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Összefoglaló. Bevezetés: A rákbetegségek incidencia- (gyakorisági) értékei világszerte, így Magyarországon is folyamatosan növekednek. Az emlőrákok előfordulása és kórlefolyása a két nemben azonban sajátosan különbözik. Célkitűzés: Célul tűztük ki, hogy megvizsgáljuk és értékeljük a női és a férfiemlőrák incidencia- és mortalitási (halálozási) adatait Magyarországon 2000 és 2016 között. Módszer: A Központi Statisztikai Hivatalból és a Nemzeti Rákregiszterből származó adatok standardizált, 100 000 főre számított feldolgozása. Eredmények: Magyarországon a vizsgált időszakban az emlőrákok gyakoriságának növekedése megközelítőleg ugyanolyan mértékű (39%) volt, mint az összes ráké (34%). Az emelkedés jelentős: a 2016-ban 8,7% részarányú női emlőrák esetében 39%, a 0,22%-os részarányú férfiráknál 60%. Ezzel szemben a halálozási adatok jelentős mértékű csökkenéseket mutatnak mind az összes daganat, mind a női emlőrák vonatkozásában, míg a férfiemlőrák esetében a csökkenés nagyobb mértékű. A rosszindulatú daganatok incidenciája és a 2-es típusú diabetes mellitus (2DM) prevalenciája egyaránt magasan szignifikáns korrelációt mutatott az egy főre jutó bruttó nemzeti össztermék (GDP) értékének növekedésével. Új megfigyelés, hogy a 2DM-növekedés időben megelőzte a daganatok incidenciájának növekedését. Következtetés: A vizsgált időszakban a női és a férfiemlőrákok magyarországi gyakorisági és halálozási adatai a nemzetköziekhez hasonló tendenciákat mutatnak. A férfiemlőrákok sokkal ritkábbak, de kezelésük kevésbé hatékony. Új szempont, hogy a rosszindulatú daganatok gyakoribb megjelenésében a klinikailag kedvezőtlenebb 2DM százalékos arányának (prevalenciájának) emelkedése is jelentős tényező lehet az elhízáshoz kapcsolódva. A GDP növekedése kedvezően hathatott a halálozások csökkenésében a kedvezőbb gyógyítási és megelőzési feltételek megteremtésével. Ugyanakkor ennek a növekedésnek szerepe lehet az elhízással összefüggő 2DM prevalenciájának emelkedésében is. Orv Hetil. 2022; 163(5): 181–186. Summary. Introduction: The incidence of malignant cancers is continuously growing. In breast cancers, the incidence and clinical course are greatly different in the two genders. Objective: We aimed to investigate the incidence and mortality of breast cancers in females and males in Hungary between 2000 and 2016. Methods: The data derived from the Hungarian Central Statistical Office and the National Cancer Registry were evaluated and standardized for 100 000 inhabitants. Results: In Hungary, the elevation of breast cancer incidence (39%) showed a similar extent as that of total tumours (34%). In female breast cancers representing a much greater percent (8.7% in 2016) than that in males (0.22%), the increase was significant (39%) as in males (60 %). On the other hand, mortality was significantly lower for both of them regarding total malignant and female breast tumours, whereas the decrease was greater in the male breast cancers. The increase of GDP per capita showed highly significant correlation with the incidence of malignant tumours and prevalence of diabetes mellitus type 2 (2DM). It was a new finding that the increase in the prevalence of 2DM precedes the elevation of the incidence of cancer. Conclusion: In Hungary, the data of incidence and mortality of female and male breast cancers showed similar tendencies as the international ones. The breast cancers of males were rarer but their treatment was less effective. However, it was a new aspect that in the increased incidence of malignant tumours also the greater prevalence of 2DM could be an important factor related to obesity. Orv Hetil. 2022; 163(5): 181–186.

The goal of this work was to elucidate the potential role of “red wine producing background” in the prevention of cardiac mortality. In 20 European countries with the lowest cardiac mortality rates it was found that in South-Europe producing mainly red wines and showing low cardiac mortality rates the type of drinking waters were hard everywhere. This fact could have a greater impact on the good results than the role of red wines. Besides, the higher values of “general domestic product” had a protective role against cardiac mortality in general. In a further study, also on large populations, five Hungarian wine territories were divided in two groups on the basis of similarities in the values of mortality rates, hardness of drinking waters and social backgrounds. Group I: Tokaj and Hódmezővásárhely: with higher cardiac mortality, soft drinking waters and worse social backgrounds; Group II: Szekszárd-Villány, Balaton, Eger: with lower cardiac mortality, hard drinking waters and better social backgrounds. In Group II the white wine producing Balaton region also presented low (good) cardiac mortality rates together with the two red wine producing territories (Szekszárd and Eger), they all had similarly hard drinking waters and good social backgrounds. It could be concluded that the red or white characters of wines produced in these territories did not make any differences in the data of cardiac age-adjusted death rates. On the other hand, the positive roles of similarly hard drinking waters and better social conditions had a greater impact on cardiac prevention than the red or white types of wines produced and supposedly consumed here. In the case of Tokaj, the soft drinking waters plus the worse social backgrounds and not the type of wines involved the bad results. The difference in the red or white types of wines produced in a region seemed negligible in the prevention of cardiac mortality compared to the roles of harder drinking waters and wealthier social backgrounds. Thus, neither the red or white wines were found to be special antidotes for cardiac diseases. However, they will remain crucial parts of the general gastronomic culture of mankind.

Összefoglaló. Bevezetés: Egy új, számítógép által segített betegminta-asszociációs analízis eredménye szerint a COVID–19 tüneteinek kialakításában kiemelt tényezőként jelenik meg a bradikinin. Eszerint a bradikinin lebontása lelassul az angiotenzinkonvertáló enzim aktivitásának csökkenése miatt, ami jelentősen megemelkedő bradikininszinthez vezet a tüdőben. Nem merült fel azonban a véralvadási faktorok lehetséges szerepe a „bradikininviharban”, annak ellenére, hogy az idősebb cardiovascularis betegekben aktiválódó XII-es faktor és a C1-észteráz-inhibitor (C1INH) alacsony szintje nagy mennyiségű bradikinin képződéséhez vezethet. Módszer: Átfogó irodalmi áttekintés. Eredmények: 1) A vírus által fertőzött, sérült endotheliumsejtek felülete az a hely, amellyel érintkezve elindulhat a XII-es véralvadási faktor aktivációja – ez serkenti a prekallikrein/kallikrein/kinin rendszert, és bradikininképződést okoz. Ez a folyamat megtörténik a súlyos vese- és tüdőkárosodást okozó hantavírus-fertőzésekben. 2) Idős betegekben az atherosclerosis miatt többszörösen sérült, merev, „stiff” erek endotheliumfelszínein jóval magasabb lehet a XII-es faktor kontakt úton történő aktivációja, mint a fiatal egyének ereiben. Ez a tény egyik oka lehet az idős, cardiovascularis betegek körében tapasztalt magasabb halálozásnak. Következtetés: Az aktivált XII-es véralvadási faktor célzott gátlása újabb gyógyítási lehetőség lehet a SARS-CoV-2-fertőzött idős betegekben. Jelenleg már hatásosnak bizonyult a bradikininképzést gátló C1INH-nak, továbbá a bradikininreceptor-gátlóknak az adása is. Orv Hetil. 2020; 161(50): 2099–2103. Summary. Introduction: Bradykinin was implicated in a new complex model of pathomechanism leading to the symptoms of COVID-19 created by a computer-assisted association analysis. According to this model, the decrease in angiotensin-converting enzyme expression leads to impaired bradykinin elimination and subsequent enrichment in the lungs. However, there is no mentioning of the importance of blood coagulation factor XII in increased bradykinin production, in spite of its age-dependent activation and the lower level of C1-esterase inhibitor (C1INH). Activated factor XII may be an important contributor to the “bradykinin storm” in elder cardiovascular patients. Method: Literature review. Results: 1) Activation of the coagulation factor XII on the surface of SARS-CoV-2 infected endothelial cells may trigger the prekallikrein/kallikrein/kinin system producing bradykinin. Such process is taking place in hantavirus infections causing severe lung and kidney damages. 2) The endothelial system is dysregulated in elderly patients, resulting in potentially higher factor XII activities on the surface of damaged endothelial cells in the stiffened arteries. This can contribute to the higher mortality rates in the elderly. Conclusion: The targeted inhibition of activated blood coagulation factor XII may represent a new therapeutic target for COVID-19, especially for elder patients. Recently, beneficial results have already been observed by the clinical applications of recombinant C1INH and bradykinin receptor antagonists. Orv Hetil. 2020; 161(50): 2099–2103.

