Koncentracije proupalnih citokina u nosnom sekretu kao indikatori težine nosne polipoze

The aim of this prospective study was to evaluate whether cytokine levels in nasal secretions may be clinical parameters of severity of nasal polyposis. Forty nasal polyp patients (20 asthmatic and 20 nonasthmatic) requiring surgical treatment were included. Nasal secretion samples were collected from nasal cavities of all 40 subjects. The levels of T-helper type 1 (Th1) proinflammatory cytokines IL -2, IL -12, IFN -g, IL -1β, TNF -α and TNF -β, Th2 cytokines IL -4, IL -5 and IL -6, antiinflammatory cytokine IL -10 and chemokine IL -8 were measured using flow cytometric method. Each of the 40 patients was staged clinically according to global nasal symptom score, endoscopic score, and Lund-Mackay computed tomography (CT) score. Eosinophils were counted in hematoxylin-eosin stained sections of all nasal polyp samples. The concentrations of Th2 proinflammatory cytokines IL -5 and IL -6 were significantly higher (p<0.05 and p<0.01, respectively) in patients with nasal polyposis and asthma compared with nasal polyp patients without asthma. Positive correlations were observed between IL -2 concentration in nasal secretions and nasal symptom score, endoscopic score, and Lund-Mackay score only in nasal polyp patients without asthma. We also found positive correlation between Lund-Mackay score and the levels of IL -8, IL -4, and IL -1β in nonasthmatic patients. A positive correlation between IL -5 levels in nasal fluid and endoscopic score was found only in asthmatic patients. Eosinophil counts were higher in asthmatic patients’ polyps compared with nonasthmatic ones, but without statistical significance. Nasal polyposis in asthmatic patients has different immunological patterns compared to those without asthma. The concentrations of cytokines measured in nasal fluid were not sensitive enough to be universal criteria to determine the severity of all forms of nasal polyposis.Cilj ove prospektivne studije bio je ispitati mogu li koncentracije citokina u nosnom sekretu poslužiti kao klinički parametri za procjenu težine nosne polipoze. U studiju je bilo uključeno 40 bolesnika s nosnom polipozom (20 astmatičnih i 20 neastmatičnih) u kojih je bilo potrebno kirurško liječenje. Uzorci nosnoga sekreta bili su sakupljeni iz nosnih šupljina svih 40 bolesnika. Koncentracije T pomoćničkih-1 (Th1) proupalnih citokina IL -2, IL -12, IFN -γ, IL -1β, TNF -α i TNF -β, Th2 citokina IL -4, IL -5 i IL -6, protuupalnog citokina IL -10 i hemokina IL -8 mjerene su primjenom metode protočne citometrije. Svaki od 40 bolesnika klinički je klasificiran prema zbiru nosnih simptoma, endoskopskom zbiru i Lund-Mackayevu zbiru. Eozinofili su se brojili u uzorcima nosnih polipa obojenim tehnikom hematoksilin-eozin. Koncentracije Th2 proupalnih citokina IL -5 i IL -6 bile su statistički značajno više u astmatičnih nego u neastmatičnih bolesnika s nosnom polipozom (P<0,05, P<0,01). Nađena je pozitivna korelacija između koncentracije IL -2 u nosnom sekretu i zbira nosnih simptoma, endoskopskog zbira i Lund-Mackayeva zbira samo u neastmatičnih bolesnika. Također su utvrđene pozitivne korelacije između Lund-Mackayeva zbira i razina IL -8, IL -4 i IL -1β u neastmatičnih bolesnika. Pozitivna koralacija između koncentracije IL -5 u nosnom sekretu i endoskopskog zbira nađena je samo kod astmatičnih bolesnika. Broj eozinofila bio je veći u tkivu nosnih polipa astmatičnih bolesnika nego u neastmatičnih, ali bez statističke značajnosti. Nosna polipoza u astmatičnih bolesnika ima drugačiji imunološki tijek u usporedbi s neastmatičnim bolesnicima. Koncentracije citokina mjerene u nosnom sekretu nisu dovoljno osjetljiv pokazatelj da bi bile univerzalni kriterij za procjenu težine svih oblika nosne polipoze

Phenylketonuria screening and management in southeastern Europe - survey results from 11 countries

