Incident Cancer Risk in Patients with Incident Type 2 Diabetes Mellitus in Hungary (Part 1).

(1) Background: Patients with type 2 diabetes mellitus (T2DM) are at higher risk of cancer but how these two diseases associate is still debated. The goal of this study was the assessment of the overall incidence of cancer among patients with newly diagnosed T2DM in Hungary. (2) Methods: A nationwide, retrospective, longitudinal study was performed using a Hungarian database. After exclusion of cases of age < 18 years, with gestational diabetes, with polycystic ovary syndrome, and with type 1 and prevalent type 2 diabetes mellitus, the incident T2DM (approx. 50,000 cases yearly) and for comparison, the diabetes-free Hungarian adult population (approx. 7,000,000 cases yearly) was included in the study. The primary endpoints were the overall and site-specific incidence and annual percentage change of the incidence of cancer in both populations. (3) Results: The overall incidence of cancer in patients amounted to 29.4/1000 and 6.6/1000 with or without T2DM, respectively, and the OR (95%CI) of cancer of the T2DM group was 4.32 (4.14-4.53), p < 0.0001. The risk of having cancer was age dependent. The incidence of cancer was declining in the non-diabetic but was unchanged in the T2DM population. The average lag time of diagnosing cancer after the detection of T2DM was 3.86 months. (4) Conclusions: Incident T2DM is associated with a significantly higher overall risk of incident cancer, with a reverse correlation of age. Newly registered T2DM patients were suggested to be screened for cancer within 6 months.

Effectiveness of SARS-CoV-2 primary vaccines and boosters in patients with type 2 diabetes mellitus in Hungary (HUN-VE 4 Study).

INTRODUCTION: Type 2 diabetes mellitus is a risk factor for severe COVID-19 infection and is associated with increased risk of complications. The present study aimed to investigate effectiveness and persistence of different COVID vaccines in persons with or without diabetes during the Delta wave in Hungary. RESEARCH DESIGN AND METHODS: Data sources were the national COVID-19 registry data from the National Public Health Center and the National Health Insurance Fund on the total Hungarian population. The adjusted incidence rate ratios and corresponding 95% CIs were derived from a mixed-effect negative binomial regression model. RESULTS: A population of 672 240 cases with type 2 diabetes and a control group of 2 974 102 non-diabetic persons free from chronic diseases participated. Unvaccinated elderly persons with diabetes had 2.68 (95% CI 2.47 to 2.91) times higher COVID-19-related mortality rate as the 'healthy' controls. Primary immunization effectively equalized the risk of COVID-19 mortality between the two groups. Vaccine effectiveness declined over time, but the booster restored the effectiveness against mortality to over 90%. The adjusted vaccine effectiveness of the primary Pfizer-BioNTech against infection in the 14-120 days of postvaccination period was 71.6 (95% CI 66.3 to 76.1)% in patients aged 65-100 years with type 2 diabetes and 64.52 (95% CI 59.2 to 69.2)% in the controls. Overall, the effectiveness tended to be higher in individuals with diabetes than in controls. The booster vaccines could restore vaccine effectiveness to over 80% concerning risk of infection (eg, patients with diabetes aged 65-100 years: 89.1 (88.1-89.9)% with Pfizer-on-Pfizer, controls 65-100 years old: 86.9 (85.8-88.0)% with Pfizer-on-Pfizer, or patients with diabetes aged 65-100 years: 88.3 (87.2-89.2)% with Pfizer-on-Sinopharm, controls 65-100 years old: 87.8 (86.8-88.7)% with Pfizer-on-Sinopharm). CONCLUSIONS: Our data suggest that people with type 2 diabetes may have even higher health gain when getting vaccinated as compared with non-diabetic persons, eliminating the marked, COVID-19-related excess risk of this population. Boosters could restore protection.

[The role of dietary factors and nutrients in rheumatoid arthritis]. / Étrendi tényezok és tápanyagok szerepe rheumatoid arthritisben.

