that during the first attack of EAE only the EAE prone-DA rats markedly upregulated the hepatic MTs, gp96, IL-6, and TGF-. In contrast, AO rats had a significantly higher expression of MT I/II, IL-6, and TGF- in intact liver ( < 0, 001), suggesting that the greater constitutive expression of these proteins contributed to the resistance of EAE. Besides, since previously we found that AO rats reacted on immunization by an early upregulation of TGF- on several hepatic structures (vascular endothelium, Kupffer cells, and hepatocytes), the data suggest that the specific hepatic microenvironment might contribute also to the faster recovery of these rats from EAE

Adult neurogenesis – accent on subgranular and subventricular zone in mammals

Donedavno se smatralo da se živčane stanice prestaju dijeliti u ranoj postnatalnoj životnoj dobi, no posljednjih 20 godina mnoga istraživanja na tom polju dokazala su suprotno. Neurogeneza u odraslom mozgu dokazana je u većine sisavaca, uključujući i čovjeka. Proces se u fiziološkim uvjetima spontano odvija pretežno u dvjema germinativnim regijama u mozgu u kojima se nalaze neuralne matične stanice; u subgranularnoj zoni dentatne vijuge hipokampusa te subventrikularnoj zoni lateralnog ventrikula. Neuralne matične stanice u njima imaju veću sposobnost proliferacije i diferencijacije prema novim budućim neuronima, astrocitima i oligodendrocitima u odnosu na neuralne matične stanice drugih područja živčanog sustava. Sposobnost proliferacije i regeneracije koju ove dvije „niše“ posjeduju ima važnu ulogu u prilagodbi mozga na vanjske podražaje tijekom odrastanja i sazrijevanja, što se naziva plastičnošću mozga. Germinativne „niše“ u mozgu su specifičan mikrookoliš u kojem se uskom interakcijom specifičnih proneurogenetskih čimbenika i rezidentnih neuralnih matičnih stanica te krvožilja stvaraju strogo kontrolirani uvjeti koji omogućuju proliferaciju, diferencijaciju, migraciju i sazrijevanje neuroblasta ili glioblastate preživljenje i integraciju novonastalih neurona i glijalnih stanica u postojeće sinaptičke mreže u mozgu. U slučaju narušavanja homeostaze tih i drugih germinativna središta u mozgu, dolazi do pojave raznih psihoneuroloških poremećaja. Boljim razumijevanjem funkcioniranja germinativnih mikrookoliša u mozgu otvaraju se nove mogućnosti u neuronanosti u pravcu manipuliranja adultnom neurogenezom potičući stvaranje neurona de novo te na taj način liječenja spomenutih psihoneuroloških poremećaja.Tillrecently was assumed that neural cells stop dividing in early postnatal period of life, but last two decades large ammount ofresearches on that field proved contrary. There are evidences confirming existance of adult neurogenesis in most mammalian species, including humans.This process occurs spontaneouslyin physiological termsin two germinal brain regionscontaining neural stem cells; in subgranular zone of hippocampal dentate gyrus and subventricular zone of lateral ventricule.Neural stem cells in this germinal regions posses higher proliferative and differential capacity toward new future neurons, astrocytes and oligidendrocytes than neural stem cells from other regions in nervous system. Proliferative and regenerative power of this two niches has important role in brain adjustment to exterior stimuli during life which is called neuroplasticity. Germinal niches in brain are specific microenvironment in which close interaction of specific proneurogenic factors and resident neural stem cells and blood vessels form strictly controled conditions providing neuroblast and glioblast proliferation, differentiation, migration andmaturation and also survival and integration of newly created neuron or glial cell in existing brain sinaptic cirtuits. In case of harming this and other germinal brain centers different psichoneurologic disorders occur. Better understanding of germinal microenvironment function in human brainopens a new possibilities in neuroscience for creating a therapy based on adult neurogenesis manipulation through creating neurons “de novo”

Modulacijsko djelovanje prehrane maslinovim i kukuruznim uljem na sadržaj minerala u submandibularnoj žlijezdi nakon parcijalne hepatektomije

To estimate the role of the submandibular gland (SMG) in liver regeneration, i) the tissue mineral dynamics in SMG after 1/3 partial hepatectomy (pHx) and ii) the influence of olive (OO) and corn-oil (CO) enriched diets on these events were investigated. Different nutrition of BALB/c mice lasted 3 weeks, and the minerals in SMG were determined by microwave digestion and ICP spectrometry. The diet containing CO initially suppressed liver regeneration (after 24 h) and then, similarly to OO, increased liver growth (on day 7). In mice fed standard food, Zn2+ and Ca2+ accumulated in SMG and the concentration of Mg2+ decreased in the early phase of liver regeneration. These changes were, however, significantly less expressed in mice fed CO and OO enriched diets, suggesting that monounsaturated oleic acid (C18:1n-9) and polyunsaturated linoleic acid (C18:2n-6) might interfere with some metal-dependent activities of SMG that participate in the control of liver regeneration