A case of eccrine carcinoma of the interdigital foot glands in a 39-yr-old female Asian elephant (Elephas maximus) from Zagreb Zoo is described. The tumor between the toenails of the right forefoot ...was surgically removed 3 yr before postmortem examination (2003), and the histopathologic diagnosis was compound eccrine carcinoma characterized with glandular tubular and papillary proliferations, mild cellular pleomorphism, proliferation of the myoepithelial cells with mucoid secretions, and necrosis. Immunohistochemistry revealed strong immunoreactivity to S-100 protein, estrogen, and high–molecular weight cytokeratin. This elephant also had chronic renal fibrosis with uremia.
HOHSTETER, M., I.-C. SOSTARI C -ZUCKERMANN, S. RELJIC, L. MEDVEN ZAGRADISNIK, B. ARTUKOVIC, Z. GRABAREVIC, J. KUSAK, D. HUBER, A. GUDAN KURILJ: Intestinal adenocarcinoma in a European brown bear ...(Ursus arctos) - a case report. Vet. arhiv 88, 569-579, 2018. This article presents the first case of intestinal adenocarcinoma in a free living, culled 12 year old, European female brown bear (Ursus arctos), with its characteristic macropathological and histopathological manifestations. Necropsy revealed thoracic gunshot injuries (compassionate shot) and the poor physical condition of the animal, with body fat loss and musculature atrophy. An infiltrative mass protruded the jejunal wall with infiltration of the mesentery, visceral and parietal peritoneum, and distal parts of the colon and rectum. The histopathological examination presented an infiltrative, unencapsulated, moderately cellular neoplastic mass, composed of an epithelial cell population, forming irregular nests, papillary and ribbon like structures and small number of tubules, surrounded by an extensive desmoplastic reaction. Within the tumor a small number of cysts filled with mucin were noted. The epithelial neoplastic cells exhibited mild anisocytosis and anisokaryosis, and a low mitotic index. Histochemical Van Gieson staining showed strong positivity in the desmoplastic proliferation. The epithelial tumor cells were positively imunostained with cytokerain, and stromal cells with vimentin. The histological features presented are characteristic of intestinal adenocarcinomas, of the mixed tubular and mucinous type, with a prominent scirrous reaction. Key words: intestinal adenocarcinoma; European brown bear (Ursus arctos); macropathology; histopathology; immunohistochemistry
The objectives of this study were to investigate whether or not the synthetic compounds, levamisole (LEVA) and polyoxyethylene-polyoxypropylene (POE-POP) copolymers, well-known to act as ...immunomodulators (IMs) in swine, may positively influence the cellular and humoral immune parameters of weaned pigs, without negatively affecting their hematological (HE), serum biochemistry (SB) and gut histocytological (HC) homeostasis. The pigs from a commercial swine farm were weaned at 26 days of age, randomly divided into 3 groups comprising 20 animals each, and kept in separate pens within the same rearing facility. At the age of 28 days (Day 0 of the experiment), the pigs were treated as follows: (1) control pigs perorally (p.o.) received 10 mL of saline, and the principals were p.o. treated with a single dose of 10 mL of either: (2) LEVA with 2.5 mg/kg body weight of the anthelmintic drug or (3) POE-POP with 2.5 mg/mL of the copolymer preparation. The experiment was conducted over 35 days, and 7 pigs per group were sampled for peripheral blood at 7 day intervals, starting at Day 0 before the treatments for immunohematology and SB analyses. At either Day 0 or Day 35 of the experiment 5 pigs per group were euthanatized and sampled for gut HC. The POE-POP-treated pigs had increased proportions of lymphocytes (P < 0.05) at Day 35. These pigs had higher levels of total serum immunoglobulins (P < 0.05) at Day 14. The LEVA-treated pigs had decreased proportions of lymphocytes (P < 0.05) at Day 14, although their total leukocyte count was similar to that recorded in the