Background: We aimed to assess the current state of PKU screening and management in the region of southeastern Europe. Methods: A survey was performed involving all identified professionals responsible for the PKU management in the 11 countries from South-Eastern region of Europe (Albania, Bulgaria, Bosnia and Herzegovina, Croatia, Kosovo, Macedonia, Moldova, Montenegro, Romania, Serbia, Slovenia). The questionnaire was designed to assess the characteristics regarding PKU management in three main areas: nation-wide characteristics, PKU screening, and characteristics of the PKU management in the responding centre. It consisted of 56 questions. The distribution and collection of the questionnaires (via e-mail) was taking place from December 2013 to March 2014. Results: Responses from participants from 11 countries were included; the countries cumulative population is approx. 52.5 mio. PKU screening was not yet introduced in 4 of 11 countries. Reported PKU incidences ranged from 1/7325 to 1/39338 (and were not known for 5 countries). National PKU guidelines existed in 5 of 11 countries and 7 of 11 countries had PKU registry (registries included 40 to 194 patients). The number of PKU centers in each country varied from1 to 6. Routine genetic diagnostics was reported in 4 of 11 countries. Most commonly used laboratory method to assess phenylalanine levels was fluorometric. Tetrahydrobiopterine was used in only 2 of 11 countries. Most frequently, pediatricians were caring for the patients. Dietitian was a member of PKU team in only 4 of 11 countries, while regular psychological assessments were performed in 6 of 11 countries. Patient's PKU society existed in 7 of 11 countries. Conclusions: The region of southeastern Europe was facing certain important challenges of PKU screening and management. Neonatal PKU screening should be introduced throughout the region. Furthermore, PKU management was falling behind internationally established standards-of-care in many aspects

Phenylketonuria screening and management in southeastern Europe - survey results from 11 countries

Background: We aimed to assess the current state of PKU screening and management in the region of southeastern Europe. Methods: A survey was performed involving all identified professionals responsible for the PKU management in the 11 countries from South-Eastern region of Europe (Albania, Bulgaria, Bosnia and Herzegovina, Croatia, Kosovo, Macedonia, Moldova, Montenegro, Romania, Serbia, Slovenia). The questionnaire was designed to assess the characteristics regarding PKU management in three main areas: nation-wide characteristics, PKU screening, and characteristics of the PKU management in the responding centre. It consisted of 56 questions. The distribution and collection of the questionnaires (via e-mail) was taking place from December 2013 to March 2014. Results: Responses from participants from 11 countries were included; the countries cumulative population is approx. 52.5 mio. PKU screening was not yet introduced in 4 of 11 countries. Reported PKU incidences ranged from 1/7325 to 1/39338 (and were not known for 5 countries). National PKU guidelines existed in 5 of 11 countries and 7 of 11 countries had PKU registry (registries included 40 to 194 patients). The number of PKU centers in each country varied from1 to 6. Routine genetic diagnostics was reported in 4 of 11 countries. Most commonly used laboratory method to assess phenylalanine levels was fluorometric. Tetrahydrobiopterine was used in only 2 of 11 countries. Most frequently, pediatricians were caring for the patients. Dietitian was a member of PKU team in only 4 of 11 countries, while regular psychological assessments were performed in 6 of 11 countries. Patient's PKU society existed in 7 of 11 countries. Conclusions: The region of southeastern Europe was facing certain important challenges of PKU screening and management. Neonatal PKU screening should be introduced throughout the region. Furthermore, PKU management was falling behind internationally established standards-of-care in many aspects

INFLUENCE OF ALLERGY ON CYTOKINE LEVEL IN NASAL DISCHARGE OF PATIENTS WITH NASAL POLYPS

Cytokine levels in nasal discharge reflect the inflammatory status of the nasal mucosa. The aim of the paper was to compare the concentrations of cytokines in nasal discharge in allergic and non-allergic patients with nasal polyps (NP). Thirty patients with NP (13 atopic and 17 non-atopic) were included in this study. Samples of nasal discharge were collected from nasal cavities of all 30 subjects. The levels of TNF-α, TNF- β, IL-1β, IL-2, IL-12, IFN-γ, IL-4, IL-5, IL-6, IL-10, and IL-8 in nasal discharge were measured using commercial flow cytometric kit. We found significantly higher concentrations of IL-4 (p<0.01), IL-5 (p<0.05), IL-6 (p<0.05) and TNF-β (p<0.05) in allergic patients with NP than in non-allergic. Polyps in non-atopic and atopic patients have different immunological patterns

Effects of different anesthetic agents on GM-CSF, MCP1, IL1α and TNFα levels in rat sepsis model

