Veterinary medicine - Repository of PHD, master's thesis
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Thyroid dysfunctions after COVID-19 infection
Glavna funkcija štitnjače proizvodnja je prohormona tetrajoditironina (T4) te aktivnog hormona trijodtironina (T3). T3 u ljudskom organizmu kontrolira bazalni metabolizam, s učincima na centralni živčani, kardiovaskularni, respiratorni, muskuloskeletni te konačno i imunološki sustav. Hormoni štitnjače T3 i T4 na staničnoj razini poznati su po raznolikim učincima na funkciju stanica, uključujući regulaciju njihove proliferacije, obnavljanje tkiva, apoptozu i angiogenezu.
COVID-19 infekcija ima izrazito širok raspon manifestacija. Osim respiratornih, gastrointestinalnih te kardiovaskularnih učinaka, otkrivene su i razne endokrine komplikacije infekcije SARS-CoV-2, uključujući poremećaje funkcije štitnjače. Jedna od ključnih značajki COVID-19 je upala. Pojam koji se često koristi u opisivanju te upale je „citokinska oluja“, odnosno preburna imunološka reakcija tijela citokinima, koja doprinosi nekim od ozbiljnijih patohistoloških i kliničkih značajki povezanih s njom, poput akutnog respiratornog sindroma (ARS), višestrukog zatajenja organa i autoimunih bolesti.
Uzročnik COVID-19 infekcije, SARS-CoV-2, karakteriziran je visokom učestalošću genetičkih rekombinacija i mutacija. Glavnu patofiziološku ulogu među njegovim proteinima ima S protein („spike“), koji svojim vezanjem za proteine stanice domaćina, poglavito ACE2, TMPRSS2 i integrin αvβ3, omogućava virusu ulazak u stanicu endocitozom ili fuzijom virusne ovojnice sa staničnom membranom. Folikularne stanice štitnjače značajno eksprimiraju te proteine na svojim stanicama te je stoga štitnjača jedna od glavnih meta SARS-CoV-2 u tijelu.
Kao komplikacije COVID-19 infekcije opisani su tireotoksikoza, hipotireoza, destruktivni i subakutani tireoiditis, de novo nastala Gravesova bolest, atipični tireoiditis te sindrom netireoidne bolesti štitnjače (NTIS). Poremećena funkcija štitnjače zabilježena je tijekom infekcije SARS-CoV-2 ili čak nekoliko tjedana nakon oporavka. Učinci „citokinske oluje“ također mogu značajno utjecati na one s postojećim poremećajima funkcije štitnjače, posebno starije osobe čiji imunološki sustav može biti manje otporan s većim rizikom od tromboembolijskih komplikacija i smrtnosti.
Pokazano je da su poremećaji štitnjače, prvenstveno hipotireoza, povezani s većim rizikom od loših ishoda, prijema u jedinicu intenzivnog liječenja i hospitalizacije u bolesnika s COVID-19, no ova povezanost značajno je pod utjecajem dobi oboljelih. Ako su bolesnici bili pod odgovarajućom terapijom, nema statistički značajne razlike u promatranim ishodima. Nasuprot tome, pokazano je da hipertireoza ne utječe značajno na ishod COVID-19 infekcije. Osobe s bolestima štitnjače mogu biti liječeni protiv COVID-19 infekcije jednako kao i zdravi pojedinci, bez rizika od dodatnih komplikacija u procesu liječenja. Niska razina FT3 i omjer FT3/FT4 pokazatelji su težine bolesti, dok je niska razina FT3 prognostički biljeg smrtnosti povezane s COVID-19.
Poremećaji štitnjače dokumentirani su nakon primjene svih vrsta cjepiva protiv COVID-19. Najčešći slučajevi poremećaja štitnjače zabilježeni su nakon cijepljenja mRNA cjepivima, zatim vektorskim virusnim cjepivima i slučajeva nakon cijepljenja inaktiviranim cjepivima. Štoviše, subakutni tireoiditis (SAT) bio je najčešći poremećaj štitnjače povezan s cijepljenjem protiv COVID-19, praćen Gravesovom bolesti.The main function of the thyroid gland is the production of the prohormone thyroxine (T4) and the active hormone triiodothyronine (T3). In the human body, T3 controls the basal metabolism, with effects on the central nervous, cardiovascular, respiratory, musculoskeletal, and ultimately, the immune system. On a cellular level, thyroid hormones T3 and T4 are known for their diverse effects on cell function, including the regulation of cell proliferation, tissue regeneration, apoptosis, and angiogenesis
COVID-19 infection has a remarkably wide range of manifestations. Besides respiratory, gastrointestinal, and cardiovascular effects, various endocrine complications of SARS-CoV-2 infection have been identified, including thyroid dysfunctions. One of the key features of COVID-19 is inflammation. A term often used to describe this inflammation is the "cytokine storm," which is an excessive immune response by the body involving cytokines, contributing to the more severe pathohistological and clinical features associated with it, such as acute respiratory syndrome (ARS), multiple organ failure and autoimmune diseases.
