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Clinical manifestations of enteric nervous system disorders
No full textCrijevni živčani sustav je autonomna mreža neurona s važnim učinkom u homeostatskom djelovanju gastrointestinalnog trakta. Disfunkcija se očituje nizom kliničkih poremećaja koji uključuju kongenitalne neuropatije, primarne poremećaje motiliteta, funkcionalne i upalne poremećaje, metaboličke i neurodegenerativne bolesti, te promjene u starenju. Manifestacije su nespecifične i preklapaju se s drugim gastroenterološkim stanjima, a prepoznavanje učinka ENS-a je ključno za postavljanje točne dijagnoze i odabir terapijskog pristupa.
Ovaj rad prikazuje pregled recentne znanstvene literature o kliničkim manifestacijama poremećaja ENS-a u odrasloj populaciji. Prikazani su osnovni mehanizmi disfunkcije ENS-a, uključujući promjene neurotransmisije, morfologije, imunoloških procesa i poremećaje crijevno-moždane osovine.
Unatoč napretku u razumijevanju uloge ENS-a, dijagnostičke mogućnosti ostaju ograničene, a terapijski pristupi najčešće simptomatski. U budućnosti se fokus prebacuje na molekularne mehanizme, razvoj biomarkera i ciljanu terapiju kako bi se unaprijedila kvaliteta života pacijenata.The enteric nervous system is an autonomic network of neurons with an important effect on the homeostatic functioning of the gastrointestinal tract. Dysfunction is manifested by a number of clinical disorders including congenital neuropathies, primary motility disorders, functional and inflammatory disorders, metabolic and neurodegenerative diseases, and changes due to aging. Manifestations are nonspecific and overlap with other gastroenterological conditions. Early recognition of the effect of the ENS is crucial for establishing an accurate diagnosis and choosing a therapeutic approach.
This thesis presents a review of the recent scientific literature on the clinical manifestations of ENS disorders in the adult population. The basic mechanisms of ENS dysfunction are presented, including changes in neurotransmission, morphology, immunological processes, and disorders of the gut-brain axis.
Despite progress in understanding the role of the ENS, diagnostic options remain limited, and therapeutic approaches are most often symptomatic. In the future, the focus is shifting to molecular mechanisms, biomarker development, and targeted therapy to significantly improve life quality of the patients
The Role of Infusion Therapy in The Treatment of Advanced Parkinson’s Disease
No full textParkinsonova bolest (PB) druga je najčešća neurodegenerativna bolest, karakterizirana gubitkom dopaminergičkih neurona i prisutnošću motoričkih i nemotoričkih simptoma. U posljednja tri desetljeća, prevalencija PB-a značajno je porasla, potaknuvši sve veći interes za istraživanjem naprednih metoda liječenja, pogotovo u uznapredovanoj fazi bolesti. Uznapredovana faza PB-a karakterizirana je neadekvatnim odgovorom na peroralnu terapiju te motoričkim fluktuacijama i diskinezijama. Kao odgovor na ove izazove razvijene su invazivne terapijske opcije, poput infuzijskih metoda, koje predstavljaju značajan napredak u liječenju uznapredovane bolesti. U ovom preglednom radu obuhvatili smo sve trenutno dostupne infuzijske terapije koje se koriste u liječenju PB-a. Prva infuzijska terapija korištena u liječenju PB-a bila je apomorfinska supkutana pumpa, koja se koristi posljednjih 30 godina i uspješno smanjuje motoričke fluktuacije i diskinezije. Intestinalni gel levodopa/karbidopa također se ističe po sposobnosti smanjenja “OFF” perioda i poboljšanju kvalitete života pacijenata, uz učinkovitost i na nemotoričke simptome. Terapija intestinalnim gelom levodopa/karbidopa/entakapon omogućuje postizanje sličnog terapijskog učinka uz manju dozu lijeka zbog dodatka entakapona. Supkutana pumpa foslevodopa/foskarbidopa novija je terapijska opcija koja postiže iste terapijske učinke, ali bez potrebe za invazivnom procedurom. Njezina prednost u odnosu na enteralne pumpe je u tome što ne zahtijeva invazivnu proceduru poput ugradnje sonde u probavni trakt. Odabir pacijenata za ove terapije zahtijeva detaljnu procjenu simptoma i odgovora na terapiju. Iako ove metode liječenja ne utječu na temeljni neurodegenerativni proces, ključne su u kontroli simptoma i poboljšanju kvalitete života pacijenata.Parkinson’s disease (PD) is the second most common neurodegenerative disease, marked by motor and non-motor symptoms due to dopaminergic neuron loss. In the past three decades, PD prevalence has