Introduction The usage of extended-criteria donors (ECD) became a routinely accepted manner in the last decade. ECD is a potential risk factor for antibody-mediated rejection. Analysis of lymphocyte subsets might be a complementary diagnostic toolkit because there is limited knowledge about this term. Method Between May 12, 2016, and September 4, 2019, a total of 130 patients who had undergone kidney transplant were investigated. Patients were divided in ECD and standard criteria donor (SCD) groups. Blood samples were collected before the operation, then in the first week and after 30, 60, 180, and 365 days. Besides routine laboratory tests, multicolor flow cytometry was performed for lymphocyte subsets. Results ECD grafts were transplanted to older recipients. The number of CD4+ cells increased in the SCDs from the first week to until the end of first month, and then decreased. The number of CD4+ cells decreased from the beginning of the study until the end of first year to 66% of its original value in ECDs. At the first month, the number of CD19+ cells was higher in SCD compared with ECD cases; the number then decreased in both groups. T-regulatory cells had a drop at the first week that lasted until the first month. A bigger increase in SCD and a moderate increase in ECD group were then observed. The kinetics of CD19+ and CD19+ naive cells are similar in the ECD and SCD groups. In the SCD group, cell count decreased in both CD19+ (13%) and CD19+ naive (12%) between third and sixth month. The count of CD19+ cells decreased by 9%, but the count of CD19+ naive cells increased by 11% between the sixth month and first year. Discussion The prolonged postoperative uremic state caused by the poorer initial function, together with an aging immune system, explains the weaker immune response in ECD patients, which may be the cause of the decreased number of memory and regulatory T cells. Older patients with an ECD graft need a tailored, personalized, and less aggressive immunosuppressive treatment.

Severe cases of COVID-19 are characterized by an inflammatory burst, which is accompanied by multiorgan failure. The elderly population has higher risk for severe or fatal outcome for COVID-19. Inflammatory mediators facilitate the immune system to combat viral infection by producing antibodies against viral antigens. Several studies reported that the pro-inflammatory state and tissue damage in COVID-19 also promotes autoimmunity by autoantibody generation. We hypothesized that a subset of these autoantibodies targets cardiac antigens. Here we aimed to detect anti-cardiac autoantibodies in severe COVID-19 patients during hospitalization. For this purpose, 104 COVID-19 patients were recruited, while 40 heart failure patients with dilated cardiomyopathy and 20 patients with severe aortic stenosis served as controls. Patients were tested for anti-cardiac autoantibodies, using human heart homogenate as a bait. Follow-up samples were available in 29 COVID-19 patients. Anti-cardiac autoantibodies were detected in 68% (71 out of 104) of severe COVID-19 patients. Overall, 39% of COVID-19 patients had anti-cardiac IgG autoantibodies, while 51% had anti-cardiac autoantibodies of IgM isotype. Both IgG and IgM anti-cardiac autoantibodies were observed in 22% of cases, and multiple cardiac antigens were targeted in 38% of COVID-19 patients. These anti-cardiac autoantibodies targeted a diverse set of myocardial proteins, without apparent selectivity. As controls, heart failure patients (with dilated cardiomyopathy) had similar occurrence of IgG (45%, p = 0.57) autoantibodies, while significantly lower occurrence of IgM autoantibodies (30%, p = 0.03). Patients with advanced aortic stenosis had significantly lower number of both IgG (11%, p = 0.03) and IgM (10%, p

Összefoglaló. Bevezetés: Az atorvasztatin (koleszterincsökkentő), nifedipin (Ca2+-antagonista), kaptopril (angiotenzinkonvertáz-gátló) vegyületek a magas vérnyomás komplex kezelésének „alap”gyógyszerei. Mindhárom antioxidáns is. Célkitűzés: A tanulmány célja annak megválaszolása volt, hogy e molekulák gátolhatják-e a vérsejtek fagocitaműködését. Betegek és módszer: Magas vérnyomásos betegek: 15 fő, 39–80 éves, nő: 6, férfi: 9. Egészséges kontroll: 7 fő, 30–75 éves, nő: 3, férfi: 4. A vizsgálat a téli hónapokban zajlott. A zimozán- (Saccharomyces cerevisiae) részecskék fagocitózisa során képződő kemilumineszcencia mérése perifériás vérben a gyógyszerek jelenlétében történt luminométerrel. A gátlást a stimulációs index értékének csökkenésével jellemeztük. Eredmények: Mindhárom vegyület gátolta a kemilumineszcenciát (oxigénszabadgyök-képzést) a 65 év feletti, magas vérnyomásos betegek többségében: 11/13 főnél. Főleg magasabb életkorban és cukorbetegségben, de más társbetegségekben nőtt a gátlás. Következtetés: Az idős, magas vérnyomásos betegek fokozott orvosi figyelmet igényelnek a téli időszakokban, mivel antioxidáns hatással is rendelkező „alap”gyógyszereiknek, egyéntől függően, lehetnek gátló hatásaik a fagociták mikrobaölő, oxigénszabadgyök-termelő képességére. Orv Hetil. 2020; 161(45): 1908–1913. Summary. Introduction: Atorvastatin (cholesterol synthesis blocker), nifedipine (Ca2+ antagonist), captopril (angiotensin-convertase inhibitor) are basic drugs in the therapy of hypertension. They are also antioxidants. Objective: To investigate whether these molecules can inhibit the phagocytic activity of peripheral blood cells. Patients and method: Hypertension group: 15 patients with ages between 39–80 years (6 women and 9 men). Healthy control group: 7 individuals with ages between 30–75 years (3 women and 4 men). The study was carried out in wintertime. The measurement of phagocytic activity was carried out by luminometry in peripheral blood samples. Chemiluminescence intensities were determined by the engulfment of zymosan (Saccharomyces cerevisiae) particles in the presence of drugs. The inhibitory effects were characterized by the decreased values of the stimulation index. Results: All three substances decreased the chemiluminescence (reactive oxygen species production) in the majority of samples from hypertensive patients over 65 years: in 11 of 13 patients. Stronger inhibition was detected in older, diabetic patients with other co-morbidities, too. Conclusion: Older patients with hypertension require a special attention in wintertime. Antihypertensive drugs with antioxidant capabilities may have individually different inhibitory effects on the production of reactive oxygen species by phagocytes, which decreases their antimicrobial potency. Orv Hetil. 2020; 161(45): 1908–1913.

