Ákos Nagy

Chronic inflammation in the pancreas and salivary glands--lessons from similarities and differences in pathophysiology and treatment modalities.

The pancreas and salivary glands have similar anatomical structures and physiological functions producing bicarbonate-rich fluid containing digestive enzymes and other components to be delivered into the gut. Despite these similarities, the two organs are also different in numerous respects, especially regarding the inflammatory diseases affecting them. This article will summarize the pathophysiology and current and potential pharmacological treatments of chronic inflammatory diseases such as chronic pancreatitis, autoimmune pancreatitis, Sjögrens syndrome and irradiation-induced salivary gland atrophy. Despite the differences, in both organs the inflammatory process is accompanied by epithelial tissue destruction and fibrosis. Both in pancreatic and in salivary research, an important task is to stop or even reverse this process. The utilization of stem/progenitor cell populations previously identified in these organs and the application of mesenchymal stem cells are very promising for such regenerative purposes. In addition, gene therapy and tissue engineering research progressively advance and have already yielded clinically beneficial preliminary results for salivary gland diseases. For the hard-to-access, hard-to-regenerate pancreas these developments may also offer new solutions, especially since salivary and pancreatic progenitors are very similar in characteristics and may be mutually useful to regenerate the respective other organ as well. These novel developments could be of great significance and may bring new hope for patients since currently used therapeutic protocols in salivary and in pancreatic chronic inflammatory diseases offer primarily symptomatic treatments and limited beneficial outcome.

Complex analysis of multiple single nucleotide polymorphisms as putative risk factors of tooth agenesis in the Hungarian population

Abstract Objectives. The role was studied of multiple single nucleotide polymorphisms in tooth agenesis in the Hungarian population using a complex approach. Methods. Eight SNPs, PAX9 -912 C/T, PAX9 -1031 A/G, MSX1 3755 A/G, FGFR1 T/C rs881301, IRF6 T/C rs764093, AXIN2-8150 A/G, AXIN2-8434 A/G and AXIN2-30224 C/T, were studied in 192 hypodontia and 17 oligodontia cases and in 260 healthy volunteers. Case-control analysis was performed to test both allelic and genotypic associations as well as associations at the level of haplotypes. Multivariate exploratory Bayesian network-based multi-level analysis of relevance (BN-BMLA) as well as logistic regression analysis were performed. Results. Conventional statistics showed that PAX9 SNP -912 C/T and the MSX1 SNP changed the incidence of hypodontia, although after Bonferroni correction for multiple hypothesis testing, the effects were only borderline tendencies. Using a statistical analysis better suited for handling multiple hypotheses, the BN-BMLA, PAX9 SNPs clearly showed a synergistic effect. This was confirmed by other multivariate analyses and it remained significant after corrections for multiple hypothesis testing (p < 0.0025). The PAX9-1031-A-PAX9-912-T haplotype was the most relevant combination causing hypodontia. Interaction was weaker between PAX9 and MSX1, while other SNPs had no joint effect on hypodontia. Conclusion. This complex analysis shows the important role of PAX9 and MSX1 SNPs and of their interactions in tooth agenesis, while IRF6, FGFR1 and AXIN2 SNPs had no detectable role in the Hungarian population. These results also reveal that risk factors in hypodontia need to be identified in various populations, since there is considerable variability among them.

Melanocortin 4 receptor ligands modulate energy homeostasis through urocortin 1 neurons of the centrally projecting Edinger-Westphal nucleus