Anesthetic agents could alter the course and outcome of physical trauma, as well as experimentally or naturally occurring severe infections, by regulating several immune response mechanisms. The aim of our study was to investigate the influence of several commercially used anesthetic agents (ketamine, propofole, pentylentetrazole - PTZ) on cytokine concentrations, animal survival and pathohistological changes in the model of rat sepsis. In adult, male Wistar rats after different anesthetic treatment and induction of sepsis by cecal ligation and punction we estimated serum levels of IL1α, TNFα, GM-CSF and MCP-1 at 12h intervals. After 48h of sepsis induction, the largest number of animals survived in the group treated with PTZ (47%), while the lowest survival rate was in the propofole treatment group (24%). Contrary to survival rate, the most abundant pathohistological changes were seen on preparations from PTZ and than in ketamine/PTZ treated groups, without any significant changes in the CNS of propofole treated animals. In the propofole treated group there was a prominent increament of GM-CSF values at 12h and 24h, followed by a significant decreament at 36h. These changes were negatively correlated to the survival rate in this group. This group had the lowest levels of MCP1 at all evaluated time intervals. After high initial levels, IL1α and TNFα levels fell to undetectable concentrations and at 24h increased to a high level. In PTZ as well as ketamine groups, at 12 h interval, GM-CSF levels were lower than in the propofole treated group. Contrary, MCP-1 levels were higher in these groups comparing to propofole group. After a high initial peak, IL1α levels decreased to low but detectable levels, followed by an intensive rise in ketamine treated, but with further decrement in pentazole treated groups. TNFα levels were low through all evaluated intervals in both these groups. Our results indicate that induction of anaesthesia of animals with sepsis with variuos anesthetic agents is connected to different pathohistological CNS changes, distinct serum cytokine profiles and diverse survival rates

Efekti različitih anestetika na nivoe GM-CSF, MCP1, IL1α i TNFα na pacovskom modelu sepse

Anesthetic agents could alter the course and outcome of physical trauma, as well as experimentally or naturally occuring severe infections, by regulating several immune response mechanisms. The aim of our study was to investigate the influence of several commercially used anesthetic agents (ketamine, propofole, pentylentetrazole - PTZ) on cytokine concentrations, animal survival and pathohistological changes in the model of rat sepsis. In adult, male Wistar rats after different anesthetic traeatment and induction of sepsis by cecal ligation and punction we estimated serum levels of IL1α, TNFα, GM-CSF and MCP-1 at 12h intervals. After 48h of sepsis induction, the largest number of animals survived in the group treated with PTZ (47%), while the lowest survival rate was in the propofole treatment group (24%). Contrary to survival rate, the most abundant pathohistological changes were seen on preparations from PTZ and than in ketamine/PTZ treated groups, without any significant changes in the CNS of propofole treated animals. In the propofole treated group there was a prominent increament of GM-CSF values at 12h and 24h, followed by a significant decreament at 36h. These changes were negatively correlated to the survival rate in this group. This group had the lowest levels of MCP1 at all evaluated time intervals. After high initial levels, IL1α and TNFα levels fell to undetectable concentrations and at 24h increased to a high level. In PTZ as well as ketamine groups, at 12 h interval, GM-CSF levels were lower than in the propofole treated group. Contrary, MCP-1 levels were higher in these groups comparing to propofole group. After a high initial peak, IL1α levels decreased to low but detectable levels, followed by an intensive rise in ketamine treated, but with further decrement in pentazole treated groups. TNFα levels were low through all evaluated intervals in both these groups. Our results indicate that induction of anaesthesia of animals with sepsis with variuos anesthetic agents is connected to different pathohistological CNS changes, distinct serum cytokine profiles and diverse survival rates.Anestetici mogu izmeniti tok i ishod uticaja fizičke traume kao i eksperimentalno ili prirodno nastalih teških infekcija, regulacijom nekoliko mehanizama imunskog odgovora. Cilj naše studije je bio da ispitamo uticaj nekoliko komercijalno korišćenih anestetika (ketamina, propofola i pentzlentetrazola) na koncentraciju citokina, preživljavanje životinja i patohistološke promene u modelu sepse indukovane u pacova. U odraslih pacova, muškog pola, po primeni različitih anestetika i indukcije sepse podvezivanjem i punkcijom cekuma, utvrđivali smo nivoe IL1α, TNFα, IL4, IFNy, GM-CSF i MCp-1 u intervalima od 12 sati. Nakon 48 sati od indukcije sepse, najveći broj životinja preživeo je u grupi tretiranoj pentylenetetrazolom (50%), potom u ketamin/pentylenetetrazol tretiranoj grupi, dok je najmanja stopa preživljavanja bila u grupi tretiranoj propofolom (22%). Nasuprot stopi preživljavanja, najizraženije patohistološke promene su utvrđene na preparatima grupa tratiranih pentazolom i ketamin/pentylenetetrazol, bez značajnih promena u CNS u grupi životinja tretiranih propofolom. U uzorcima grupe tretirane propofolom detektovali smo intezivan porast vrednosti GM-CSF 12h i 24h, praćen značajnim padom posle 36h. Ove promene su negativno korelirale sa stopom preživljavanja u ovoj grupi. Ova grupa je imala i najniže vrednosti MCP-1 u svim praćenim vremenskim intervalima. Posle visokih inicijalnih nivoa, vrednosti IL1a i TNFα pale su na nedetektabilne a u terminu od 24h porasle su na visok nivo. U grupama tretiranim pentazolom i ketaminom, 12. sata, vrednosti GM-CSF bile su niže od grupe tretirane propofolom. Nasuprot tome, vrednosti MCP-1 su bile veće u ovim grupama u odnosu na propofolom tretiranu grupu. Posle visokog inicijalnog skoka, vrednosti IL1α smanjuju se na niske ali detektabilne vrednosti, a zatim sledi intezivan rast u ketaminom tretiranoj grupi i dalji pad vrednosti u pentilenetetrazol tretiranoj grupi. Vrednosti TNFα su u ove dve grupe bile niske u svim ispitivanim intervalima. Vrednosti IL4 i IFNy su bile praktično nedetektabilne u svim ispitivanim grupama. Naši rezultati ukazuju da je indukcija anestezije u životinja sa sepsom različitim anesteticima povezana sa različitim patohistološkim nalazima u CNS, različitim serumskim profilom citokina i različitom stopom preživljavanja