The causative agent of COVID-19 infection, SARS-CoV-2, is characterized by a high frequency of genetic recombination and mutations. Among its proteins, protein S ("spike") plays the main pathophysiological role; by binding to host cell proteins, primarily ACE2, TMPRSS2, and integrin αvβ3, it enables the virus to enter the cell through endocytosis or fusion of the viral envelope with the cell membrane. Thyroid follicular cells significantly express these proteins on their surface, making it one of the main targets of SARS-CoV-2 in the body.
As complications of COVID-19 infection, thyrotoxicosis, hypothyroidism, destructive and subacute thyroiditis, de novo Graves' disease, atypical thyroiditis, and non-thyroidal illness syndrome (NTIS) have been described. Thyroid dysfunction has been recorded during SARS-CoV-2 infection or even several weeks after recovery. The effects of the "cytokine storm" can also significantly impact those with pre-existing thyroid dysfunctions, especially older adults, whose immune systems may be less resilient, with a higher risk of thromboembolic complications and mortality.
It has been shown that thyroid disorders, primarily hypothyroidism, are associated with a higher risk of poor outcomes, admission to intensive care units, and hospitalization in patients with COVID-19; however, this association is significantly influenced by the age of the patients. If patients were on appropriate therapy, there was no statistically significant difference in the observed outcomes. In contrast, it has been shown that hyperthyroidism does not significantly affect the outcome of COVID-19 infection. Individuals with thyroid diseases can be treated for COVID-19 infection just like healthy individuals, without the risk of additional complications during the treatment process. Low levels of FT3 and the FT3/FT4 ratio are indicators of disease severity, while low levels of FT3 are prognostic markers of COVID-19-related mortality.
Thyroid disorders have been documented after the administration of all types of COVID-19 vaccines. The most common cases of thyroid disorders have been reported after mRNA vaccines, followed by viral vector vaccines and cases after inactivated vaccines. Moreover, subacute thyroiditis (SAT) was the most common thyroid disorder associated with COVID-19 vaccination, followed by Graves' disease
Difference between twin and singleton pregnancy
Jednoplodna trudnoća se definira kao razvoj jednog fetusa u maternici. Blizanačka trudnoća podrazumijeva razvoj dvaju fetusa u maternici. Planiranje prehrane i praćenje povećanja tjelesne težine ključni su za održavanje zdravlja majke i fetusa u svakoj trudnoći. Smjernice i preporuke ovise o potrebama jednoplodne odnosno blizanačke trudnoće. Preporuča se unos istih nutrijenata, ali u povećanim dozama kod blizanačke trudnoće. Antenatalna skrb važan je dio svake trudnoće. Neinvazivni i invazivni prenatalni testovi neophodni su za otkrivanje kromosomskih anomalija i drugih komplikacija u obje vrste trudnoća. Ultrazvuk se u jednoplodnim trudnoćama koristi u određivanju gestacijske dobi, ranom otkrivanju anomalija i praćenja rasta fetusa. Uz sve navedeno u blizanačkim se trudnoćama također koristi za diferenciranje zigociteta i korioniciteta. Jednoplodne trudnoće obično traju oko 40 tjedana, dok blizanačke u prosjeku traju 37 tjedana. Vaginalni porođaj najsigurniji je za fetus i majku kada se radi o terminskoj jednoplodnoj trudnoći te kao takav je najčešći način dovršenja jednoplodne trudnoće. S druge strane, blizanci se također porađaju vaginalno, ali zbog veće stope prijevremenih porođaja u toj skupini je veća učestalost carskog reza nego kod jednopodnih trudnoća. Također se u blizanačkim trudnoćama češće javljaju komplikacijama poput gestacijskog dijabetesa i preeklampsije. Postoje univerzalne smjernice za vođenje jednoplodne trudnoće, dok blizanačke trudnoće često ovise o iskustvu opstetričara zbog manjka istih. Veća je učestalost maternalnih i perinatalnih komplikacijama kod blizanačkih nego kod jednoplodnih trudnoća. Uz fetalne komplikacije koje se viđaju u jednoplodnoj trudnoći, postoje komplikacije specifične za monokorijate poput sindroma transfuzije blizanaca na blizance (TTTS) i sekvence policitemije blizanačke anemije (TAPS). Učinkovita prenatalna skrb i pravovremene intervencije ključni su za poboljšanje ishoda za majku i dijete u oba tipa trudnoće. Svaka trudnoća je jedinstvena i zahtijeva personalizirana razmatranja za povoljne ishode.A singleton pregnancy is defined as the development of one fetus in the uterus, while a twin pregnancy is the development of two fetuses in the uterus. Planning nutrition and monitoring weight gain are crucial for maintaining the health of both the mother and fetus in