Rheumatoid arthritis is the most common autoimmune inflammatory joint disease. Internal and external factors may play a role in its development. In recent years, an increasing number of studies highlighted that diet has a central role in the risk and progression of the disease. Several foods and nutrients present anti-inflammatory and antioxidant properties that have protective effects on the development and outcome of rheumatoid arthritis. The aim of this review is to summarize and describe the results of randomized clinical trials or cohorts that have investigated the effects of diet and nutrition in relation to rheumatoid arthritis and the potential role of dietary therapy in the management of rheumatoid arthritis. Certain dietary patterns and components can be used as adjunctive therapies in the treatment of rheumatoid arthritis and may contribute to the effective reduction of disease activity, the induction of remission and its long-term maintenance. At present, there is no nutrition guideline on the dietary management of rheumatoid arthritis and it is therefore important to objectively assess the potential effects and risks of dietary factors and dietary habits. Orv Hetil. 2023; 164(27): 1052-1061.

Expression of Wilms-tumor 1 antigen, vimentin and corticotropin releasing factor in human kidney with focal segmental glomerulosclerosis and effect of oxidative stress on these markers in HEK 293 cells.

INTRODUCTION: Wilms-tumor 1 antigen (WT1) expression in podocytes has the important role of maintaining their integrity and glomerular function. Vimentin also plays a role in preserving podocyte function and in morphologic changes observed after injury. Corticotropin releasing factor (CRF) is important in stress and in maintaining homeostasis. According to our previous studies, tyrosine (Tyr) isoforms (meta- and ortho-Tyr) may play a role in the development of many diseases. INTRODUCTION: Wilms-tumor 1 antigen (WT1) expression in podocytes has the important role of maintaining their integrity and glomerular function. Vimentin also plays a role in preserving podocyte function and in morphologic changes observed after injury. Corticotropin releasing factor (CRF) is important in stress and in maintaining homeostasis. According to our previous studies, tyrosine (Tyr) isoforms (meta- and ortho-Tyr) may play a role in the development of many diseases. METHODS: Our aim was to investigate the expression of WT1, vimentin and CRF in human kidney and in HEK 293 cell cultures. Histological and clinical feature of 42 FSGS patients were evaluated and compared to patients with thin-basement membrane as a control group. Cells were cultured in medium containing para-, meta-, and ortho-tyrosine, and their expression of WT1, vimentin, and CRF were determined by immunocytochemistry. Podocyte foot process effacement was investigated by electron microscope (EM). RESULTS: The intensity of WT1 staining in glomeruli was the same in focal segmental glomerulosclerosis (FSGS) and control groups, but it was lower in the tubulointerstitium of FSGS patients. Vimentin was lower in glomeruli of FSGS patients (p=0.009), and it was higher in the tubulointerstitium compared to the control group (p=0.003). CRF intensity was lower in the glomeruli (p=0.002). Podocyte foot process effacement determined by electron microscope (EM) showed correlation with vimentin and CRF in glomeruli. WT1 staining intensity was lower in meta- and ortho-Tyr group (p=0.001; p=0.009). Vimentin was lower in the meta-Tyr group (p=0.001). DISCUSSION: Our observations on kidney biopsy samples support that the reduction of WT1 and vimentin could be characteristic for FSGS. Our results on HEK cells suggest that meta- and ortho-tyrosine may play a role in the development of FSGS.

The practice of using non-steroidal anti-inflammatory drugs in rheumatology in the light of cardiovascular prevention. / A nemszteroid gyulladáscsökkento szerek reumatológiai alkalmazása a cardiovascularis prevenció tükrében.