significantly increased, arousing growing interest in exploring advanced treatment methods, especially for advanced stages of the disease. The advanced stage of PD is characterized by an inadequate response to oral therapy as well as motor fluctuations and dyskinesias. In response to these challenges, invasive therapeutic options such as infusion therapies have been developed, representing a significant advance in treating advanced PD. This review covers currently available infusion therapies used in PD patients. The first infusion therapy used in PD was the apomorphine subcutaneous pump, which has been used for 30 years and effectively reduces motor fluctuations and dyskinesias. Levodopa/carbidopa intestinal gel also reduces “OFF” periods and improves patients’ quality of life, with effectiveness in addressing non-motor symptoms as well. Levodopa/carbidopa/entacapone intestinal gel therapy allows for a similar therapeutic effect with a lower drug dose due to the addition of entacapone. The foslevodopa/foscarbidopa subcutaneous pump is a newer therapeutic option that achieves the same therapeutic effects without the need for an invasive procedure. Its advantage over enteral pumps is that it does not require an invasive procedure, such as the placement of a tube in the digestive tract. Selecting patients for these therapies requires a detailed assessment of symptoms and response to treatment. Although these treatment methods do not affect the underlying neurodegenerative process, they are crucial in symptom management
Neuroprotection by Anti-Oxidative Stress Response After Severe Traumatic Brain Injury – Do Extracellular Vesicles Count?
No full textTeška traumatska ozljeda mozga (tTOM) ozbiljna je i potencijalno životno ugrožavajuća ozljeda koju obično uzrokuje snažan udarac glavom ili djelovanje vanjske sile. Klinička manifestacija može jako varirati obuhvaćajući gubitak svijesti, kognitivno oštećenje, probleme s pamćenjem te senzorne, motorne i bihevioralne smetnje. tTOM zahtijeva hitno medicinsko liječenje jer se početna ozljeda mozga može dodatno pogoršati uslijed prateće hipoksije, hipotenzije i povišenog intrakranijskog tlaka. Akutno je zbrinjavanje stoga usmjereno na sprječavanje i/ili ublažavanje dodatnog oštećivanja mozga oslanjajući se pritom na makrofiziološke parametre. Međutim, bolje razumijevanje staničnih i molekularnih patofizioloških mehanizama omogućava detaljniji uvid u moždana zbivanja uz lakše kliničko vođenje bolesnika. U ovom preglednom članku prikazane su opće karakteristike tTOM‑a, kao i rane terapijske intervencije. Opisani su molekularni patofiziološki mehanizmi s naglaskom na oksidativni stres – jednim od glavnih štetnih intrakranijskih zbivanja tijekom akutnog tTOM‑a. Nadalje je raspravljena moguća uloga izvanstaničnih vezikula (IV) u antioksidativnom odgovoru nakon tTOM-a. Izvanstanične vezikule su nanočestice oslobođene iz stanica u tjelesne tekućine uključujući cerebrospinalnu (CST). Zbog raznovrsnog molekularnog sastava, izvanstanične vezikule iz CST-a mogu pridonijeti antioksidativnom odgovoru, ali i oksidativnom stresu, kako pokazuju nedavna istraživanja. Sveukupno uzevši, tTOM čine kompleksni i veoma dinamični patofiziološki procesi s ključnom ulogom oksidativnog stresa. Nedavno otkriveni posrednici antioksidativnog odgovora jesu izvanstanične vezikule koje su i sastavni dio CST‑a te mogu pomoći u otkrivanju podliježućih moždanih zbivanja. Daljnja ispitivanja trebaju otkriti pridonose li i u kojoj mjeri izvanstanične vezikule iz CST‑a antioksidativnom odgovoru nakon tTOM‑a.Severe traumatic brain injury (sTBI) is a serious and potentially life-threatening brain injury typically caused by a severe blow or impact to the head. The clinical manifestation can vary greatly and include loss of consciousness, cognitive impairment, memory problems, and sensory, motor, and behavioural disturbances. sTBI requires emergent treatment because the initial injury can be further aggravated by hypoxia, hypotension, and raised intracranial pressure. Acute management is therefore focused on preventing and/or mitigating additional damage to the brain by relying on macrophysiological parameters. However, a deeper understanding of the cellular and molecular pathophysiology of sTBI might offer additional insight into underlying processes in the brain and contribute to medical decision-making. Here we provide an overview of the main TBI features, including treatment in the acute phase. We describe the molecular pathophysiology with emphasis