Összefoglaló. Bevezetés: A rákbetegségek incidencia- (gyakorisági) értékei világszerte, így Magyarországon is folyamatosan növekednek. Az emlőrákok előfordulása és kórlefolyása a két nemben azonban sajátosan különbözik. Célkitűzés: Célul tűztük ki, hogy megvizsgáljuk és értékeljük a női és a férfiemlőrák incidencia- és mortalitási (halálozási) adatait Magyarországon 2000 és 2016 között. Módszer: A Központi Statisztikai Hivatalból és a Nemzeti Rákregiszterből származó adatok standardizált, 100 000 főre számított feldolgozása. Eredmények: Magyarországon a vizsgált időszakban az emlőrákok gyakoriságának növekedése megközelítőleg ugyanolyan mértékű (39%) volt, mint az összes ráké (34%). Az emelkedés jelentős: a 2016-ban 8,7% részarányú női emlőrák esetében 39%, a 0,22%-os részarányú férfiráknál 60%. Ezzel szemben a halálozási adatok jelentős mértékű csökkenéseket mutatnak mind az összes daganat, mind a női emlőrák vonatkozásában, míg a férfiemlőrák esetében a csökkenés nagyobb mértékű. A rosszindulatú daganatok incidenciája és a 2-es típusú diabetes mellitus (2DM) prevalenciája egyaránt magasan szignifikáns korrelációt mutatott az egy főre jutó bruttó nemzeti össztermék (GDP) értékének növekedésével. Új megfigyelés, hogy a 2DM-növekedés időben megelőzte a daganatok incidenciájának növekedését. Következtetés: A vizsgált időszakban a női és a férfiemlőrákok magyarországi gyakorisági és halálozási adatai a nemzetköziekhez hasonló tendenciákat mutatnak. A férfiemlőrákok sokkal ritkábbak, de kezelésük kevésbé hatékony. Új szempont, hogy a rosszindulatú daganatok gyakoribb megjelenésében a klinikailag kedvezőtlenebb 2DM százalékos arányának (prevalenciájának) emelkedése is jelentős tényező lehet az elhízáshoz kapcsolódva. A GDP növekedése kedvezően hathatott a halálozások csökkenésében a kedvezőbb gyógyítási és megelőzési feltételek megteremtésével. Ugyanakkor ennek a növekedésnek szerepe lehet az elhízással összefüggő 2DM prevalenciájának emelkedésében is. Orv Hetil. 2022; 163(5): 181-186.The incidence of malignant cancers is continuously growing. In breast cancers, the incidence and clinical course are greatly different in the two genders.We aimed to investigate the incidence and mortality of breast cancers in females and males in Hungary between 2000 and 2016.The data derived from the Hungarian Central Statistical Office and the National Cancer Registry were evaluated and standardized for 100 000 inhabitants.In Hungary, the elevation of breast cancer incidence (39%) showed a similar extent as that of total tumours (34%). In female breast cancers representing a much greater percent (8.7% in 2016) than that in males (0.22%), the increase was significant (39%) as in males (60 %). On the other hand, mortality was significantly lower for both of them regarding total malignant and female breast tumours, whereas the decrease was greater in the male breast cancers. The increase of GDP per capita showed highly significant correlation with the incidence of malignant tumours and prevalence of diabetes mellitus type 2 (2DM). It was a new finding that the increase in the prevalence of 2DM precedes the elevation of the incidence of cancer.In Hungary, the data of incidence and mortality of female and male breast cancers showed similar tendencies as the international ones. The breast cancers of males were rarer but their treatment was less effective. However, it was a new aspect that in the increased incidence of malignant tumours also the greater prevalence of 2DM could be an important factor related to obesity. Orv Hetil. 2022; 163(5): 181-186.

Abstract: Immunglobulin E (IgE)-based, irregularly recurring, severe anaphylactic reactions occurred in a 50-year-old European white male patient suffering also from Crohn’s disease. On the base of immunologic laboratory tests concerning the mechanism of the phenomenon, the idea arose whether molecules derived for certain microbial derivatives could enter the blood circulation via the damaged bowel walls in the patient with Crohn’s disease and they might act as allergens. The microbial analysis diagnosed atypical Staphylococcus in the stool. The serum level of IgE was very high. The concomitant use of targeted antibiotics and anti-allergy and immunosuppressive agents resulted in a complete remission during a couple of months. Not only Crohn’s disease has improved, but also the total serum IgE level has decreased significantly, and the unpredictable anaphylactic attacks have been completely eliminated. In Crohn’s disease, the anaphylactic complications induced by atypical microbial allergens (e.g., derivatives of Staphylococcus) can be effectively treated after the recognition of this pathological mechanism. This is the first description of such a pathologic state. Orv Hetil. 2019; 160(38): 1514–1518.

Összefoglaló. Bevezetés: Egy új, számítógép által segített betegminta-asszociációs analízis eredménye szerint a COVID-19 tüneteinek kialakításában kiemelt tényezőként jelenik meg a bradikinin. Eszerint a bradikinin lebontása lelassul az angiotenzinkonvertáló enzim aktivitásának csökkenése miatt, ami jelentősen megemelkedő bradikininszinthez vezet a tüdőben. Nem merült fel azonban a véralvadási faktorok lehetséges szerepe a "bradikininviharban", annak ellenére, hogy az idősebb cardiovascularis betegekben aktiválódó XII-es faktor és a C1-észteráz-inhibitor (C1INH) alacsony szintje nagy mennyiségű bradikinin képződéséhez vezethet. Módszer: Átfogó irodalmi áttekintés. Eredmények: 1) A vírus által fertőzött, sérült endotheliumsejtek felülete az a hely, amellyel érintkezve elindulhat a XII-es véralvadási faktor aktivációja - ez serkenti a prekallikrein/kallikrein/kinin rendszert, és bradikininképződést okoz. Ez a folyamat megtörténik a súlyos vese- és tüdőkárosodást okozó hantavírus-fertőzésekben. 2) Idős betegekben az atherosclerosis miatt többszörösen sérült, merev, "stiff" erek endotheliumfelszínein jóval magasabb lehet a XII-es faktor kontakt úton történő aktivációja, mint a fiatal egyének ereiben. Ez a tény egyik oka lehet az idős, cardiovascularis betegek körében tapasztalt magasabb halálozásnak. Következtetés: Az aktivált XII-es véralvadási faktor célzott gátlása újabb gyógyítási lehetőség lehet a SARS-CoV-2-fertőzött idős betegekben. Jelenleg már hatásosnak bizonyult a bradikininképzést gátló C1INH-nak, továbbá a bradikininreceptor-gátlóknak az adása is. Orv Hetil. 2020; 161(50): 2099-2103.Bradykinin was implicated in a new complex model of pathomechanism leading to the symptoms of COVID-19 created by a computer-assisted association analysis. According to this model, the decrease in angiotensin-converting enzyme expression leads to impaired bradykinin elimination and subsequent enrichment in the lungs. However, there is no mentioning of the importance of blood coagulation factor XII in increased bradykinin production, in spite of its age-dependent activation and the lower level of C1-esterase inhibitor (C1INH). Activated factor XII may be an important contributor to the "bradykinin storm" in elder cardiovascular patients.Literature review.1) Activation of the coagulation factor XII on the surface of SARS-CoV-2 infected endothelial cells may trigger the prekallikrein/kallikrein/kinin system producing bradykinin. Such process is taking place in hantavirus infections causing severe lung and kidney damages. 2) The endothelial system is dysregulated in elderly patients, resulting in potentially higher factor XII activities on the surface of damaged endothelial cells in the stiffened arteries. This can contribute to the higher mortality rates in the elderly.The targeted inhibition of activated blood coagulation factor XII may represent a new therapeutic target for COVID-19, especially for elder patients. Recently, beneficial results have already been observed by the clinical applications of recombinant C1INH and bradykinin receptor antagonists. Orv Hetil. 2020; 161(50): 2099-2103.