Összefoglaló. A reumatológiai betegségek gyakoribb cardiovascularis megbetegedéssel és halálozással járnak. Ennek oka a veleszületett fogékonyság, a tradicionális cardiovascularis rizikófaktorok, a folyamatos gyulladásos háttér és a mozgásszegénység, amelyek mellett a gyógyszerszedés sem elhanyagolható tényezo. A nemszteroid gyulladáscsökkento szerek egyik legismertebb mellékhatása a cardiovascularis megbetegedés és halálozás elofordulásának fokozódása, amely az egyes készítmények esetében eltéro mértéku. Ezt a különbséget sokáig a ciklooxigenáz-1 és -2 enzim eltéro mértéku gátlásával magyarázták. A prospektív összetett cardiovascularis végpontú vizsgálatok azonban nem igazoltak jelentos különbséget a ciklooxigenáz-1 és -2 gátlása között. A megfelelo gyógyszerválasztás a klinikai vizsgálatok tapasztalatai alapján történik, figyelembe véve a beteg és a betegség adottságain túl az adott készítmény tulajdonságait. A jelenlegi ismeretek alapján a cardiovascularis rizikó szempontjából a kis és közepes adagú ibuprofén vagy dexibuprofén, valamint naproxén tunik elonyösnek, habár ez utóbbi esetében gastrointestinalis szövodményekkel kell számolni. Orv Hetil. 2022; 163(3): 93-97. Summary. Rheumatological diseases are associated with more common cardiovascular morbidity and mortality. This is due to inherited susceptibility, traditional cardiovascular risk factors, persistent inflammatory background, and lack of exercise. Medication is also not a negligible factor. One of the best known side effects of non-steroidal anti-inflammatory drugs is the increased incidence of cardiovascular morbidity and mortality, which varies among the different treatments. This difference has long been explained by different levels of inhibition of cyclooxygenase-1 and -2 enzymes. However, prospective composite cardiovascular endpoint studies did not demonstrate a significant difference between cyclooxygenase-1 and -2 inhibition. The choice of the appropriate drug is based on the experience of clinical trials, taking into account the characteristics of the particular product in addition to the patient and the characteristics of the disease. Based on the current knowledge, low and moderate doses of ibuprofen or dexibuprofen and naproxen appear to be beneficial for cardiovascular risk, although gastrointestinal complications are to be expected in the latter. Orv Hetil. 2022; 163(3): 93-97.

Sodium-Glucose Co-Transporter 2 Inhibitors May Change the Development of Urinary Tract and Hematological Malignancies as Compared With Dipeptidyl Peptidase-4 Inhibitors: Data of the Post-Hoc Analysis of a Nationwide Study.

BACKGROUND: In diabetes mellitus, during the last years, cancer became of equivalent importance as a cardiovascular disease in terms of mortality. In an earlier study, we have analyzed data of the National Health Insurance Fund (NHIF) of Hungary with regards all patients treated with sodium-glucose co-transporter 2 (SGLT2) inhibitors (SGLT2is) vs. those treated with dipeptidyl peptidase-4 (DPP-4) inhibitors (DPP-4is) in a given timeframe. In propensity score-matched groups of SGLT2i- vs. DPP-4i-treated patients, we found a lower incidence of cancer in general. In this post-hoc analysis, we aimed to obtain data on the incidence of site-specific cancer. PATIENTS AND METHODS: All patients starting an SGLT2i or a DPP-4i between 2014 and 2017 in Hungary were included; the two groups (SGLT2i vs. DPP-4i) were matched for 54 clinical and demographical parameters. The follow-up period was 639 vs. 696 days, respectively. Patients with a letter "C" International Classification of Diseases, 10th Revision (ICD-10) code have been chosen, and those with a known malignancy within a year before the onset of the study have been excluded from the analysis. RESULTS: We found a lower risk of urinary tract [HR 0.50 (95% CI: 0.32-0.79) p = 0.0027] and hematological malignancies [HR 0.50 (95% CI: 0.28-0.88) p = 0.0174] in patients treated with SGLT2i vs. those on DPP-4i. Risk of other types of cancer (including lung and larynx, lower gastrointestinal (GI) tract, rectum, pancreas, non-melanoma skin cancers, breast, or prostate) did not differ significantly between the two groups. When plotting absolute risk difference against follow-up time, an early divergence of curves was found in case of prostate, urinary tract, and hematological malignancies, whereas late divergence can be seen in case of cancers of the lung and larynx, the lower GI tract, and the breast. CONCLUSIONS: Urinary tract and hematological malignancies were less frequent in patients treated with SGLT2i vs. DPP-4i. An early vs. late divergence could be observed for different cancer types, which deserves further studies.

Undenatured type II collagen in the treatment of osteoarthritis / A nem denaturált 2-es típusú kollagén hatása az arthrosisra.