on oxidative stress as one of the major detrimental events in acute sTBI. Furthermore, we discuss if the anti-oxidative response after sTBI might be mediated by extracellular vesicles, nano-sized particles secreted by cells into body fluids including cerebrospinal fluid (CSF). EVs were attributed different roles in oxidative stress, and as carriers of various macromolecules, CSF-EVs might further combat oxidative stress in sTBI. Taken together, sTBI has a complex and dynamic pathophysiology with oxidative stress playing a significant part. Newly discovered mediators of anti-oxidative response are EVs which are present in CSF and can reveal ongoing processes in the brain. Further studies are required to determine if and how CSF-EVs participate in anti-oxidative response in sTBI
InterobServer AgreeMent in Pd‐l1 evaLuatIoN on cytoloGical samples—SAMPLING project: A multi‐institutional, international study
No full textThe overall moderate agreement observed highlights that improvement is still needed in inter‐pathologist agreement for programmed death‐ligand 1 (PD‐L1) evaluation on cytological samples. Sample preparation standardization, focused training in PD‐L1 evaluation on cytological material, its inclusion in External Quality Assessment, and machine learning‐derived image analysis tools could improve interobserver agreement
Absorption of Toxicants from the Ocular Surface: Potential Applications in Toxicology
No full textIn relation to the eye, the body can absorb substances from the ocular surface fluid (OSF) in a few ways: directly through the conjunctival sac, through the nasal mucosa as the fluid drains into the nose, or through ingestion. Regardless of the absorption method, fluid from the conjunctival sac should be used as a toxicological matrix, even though only small quantities are needed. Contemporary analytical techniques make it a suitable matrix for toxicological research. Analyzing small quantities of the matrix and nano-quantities of the analyte requires high-cost, sophisticated tools, which is particularly relevant in the high-throughput environment of new drug or cosmetics testing. Environmental toxicology also presents a challenge, as many pollutants can enter the system using the same ocular surface route. A review of the existing literature was conducted to assess potential applications in clinical and forensic toxicology related to the absorption of toxicants from the ocular surface. The selection of the studies used in this review aimed to identify new, more efficient, and cost-effective analytical technology and diagnostic methods
The impact of MITF expression on tumor-infiltrating lymphocytes in melanoma: Insights into immune microenvironment dynamics
No full textMelanoma progression is influenced by complex interactions between tumor cells and the immune microenvironment. This study examined the relationship between microphthalmia-associated transcription factor (MITF) expression and the immune microenvironment in primary melanoma using a modified classification of tumor-infiltrating lymphocytes (TILs) based on conventional BRISK categories. Archival formalin-fixed, paraffin-embedded tissue samples from 81 primary melanoma patients were analyzed via tissue microarray immunohistochemistry to assess MITF protein levels. TIL patterns were categorized into six groups, refining the traditional BRISK classification to distinguish between continuous and discontinuous infiltration, as well as peripheral vs intratumoral distribution. The analysis revealed that melanomas classified under the BRISK B category exhibited the highest MITF expression, often exceeding 50%. In contrast, tumors in the NON-BRISK and ABSENT TIL groups showed significantly lower MITF expression (mean values: 32.73% ± 16.98% and 22.00% ± 10.54%, respectively), with statistically significant differences (Kruskal–Wallis test, P = 0.027; modified classification, P = 0.011). Additionally, the presence of CD20+ B lymphocytes correlated with increased MITF expression (P = 0.009). MITF gene amplification was detected in 29% of cases, though its association with protein expression showed only a trend (P = 0.058). These findings highlight the complex interplay between MITF expression and TIL distribution in melanoma, suggesting that refined TIL classification may offer deeper insights into tumor immunobiology and help predict responses to immunotherapy
Could systemic infections influence the effectiveness of deep brain stimulation therapy in patients with dystonia?