controls. None of the tested IMs affected the values of HE parameters, indicating that they did not cause any harmful side effects during the observation period of 5 weeks following the treatments. Minor oscillations in SB parameters were observed, but their values were within the normal range for swine and in accordance with the ages of the pigs. The HC features of gut mucosa in the pigs from the principal groups showed very mild damage and were quite normal for farm pigs exposed to natural infections, indicating that the tested IMs did not induce any additional HC changes. The obtained results imply that immunomodulating treatment with tested IMs was not associated with any adverse effects on the monitored HE, SB and gut HC parameters, and thus, does not suggest any putative impairment in the general health status of weaned pigs throughout the experimental period. Key words: immunemodulation, levamisole, copolymers polyoxyethylene-polyoxypropylene, hematology, serum biochemistry, gut histocytology, homeostasis, pigs Ciljevi ovoga rada bili su istraziti mogu li, ili ne, sinteticki spojevi levamisol (LEVA) i polioksietilenskipolioksipropilenski (POE-POP) kopolimeri, dobro znani da djeluju kao imunomodulatori (IM) u svinje, pozitivno utjecati na stanicne i humoralne imunosne pokazatelje odbijene prasadi a da negativno ne djeluju na njihovu hematolosku (HE), serumsku biokemijsku (SB) i crijevnu histocitolosku (HC) homeostazu. Na komercijalnoj svinjogojskoj farmi prasad je bila odbijena u dobi od 26 dana, nasumicno podijeljena u tri skupine od po 20 zivotinja u svakoj, te drzana u odvojenim odjeljcima u istoj uzgojnoj nastambi. U dobi od 28 dana (= 0. dan pokusa), prasad je tretirana kako slijedi: (1) kontrolna prasad je per os (p.o.) primila 10 mL fizioloske otopine, a pokusna je prasad bila p.o. tretirana jednokratnom dozom od 10 mL ili (2) LEVA s 2,5 mg/kg tjelesne tezine antihelmintickog lijeka, ili POE-POP sa 2,5 mg/mL kopolimerskog pripravka. Pokus je proveden tijekom 35 dana, a od 7 prasadi po skupini uzimani su uzorci periferne krvi za imunohematoloske i SB pretrage u razmacima od 7 dana pocevsi od 0. dana prije tretmana. Po pet prasadi iz svake skupine bilo je eutanazirano 0. i 35. dana pokusa radi uzimanja uzoraka za crijevnu HC. Prasad koja je primila POE-POP imala je veci udjel limfocita (P < 0,05) 35. dana. Ta je prasad imala visu razinu ukupnih serumskih imunoglobulina (P < 0,05) 14. dana. Prasad tretirana s LEVA imala je smanjen udjel limfocita (P < 0,05) 14. dana, premda je ukupan broj njihovih leukocita bio slican onom zabiljezenom u kontrolne prasadi. Niti jedan od testiranih IM nije utjecao na vrijednosti HE pokazatelje, upucujuci na to da nisu uzrokovali nikakve stetne popratne ucinke tijekom razdoblja pracenja pokusa od pet tjedana nakon tretmana. Utvrdene su manje oscilacije pokazatelja SB, ali su te vrijednosti bile u rasponu normalnih vrijednosti za svinju i primjerene dobi prasadi. HC nalazi u sluznici crijeva prasadi pokusnih skupina pokazivali su vrlo blaga ostecenja i bili su gotovo normalni za farmsku prasad koja je izlozena prirodnim infekcijama te upucuju na to da testirani IM nisu izazivali nikakve dodatne HC promjene. Dobiveni rezultati podrazumijevaju da imunomodulacijski tretman s testiranim IM nije bio povezan s bilo kakvim nepovoljnim ucincima na HE, SB i crijevne HC pokazatelje. Kljucne rijeci: imunomodulacija, levamisol, kopolimeri POE-POP, hematologija, serum, biokemijski pokazatelji, histocitoloski nalaz, homeostaza, prasad