Coronavirus disease 2019 (COVID-19) has a high mortality in elderly patients with pre- existing cardiovascular diseases. The cellular receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the angiotensin converting enzyme 2 (ACE2), thereby implicating a link between cardiovascular diseases and SARS-CoV-2 susceptibility. Aortic stenosis (AS) represents a chronic inflammatory state with severe cardiovascular complications in the elderly, a prime condition for COVID-19 mortality. The circulating ACE2 levels were measured in 111 patients with severe AS and compared to patients with hypertension and healthy individuals.About 4-times higher circulating ACE2 activity was found in patients with severe AS than in hypertensives or healthy individuals (103.4±5.4, n=111, 24.4±0.6, n=540 and 17.3±1.3±0.6 mU/L, n=46, respectively). Patients with severe AS were older than patients with hypertension (79±0.7 years vs. 60±0.5 years, P

Coronavirus disease 2019 (COVID-19) has a high mortality in elderly patients with pre-existing cardiovascular diseases. The cellular receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the angiotensin-converting enzyme 2 (ACE2), thereby implicating a link between cardiovascular diseases and SARS-CoV-2 susceptibility. Aortic stenosis (AS) represents a chronic inflammatory state with severe cardiovascular complications in the elderly, a prime condition for COVID-19 mortality. The circulating ACE2 levels were measured in 111 patients with severe AS and compared to patients with hypertension and healthy individuals. About 4 times higher circulating ACE2 activity was found in patients with severe AS than in hypertensives or healthy individuals (88.3 ± 61.6., n = 111, 20.6 ± 13.4, n = 540, and 16.1 ± 7.4 mU/L, n = 46, respectively). Patients with severe AS were older than patients with hypertension (80 ± 6 years vs. 60 ± 15 years, P

Összefoglaló. Bevezetés: Az atorvasztatin (koleszterincsökkentő), nifedipin (Ca2+-antagonista), kaptopril (angiotenzinkonvertáz-gátló) vegyületek a magas vérnyomás komplex kezelésének "alap"gyógyszerei. Mindhárom antioxidáns is. Célkitűzés: A tanulmány célja annak megválaszolása volt, hogy e molekulák gátolhatják-e a vérsejtek fagocitaműködését. Betegek és módszer: Magas vérnyomásos betegek: 15 fő, 39-80 éves, nő: 6, férfi: 9. Egészséges kontroll: 7 fő, 30-75 éves, nő: 3, férfi: 4. A vizsgálat a téli hónapokban zajlott. A zimozán- (Saccharomyces cerevisiae) részecskék fagocitózisa során képződő kemilumineszcencia mérése perifériás vérben a gyógyszerek jelenlétében történt luminométerrel. A gátlást a stimulációs index értékének csökkenésével jellemeztük. Eredmények: Mindhárom vegyület gátolta a kemilumineszcenciát (oxigénszabadgyök-képzést) a 65 év feletti, magas vérnyomásos betegek többségében: 11/13 főnél. Főleg magasabb életkorban és cukorbetegségben, de más társbetegségekben nőtt a gátlás. Következtetés: Az idős, magas vérnyomásos betegek fokozott orvosi figyelmet igényelnek a téli időszakokban, mivel antioxidáns hatással is rendelkező "alap"gyógyszereiknek, egyéntől függően, lehetnek gátló hatásaik a fagociták mikrobaölő, oxigénszabadgyök-termelő képességére. Orv Hetil. 2020; 161(45): 1908-1913.Atorvastatin (cholesterol synthesis blocker), nifedipine (Ca2+ antagonist), captopril (angiotensin-convertase inhibitor) are basic drugs in the therapy of hypertension. They are also antioxidants.To investigate whether these molecules can inhibit the phagocytic activity of peripheral blood cells.Hypertension group: 15 patients with ages between 39-80 years (6 women and 9 men). Healthy control group: 7 individuals with ages between 30-75 years (3 women and 4 men). The study was carried out in wintertime. The measurement of phagocytic activity was carried out by luminometry in peripheral blood samples. Chemiluminescence intensities were determined by the engulfment of zymosan (Saccharomyces cerevisiae) particles in the presence of drugs. The inhibitory effects were characterized by the decreased values of the stimulation index.All three substances decreased the chemiluminescence (reactive oxygen species production) in the majority of samples from hypertensive patients over 65 years: in 11 of 13 patients. Stronger inhibition was detected in older, diabetic patients with other co-morbidities, too.Older patients with hypertension require a special attention in wintertime. Antihypertensive drugs with antioxidant capabilities may have individually different inhibitory effects on the production of reactive oxygen species by phagocytes, which decreases their antimicrobial potency. Orv Hetil. 2020; 161(45): 1908-1913.

Abstract: Introduction: Eating habits act on mortalities from gastrointestinal tumors and cardiovascular diseases. Aim: To investigate the role of wine drinking on these mortalities in Hungary. Method: The standardized mortality data of people from 206,159 subjects died of gastrointestinal tumors and cardiovascular diseases between 2000–2010 were compared in four wine regions: Tokaj (white), Eger (red), Balaton (white), Szekszárd/Villány (red) and in Hódmezővásárhely (not-wine region). Results: The significantly smallest number of tumors (664) occurred in Tokaj, but the cardiovascular mortality here was the highest (5955). On the other hand, the fewest cardiovascular mortality occurred in Szekszárd/Villány (3907), but showing here (831) and in Eger (934) the highest values of tumor death. Conclusions: The protective effect of red wine on cardiovascular mortality was verified. Surprisingly, the low value of gastrointestinal mortality in “Tokaj” – besides the higher level of selenium in tap water – shows some hidden features of these white wines. Orv Hetil. 2017; 158(25): 992–998.

Introduction Accelerated antibody-mediated rejection is a major challenge after kidney transplantation. While the clinical course, diagnosis, and treatment of cell-mediated acute rejection is agreed upon and has been successfully performed, the antibody-mediated rejection remains a problem. Biopsies cannot be repeated several times, are not always representative, and are refused by many patients. Analysis of T-cell subsets and donor-specific antibodies (DSAs) might be an additive diagnostic tool in the case of kidney transplantation. Method Between 2015 and 2017, 50 kidney transplant patients were enrolled in the study. Patients were divided into 2 clinical groups: primary transplants and regrafted patients. Serum samples were collected right before the operation, then in 1 week; 30, 60, and 180 days; and yearly. Besides routine laboratory, multicolor flow cytometry was performed for T cell subsets, and Luminex Single Antigen Bead assay for the detection on donor-specific anti-HLA antibodies. Medical data were also fixed. Results The percentage of CD4+ and CD8+ cells (the CD4+/CD8+ rate) did not change much over time in either group. The percentage of CD19+ cells increased until week 1, then decreased back to its original level by day 180. CD56+/3-% was high in both groups and had no characteristic kinetics by the time. The CD4+ naive absolute cell count increased in first-time transplants and did not decreased back to its original value until the end of year 1. This is in contrast to retransplants, where CD4+ naive cell count rapidly dropped below its original value and remained low throughout the first year after transplantation. The CD8+ effector memory absolute cell-count was higher in first-time transplants compared to retransplanted patients in all time points. By the end of month 1, the CD19+ naive absolute cell-count increased in first-time transplants to 170% of its original value; however, it remained or decreased in second transplants. By the end of the first year, the CD19+ naive absolute cell count diminished to 70% in first-time transplants and 38% in second transplants. DSA was detected in 9 out of the 38 first-time transplants (23.7%) compared to 7 out of 12 (58.3%) in regrafted patients during the observational period (P = .001). It was typical for regrafted patients for DSAs to appear earlier after transplantation, and that more simultaneously different antibodies were detected against more antigens at the first time point compared to first-time transplants. Discussion The 2 groups were similar in demographics and there were no differences regarding the clinical course, complications, or output data. However, we found statistical differences regarding the dynamics of T cell subsets and DSAs. The parallel measurement of CD subsets and DSAs might be a sensitive and useful additive tool in diagnosing subclinical immunologic changes after transplantation.