any pregnancy. Guidelines and recommendations depend on the needs of singleton and twin pregnancies. The intake of the same nutrients is recommended, but in increased amounts for twin pregnancies. Antenatal care is an important part of every pregnancy. Non-invasive and invasive prenatal tests are essential for detecting chromosomal abnormalities and other complications. Ultrasound is used in singleton pregnancies to determine gestational age, early detection of anomalies, and monitoring fetal growth. In addition to these, in twin pregnancies, it is also used to differentiate zygosity and chorionicity. Singleton pregnancies usually last around 40 weeks, while twin pregnancies 37 weeks on average. Vaginal delivery is the safest option for both the fetus and the mother in term singleton pregnancies, making it the most common way to complete a singleton pregnancy. On the other hand, twins can be delivered vaginally in only about 40% of cases, with most being born via cesarean section. Twin pregnancies result in higher rates of preterm births and complications such as gestational diabetes and preeclampsia. There are universal guidelines for managing singleton pregnancies, whereas twin pregnancies often depend on the experience of the obstetrician due to a lack of specific guidelines. There is a higher incidence of maternal and perinatal complications in twin pregnancies compared to singleton pregnancies. In addition to fetal complications seen in singleton pregnancies, there are complications specific to monochorionic twins, such as twin-to-twin transfusion syndrome (TTTS) and twin anemia-polycythemia sequence (TAPS). Effective prenatal care and timely interventions are key to improving outcomes for both the mother and child in both types of pregnancies. Each pregnancy is unique and requires personalized considerations for favorable outcomes
Perfierni i središnji učinci botulinum toksina tipa A u motoričkom živčanom sustavu štakora
Introduction: Intramuscular administration of botulinum toxin type A (BoNT-A) is used to treat
hyperkinetic disorders such as dystonia and spasticity. Our research suggests that BoNT-A, in
addition to its primary peripheral action, also exerts effects on the central nervous system, which
could explain its prolonged effect.
Methods: Studies were conducted on Wistar Han rats and primary cultures of rat cerebellar
neurons. Peripheral and central effects of BoNT-A were assessed using motor tests,
electromyography, intrathecal administration of antitoxin, and latrotoxin (LTX). The protease
activity of the toxin was analyzed using the Western blot method.
Results: The antispastic effect of BoNT-A was dose-dependent in the later phase, with higher
doses preventing spasm and improving motor performance. Intrathecal antitoxin accelerated
the recovery of muscle weakness. BoNT-A reduced muscle tone induced by tetanus toxin
(TeNT) without affecting the monosynaptic reflex. Central transsynaptic activity contributed to
the late antispastic effect, with the presence of BoNT-A enzymatic activity in muscles and the
spinal cord. LTX accelerated the recovery of neuroparalysis and reduced the late antispastic
effects of BoNT-A.
Conclusion: Peripheral and central activities of BoNT-A act synergistically, with the later
central effect dependent on the reduction of intense peripheral action. This is also confirmed by
the initial dominance of the flaccid neuroparalytic effect of TeNT on peripheral NMJ, in relation
to the central disinhibitory effect and the occurrence of spasms in cephalic tetanus.Uvod: Intramuskularna primjena botulinum toksina tipa A (BoNT-A) koristi se za liječenje
hiperkinetičkih poremećaja poput distonije i spastičnosti. Naša istraživanja upućuju da BoNTA,
osim primarnog perifernog djelovanja, ostvaruje i učinke na središnji živčani sustav, što bi
moglo objasniti njegov produljeni učinak.
Metode: Istraživanja su provedena na štakorima soja Wistar Han i primarnoj kulturi neurona
malog mozga štakora. Periferni i središnji učinci BoNT-A procijenjeni su motoričkim
testovima, elektromiografijom, intratekalnom primjenom antitoksina i latrotoxinom (LTX).
Proteazna aktivnost toksina analizirana je Western blot metodom.
Rezultati: Antispastični učinak BoNT-A pokazao se ovisan o dozi u kasnijoj fazi, te su veće
doze spriječile spazam i poboljšale motoričke izvedbe. Intratekalni antitoksin ubrzao je
oporavak mišićne slabosti. BoNT-A je smanjio mišićni tonus induciran tetanus toksinom
(TeNT), bez utjecaja na monosinaptički refleks. Središnja transsinaptička aktivnost
pridonijela je kasnom antispastičkom učinku, uz prisutnost enzimske aktivnosti BoNT-A u
mišićima i leđnoj moždini. LTX je ubrzao oporavak neuroparalize i smanjio kasne
antispastične učinke BoNT-A.