The known effects of a novel stomach pentadecapeptide BPC157 (10 microg or 10 ng/kg), namely its salutary activity against ethanol (96%, i.g.)-induced gastric lesions (simultaneously applied i.p.) ...and in blood pressure maintenance (given i.v.), were investigated in rats challenged with a combination of N(G)-nitro-L-arginine methylester (L-NAME) (5 mg/kg i.v.), a competitive inhibitor of endothelium nitric oxide (NO)-generation and NO precursor, L-arginine (200 mg/kg i.v.) (D-arginine was ineffective). In the gastric lesions assay, NO agents were given 5 min before ethanol injury and BPC 157 medication. Given alone, BPC157 had an antiulcer effect, as did L-arginine, but L-NAME had no effect. L-NAME completely abolished the effect of L-arginine, whereas it only attenuated the effect of BPC 157. After application of the combination of L-NAME + L-arginine, the BPC157 effect was additionally impaired. In blood pressure studies, compared with L-arginine, pentadecapeptide BPC 157 (without effect on basal normal values) had both a mimicking effect (impaired L-NAME-blood pressure increase, when applied prophylactically and decreased already raised L-NAME values, given at the time of the maximal L-NAME-blood pressure increase (i.e., 10 min after L-NAME)) and preventive activity (L-arginine-induced moderate blood pressure decrease was prevented by BPC 157 pretreatment). When BPC 157 was given 10 min after L-NAME + L-arginine combination, which still led to a blood pressure increase, its previously clear effect (noted in L-NAME treated rats) disappeared. In vitro, in gastric mucosa from rat stomach tissue homogenates, BPC 157, given in the same dose (100 microM) as L-arginine, induced a comparable generation of NO. But, BPC 157 effect could not be inhibited by L-NAME, even when L-NAME was given in a tenfold (100 versus 1000 microM) higher dose than that needed for inhibition of the L-arginine effect. NO synthesis was blunted when the pentadecapeptide BPC 157 and L-arginine were combined. In summary, BPC 157 could interfere with the effects of NO on both gastric mucosal integrity and blood pressure maintenance in a specific way, especially with L-arginine, having a more prominent and/or particularly different effect from that of NO.
Adaptive cytoprotection in the stomach was originally defined by applying the exogenous irritants only. The contribution of endogenous irritants as inductors of initial lesions was not specially ...evaluated. No attempt was made to either focus antiulcer agent activity on adaptive cytoprotection, or split their `cytoprotection' into complex adaptive cytoprotective activity and simple cytoprotective effects. Agents had so far not been applied simultaneously with the second challenge with ethanol (or irritant), when differences between cytoprotection and adaptive cytoprotection appear. Gastrojejunal anastomosis for 24 h in rats was introduced as new model for analyzing cytoprotection/adaptive cytoprotection. The contribution of the up-normal level of endogenous irritants and the endogenous small irritant-induced minor lesions during the adaptive cytoprotection were studied. The effect of late challenge with 96% ethanol in the presence of an up-normal level of endogenous irritants and endogenous small irritant-induced minor lesions was compared with results of classic studies of ethanol-induced gastric lesions in normal rats (1 ml/rat i.g.). Antiulcer agents or a prostaglandins-synthesis inhibitor, indomethacin, given once only in classic studies, were given at several points during injury induction: (i) surgery, (ii) mild ethanol, (iii) strong ethanol, (iv) strong ethanol applied after a suitable period following either mild ethanol or surgery). Their effects were compared in rats treated as follows: exogenous irritant studies (96% or 20% ethanol), exogenous/exogenous irritant studies (20% ethanol 1 h before 96% ethanol), endogenous irritant studies (gastrojejunal anastomosis for 24 h), and endogenous/exogenous irritant studies (gastrojejunal anastomosis for 24 h before 96% ethanol). Characteristic of the various irritants differed: the (preceding) small irritants (exogenous (i.e., mild ethanol in healthy intact rats) (exogenous irritant studies) vs. endogenous (e.g., (increased) gastric acid secretion, duodenal reflux in gastric content in rats with termino-lateral gastrojejunal anastomosis) (endogenous irritant studies)). These factors caused modifications of agents' activities not, as initially thought, giving simple `cytoprotection', but being only