Current State of Compulsory Basic and Clinical Courses in Genetics for Medical Students at Medical Faculties in Balkan Countries With Slavic Languages

In this study we aimed to perform the first research on the current state of compulsory basic and clinical courses in genetics for medical students offered at medical faculties in six Balkan countries with Slavic languages (Bosnia and Herzegovina, Croatia, Montenegro, North Macedonia, Serbia, and Slovenia). The study was conducted from June to September 2021. One representative from each country was invited to collect and interpret the data for all medical faculties in their respective country. All representatives filled a questionnaire, which consisted of two sets of questions. The first set of questions was factual and contained specific questions about medical faculties and design of compulsory courses, whereas the second set of questions was more subjective and inquired the opinion of the representatives about mandatory education in clinical medical genetics in their countries and internationally. In addition, full course syllabi were analysed for course aims, learning outcomes, course content, methods for student evaluation and literature. Detailed analysis was performed for a total of 22 medical faculties in Bosnia and Herzegovina (6), Croatia (4), Montenegro (1), North Macedonia (3), Serbia (6), and Slovenia (2). All but the two medical faculties in Slovenia offer either compulsory courses in basic education in human genetics (16 faculties/courses) or clinical education in medical genetics (3 faculties/courses). On the other hand, only the medical faculty in Montenegro offers both types of education, including one course in basic education in human genetics and one in clinical education in medical genetics. Most of the basic courses in human genetics have similar aims, learning outcomes and content. Conversely, clinical courses in medical genetics are similar concerning study year position, number of contact hours, ECTS (European Credit Transfer and Accumulation System) and contents, but vary considerably regarding aims, learning outcomes, ratio of types of classes, teaching methods and student evaluation. Our results emphasise the need for future collaboration in reaching a consensus on medical genetics education in Balkan countries with Slavic languages. Further research warrants the analysis of performance of basic courses, as well as introducing clinical courses in medical genetics to higher years of study across Balkan countries

A novel splice-site FHOD3 founder variant is a common cause of hypertrophic cardiomyopathy in the population of the Balkans-A cohort study.

Founder variants in sarcomere protein genes account for a significant proportion of disease-causing variants in patients with hypertrophic cardiomyopathy (HCM). However, information on founder variants in non-sarcomeric protein genes, such as FHOD3, which have only recently been associated with HCM, remains scarce. In this study, we conducted a retrospective analysis of exome sequencing data of 134 probands with HCM for recurrent pathogenic variants. We discovered a novel likely pathogenic variant c.1646+2T>C in FHOD3 in heterozygous state in eight probands with HCM and confirmed its presence in seven additional relatives. Individuals with this variant had a wide range of ages at onset of the disease (4-63 years). No adverse cardiac events were observed. Haplotype analysis revealed that the individuals with this variant shared a genomic region of approximately 5 Mbp surrounding the variant, confirming the founder effect of the variant. FHOD3 c.1646+2T>C is estimated to have arisen 58 generations ago (95% CI: 45-81) in a common ancestor living on the Balkans. A founder FHOD3 c.1646+2T>C variant is the second most common genetic variant in our cohort of patients with HCM, occurring in 16% of probands with a known genetic cause of HCM, which represents a substantially higher proportion than the currently estimated 0.5-2% for causal FHOD3 variants. Our study broadens the understanding of the genetic causes of HCM and may improve the diagnosis of this condition, particularly in patients from the Balkans