Herniation of the intervertebral disc (IVDH) is the most common cause of neurological and intervertebral disc degeneration-related diseases. Since the disc starts to degenerate before it can be ...observed by currently available diagnostic methods, there is an urgent need for novel diagnostic approaches. To identify molecular networks and pathways which may play important roles in intervertebral disc herniation, as well as to reveal the potential features which could be useful for monitoring disease progression and prognosis, multi-omics profiling, including high-resolution liquid chromatography-mass spectrometry (LC-MS)-based metabolomics and tandem mass tag (TMT)-based proteomics was performed. Cerebrospinal fluid of nine dogs with IVDH and six healthy controls were used for the analyses, and an additional five IVDH samples were used for proteomic data validation. Furthermore, multi-omics data were integrated to decipher a complex interaction between individual omics layers, leading to an improved prediction model. Together with metabolic pathways related to amino acids and lipid metabolism and coagulation cascades, our integromics prediction model identified the key features in IVDH, namely the proteins follistatin Like 1 (FSTL1), secretogranin V (SCG5), nucleobindin 1 (NUCB1), calcitonin re-ceptor-stimulating peptide 2 precursor (CRSP2) and the metabolites N-acetyl-D-glucosamine and adenine, involved in neuropathic pain, myelination, and neurotransmission and inflammatory response, respectively. Their clinical application is to be further investigated. The utilization of a novel integrative interdisciplinary approach may provide new opportunities to apply innovative diagnostic and monitoring methods as well as improve treatment strategies and personalized care for patients with degenerative spinal disorders.
Spike glycoprotein is essential for the reproduction of the SARS-CoV-2 virus, and its inhibition using already approved antiviral drugs may open new avenues for treatment of patients with the ...COVID-19 disease. Because of that we analyzed the inhibition of SARS-CoV-2 spike glycoprotein with FDA-approved antiviral drugs and their double and triple combinations. We used the VINI in silico model of cancer to perform this virtual drug screening, showing HIV drugs to be the most effective. Besides, the combination of cobicistat-abacavir-rilpivirine HIV drugs demonstrated the highest in silico efficacy of inhibiting SARS-CoV-2 spike glycoprotein. Therefore, a clinical trial of cobicistat-abacavir-rilpivirine on a limited number of COVID-19 patients in moderately severe and severe condition is warranted.
Marked lateral ventricular enlargement associated with atrophic cerebral cortex is described in three dogs. In case 1 (Irish terrier) and case 2 (German shepherd), hydranencephaly was diagnosed and ...it was characterized by the complete loss of cerebral hemispheres, leaving only about 2 mm of brain tissue that encircled fluid filled sacs. Clinically, the Irish terrier showed only sleepines and retroflexion of the head during sleeping, while the German shepherd showed no neurological or any other symptoms. In the third case (English setter), internal hydrocephalus was found, probably secondary to the severe periventricular lesions characterized by neutrophilic/ mononuclear cell infiltration. This lesion was diagnosed as hydrocephalus associated with periventricular encephalitis, and this dog showed more severe neurological symptoms, such as: somnolence, opisthotonus, rigor of muscles due to seizures, poor eye-sight, stager, ataxia, and unresponsivness to vocalisation. In all cases, no infectious agent or specific cause was determined. Key words: dog, cavitatory lesions, hydranencephaly, hydrocephalus, periven_ricular encephalitis Vrlo jako prosirenje lateralnih mozdanih klijetki praceno s jakom atrofijom mozdane kore prikazano je kod tri psa. U prvom slucaju (irski terijer) i drugom slucaju (njemacki ovcar) opisana je hidranencefalija karakterizirana potpunim gubitkom mozdanih polutki ostavljajuci samo oko 2 mm mozdanog tkiva sto predstavlja tekucinom ispunjene vrece. Klinicki je irski terijer pokazivao samo pospanost i retrofleksiju glave tijekom spavanja, a njemacki ovcar nije pokazivao neuroloske ni druge znakove bolesti. U trecem slucaju (engleski seter), unutarnji hidrocefalus vjerojatno je bio sekundaran zbog teskog periventrikularnog ostecenja karakteriziranog neutrofilnim/mononuklearnim stanicnim infiltratom. Ta je lezija dijagnosticirana kao hidrocefalus povezan s periventrikularnim encefalitisom, a pas je pokazivao teske neuroloske znakove kao sto su pospanost, opistotonus, grcevi misica, poteskoce s vidom, vrtoglavica, ataksija i nereagiranje na zvucne podrazaje. U sva tri slucaja nije utvrden infekciozni ni drugi specifican uzrok. Kljucne rijeci: pas, kavitatorne lezije, hidranencefalija, hidrocefalus, perivaskularni encefalitis