cytoprotective, or adaptive cytoprotective, or both cytoprotective and adaptive cytoprotective. Atropine (10 mg/kg i.p.) and ranitidine (10 mg) had only cytoprotective activity (exogenous irritant-studies), whereas pentadecapeptide BPC157 (10 μg or 10 ng), and omeprazole (10 mg) had mainly adaptive cytoprotective activity (endogenous/exogenous irritant studies) or both cytoprotective and adaptive cytoprotective activities (exogenous/exogenous irritant studies). Augmentation of the lesions by indomethacin (5 mg/kg s.c.), showed that only events preceding the late challenge with ethanol may be prostaglandin-dependent in both models. The second, adaptive cytoprotective part, seen after late ethanol challenge, may be either prostaglandin-dependent (exogenous/exogenous irritant studies) or non-dependent (endogenous/exogenous irritant studies). Both spontaneous lesion reduction, as an essential mechanism of adaptive cytoprotection, and the further lesion reduction by agents, such as pentadecapeptide BPC 157 and omeprazole, suggests that these agents function as an essential link between the various reactions in cytoprotection/adaptive cytoprotection.
Tuberculosis due to Mycobacterium africanum was diagnosed in an adult female hyrax (Procavia capensis). Pathologic examination revealed disseminated tuberculous lesions. The same pathologic changes ...were also found in a male hyrax that died a year later. Both animals were imported from the United Arab Emirates and were held in captivity at the Zagreb Zoo in Croatia. The source of infection remains unknown. The acid-fast bacteria isolated from the lungs of the female hyrax were identifyed by polymerase chain reaction as Mycobacterium tuberculosis complex and Geno Type® MTBC test confirmed the strain to be M. africanum I.
The known effects of a novel stomach pentadecapeptide BPC157 (10 μg or 10 ng/kg), namely its salutary activity against ethanol (96%, i.g.)-induced gastric lesions (simultaneously applied i.p.) and in ...blood pressure maintenance (given i.v.), were investigated in rats challenged with a combination of
N
G-nitro-
l-arginine methylester (
l-NAME) (5 mg/kg i.v.), a competitive inhibitor of endothelium nitric oxide (NO)-generation and NO precursor,
l-arginine (200 mg/kg i.v.) (
d-arginine was ineffective). In the gastric lesions assay, NO agents were given 5 min before ethanol injury and BPC 157 medication. Given alone, BPC157 had an antiulcer effect, as did
l-arginine, but
l-NAME had no effect.
l-NAME completely abolished the effect of
l-arginine, whereas it only attenuated the effect of BPC 157. After application of the combination of
l-NAME+
l-arginine, the BPC157 effect was additionally impaired. In blood pressure studies, compared with
l-arginine, pentadecapeptide BPC 157 (without effect on basal normal values) had both a mimicking effect (impaired
l-NAME-blood pressure increase, when applied prophylactically and decreased already raised
l-NAME values, given at the time of the maximal
l-NAME-blood pressure increase (i.e., 10 min after
l-NAME)) and preventive activity (
l-arginine-induced moderate blood pressure decrease was prevented by BPC 157 pretreatment). When BPC 157 was given 10 min after
l-NAME+
l-arginine combination, which still led to a blood pressure increase, its previously clear effect (noted in
l-NAME treated rats) disappeared. In vitro, in gastric mucosa from rat stomach tissue homogenates, BPC 157, given in the same dose (100 μM) as
l-arginine, induced a comparable generation of NO. But, BPC 157 effect could not be inhibited by
l-NAME, even when
l-NAME was given in a tenfold (100 versus 1000 μM) higher dose than that needed for inhibition of the
l-arginine effect. NO synthesis was blunted when the pentadecapeptide BPC 157 and
l-arginine were combined. In summary, BPC 157 could interfere with the effects of NO on both gastric mucosal integrity and blood pressure maintenance in a specific way, especially with
l-arginine, having a more prominent and/or particularly different effect from that of NO.