Objective: The objective was to investigate the early (20 minutes) effects of 21 L-amino acids on the activation of human neutrophils and to determine in healthy individuals the effects of a meal on the 1) number and relative luminescence unit (RLU) of peripheral neutrophils, 2) serum glutamate and glucose levels and 3) mTOR signaling network. Methods: The RLU of neutrophils stimulated by Ca2+ ionophor (CaI) and phorbol myristate acetate (PMA) following amino acid supplementation (3 x 10-4 M) or after consuming a meal was determined. L-glutamate was measured by HPLC. Results: All amino acids resulted in significant inhibitions of neutrophil RLU, except for arginine, which stimulated neutrophils. The ratios of amino acid induced inhibition were significantly higher in the cells stimulated by PMA than by CaI. The consumption of a meal resulted in a significant serum glutamate elevation compared to baseline (2.3 versus 0.9 x10-4 M) 90 minutes after ingestion of the meal. It was independent of the body mass index and returned near fasting levels after 150 minutes. The number of neutrophils was significantly elevated 90 minutes after the meal but the PMA induced RLU was significantly decreased. Conclusion: Our ex vivoand in vivoresults suggest that the L-amino acids, independent of their metabolic significance, may continuosly and quickly modify the activity of human peripheral neutrophils, and also the outcome of various immunologic reactions. The activation of the mTORC1 complex likely involves a transient impairment in the function of mTORC2 complex in these processes.

In this study, we examined the relationship between levels of lactoferrin (LF) and IL-17 in human serum and breast milk and the development of allergy in children. LF and IL-17 levels were determined by ELISA in healthy (n=19) and allergic mothers (n=21) on the 5th day after delivery. Two years later, information on breastfeeding and allergic outcomes was collected by questionnaires from parents of both groups and district child care nurses. Significantly higher concentrations of LF were found in the breast milk of allergic mothers compared to the healthy controls. At 2 years of age, only those three infants became allergic from the atopic group in whose starting breast milk samples a very high LF level (306 μg mg–1 protein) or simultaneously elevated concentrations of LF and IL-17 were measured. These findings indicate that the very early measurement of LF and IL-17 levels in the breast milk of allergic mothers may help to predict the allergy development in their infants.

Background MDR transporters are important biomarkers of drug resistance in cancer and in autoimmune conditions. We determined the MDR1, MRP1 and BCRP activity in CD3+ lymphocytes using a flow cytometry based method from 120 healthy volunteers in order to describe normal reference values of the activity of these transporters. The effects of gender and age were also determined. Methods The Solvo MDQ Kit™ was used for measurements. In this assay, fluorescent reporter substrates (Calcein-AM for MDR1 and MRP1 and mitoxantrone for BCRP, respectively) are trapped in the cytoplasm and pumped out by MDR proteins depending on the presence or absence of specific inhibitors (verapamil for MDR1 and MRP1, indomethacin for MRP1 and KO134 for BCRP, respectively), allowing for quantitative, standardized assessment. Cell surface staining was applied to select CD3+ cells. Results MAF values of MRP1 and BCRP are independent from age. MAFC and MAF of MDR1 show negative correlation with the age of the studied subjects (P = 0.003, r = -0.27 and P = 0.0001, r = -0.34, respectively). No difference was detected in any of the four MAF values between men and women. Gender does not affect the presence or lack of correlation between MAF values and age. Conclusions The determination of the functional activity of MDR-ABC transporters is achievable using a flow cytometry based standardized method. Having established the normal range of MAF values on CD3+ lymphocytes of a healthy population, our results allow for the development of novel flow cytometry based diagnostic tools. © 2018 International Clinical Cytometry Society.

Up to know the indications for the optimal applications of laboratory diagnosis of allergic diseases have become widely known. Measurements of allergy specific IgE and various tests of cell mediated immunity are included in the practice. It can be stated that measurements of total serum IgE and allergen specific IgE (kU/l and RAST classes) can be maintained further in the Hungarian practice with the expected continuous participation of all laboratories in the external quality control program (QualiCont). However, it is also apparent that regional introduction of the urgent “molecular (component) based allergy diagnostics” has become necessary for efficient allergen specific immunotherapy in Hungary. In cases of the allergen specific cell mediated immunologic reactions, allergen induced cell proliferation and cytokine release measurements are recommended. However, it is also obvious that application of these measurements in clinical practice need correct financial support from health care authorities. Orv. Hetil., 2015, 156(32), 1275–1280.

Eating habits act on mortalities from gastrointestinal tumors and cardiovascular diseases.To investigate the role of wine drinking on these mortalities in Hungary.The standardized mortality data of people from 206,159 subjects died of gastrointestinal tumors and cardiovascular diseases between 2000-2010 were compared in four wine regions: Tokaj (white), Eger (red), Balaton (white), Szekszárd/Villány (red) and in Hódmezővásárhely (not-wine region).The significantly smallest number of tumors (664) occurred in Tokaj, but the cardiovascular mortality here was the highest (5955). On the other hand, the fewest cardiovascular mortality occurred in Szekszárd/Villány (3907), but showing here (831) and in Eger (934) the highest values of tumor death.The protective effect of red wine on cardiovascular mortality was verified. Surprisingly, the low value of gastrointestinal mortality in "Tokaj" - besides the higher level of selenium in tap water - shows some hidden features of these white wines. Orv Hetil. 2017; 158(25): 992-998.

Aim We described earlier a simultaneously increased that the increased expression of miRNA-146a/b was accompanied by an increase in the expression of and TRAF6 and a decrease in the expression of IRAK1 genes in the peripheral mononuclear cells (PBMCs) of patients with primary Sjogren's syndrome (pSS) patients. Recently, the expression of EBV encoded. RNA (EBER) was published in the B cells of salivary glands of in pSS. In the present study, we applied an EBV-EBER1 specific synthetic single stranded complementary DNA molecule (EBV-EBER1-cDNA) to test whether any EBER1 related effect exists also in PBMCs of pSS patients. Methods In the PBMCs of pSS patients and healthy controls, we investigated in vitro the effects of a synthetic single stranded EBV-EBER1-cDNA molecule, synthetic double-stranded (ds)RNA polyinosinic-polycytidylic acid [poly (I:C)] and polyadenylic acid potassium salt poly-adenylic acid [poly-(A)] on the expression of TRAF6 gene tested by qRTPCR. The release of interferon -α was detected by ELISA. Results EBV-EBER1-cDNA resulted in a significant reduction in the expression of TRAF6 in the cells of patients, but in the healthy controls not, whereas the treatments with poly (I:C) and poly-(A) could not reduce the TRAF6 over-expression. No release of EBER1 could be observed in the culture supernatants of patients with pSS. Only the treatment with poly (I:C) resulted in a significant increase of interferon -α release, and only in the heathy controls. No release of EBER1 molecules took place during the culturing of cells. EBV-EBER- cDNA acted functionally on the cells of patients only. Conclusion These findings give a further evidence of the linkage between EBV and pSS, furthermore, they show the possible role of EBV-EBER1 in the induction of increased TRAF6 expression in the peripheral B cells of Sjogren's patients.