No full textDystonia is a movement disorder characterized by sustained or intermittent muscle contractions resulting from aberrant sensory integration, enhanced cortical plasticity, and lack of intracortical inhibition. Deep brain stimulation of the globus pallidus internus (GPi-DBS) effectively treats dystonia, reducing abnormal neural oscillations and improving motor function. However, systemic infections can significantly impact brain function, altering brain wave dynamics and cortical excitability. We hypothesize that dystonia patients treated with DBS exhibit altered cortical excitability and changes in brain wave dynamics during early recovery from systemic infections, necessitating DBS parameters adjustment to prevent symptoms exacerbation. We propose a two-year clinical study involving 15 dystonia patients with DBS capable of local field potential (LFP) recording to evaluate this hypothesis. The study will analyze brain activity patterns, symptom severity and infection impact on neural activity. Continuous and infection-triggered LFP recording will provide data for advanced analysis to identify LFP patterns associated with dystonia symptoms and the effects of infections. This paper underscored the importance of individualized and dynamic DBS management, especially post-infection. Systemic infections can induce neuroinflammation, disrupting neural circuits and increasing brain sensitivity to DBS. Timely DBS adjustments are crucial to mitigate overstimulation and optimize outcomes. Enhanced post-infection care, including thorough evaluations and parameter adjustments, is essential for managing dystonia patients with DBS. Future research into the neuroinflammatory mechanism and their effect on neural circuits will improve our understanding and treatment of dystonia in the context of systemic infections
Latentna infekcija citomegalovirusom u središnjem živčanom sustavu (CMV-CNS): Plan upravljanja istraživačkim podacima
No full textAirborne desert dust in the Northern Adriatic area (Croatia): Different sources
No full textDuring the implementation of the INTERREG IT-HR project ECOMOBILITY, whose one of the goals was to estimate the impact of ship emissions on air quality in the port city of Rijeka (Croatia) and Venice (Italy), two particular weekly samples were collected in Rijeka, during the first and the thirteen weeks of sampling, i.e. S01 (16.10.-23.10.2018) and S13 (24.04.-30.04.2019.), respectively. Both samples have similarities regarding species characteristic for desert dust contribution, but HYSPLIT analyses excluded Saharan desert to be the source of the S01 sample. Unlike Saharan dust, this sample had a high contribution of fine and ultrafine particles (>50 % and 9.8 %, respectively), as well as secondary inorganic (sulfates, ammonium) and organic (water soluble organic compounds - WSOC) aerosols. Detailed synoptic situation and HYSPLIT backward trajectories pointed out the Syrian Desert as the source of this collected sample. The same source was proved by MERRA-2 reanalysis of the desert dust emission. Although the Saharan dust episodes, mostly in precipitation, are well known in the Northern Adriatic area, this is the first time to indicate Syrian Desert as a source of airborne particulates. This assumption was confirmed with chemical species characteristic for the Syrian Desert, i.e. higher content of potassium from K- feldspar and phosphates