A novel gastric pentadecapeptide, BPC 157, has been shown to attenuate different lesions (i.e., gastrointestinal tract, liver, pancreas, somatosensory neurons). This suggests an interaction with the ...dopamine system. When used alone, BPC 157 does not affect gross behavior or induce stereotypy.
We first investigated the effect of pentadecapeptide BPC 157 on stereotypy and acoustic startle response in rats, given as either a prophylactic (10 μg/kg IP) or therapeutic (10 ng/kg IP) regimen, with the dopamine indirect agonist amphetamine (10 mg/kg IP).
There was a marked attenuation of stereotypic behavior and acoustic startle response. When the medication was given at the time of maximum amphetamine-induced excitability, there was a reversal of this behavior. A further focus was on the effect of this pentadecapeptide on increased climbing behavior in mice pretreated with the dopamine antagonist haloperidol (5.0 mg/kg IP), and subsequently treated with amphetamine (20 mg/kg IP challenge 1, 2, 4, and 10 days after haloperidol pretreatment). This protocol is usually used for the study of behavioral supersensitivity to the amphetamine stimulating effect.
An almost complete reversal was noted when pentadecapeptide was coadministered with haloperidol. Together, these data provide compelling evidence for the interaction of pentadecapeptide BPC 157 with the dopamine system.
Canine distemper is a contagious, potentially lethal disease of mainly domestic and wild canids, but also of many other mammalian species including large felids. In February 2004, two Siberian tiger ...(
Panthera tigris altaica
) cubs at the age of six months died at the Zagreb ZOO. The animals were presented for necropsy with two days history of severe digestive disorders, characterized mainly by haemathemesis. Dissections revealed catarrhal to pseudomembranous gastroenteritis (depending on the animal) accompanied with haemorrhagic oedema of the lungs. Necrotic tonsillitis and disseminated depletion of the lymphocytes were the most prominent histological findings in both examined animals, while intranuclear and intracytoplasmatic inclusion bodies were found in the samples of the tongues and intestines. Representative portions of the livers, intestines, tonsils and lymph nodes were submitted for bacteriological and mycological analysis. The presence of
Clostridium
spp.,
Campylobacter coli
and
Escherichia coli
was detected in gut samples, coli-like bacteria were found in samples of liver, tonsils and lymph nodes, while
Candida
sp. was found in the gut and pharynx samples. Toxicological analysis excluded anticoagulant and organophosphorous intoxication as the cause of death. Immunohistochemical analysis was positive for canine distemper virus. Based on all this, epizootiological, clinical and additional findings, canine distemper was recognized as the cause of the observed condition in these animals.
Concerning the important differences in the ethiopathology of hepatocelular carcinomas (HCC) in humans and dogs, our work describes the expression of epidermal growth factor receptor (EGFr), ...cytokeratine 19 (CK19), vascular endothelial growth factor (VEGF) and transforming growth factor beta receptor (TGFbeta-r) in tumors arising in both species. Investigation included 25 cases of human and 8 cases of dog tumors. All human cases were noted in cirrhotic livers, while in dogs the tissue adjacent to tumor was not changed. In humans in two cases hepatitis B virus (HBV) and in one case hepatitis C virus (HCV) were determined. Investigation showed lack of TGFbeta-r reaction in six cases of canine HCC, while in humans only one case was negative. In most tumors specific hepatocyte antigen Hepatocyte Paraffin 1 marker (Hep Par 1) was mainly positive with markedly decreased reaction compared to the normal hepatocytes, while cytokeratine 19 for billiary epithelium was negative. The result of our investigation rise the question about the possible role of tumor suppressor gene TGFbeta-r in the development of HCC in dogs and in the same time emphasizes its importance in human diseases.
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