Zaključci: Periferna i središnja aktivnost BoNT-A djeluju sinergistički, a kasniji središnji
učinak ovisi o smanjenju intenzivnog perifernog djelovanja, što također potvrđuje i početna
dominacija perifernog mlohavog neuroparalitičkog učinka TeNT u odnosu na središnji
dezinhibicijski učinak i nastanak spazma kod cefaličkog tetanusa
First trimester combined screening and non-invasive prenatal testing in prenatal screening for chromosomal abnormalities
Kromosomopatija je promjena u strukturi ili broju kromosoma koja može uzrokovati različite kliničke posljedice. Abnormalnosti broja kromosoma dijele se na poliploidije i aneuploidije, gdje dolazi do gubitka ili dobitka jednog kromosoma. Identifikacija ovih abnormalnosti je ključna za preventivne strategije, genetsko savjetovanje i odgovarajuće liječenje. Najčešći test koji se nudi je rani kombinirani probir u prvom tromjesečju. On uključuje detaljni ultrazvuk za mjerenje udaljenosti tjeme-trtica i nuhalne translucencije fetusa u razdoblju od 11. do 13. tjedna gestacije, uz serumski probir slobodnog beta-humanog korionskog gonadotropina (βhCG) i proteina A povezanog s trudnoćom (PAPP-A) između 8. i 13. tjedna gestacije. Iako rani kombinirani probir ima stopu detekcije od 90 %, glavni problem je relativno visoka stopa lažno pozitivnih rezultata, gdje bi 1 od 20 (5 %) pacijentica bila nepotrebno zabrinuta. S pojavom neinvazivnog prenatalnog testiranja (NIPT) vrlo je izgledno da će upravo ono zamijeniti klasični rani probir, a neke zemlje su ga već uvele u svoj nacionalni probirni program. Radi se o tehnici koja analizira kratke fragmente slobodne fetalne DNK uzduž cijelog genoma kako bi se identificirale kromosomske abnormalnosti poput Patauovog (T13), Edwardsovog (T18) i Downovog sindroma (T21). Zahvaljujući napretku masovnog paralelnog sekvenciranja, NIPT je značajno smanjio upotrebu invazivnih metoda poput amniocenteze i biopsije korionskih resica te postaje ključan probirni test zbog svoje jednostavnosti, neinvazivnosti i niskog rizika. Međutim, ovi testovi se često provode bez adekvatnog genetičkog savjetovanja te su katkad pogrešno interpretirani kao dijagnostički testovi, a zapravo su testovi probira. Neovisno o tome, uvođenje neinvazivnog prenatalnog testiranja predstavlja značajan napredak u identifikaciji kromosomopatija, omogućujući precizniju dijagnostiku i unaprjeđujući skrb za trudnice i nerođene potomke.Chromosomopathy is a change in the structure or number of chromosomes that can cause various clinical consequences. Numerical chromosomal abnormalities can be polyploidies or aneuploidies, involving the loss or gain of a single chromosome. Identifying these abnormalities is crucial for preventive strategies, genetic counselling, and appropriate treatment. The most common test offered is the combined first trimester screening. It includes detailed ultrasound to measure the crown-rump length and nuchal translucency of the fetus between the 11th and 13th weeks of gestation, combined with serum screening of free beta-human chorionic gonadotropin (βhCG) and pregnancy-associated plasma protein A (PAPP-A) between the 8th and 13th weeks of gestation. Although early combined screening has a detection rate of 90 %, the main issue is the relatively high rate of false positive results, where 1 out of 20 (5 %) patients would be unnecessarily concerned. With the emergence of non-invasive prenatal testing (NIPT), it is very likely that it will replace traditional early screening, and some countries have already incorporated it into their national screening programs. This technique analyses cell-free DNA fragments across the whole genome to identify chromosomal abnormalities such as Patau (T13), Edwards (T18), and Down syndrome (T21). Thanks to the advancement of massive parallel sequencing, NIPT has significantly reduced the use of invasive methods such as amniocentesis and chorionic villus sampling and will probably become a key screening test due to its simplicity, non-invasiveness, and low risk. However, these tests are often performed without adequate genetic counselling and are sometimes wrongly interpreted as diagnostic tests, when in fact they are screening tests. Nonetheless, the introduction of non-invasive prenatal testing represents a significant advancement in the identification of chromosomal abnormalities, enabling more precise diagnosis and improving care for pregnant women and their unborn children
Endocrine disorders and infertility