ObjectiveThis study aimed to quantify the cartilage- and subchondral bone-related effects of low-dose and high-dose meloxicam treatment in the late phase of mono-iodoacetate-induced osteoarthritis of the stifle.MethodsThirty-four male Wistar rats received intra-articular injection of mono-iodoacetate to trigger osteoarthritis; 10 control animals (Grp Co) received saline. The mono-iodoacetate-injected rats were assigned to three groups and treated from week 4 to the end of week 7 with placebo (Grp P,n = 11), low-dose (GrpM Lo, 0.2 mg/kg,n = 12) or high-dose (GrpM Hi, 1 mg/kg,n = 11) meloxicam. After a period of 4 additional weeks (end of week 11) the animals were sacrificed, and the stifle joints were examined histologically and immunohistochemically for cyclooxygenase 2, in conformity with recommendations of the Osteoarthritis Research Society International. Serum cytokines IL-6, TNFα and IL-10 were measured at the end of weeks 3, 7, and 11.ResultsCompared with saline-treated controls, animals treated with mono-iodoacetate developed various degrees of osteoarthritis. The cartilage degeneration score and the total cartilage degeneration width were significantly lower in both the low-dose (p = 0.012 andp = 0.014) and high-dose (p = 0.003 andp = 0.006) meloxicam-treated groups than in the placebo group. In the subchondral bone, only high-dose meloxicam exerted a significant protective effect (p = 0.011). Low-grade Cox-2 expression observed in placebo-treated animals was abolished in both meloxicam groups. Increase with borderline significance of TNFα in GrpP from week 3 to week 7 (p = 0.049) and reduction of IL-6 in GrpM Lo from week 3 to week 11 (p = 0.044) were observed.ConclusionIn this rat model of osteoarthritis, both low-dose and high-dose meloxicam had a chondroprotective effect, and the high dose also protected against subchondral bone lesions. The results suggest a superior protection of the high-dose meloxicam arresting the low-grade inflammatory pathway accompanied by chronic cartilage deterioration.

The author describes the concept of "personalized medicine" and the newly introduced "precision medicine". "Precision medicine" applies the terms of "phenotype", "endotype" and "biomarker" in order to characterize more precisely the various diseases. Using "biomarkers" the homogeneous type of a disease (a "phenotype") can be divided into subgroups called "endotypes" requiring different forms of treatment and financing. The good results of "precision medicine" have become especially apparent in relation with allergic and autoimmune diseases. The application of this new way of thinking is going to be necessary in Hungary, too, in the near future for participants, controllers and financing boards of healthcare. Orv. Hetil., 2016, 157(44), 1739-1741.

The changes in the number of CD8⁺ T lymphocytes were studied before (0 day) and then 30 days after the autologous hematopoietic stem cell transplantations (AHSCT) in 14 therapy refractory patients with autoimmune diseases. The years of survival and the clinical states were also evaluated. The number of CD8⁺ T cells was determined by an hematologic automat and by flow cytometry. Longer than 5-year survival times were found in 6 cases, whereas there was no progression (improvement) in 2 cases, and 4 patients were lost. The increase in the number of CD8⁺ cytotoxic T cells was gradual in the first 2 months and reached the significantly highest values among all subtypes of lymphocytes. It was of a special interest that in all the 4 patients who died, the numbers of CD8⁺ T cells were less than 150/μl on the 30th day after AHSCT, whereas all the 10 patients with a higher cell number survived. These results suggest that the early monitoring of the number (not only the ratio) of regenerating CD8⁺ T cells in the peripheral blood can be a useful and quantitative laboratory measurement after AHSCT, and it has a significant relation also to the survival times of transplanted patients.

SUMMARY Toxocara infection is associated with an increased prevalence of airway symptoms and may be a possible aetiologic agent of chronic cough. The occurrence of toxocariasis in Hungary is mild and/or sporadic. The purpose of this study was to investigate the levels of serum cytokines (IL-1, IL-2, IL-4, IL-5, IL-6, IL-10, IL-13, IFN-gamma and TNFalpha) and total IgE, the blood eosinophil count, the results of skin prick and non-specific bronchus provocation tests in Toxocara-seropositive children with chronic cough relative to those in healthy controls. The patients exhibited moderate eosinophilia, significantly elevated levels of serum total IgE, IL-6, IL-10, IL-13 and IFN-gamma, and higher skin reactivity to common allergens, whereas the bronchial hyperreactivity was similar in the two groups. The protective proinflammatory cytokines (IL-6, IFN-gamma and IL-13) in association with the anti-inflammatory cytokine (IL-10) were simultaneously increased in Toxocara-infected children with chronic cough. During infections, the activation and suppression of immune processes occur simultaneously and cytokines of Th1/Th2 and regulatory T cells contribute to the regulation of the immune response evoked by helminth infections (depending on the parasite load, the timing and duration of the infection and the status of the host immune system).

QT interval prolongation on the electrocardiogram is considered a precursory sign for imminent, potentially lethal ventricular arrhythmias. Beside the inherited condition of long QT syndrome, numerous drugs, certain electrolyte disturbances and early transmural ischemia have been identified to induce reversible prolongation of the QT interval, collectively called as acquired long QT syndrome. Herein we describe a case of a patient with transient QT prolongation and Takotsubo cardiomyopathy, a rather infrequent cause of long QT development. Serial changes of the repolarization pattern were documented to demonstrate progression and resolution of the abnormal QT interval.

The author describes the concept of “personalized medicine” and the newly introduced “precision medicine”. “Precision medicine” applies the terms of “phenotype”, “endotype” and “biomarker” in order to characterize more precisely the various diseases. Using “biomarkers” the homogeneous type of a disease (a “phenotype”) can be divided into subgroups called “endotypes” requiring different forms of treatment and financing. The good results of “precision medicine” have become especially apparent in relation with allergic and autoimmune diseases. The application of this new way of thinking is going to be necessary in Hungary, too, in the near future for participants, controllers and financing boards of healthcare. Orv. Hetil., 2016, 157(44), 1739–1741.

The effects of proteosome inhibitor Bortezomib (BZ) were studied in vitro for 24 h on the protein kinase C (PKC) profiles, rates of proliferation and apoptosis in Jurkat cells and lymphocytes of 10 patients with systemic lupus erythematosus (SLE) and nine healthy subjects. The expressions of PKC proteins, the rates of proliferation and apoptosis were determined. The effects of BZ were different in the Jurkat and lupus T cells. Whereas BZ elevated the expression of PKC θ, δ and ξ isoenzymes in the Jurkat cells, it was unable to do that in the lupus T cells. BZ induced a dose-dependent increase in the apoptosis of Jurkat cells, while decreased the proliferation. The same effect of BZ was observed on the apoptosis of lymphocytes both in SLE and healthy subjects at concentrations higher than the therapeutic dose. We conclude that BZ treatment in vitro was not able to restore the SLE-specific defect (decrease) in the expression of PKC isoenzymes in the T cells as it was expected. This can be a limiting factor in the positive clinical effects of BZ in lupus.

Aim The microRNA-155 (miR-155) is regarded as a central modulator of T-cell responses and could be a potential therapeutic target for certain inflammatory diseases. In our present study we analyzed the expression rate of miR-155 and its functionally linked gene, the suppressor gene of cytokine signaling 1 (SOCS1) in primary Sjogren's syndrome (pSS). Method We enrolled 23 pSS patients and 10 healthy individuals in the study. The expression of miR-155 and SOCS1 gene were measured by real-time polymerase chain reaction. Results We observed the over-expression of miR-155 in the peripheral mononuclear cells of patients with pSS. Surprisingly, SOCS1 gene was also over-expressed in pSS patients. Conclusion This unanticipated phenomenon might be a laboratory characteristic of Sjogren's syndrome, and presumably a consequence of the noteworthy difference in the pSS immune system reacting with Epstein–Barr virus.

Conflicting data exist on the number of invariant NKT (iNKT) cells in atopic dermatitis (AD); furthermore, no data have been published on their functional capacity.The frequency and number of circulating CD3+6B11+ iNKT cells and their CD4+ and CD4- subpopulations were evaluated in peripheral blood obtained from 41 patients with AD by four-color flow cytometry. Likewise, functional properties of iNKT cells were measured by five-color intracellular cytokine staining.The number and percentage of total iNKT cells and their CD4/CD8 subpopulations were significantly lower than the controls. Of further importance, the CD4-CD8- (double negative, DN) iNKT subgroup showed the strongest positive correlation with total iNKT cells. In addition, the DN subgroup exhibited the most pronounced functional alteration with significantly decreased levels of intracellular IFNγ and significantly increased levels of intracellular IL-4 in AD patients compared with the controls.The significantly altered number and cytokine production of iNKT cells from AD patients suggests that these cells may play an important role in the pathogenesis of AD.