Összefoglaló. Az arthrosis az ízületeket alkotó porc, csont és a környezo lágy részek leépülésével járó betegség. A betegség jelentos fájdalommal jár, progresszív, az ízület strukturális átalakulását és ennek következtében jelentos funkcióvesztést és életminoség-romlást okoz. Kialakulásában immunológiai gyulladásos folyamatok is szerepet játszanak, amelyek befolyásolása lehetoséget ad nemcsak tüneti kezelésre, hanem betegségmódosító terápia kialakítására is. A nem denaturált 2-es típusú kollagén oralis alkalmazása szisztémás toleranciát hoz létre, ami a proinflammatoricus folyamatok gátlása és az antiinflammatoricus hatások erosítése révén új lehetoség az immunmodulációra. A klinikai vizsgálatok a betegeknél a fájdalom jelentos csökkenésérol, a mozgásszervek funkciójának javulásáról számolnak be, és a kezelés egészséges ízületben is nyújthat védelmet a mechanikus stressz okozta ízületi károsodással szemben. Orv Hetil. 2021; 162(37): 1481-1484. Summary. Osteoarthritis is a disease of the cartilage, bone and surrounding soft tissues that make up the joints. The disease is associated with significant pain, it is progressive, causing structural transformation of the joint and, as a result, significant loss of function and deterioration in the quality of life. Immunological inflammatory processes also play a role in its development, the influence of which allows not only symptomatic treatment, but also the development of disease-modifying therapy. Oral administration of undenatured type II collagen creates systemic tolerance, which is a new opportunity for immunomodulation by inhibiting proinflammatory processes and enhancing anti-inflammatory effects. Clinical trials have reported significant reduction in pain, improved musculoskeletal function in patients, and the therapy may provide protection against joint damage caused by mechanical stress in healthy joints. Orv Hetil. 2021; 162(37): 1481-1484.

Inverse association between use of broad spectrum penicllin with beta-lactamase inhibitors and prevalence of type 1 diabetes mellitus in Europe.

Increasing incidence of type 1 diabetes is supposed to be induced by environmental factors. Microbiome modulated by antibiotics seems to serve as one of the environmental factors which could influence the development of T1DM. Mitochondria, as autochthonous environmental bacteria living in our cells, and other bacteria share many common enzymes including beta-lactamases and it is supported by evidence that some beta-lactamase inhibitors are able to interact with counterpart enzymes. Thus, antibiotics may utilize two different pathways influencing the development of T1DM; one through modulation of microbiome and a second one via the interaction of mitochondrial enzymes. Data of consumption of penicillin (both narrow and broad spectrum) and beta-lactamase inhibitors in 30 European countries were collected from the database of the European Centre for Disease Prevention and Control. These data were correlated with the prevalence reported by the International Diabetes Federation (2019) referring to type 1 diabetes in Europe. No correlation was found between total penicillin consumption or use of broad spectrum penicillin and the prevalence of type 1 diabetes. Nevertheless, broad spectrum penicillin, in combination with beta-lactamase inhibitor, was in inverse correlation with the prevalence of type 1 diabetes (r = - 0.573, p = 0.001). On the other hand, narrow spectrum penicillin was in positive correlation with type 1 diabetes (r = 0.523, p = 0.003). Prevalence of type 1 diabetes showed an inverse correlation with the use of beta-lactamase inhibitors and a positive one with that of narrow spectrum penicillin. Such a detailed analysis has not so far been provided referring to the penicillin group. In the background of this association either microbiomal or direct mitochondrial effects can be supposed.

Risk of morbidity and mortality in patients with type 2 diabetes treated with sodium-glucose cotransporter-2 inhibitor and/or dipeptidyl peptidase-4 inhibitor: a nationwide study.

INTRODUCTION: Mortality and disability in diabetes mellitus are determined mostly by cardiovascular complications and cancer. The impact of dipeptidyl peptidase-4 inhibitor (DPP-4i) and sodium-glucose cotransporter-2 inhibitor (SGLT2i) monotherapy or combination on long-term complications of type 2 diabetes mellitus was studied. RESEARCH DESIGN AND METHODS: Patients with type 2 diabetes treated with DPP-4i or SGLT2i during a 3-year period were identified in the database of the National Institute of Health Insurance Fund in Hungary. All-cause mortality, acute myocardial infarction, stroke, hospitalization for heart failure (HHF), lower limb amputation (LLA) and cancer were assessed. Outcomes of add-on SGLT2i to DPP-4i treatment in comparison with switching DPP-4i therapy to SGLT2i were also evaluated. After propensity score matching, survival analysis was performed with a Cox proportional hazards model. RESULTS: After propensity score matching, both SGLT2i and DPP-4i groups included 18 583 patients. All-cause mortality (HR, 0.80; 95% CI 0.68 to 0.94; p=0.0057), HHF (HR, 0.81; 95% CI 0.71 to 0.92; p=0.0018), and risk of cancer (HR, 0.75; 95% CI 0.66 to 0.86; p<0.0001) were lower in the SGLT2i population compared with DPP-4i. Risk of LLA was higher in the SGLT2i group (HR, 1.35; 95% CI 1.03 to 1.77; p=0.0315). SGLT2i in combination with DPP-4i results in lower all-cause mortality (HR, 0.46; 95% CI 0.31 to 0.67; p=0.0001), with a lower trend in stroke, LLA, HHF and cancer, but without any statistical difference. CONCLUSIONS: SGLT2i treatment leads to a lower risk of overall mortality, HHF and cancer when compared with DPP-4i treatment. Adding SGLT2i to DPP-4i instead of switching from DPP-4i to SGLT2i further lowers the risk of all-cause mortality.