Neplodnost je značajan javnozdravstveni problem s kojim se susreće oko 20% parova diljem svijeta. Uzroci neplodnosti su brojni i raznovrsni, a među njima poseban položaj zauzimaju endokrinološke bolesti. Poremećaj lučenja hormona važnih za reprodukciju te posljedična neplodnost može se dogoditi na razini hipotalamusa i hipofize kao posljedica pretilosti, stresa, preniske tjelesne težine, Sheehanovog sindroma ili stanja hiperprolaktinemije. Nadalje, poremećaji rada štitnjače poput hipertireoze i hipotireoze uvelike utječu na plodnost žena, dok njihov utjecaj na mušku plodnost nije u potpunosti jasan. Timus također utječe na plodnost, a najčešće opisana patologija je mutacija AIRE gena koja dovodi do autoimunog poliglandularnog sindroma 1 (APS 1). Od bolesti gušterače ističu se šećerna bolest tipa 1 i 2 koje različitim mehanizmima utječu na plodnost kako muškaraca, tako i žena. Pravovremena dijagnoza i valjana kontrola glikemije izrazito su važni u ovih bolesnika kako bi se spriječio negativan utjecaj bolesti na reproduktivno zdravlje. Kod žena je najčešći uzrok neplodnosti anovulacija, a najčešći uzrok anovulacijskih ciklusa je sindrom policističnih jajnika (PCOS). Primarna ovarijska insuficijencija rijetko je stanje koje pogađa tek 1% žena, ali ipak se treba uzeti u obzir prilikom obrade neplodnosti. Po novijim istraživanjima, muškarci su odgovorni za 40 do 50% neplodnosti parova, a uzroci mogu biti različiti. Primarna testikularna insuficijencija odnosi se na stanja u kojima testisi ne proizvode dovoljno testosterona i spermija, dok je sekundarna testikularna insuficijencjia stanje u kojem postoji patologija hipotalamusa ili hipofize te je posljedično smanjena sinteza testosterona. Prilikom obrade neplodnosti parova, važno je isključiti poremećaje ili kronične bolesti koje su povezane s neplodnošću. Ukoliko se detektiraju, potrebno ih je korigirati prije liječenja metodama potpomognute oplodnje (MPO).Infertility is a significant public health problem that affects about 20% of couples worldwide. The causes of infertility are numerous and diverse, with endocrine disorders holding a unique position among them. Disruption in secretion of reproductive hormones and consequent infertility may occur at hypothalamus and pituitary gland level because of obesity, stress, low body weight, Sheehan syndrome or hyperprolactinemia. Furthermore, disorders like hyper or hypothyroidism greatly affect female fertility, whereas the effect on male fertility is not fully understood. The thymus may also affect fertility, with the most commonly described pathology being mutations in the AIRE gene leading to autoimmune polyglandular syndrome 1 (APS 1). Pancreas diseases, such as diabetes mellitus type 1 and 2, stand out as conditions that affect fertility in both men and women through various mechanisms. Prompt diagnosis and proper glycemic control are extremely important in these patients to prevent negative impact of the disease on reproductive health. The most common cause of infertility in women is anovulation, and the main cause of anovulatory cycles is polycystic ovary syndrome (PCOS). Primary ovarian insufficiency is a rare condition that only affects 1% of women, however, it should be considered when evaluating couple’s infertility. New research suggest that men are responsible for 40 to 50% of couples’ infertility, and the causes are diverse. Primary testicular insufficiency refers to conditions in which the testicles do not produce enough testosterone and sperm, while secondary testicular insufficiency is a condition in which there is a pathology of the hypothalamus or pituitary gland and, as a result, testosterone synthesis is reduced. When assessing infertility in couples, it is important to rule out disorders or chronic diseases associated with infertility. If detected, they need to be corrected before proceeding with assisted reproductive technologies (ART)
Hemophilic arthropathy - pathophysiology and treatment
Hemofilija je X vezana nasljedna bolest, oboljele su pretežito osobe muškog spola, a prenositeljice su uglavnom heterozigoti tj. osobe ženskog spola. Hemofilija A nastaje zbog disfunkcije ili nedostatka koagulacijskog faktora VIII, a Hemofilija B zbog faktora IX. Deficijencija faktora XI, nekad zvana hemofilija C spada u skupinu rijetkih poremećaja krvarenja. Klasifikacija hemofilija se temelji na aktivnosti faktora VIII i IX: teška (<1 IU/dL), 1 umjerena (1 - 5 IU/dL) i blaga (6 - <40 IU/dL). Jedno od najčešćih komplikacija hemofilije je hemartoza odnosno krvarenje u zglobove. Ako se ne prepozna i liječi, čak i subklinička hemartoza može dovest do nastanka artropatije. Patofiziologija hemofilične artropatije se sastoji od dva glavna mehanizma nastanka. Prvi je kemijska reakcija koja nastaje zbog nakupljanja željeza iz krvi, a koje zbog učestalih krvarenja stanice sinovije zgloba nisu u mogućnosti uklonit. Drugi mehanizam je upala, potaknuta kemijskom reakcijom zbog hiperplazije sinovije te destrukcije hrskavice i kosti. Hemofilična artropatija značajno smanjuje kvalitetu života, uzrokuje kroničnu bol i deformacije zglobova što ponekad zahtjeva operativno liječenje. Sprječavanje nastanka hemartroze primarno se temelji na profilaktičkom liječenju hemofilije. Danas su na tržištu brojni lijekovi koji reduciraju broj slučajeva u pacijenata koji boluju od hemofilije. Osim prevencije, nastalu artropatiju je potrebno liječiti konzervativno i/ili kirurški. Cilj ovog diplomskog rada je opisati