Cerebrospinalni likvor je bistra tekućina koja svojim sastavom nalikuje krvnoj plazmi; oplahuje cijeli središnji živčani sustav, osigurava njegovu normalnu funkciju i sudjeluje u mehaničkoj zaštiti ...mekih struktura središnjeg živčanog sustava. Osim toga, likvor djeluje kao „čistač“ središnjeg živčanog sustava jer uklanja nusproizvode sinaptičkog metabolizma, ali i štetne tvari. Premda su funkcije likvora brojne, mnoga pitanja o njegovom nastanku, kruženju i nestanku ostaju neodgovorena. Klasična hipoteza o fiziologiji likvora, poznata i kao „Weed–Dandy–Cushing hipoteza“, nastala je pred nešto više od 100 godina i ostaje duboko ukorijenjena u literaturi. Ovaj klasični koncept opisuje stvaranje likvora u koroidnim spletovima moždanih komora i resorpciju u arahnoidnim resicama, dok kruženje likvora opisuje kao jednosmjerno i naziva ga „trećom cirkulacijom“. Međutim, unatrag 30-ak godina, sve se više istraživača protivi klasičnoj teoriji o stvaranju i kruženju likvora i predlažu novu, potpuno drugačiju teoriju fiziologije likvora. Ovaj moderni koncept, u literaturi poznat i kao „Bulat ‒ Orešković ‒ Klarica hipoteza“, sugerira da se likvor stvara i apsorbira u svim dijelovima središnjeg živčanog sustava i giba se pod utjecajem pulzacije krvnih žila, a opisuje stvaranje i apsorpciju likvora kao kontinuirani proces izmjene vode, pri čemu ključnu ulogu imaju hidrostatski i osmotski tlakovi. Premda su potrebna dodatna istraživanja u svrhu utvrđivanja točnosti oba koncepta, vrijeme je da preispitamo klasično učenje da bismo mogli unaprijediti liječenje patoloških stanja u likvorskom sustavu.
Bolest međukralježničnog diska čest je uzrok ozljede leđne moždine i motorne disfunkcije te se najčešće javlja u grudno-slabinskom segmentu kralježnice. Retrospektivnim istraživanjem u razdoblju od ...sedam godina obuhvaćena su 104 slučaja pasa s grudno-slabinskim (GS) sindromom liječenih na Klinici za kirurgiju, ortopediju i oftalmologiju Veterinarskog fakulteta Sveučilišta u Zagrebu. Većina pasa imala je akutnu kliničku sliku s visokim stupnjem neurološkog deficita. Francuski buldog bio je najčešći hondrodistrofični tip pasmine u koje se javljao GS sindrom dok je njemački ovčar bio najbrojniji u nehondrodistrofičnom tipu pasmine. GS sindrom u većem broju javljao se u muških jedinki. Ekstruzija diska u oba tipa pasmine javljala se u području T12-T13 i T13-L1 međukralježničnog prostora. Podatci o oporavku poznati su za 61,53 % pacijenata od čega je 70,44 % pacijenata postiglo zadovoljavajući oporavak. Nad svim pacijentima u provedenom istraživanju kao operacijska tehnika koristila se bilateralna mini hemilaminektomija izvedena od strane istog operatera. U 30 % pacijenata neovisno o nalazu mijelografije, materijal diska uočen je s obje strane međukralježničnog prostora zbog čega je opravdano razmotriti primjenu bilateralne mini-hemilaminektomije kao metodu izbora pri liječenju pasa s GS sindromom. Ovi rezultati će koristiti u budućim istraživanjima GS sindroma te će doprinijeti u njegovoj dijagnostici i liječenju.
Similarly as in other organ structures stem cells are present in cornea residing basal epithelial layer termed palisade of Voight. A growing interest in allografts and xenografts implies a thorough ...study of regenerative potentials of these cells, as well as a clear description of their patterns in in vitro tissue cultures to be grafted. Recently we have developed a simple method for cultivation of porcine corneal epithelial stem cells obtained by biopsy from the limbal region. Eight enucleated eyes were obtained from four slaughtered pigs. 5 mm
2
samples of limbal epithelium were taken by keratotomy method. The primary cultures of these cells showed phenotypic and morphometric characteristics of porcine corneal epithelial cells following May-Grunwald-Giemsa staining. After 5d of sowing they reached 80% of confluence. With the «Night & Day» lenses a total confluence was achieved 5d earlier in comparison to the cells that were grown in the secondary cultures. Accordingly, the use of porcine limbal stem cells has potentials in veterinary medicine (as novel approach in reparative/regenerative medicine of pets, horses and selected breeds), but also are in accordance with the extensive studies on the potential use of xenografts, mainly swine tissues/organs, in humans.