The role of ibuprofen in the treatment of coronavirus infection / Az ibuprofén helye a koronavírus-fertozés kezelésében.

Összefoglaló. A koronavírus-fertozés 2019 végén indult útjára, lassan a Föld teljes lakosságát eléro pandémiaként. Egy olyan kórokozóról van szó, amely ilyen nagy számú megbetegedést még nem okozott, ezért annak természetes lefolyásáról, a szövodmények kialakulásáról és a kezelési lehetoségekrol még keveset tudunk. Ennek következtében a kezdetben megjelent információk nagyon felületesek voltak, a következtetések nemritkán tévútra vezették mind az orvosokat, mind a betegeket. Az adatok gyarapodásával azonban egyre több kérdésre kapunk választ. Erre a folyamatra az egyik legreprezentánsabb példa az ibuprofén története, amely kezdetben tiltott, késobb turt terápiás szer volt, de ma már támogatott kezelési lehetoség a koronavírus-fertozésben. Orv Hetil. 2020; 161(50): 2104-2106. Summary. The coronavirus infection started in late 2019, as a pandemic slowly reaching the entire population of the earth. This pathogen has not yet caused such a large number of diseases, so little is known about its natural course, the development of complications, and treatment options. As a result, the information initially published was very superficial, and the conclusions often misled both physicians and patients. As the data grows, however, we get more and more questions answered. One of the most representative examples of this process is the history of ibuprofen, which was initially banned, thereafter tolerated, and is now a supported treatment option for coronavirus infection. Orv Hetil. 2020; 161(50): 2104-2106.

[Possibilities of immunotherapy in cancer patients with autoimmune disease]. / A tumor-immunterápia lehetõségei autoimmun betegekben.

The immune checkpoint inhibitors (ICI) opened a new era in anticancer treatment. This type of treatment is beneficial for a subset of patients who had a restricted success in the past. However, manipulation of the immune system may lead to the flare up of preexisting autoimmune diseases, requiring intervention. Furthermore, immune suppression strongly influences the outcome of ICI treatment. The ICI treatment of cancer patients with autoimmune disease is a complex task: pre-treatment assessment of the patients, early management of flare ups, and introduction of effective immune suppression is required to achieve the best outcome.

[Non-steroidal anti-inflammatory drugs for relieving pain in musculoskeletal disorders]. / Nemszteroid gyulladáscsökkento szerek a mozgásszervi fájdalom csillapításában.

Pain control in musculoskeletal disorders is still a challenging task. The most effective treatment of pain in autoimmune and immune-mediated diseases is the treatment of the disease itself. Analgesics, non-steroidal anti-inflammatory drugs and opioids are used to relieve pain. Analgesia is the central intervention of degenerative disorders. The most effective analgesic compounds are the non-steroidal anti-inflammatory drugs (NSAIDs). Concerns are raised regarding the safety of NSAIDs. There is not any organ which is not involved in adverse reactions, but the damage of the gastrointestinal system has been considered the most serious one for a long time. In the 21st century, the recognition of cardiovascular complications led to the re-evaluation of the role of these drugs in analgesia. Orv Hetil. 2019; 160(22): 855-860.

Image analysis of fibrosis in labial salivary glands of patients with systemic autoimmune diseases. Close correlation of lobular fibrosis to seropositive rheumatoid arthritis and increased anti-CCP and RF titres in the serum.