patofiziologiju nastanka hemofiličke artrpatiju te njeno liječenje.Hemophilia is an X-linked inherited disorder, predominantly affecting males, while carriers are typically heterozygous females. Hemophilia A results from dysfunction or deficiency of coagulation factor VIII, while hemophilia B arises from factor IX deficiency. Deficiency of factor XI, formerly known as hemophilia C, has been recategorized under rare bleeding disorders. The classification of hemophilia is based on the activity of factors VIII and IX: severe (<1 IU/dL), moderate (1 - 5 IU/dL), and mild (6 - <40 IU/dL). Frequent bleeding in joints (hemarthrosis) is one of hemophilia's most common clinical complications. If unrecognized and untreated, even subclinical hemarthrosis can lead to the development of arthropathies. The pathophysiology of hemophilic arthropathy involves two main mechanisms. The first is a chemical reaction resulting from the iron accumulation from the blood, which, due to frequent bleeding, synovial cells of the joint aren’t able to remove. The second mechanism involves inflammation, triggered by the chemical reaction due to synovial hyperplasia and the destruction of cartilage and bone. Hemophilic arthropathy significantly reduces the quality of life, causing chronic pain and joint deformities, sometimes necessitating surgical intervention in the treatment. Preventing the occurrence of hemarthrosis largely relies on prophylactic treatment of hemophilia. Today, numerous medications are available on the market that have reduced hemophilic arthropathy in patients with hemophilia. In addition to prevention, existing arthropathy requires conservative and/or surgical treatment. This thesis aims to describe the pathophysiology of hemophilic arthropathy and its treatment
Assessment of bladder dysfunction in multiple sclerosis patients
Multipla skleroza autoimuna je bolest s kroničnim progresivnim tijekom. Imunosni sustav u bolesti oštećuje mijelinsku ovojnicu živaca, što dovodi do oslabljenoga aksonskog provođenja, koje se manifestira neurološkim ispadima ovisno o mjestu lezije. Kako je mokrenje regulirano iz više centara koji se nalaze na različitim mjestima u živčanome sustavu, lezije na bilo kojoj od tih lokacija mogu dovesti do urinarnih smetnji. Kod 42 ispitanika učinjen je neurološki status s određivanjem EDSS-a i Urinary FS-a, snimljen je SSEP n. medianusa i tibialisa te su svi ispitanici ispunili ICIQ ocjenske ljestvice kvalitete života i prekomjerno aktivnoga mjehura. Za analizu su uzeti nalazi posljednjega dostupnog MR-a moždanoga debla i kralježnične moždine koji su učinjeni u sklopu rutinske obrade. Cilj istraživanja bilo je utvrđivanje povezanosti rezultata neurološkoga statusa, neurofiziološke i neuroradiološke obrade s ICIQ upitnicima. Rezultati istraživanja pokazali su statistički značajnu povezanost ICIQ upitnika s kliničkim vrijednostima EDSS-a i Urinary FS-a s kao i s vrijednostima P40 vala u SSEP n. tibialisa. Još jednom je potvrđena korelacija između onesposobljenosti u neurološkome statusu i vrijednostima SSEP n. tibialisa. Multimodalnom obradom bolesnika i specijaliziranim upitnicima možemo objektivizirati probleme s mokraćnim sustavom, koji često prate bolesnike s MS-om i narušavaju im kvalitetu života, te im omogućiti rano liječenje.Multiple sclerosis is an autoimmune disease with chronic progressive course. The immune system in the disease damages the myelin lining of the nerves, leading to impaired axone conduction, which is manifested by neurological outbursts depending on the location of the lesion. As urination is regulated from multiple centers located in different locations in the nervous system, lesions at any of these locations can lead to urinary disturbances. In 42 subjects, neurological status was performed with determination of EDSS and urinary FS, SSEP n. medianus and tibialis were recorded, and all subjects fulfill ICIQ quality of life and overactive bladder rating scale. The last available brain and spinal cord MRI recorded as part of routine work-up was analysed. The aim of the study was to determine the correlation of neurological status, neurophysiological and neuroradiological work-up with the results of the ICIQ questionnaires. The results of the study showed a statistically significant association of the ICIQ questionnaire with clinical parameters EDSS and urinary FS as well as with P40 wave values in SSEP n. tibialis. The correlation between neurological disability and SSEP n. tibialis values was once again confirmed. Multimodal evaluation of patients and specialized questionnaires can objectify problems with the urinary system that often accompany MS patients and greatly impair their quality of life, allowing them to receive early treatment
The influence of external lumbar drainage on cerebrospinal fluid pressure and volume, amyloid beta and tau protein concentrations, and on the clinical status of patients with idiopathic normal pressure hydrocephalus