Background Intra-abdominal hypertension (IAH) can cause high mortality. Recently, we found that IAH was associated with increased serum levels of adenosine and interleukin 10. Our present “hypothesis-generated study” was based on the abovementioned results. Materials and methods In this uncontrolled clinical trial, a total of 78 patients with IAH were enrolled representing a 13–20 mmHg range of intra-abdominal pressure (IAP). Patients requiring surgical abdominal decompression were excluded. Patients were treated with the following protocols: standard supportive therapy (ST, n=38) or ST plus infusion with the adenosine receptor antagonist theophylline (T, n= 40). Over the 5-day measurement period, IAP was monitored continuously and serum adenosine concentration and other clinical and laboratory measurements were monitored daily. Mortality was followed for the first 30 days following the diagnosis of IAH. Results Mortality of ST patients was 55%, which is compatible to other studies. Serum adenosine concentration was found to be directly proportional to IAP. Of the 40 patients receiving T treatment, survival was 100%. An increased survival related to theophylline infusion correlated with improving serum concentrations of IL-10, urea, and creatinine, as well as 24-h urine output, fluid balance, mean arterial pressure, and O2Sat. Conclusions Adenosine receptorantagonism with Tfollowing IAH diagnosis resulted in markedly reduced mortality in patients with moderated IAH (

The aim of this study was to evaluate a wide spectrum of peripheral immune-competent cell types, reflecting overall disturbances in immune homeostasis, characteristic of systemic sclerosis (SSc). We also assessed visceral organ involvement and evaluated the relationship between cell proportions and clinical symptoms of the disease.Twenty-one patients with diffuse cutaneous SSc (dcSSc) and 15 healthy individuals participated in the study. Peripheral blood lymphocyte subgroups were quantified by flow cytometry, soluble cytokines were assessed by enzyme-linked immunosorbent assay (ELISA), serum complement levels were measured by nephelometry, and autoantibodies were determined by indirect immunofluorescence staining and ELISA technique. Functional tests of regulatory T (Treg) cells were also carried out.Patients with SSc had higher percentages of activated CD3+/HLA-DR+ T cells. Comparing naive vs. memory subsets of CD4+ and CD8+ T cells, a shift towards central memory phenotype was observed in SSc. Natural killer (NK) and T-helper (Th)17 cell percentages were increased, while NKT, Th1, Treg type 1 (Tr1), and CD4+CD25+ Treg cell percentages were decreased in patients. Moreover, the suppressor activity of CD4+CD25+ Treg cells was lower in SSc. Negative correlations occurred between modified Rodnan skin score (MRSS) and Tr1 cell percentages and between complement levels and CD4+CD25+ Treg cells. We also found decreased interleukin (IL)-10 levels in SSc.Our data suggest that the increased Th17/CD4+CD25+ Treg ratio and the altered regulatory function of CD4+CD25+ Treg cells play an important role in the development of SSc. Moreover, our study reveals the potential role of the decreased profile of IL-10-producing Tr1 cells in the progression of disproportionate immune responses in SSc.

Objective.Studies indicate that ankylosing spondylitis (AS), as well as rheumatoid arthritis, may be associated with accelerated atherosclerosis and vascular disease. We assessed endothelial dysfunction, carotid atherosclerosis, and aortic stiffness in AS in context with clinical and laboratory measurements.Methods.Forty-three patients with AS and 40 matched healthy controls were studied. We assessed common carotid intima-media thickness (ccIMT), flow-mediated vasodilation (FMD), and pulse-wave velocity (PWV) in association with age, disease duration, smoking habits, body mass index, patient’s assessment of pain and disease activity, Bath AS Disease Activity Index, Bath AS Functional Index (BASFI), metric measurements, erythrocyte sedimentation rate, C-reactive protein, and HLA-B27 status.Results.We found impaired FMD (6.85 ± 2.98% vs 8.30 ± 3.96%; p = 0.005), increased ccIMT (0.65 ± 0.15 vs 0.54 ± 0.15 mm; p = 0.01), and higher PWV (8.64 ± 2.44 vs 8.00 ± 1.46 m/s; p = 0.03) in patients with AS compared to controls, respectively. We also found that ccIMT negatively correlated with FMD (r = −0.563; p = 0.0001) and positively correlated with PWV (r = 0.374; p = 0.018). Both ccIMT and PWV correlated with disease duration (r = 0.559; p = 0.013 and r = 0.520; p = 0.022, respectively), BASFI (r = 0.691; p = 0.003 and r = 0.654; p = 0.006), decreased lumbar spine mobility (r = −0.656; p = 0.006 and r = −0.604; p = 0.013), chest expansion (r = −0.502; p = 0.047 and r = −0.613; p = 0.012), and increased wall-occiput distance (r = 0.509; p = 0.044 and r = 0.614; p = 0.011).Conclusion.In this well characterized AS population, impaired FMD and increased ccIMT and PWV indicate abnormal endothelial function and increased atherosclerosis and aortic stiffness, respectively. The value of noninvasive diagnostic tools needs to be further characterized.

Interleukin-1 receptor antagonist (IL-1Ra) is a good indicator of disease activity in patients with systemic lupus erythematosus (SLE). Glucocorticosteroids are the most frequently used drugs in SLE. Our goal was to compare IL-1Ra activity in SLE patients with and without renal involvement and to determine the effect of different dosage of glucocorticosteroids used in 17 patients with active SLE without nephritis, 7 patients with inactive lupus nephritis (LN), and 8 patients with active LN, along with 10 healthy controls. IL-1Ra levels were measured in the serum of SLE patients by Human Luminex [100] analyzer. Both in patients with active SLE without nephritis and in patients with LN, serum levels of IL-1Ra (p

Oxidized low-density lipoprotein (oxLDL) is a key feature of the atheromatosus plaque and plays a critical role in foam cell formation and perpetuation of inflammatory processes. In antiphospholipid syndrome (APS), oxLDL molecules form complexes with beta2GPI and become target antigens for autoantibodies, which are detectable in the sera of these patients. oxLDL takes part in the pathogenesis of APS and in the concomitant accelerated atherosclerosis, yet the exact associated immune mechanisms are not clear in details. The aim of this study was to assess the activation and proliferation response of peripheral blood mononuclear cells (PBMCs) derived from patients with APS in the presence of oxLDL. Thirteen patients with APS and nine healthy individuals were enrolled in the study. Separated PBMCs of these patients were cultured in the presence of immunogenic epitope of oxLDL. Lymphocyte proliferation and cytokine secretion (TNF-alpha, IL-2, IFN-gamma, IL-4, and IL-10) were assessed by ELISA. We found significant PBMC proliferation in APS compared to healthy controls (PI/proliferation index/APS: 1.76 vs. PI control: 0.56; p = 0.032). A significant IL-2 and IFN-gamma secretion were detected upon oxLDL stimulus in patients with APS compared to controls (IL-2 cytokine secretion index (CSI) APS: 278.5, IL-2 CSI controls: 65.1; p = 0.025; IFN-gamma CSI APS: 163.2, IFN-gamma CSI controls: 77.4; p = 0.025). Based on our findings, we assume that oxLDL via Th1-type cytokine production and lymphocyte proliferation may contribute to the perpetuation of immune processes in APS.