Lobular fibrosis in labial salivary glands of patients with systemic autoimmune disease is a rarely examined and rather neglected histological change. Its significance and disease association is poorly understood. Our aim was to explore the clinical correlations of fibrosis in labial salivary gland samples using objective methods and laboratory parameters. Labial salivary gland samples from more than 300 patients over a 3-year period were selected from the archives of the pathology department, histologically examined, digitised, image analysed and statistically evaluated to identify the presence and intensity of lobular fibrosis, its relation to age, clinical diagnoses of systemic autoimmune disease and the presence of rheumatoid factor (RF), anti-cyclic citrullinated peptide (CCP), antinuclear antibodies (ANAs), and anti-dsDNA serum markers. Significant correlation was found between lobular fibrosis and the presence of autoimmune disease (p = 0.023), mainly seropositive rheumatoid arthritis (p < 0.001). Also significant association was found between the fibrosis and the presence of serum anti-CCP (p < 0.001) and IgA/IgG/IgM-RF (p < 0.001, p < 0.001 and p = 0.008, respectively). Significant association was explored between the anti-dsDNA positivity and the negative histology groups (p = 0.033) and between the ANA positivity and the inflammation only group (p = 0.021). The results suggest that lobular fibrosis tends to associate to certain systemic autoimmune diseases, mainly seropositive rheumatoid arthritis, and seems to be rare in labial salivary gland biopsies of autoimmune diseases characterised by presence of anti-dsDNA. The close correlation of ANA positivity and the inflammation only histology was not surprising, since the majority of patients (62%) have Sjögren's syndrome, known for its inflammatory infiltrate. These findings emphasise that evaluation of lobular fibrosis and inflammation in histological samples of labial salivary gland biopsies are equally important.

Adipose tissue infiltration in minor salivary glands of patients with Sjögren's syndrome: Lack of significant correlation with the disease. An image analysis of 174 cases.

Fatty infiltration in minor salivary gland biopsies and its correlation to systemic autoimmune diseases are controversial in the literature. Presence and extent of fatty infiltration in minor salivary glands of 107 Sjögren's syndrome patients and 67 age-matched sicca controls were compared with statistical analyses. No significant difference was found regarding the presence or the extent of fatty infiltration between the two groups. Fatty infiltration seems to be unrelated to Sjögren's syndrome thus its examination in salivary gland biopsy samples cannot improve the diagnostic accuracy of the disease.

Image analysis of fatty infiltration in labial salivary gland biopsies: extent and its correlation to age, obesity and diabetes.

BACKGROUND: Fatty infiltration of minor salivary gland parenchyma is relatively frequent, but not extensively examined histopathological phenomenon in biopsy samples. Its extent and relation to several suspected background diseases are not well understood. METHODS: In this study, we examined the presence and extent of fatty infiltration on digitally scanned versions of the periodic acid/Schiff-stained minor salivary gland slides of 275 patients. As a result of the image analysis, fatty infiltration was expressed in per cent of the whole selected area. The presence and extent of this change were compared to age, diabetes mellitus and body mass index in various statistical analyses. RESULTS: Significantly higher age and body mass index values were found in the fatty infiltration positive than in the negative group. We also found that not only the number of fatty infiltration positive cases was increased significantly in the gradually worsened body mass index groups, but the extent of fatty infiltration also increased as the obesity worsened. Age also showed significant correlation with the extent of fatty infiltration. DISCUSSION: All of these findings support that the age (which seemed the only independent variable) shows strong correlation with the presence of the fatty infiltration but obesity may also play important role in the development and the extent of this change. Because of its frequency in elderly, at least partly, the fatty infiltration might be responsible for the xerostomia. We also think that presence of fatty infiltration should be mentioned in the histopathological report of salivary gland biopsies.

[The role of immune system in the control of cancer development and growth]. / Hogyan ellenorzi az immunrendszer a daganatok kialakulásának és növekedésének folyamatát?