Patofiziologija normotenzivnog hidrocefalusa (NPH) nije jasna, te se danas ispituju razni prognostički čimbenici na osnovu kojih bi se mogli odabrati bolesnici za operacijsko liječenje. Cilj ovog istraživanja je bio ispitati po prvi put da li promjene kranijskog i spinalnog volumena cerebrospinalne tekućine (CST) mjenjaju intrakranijsku hidrodinamiku i koncentracije biomarkera, te intrakranijski tlak uz poboljšanje kliničkog stanja bolesnika koje opravdava operacijsko postavljanje trajne drenaže. Dvadeset bolesnika s kliničkom i neuroradiološkom sumnjom na NPH su bili podvrgnuti vanjskoj lumbalnoj drenaži tijekom razdoblja od 72 h, uz praćenje promjena koncentracije biomarkera u CST-u i intrakranijskog tlaka, te mjerenje volumena CST-a u kraniospinalnom prostoru prije i nakon drenaže. Kod 10 bolesnika došlo je do kliničkog poboljšanja. Rezultati su pokazali da je sposobnost regulacije tlaka CST-a s promjenama volumena znatno smanjena u bolesnika s negativnim kliničkim odgovorom. MR volumetrijom uočeno je kako volumen CST-a u kraniju čini oko 20% ukupnog intrakranijskog volumena, te da je taj volumen kao i ukupni kraniospinalni volumen veći u bolesnika koji imaju pozitivan klinički odgovor na produženu lumbalnu drenažu. Zbroj ukupnog volumena CST-a u kraniju i u spinalnom prostoru ukazuje da taj volumen iznosi oko 466 ml u odraslih osoba što je znatno više nego se to do sada mislilo čak i kad se umanji volumen za 150 ml što predstavlja prosječno povećanje komora kod NPH bolesnika. Promjene koncentracije odabranih biomarkera (amiloid β, ukupni i fosforilirani tau proteini) iz uzoraka CST-a u tri vremenske točke (0, 36 i 72 h) tijekom drenaže povezane su s promjenom kliničkog stanja. Pokazano je kako postupni porast koncetracije Aβ1-42 koji se događa tijekom trodnevne drenaže CST-a predstavlja mogući pozitivni prognostički čimbenik za postavljanje trajne CST drenaže u bolesnika s NPH-om.The pathophysiology of normal pressure hydrocephalus (NPH) is not clear, and various prognostic factors are currently being investigated that could facilitate the selection of patients who would benefit from surgical treatment. This research aimed to examine for the first time whether changes in cranial and spinal volume of cerebrospinal fluid (CSF) influence intracranial hydrodynamics and biomarker concentrations, as well as intracranial pressure while improving the patient's clinical condition, which justifies surgical placement of permanent drainage. Twenty patients with clinical and euroradiological signs of NPH underwent external lumbar drainage during a period of 72 h. During this period we monitored changes in the concentration of biomarkers in the CSF and intracranial pressure, and also measured the volume of CSF in the craniospinal space before and after drainage. Clinical improvement was observed in 10 patients. The results showed that the ability to regulate CSF pressure with volume changes was significantly reduced in patients with negative clinical response. MRI volumetry showed that intracranial CSF accounts for 20% of the total intracranial volume, and that this CSF
volume, as well as the total craniospinal volume, is greater in patients who have a positive clinical response (responders) to extended lumbar drainage. The sum of the total volume of the CSF in the cranium and in the spinal space indicates that this volume is about 466 ml in adults, which is significantly higher than previously thought, even when the volume is reduced by 150 ml, which represents the average increase in the ventricles in NPH patients. Changes in the concentration of selected biomarkers (amyloid β, total, and phosphorylated tau proteins) from CSF samples at three-time points (0, 36, and 72 h) during drainage are associated with changes in the clinical condition. The gradual increase in Aβ1-42 concentration that occurs during the three-day CSF drainage represents a possible positive prognostic factor for the placement of permanent CSF drainage in patients with NPH
Substances of plant origin in the treatment of psychiatric disorders
Sve je veća incidencija psihijatrijskih poremećaja, posebno poremećaja raspoloženja poput depresije i anksioznosti, kao i insomnije i demencije. Stoga je i veća potreba za korištenjem alternativnih terapijskih metoda liječenja uz standardne terapije. Fitoterapija je grana medicine koja se bavi liječenjem bolesti i unaprjeđenjem zdravlja biljnim lijekovima poznatima kao fitoterapeutici. Biljni pripravci tradicionalno su korišteni stoljećima za razne tegobe, od psihijatrijskih do somatskih. Neke od najistraživanijih biljnih tvari za liječenje depresije, anksioznosti i insomnije su kantarion, valerijana, pasiflora, kava kava i matičnjak dok se ginko smatra posebno učinkovit u poboljšanju pamćenja i kognicije. Usprkos svojim prednostima imaju i nuspojave kao i interakcije s ostalim lijekovima i tvarima te ih se mora uzimati s oprezom. Od posebne je važnosti edukacija liječnika o biljnim