Akutni idiopatski poliradikuloneuritis (AIP) je stečena periferna neuropatija koja primarno zahvaća ventralne korijene spinalnih
živaca i periferne živce. Bolest je vrlo slična Guillain-Barré ...sindromu u ljudi, a nema dobne, pasminske ni spolne predispozicije te ne postoji specifična terapija. Oporavak traje 2 - 6 mjeseci. Fizikalna terapija i njega pacijenata preporučuju se kao potporna terapija. Dva psa, križane pasmine u dobi od šest i deset godina zaprimljeni su sa znacima akutne flakcidne tetrapareze/tetraplegije, u bočnom položaju bez mogućnosti da samostalno zauzmu sternalni položaj posljedično
generaliziranoj zahvaćenosti nižih motoričkih neurona. Na svim ekstremitetima mišićni tonus je bio veoma slab. Dijagnoza AIP-a je
bazirana na anamnezi, kliničkoj manifestaciji, neurološkom pregledu, slikovnoj dijagnostici i laboratorijskim testovima. Rehabilitacijski
program je uključivao masažu ekstremiteta i pasivne kretnje zglobova kao važan dio kućnog programa, elektroterapiju, idroterapiju i proprioceptivne vježbe. Nakon dva tjedna fizikalne terapije psi su se mogli samostalno podignuti u sternalni položaj, a na stražnjim nogama pokazivali su i voljne pokrete. Potpomognuto stajanje i voljni pokreti svih ekstemiteta bili su prisutni na kraju trećeg tjedna u jednog psa i krajem petog tjedna u drugog psa. Nakon toga u proces rehabilitacije uključena je hidroterapija. Jedan pas je mogao samostalno hodati dvadeset petog dana od početka fizikalne terapije, dok je drugom psu bilo potrebno pedeset dana. Fizikalna terapija u kombinaciji s adekvatnim kućnim rehabilitacijskim programom može rezultirati skraćenim razdobljem oporavka za pacijente s AIP-om.
Fotofobija, kao posljedica perzistentne midrijaze, može biti znak disfunkcije parasimpatičke inervacije oka ili primarne lezije šarenice. U ovom prikazu opisuje se slučaj petogodišnjeg psa mješanca ...koji je zaprimljen zbog perzistentne bilateralne midrijaze, abnormalnog pupilarnog refleksa i fotofobije. Kliničkim i oftalmološkim pregledom nisu utvrđene nikakve abnormalnosti osim neresponsivne midrijaze i fotofobije. Na temelju navedenog dijagnosticirana je idiopatska midrijaza s očuvanim vidom.
Interleukin-1 (IL-1) is the most important cytokine in the inflammation cascade activation in all tissues and is present in acute and chronic phases of inflammation. By blocking IL-1 binding to ...target cells, numerous inflammation processes are prevented. The use of autologous conditioned serum rich with IL-1 receptor antagonist protein (IL-1Ra) is a novel treatment method of tendon inflammation in domestic animals and humans. Injections of autologous conditioned serum (ACS) have demonstrated clinical efficacy and safety in animal models and humans in the treatment of osteoarthritis, disc prolapse and muscles and tendons injuries with low side effect. Neutropaenia, reduced white blood cell count, and infections or local irritations are described as side effects of IL-1 antagonist use in humans. Therefore, a study of blood changes in rabbits after local administration of IL-1Ra in the Achilles tendon tissue after iatrogenic inflammation was conducted. Interleukin-1 receptor antagonist protein was used to prevent and reduce tendon inflammation after longitudinal tenotomy. The study was done on 26 white Californian rabbits, divided into two equal groups consisting of 13 animals each; the experimental interleukin-1 receptor antagonist protein (irap) group, and the control group. In the irap group, autologous serum rich with IL-1Ra was used (Orthokine
®
vet irap, Alfa-Arthro, Croatia). Differences between two groups were considered significant as changes in the blood for certain blood elements at
P
< 0.01. The
P
value was
P
= 0.0153 for the white blood cells,
P
= 0.00153 for neutrophils,
P
= 0.00017 and for platelets. In the control group, an increased platelet count was noticed in 70% of blood samples and a decreased neutrophil count was found in all of the irap group samples at the end of the study in comparison to the initial blood count prior to application.
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