Increased intra-abdominal pressure (IAP), intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) are severe complications of surgical interventions with a high rate of mortality. The technique of IAP measurement is accurate, precise, reproducible and cost-effective. However, laboratory measures for monitoring of IAH have not been defined. We investigated the linkage between the serum levels of adenosine and interleukin 10 (IL-10) with IAP.The sera of 25 surgical patients with IAP12 mmHg and of 45 surgical patients with IAP12 mmHg were tested. Serum adenosine concentration was measured by HPLC. Serum IL-1β, IL-2, IL-4, IL-10, TNFα, IFNγ and IL-10 were determined by enzyme linked immunosorbent assay (ELISA). CRP was measured by nephelometry.Significant correlations of IAP were found only with serum levels of adenosine and IL-10. In the sera of patients with IAP12 mmHg, the levels of both adenosine (1.61 versus 0.06 µM, p0.01) and IL-10 (63.23 versus 27.27 pg/ml, p0.01) were significantly higher than those in patients with IAP12 mmHg. Moreover, significant correlations were found between individual patient IAP-adenosine values (r = 0.766, p0.001), IAP-IL-10 values (r = 0.792, p0.001) and adenosine-IL-10 values (r = 0.888, p0.001). A direct linear correlation between IAP-adenosine and IAP-10 values was only observed with IAP15 (Grade II-IV).We report associations between IAP and the serum adenosine and IL-10 levels providing new tools for the laboratory monitoring of IAH as well as further understanding of the pathomechanisms contributing to ACS.

Summary The aim of the present study was to describe subsets of cells with regulatory properties in primary Sjögren’s syndrome (pSS), and to correlate these cell populations with clinical symptoms. Among the 32 investigated patients, 23 had extraglandular manifestations (EGMs), while nine had only glandular symptoms. Twenty healthy individuals served as controls. The percentages of natural killer (NK), natural killer T cells (NK T), interleukin (IL)-10 producing T regulatory type 1 (Tr1) cells and CD4+CD25+ regulatory T cells (Treg) cells were determined by flow cytometry and serum cytokine levels of IL-4, IL-6, IL-10, tumour necrosis factor (TNF)-α and interferon (IFN)-γ were evaluated by enzyme-linked immunosorbent assay (ELISA). Functional tests were carried out to assess the suppressor properties of Treg cells in patients and controls. Peripheral NK, NK T and Tr1 cell percentages were elevated in pSS, while CD4+CD25+ Treg cells showed reduced frequencies in patients compared to controls. In pSS, elevated percentages of NK T, Tr1 and CD4+CD25+ Treg cells were observed in patients with EGMs, when compared to patients with sicca symptoms only. CD4+CD25+ Treg cell percentages showed a negative correlation with sialometry values. The in vitro functional assay demonstrated lower suppression activity of CD4+CD25+ Treg cells in patients compared to controls. Serum IL-6 and TNF-α levels were elevated, while IL-10 was decreased in patients compared to controls. Negative correlation was found between IL-10 levels and the percentages of Tr1 cells. Changes in the investigated subsets of regulatory cells in pSS may contribute to the development and progression of the disease.

ObjectiveTo determine the role of inflammatory mediators in the pathogenesis of ankylosing spondylitis (AS), we investigated peripheral blood lymphocyte subsets and their intracellular cytokine production.MethodsThe percentages of T and B lymphocytes, natural killer (NK) cells, activated T lymphocytes, CD4+ T helper (Th), and CD8+ T cytotoxic (Tc) cells were determined by flow cytometry in 42 patients with AS compared to 52 healthy controls. In order to assess circulating Th1/Th2 and Tc1/Tc2 subsets, we used a whole-blood cytometric assay based on the intracellular interferon-γ, interleukin 4 (IL-4), and IL-10 expression of the cells.ResultsIn the peripheral blood, the frequencies of CD4+ T helper and CD56+ NK cells were higher in AS (54.8% and 16.2%, respectively) compared to controls (45.3% and 10.8%) (p < 0.05). The frequencies of Th0 (1.9% vs 0.8%) and Tc0 (2.1% vs 0.8%) cells were higher, while that of Tc1 cells was lower (26.6% vs 40.1%) in patients with AS versus controls (p < 0.05). The percentage of IL-10-producing Tc cells was significantly higher in AS (18.4%) versus controls (8.5%) (p < 0.05). Finally, the active phase of AS was associated with significantly lower percentage of IL-10-producing Tc cells in the peripheral blood (6.6%) compared to patients with inactive AS (23.1%).ConclusionOur results provide further evidence for an altered T cell subset distribution and intracytoplasmic cytokine balance in AS.

Objectives: Besides the central role of the adaptive immune system, a disturbance of innate immunity is also involved in the pathogenesis of celiac disease (CD). Inasmuch as CD and type 1 diabetes mellitus (T1DM) frequently coexist because of a common genetic predisposition, our aim was to study the frequency of CD14 C-260T and TLR4 A+896G single nucleotide polymorphisms (SNPs) and the distribution of HLA-DQ genotypes in children affected by CD, T1DM, or both. Patients and Methods: TLR4 and CD14 SNPs were tested by polymerase chain reaction, followed by restriction fragment length polymorphism analysis in 80 children with TIDM, 100 children with CD, and 47 children with both CD and T1DM. Determination of HLA-DQ alleles was done by sequence-specific polymerase chain reaction. Frequencies were compared with those of healthy control children. Results: The prevalence of the homozygous CD14 C-260TT genotype was significantly (P = 0.0081) lower in children with T1DM but not in those with CD and T1DM, compared with control children. No difference was found in the genotype and allele frequencies of TLR4 between the studied groups. In patients with T1DM, the frequency of the homozygous HLA-DQ8 genotype was significantly higher than in CD, whereas the frequency of homozygous or heterozygous HLA-DQ2 genotypes did not differ from that in control children. In patients with CD, both homozygous and heterozygous HLA-DQ2 genotypes were significantly more frequent than in the control and T1DM groups, and no elevation in the frequency of the HLA-DQ8 genotypes was observed. In patients with T1DM and those with CD and T1DM, the occurrence of HLA-DQ2/8 heterozygosity was significantly higher than in children with CD only and in control children. Conclusions: Our results suggest that in patients with T1DM, the CD14 C-260TT homozygous genotype increases the risk for the development of CD. The distribution of HLA-DQ genotype is different in children with CD and T1DM than in children with CD or T1DM only. Determination of the HLA-DQ genotype in children with T1DM may help in estimating the risk for the development of CD.

To characterize the groups of middle ear effusions (MEE) defined on the basis of the ratio of albumin and immunoglobulin G concentrations (A/G) in the effusion and to identify the correlation between these groups of MEE and the clinical features of otitis media with effusion (OME).A laboratory analysis of 88 samples of MEE and a retrospective analysis of the medical history of all patients was performed.Tertiary referral center.Thirty-three girls and 23 boys with OME were included in the study.The concentrations of albumin, immunoglobulins (IgG, IgA, and IgM), complement factors (C3, C4), and C-reactive protein were determined by means of nephelometry. Enzyme-linked immunosorbent assay was used to measure cytokines interferon-gamma, tumor necrosis factor alpha, interleukin (IL)-4, and IL-10 concentrations. Groups were defined according to A/G ratio in the effusions. Thirty-five children underwent allergy testing.Two groups of MEE could be recognized on the basis of A/G ratio; the ratio was lower than 0.7 in group A and was higher than 0.7 in group B.Increased levels of interferon-gamma and tumor necrosis factor alpha were observed in group A, whereas IL-4 and IL-10 were dominating in group B. No association was found between the MEE groups and the clinical features of the disease or the atopic status of the patient.These results suggest that various groups of OME can be categorized according to the differences in A/G ratio in the effusions. These differences can reflect the variances in the pathomechanism of the development of the effusion, the stage of the disease, or the clinical background of the patients.