pripravcima te komunikacija s pacijentom o prednostima i rizicima njihovog uzimanja. Jedna od glavnih mana korištenja fitoterapeutika je manjak kliničkih istraživanja o učinkovitosti i sigurnosti njihova korištenja zbog čega još nije moguće zamijeniti standardne lijekove biljnim pripravcima.There is an increasing incidence of psychiatric disorders, especially mood disorders such as depression and anxiety, as well as insomnia and dementia. Consequently, there is a greater need for the use of alternative therapeutic methods in addition to standard therapies. Phytotherapy is a branch of medicine that deals with the treatment of diseases and the promotion of health using plant-based medicines known as phytotherapeutics. Herbal preparations have been traditionally used for centuries for various ailments, from psychiatric to somatic. Some of the most researched plant substances for the treatment of depression, anxiety, and insomnia are St. John's Wort, valerian, passionflower, kava kava, and lemon balm, while ginkgo is considered particularly effective in improving memory and cognition. Despite their advantages, they also have side effects and interactions with other medications and substances, and must therefore be taken with caution. It is particularly important to educate physicians about herbal preparations and to communicate with patients about the benefits and risks of their use. One of the main drawbacks of using phytotherapeutics is the lack of clinical research on their effectiveness and safety, and thus it is not yet possible to replace standard medications with herbal preparations
Peculiarities of severe asthma treatment compared to the treatment of other types of asthma
Liječenje teške astme razlikuje se od liječenja drugih oblika astme zbog složenosti i težine simptoma te potrebe za specifičnim terapijskim pristupima. Teška astma često zahtijeva kombinaciju različitih terapija kako bi se postigla kontrola nad simptomima i poboljšala kvaliteta života pacijenata. Temelj liječenja teške astme je uporaba visokih doza inhalacijskih kortikosteroida (ICS) u kombinaciji s dugodjelujućim beta2-agonistima (LABA), kombinacija koja djeluje protuupalno. U slučaju da temeljna terapija nije dovoljna, dodaju se i drugi lijekovi poput dugodjelujućih antikolinergika ili antagonisti leukotrijenskih receptora koji pomažu u kontroliranju upale. Biološki lijekovi predstavljaju značajan napredak u liječenju teške astme. Oni ciljaju specifične molekule u imunološkom sustavu koje su odgovorne za upalu i bronhospazam. Osim farmakološkog liječenja, važno je izbjegavanje okidača koji mogu pogoršati astmu (identifikacija i izbjegavanje alergena, prestanak pušenja). Edukacija pacijenata o pravilnom korištenju inhalatora i praćenju simptoma ključna je za uspješno upravljanje teškom astmom. Za razliku od blažih oblika astme, teška astma zahtijeva i upućivanje u ustanove specijalizirane za liječenje teške astme, gdje pacijenti dobivaju sveobuhvatnu procjenu i personalizirani plan liječenja. Redoviti pregledi i prilagodbe terapije na temelju odgovora pacijenta bitni su za postizanje optimalne kontrole bolesti. Liječenje teške astme zahtijeva multidisciplinarni pristup i kontinuiranu suradnju između pacijenta i zdravstvenih radnika kako bi se smanjila učestalost egzacerbacija i poboljšala kvaliteta života.The treatment of severe asthma differs from the treatment of other types of asthma due to the complexity and severity of symptoms and the need for specific therapeutic approaches. Severe asthma often requires a combination of different therapies to achieve symptom control and improve the quality of life. The cornerstone of severe asthma treatment is the use of high doses of inhaled corticosteroids (ICS) in combination with long-acting beta2-agonists (LABA), a combination that acts anti-inflammatory. If the basic therapy is not sufficient, other drugs such as anticholinergics or leukotriene modifiers, which help control inflammation, are added. Biologic drugs represent a significant advancement in the treatment of severe asthma. They target specific molecules in the immune system responsible for inflammation and bronchospasm. In addition to pharmacological treatment, it is important to avoid triggers that can worsen asthma (identification and avoidance of allergens, smoking cessation). Patient education on the proper use of inhalers and monitoring symptoms is crucial for the successful management of severe asthma. Unlike milder forms of asthma, severe asthma also requires referral to specialist departments, where patients receive a comprehensive assessment and personalized treatment plan. Regular check-ups and adjustments to therapy based on the patient's response are essential for achieving optimal disease control. Treating severe asthma requires a multidisciplinary approach and continuous collaboration between the patient and healthcare providers to reduce the frequency of exacerbations and improve quality of life