The role of immune system is the maintenace of the integritiy of the living organism. The elements of the immune system are connected by several ways forming a complex biological network. This network senses the changes of the inner and outer environment and works out the most effective response against infections and tumors. Dysfunction of the immune system leads to the development of cancer development and chronic inflammatory diseases. Modulation of the checkpoints of the immune system opened new perspecitves in the treatment of rheumatological and oncological diseases as well. Beside the potent antiinflammatory activity, new therapies are able to stimulate anticancer activity of the immune system. The result of these recent developments is a better outcome of malignant diseases, which had an unfavorable outcome in the past. Orv. Hetil., 2016, 157(Suppl. 2), 3-8.

Importance of intestinal microenvironment in development of arthritis. A systematic review.

A strong connection between spondylarthropathies and inflammatory bowel diseases (IBD) is well established. About 10-15% of IBD are associated with different forms of spondylarthritis. Arthritis can be manifested as axial, peripheral form or both. The primary functions of the gastrointestinal tract are digestion and absorption of nutrients, electrocytes and maintenance of water homoeostasis. The anatomic and functional lesions could lead to the development of IBD based on molecular mimicry and bystander effects. The mechanism of the macromolecules is uptaken may affect intestinal and extraintestinal manifestation in genetically susceptible individuals by gut-associated lymphoid tissue, the interplay between innate and adaptive immunity and the neuroendocrine network.

Role of nitric oxide in the central interferon-alpha-induced inhibition of gastric acid secretion in rats.

Cytokines are known to play a key role in regulation of gastric functions. Interferon-alpha (IFN-α) has been published to impair gastric motility. Aims of this study were to clarify effect of IFN-α on gastric acid secretion (GAS) and determine role of nitric oxide (NO) in the process. Both subcutaneous (1000, 10000, 100 000 IU, s.c.) and intracisternal (10, 100, 1000 IU, i.c.) injections of IFN-α dose-dependently inhibited GAS induced by pylorus ligation in male SD rats in 2 hrs (370±40, 233±39, 208±50 micromol vs control 415±59 micromol and 481±50, 249±75, 141±25 micromol vs control 485±65 micromol, respectively). Central doses inducing same level inhibition were 100 times lower. NOS inhibitor L-NAME (3 mg/kg, i.v.) blocked the inhibitory effect of i.c. ED(50) dose 100 IU IFN-α (507±75 micromol/2 hrs), while L-arginine, the substrate of nitric oxide synthase (NOS) prevented L-NAME action (266±82 micromol/2 hrs). D-arginine failed to prevent L-NAME action on IFN-α-induced inhibition of GAS. Aminoguanidine, a selective inhibitor of inducible NOS (iNOS) failed to block IFN-α induced inhibition of GAS. Results suggest that IFN-α inhibits GAS centrally through nitric oxide pathways probably mediated by continuous isoform of NOS that can be important in regulation of GAS in healthy or pathological conditions.

[Tolosa-Hunt syndrome]. / A Tolosa-Hunt-szindróma.

Both men and women are affected by the rare disease called Tolosa-Hunt syndrome. We don't know exactly what causes it to evolve. It is usually put into the categories of either idiopathic inflammation or pseudotumor. Its pathological feature is a non-specific inflammatory process with fibroblastic, lymphocytic, plasmocytic infiltration, which can be found, for the most part, in the wall of the sinus cavernosus. Granulocytic and giant-cell infiltrations have been described too. The possibility of autoimmune disease has also come up. In our current study we describe the case of a female patient who recovered with the help of a steroid therapy. Through examining her, we also found immunological alterations, which should urge us to thoroughly examine the further observations of this kind.

[Shared and distinctive characteristics of systemic autoimmune disorders]. / A szisztémás autoimmun betegségek közös és eltéro sajátosságai.

Systemic autoimmune disorders constitute a well-characterized and separate group of diseases in the field of clinical immunology and rheumatology. Despite their shared characteristics, these diseases have several distinctive features. The similarity and the difference are manifested both in etiology (i.e. the importance and ratio of genetic and environmental factors), in pathomechanism (i.e. the dominance of cellular or humoral immune response), in the disease outcome (fluctuating or chronic progressive) and in the diversity of clinical manifestations (i.e. multiple organ involvements or some dominant target organs/tissues). In the present work the authors describe the features of four prototypic autoimmune disorders - systemic lupus erythematosus, Sjogren's disease, dermato-polymyositis and systemic sclerosis - and characterise in general the common and particular specific points of systemic autoimmune disorders focusing on the variability and subgroups which can be observed even within certain diseases.