ABSTRACT The role of the urocortin 1 (Ucn1) expressing centrally projecting Edinger‐Westphal (EWcp) nucleus in energy homeostasis and stress adaptation response has previously been investigated. Morphological and functional studies have proven that orexigenic and anorexigenic peptidergic afferents and receptors for endocrine messengers involved in the energy homeostasis are found in the EWcp. The central role of the hypothalamic melanocortin system in energy homeostasis is well known, however, no data have been published so far on possible crosstalk between melanocortins and EWcp‐Ucn1. First, we hypothesized that members of the melanocortin system [i.e. alpha‐melanocyte stimulating hormone (alpha‐MSH), agouti‐related peptide (AgRP), melanocortin 4 receptor (MC4R)] would be expressed in the EWcp. Second, we put forward, that alpha‐MSH and AgRP contents as well as neuronal activity and Ucn1 peptide content of the EWcp would be affected by fasting. Third, we assumed that the intra‐EWcp injections of exogenous MC4R agonists and antagonist would cause food intake‐related and metabolic changes. Ucn1 neurons were found to carry MC4Rs, and they were contacted both by alpha‐MSH and AgRP immunoreactive nerve fibers in the rat. The alpha‐MSH immunosignal was reduced, while that of AgRP was increased upon starvation. These were associated with the elevation of FosB and Ucn1 expression. The intra‐EWcp administration of MC4R blocker (i.e. HS024) had a similar, but enhanced effect on FosB and Ucn1. Furthermore, alpha‐MSH injected into the EWcp had anorexigenic effect, increased oxygen consumption and caused peripheral vasodilation. We conclude that the melanocortin system influences the EWcp that contributes to energy‐homeostasis. HIGHLIGHTSAlpha‐MSH and AgRP containing nerve fibers are juxtaposed to EWcp‐Ucn1 neurons.Ucn1 neurons in EWcp carry MC4Rs in the rat.Food restriction increased Ucn1 content and FosB neuronal activity in the EWcp.Exogenous MC4R ligands modulate the Ucn1 immunoreactivity in EWcp.Intra‐EWcp alpha‐MSH injection reduced FI and increased VO2 and heat loss.

Stress and Salivary Glands

Salivary glands produce a bicarbonate-rich fluid containing digestive and protective proteins and other components to be delivered into the gastrointestinal tract. Its function is under strict control of the autonomic nervous system. Salivary electrolyte and fluid secretion are primarily controlled by parasympathetic activity, while protein secretion is primaily triggered by sympathetic stimulation. Stress activates the hypothalamic - pituitary - adrenal axis. The peripheral limb of this axis is the efferent sympathetic/adrenomedullary system. Stress reaction, even if it is sustained for long, does not cause obvious damage to salivary glands. However, stress induces dramatic changes in the constituents of secreted saliva. Since salivary protein secretion is strongly dependent on sympathetic control, changes in saliva can be utilized as sensitive stress indicators. Some of the secreted compounds are known for their protective effect in the mouth and the gut, while others may just pass through the glands from blood plasma because of their chemical nature and the presence of transcellular salivary transporting systems. Indeed, most compounds that appear in blood circulation can also be identified in saliva, although at different concentrations. This work overviews the presently recognized salivary stress biosensors, such as amylase, cortisol, heat shock proteins and other compounds. It also demonstrates that saliva is widely recognised as a diagnostic tool for early and sensitive discovery of salivary and systemic conditions and disorders. At present it may be too early to introduce most of these biomarkers in daily routine diagnostic applications, but advances in salivary biomarker standardisation should permit their wide-range utilization in the future including safe, reliable and non-invasive estimation of acute and chronic stress levels in patients.

Klasszikus és modern vizsgálómódszerek a csontérettségi kor és a pubertáskori növekedési csúcs meghatározására

The assessment of skeletal age is of utmost importance not only in the field of anthropology, forensic medicine, pediatrics, endocrinology but also in orthodontics and jaw orthopedics. Bone age refers to the individuals biological development which can differ within a relatively wide range for the same chronological age. Therefore, accurate assessment of skeletal maturity and pubertal growth plays an important role in establishing a diagnosis for certain diseases. In addition, it is essential for proper timing and success of treatments in many cases. Currently, there are many methods available to determine skeletal age and pubertal growth spurt. During growth, bones undergo significant changes, the sequence of which is strongly determined. These changes can be measured by various methods including radiological examinations. More specifically, these classical methods are often based on the radiological evaluation of morphological changes in the hand bones and cervical vertebrae. Methods based on dental development also exist to assess the biologic maturity of an individual. However, thanks to three-dimensional imaging techniques and molecular diagnostic methods, even more accurate tests can be performed to determine biological maturity. These modern methods rely on the information obtained from the cone-beam computer tomograph records and on the measurements of biomarkers present in different circulatory or other body fluids. The purpose of this summary is to provide an overview of the various classical and modern methods for the assessment of skeletal age that could aid us in many fields of science. Orv Hetil. 2018; 159(35): 1423-1432.: The assessment of skeletal age is of utmost importance not only in the field of anthropology, forensic medicine, pediatrics, endocrinology but also in orthodontics and jaw orthopedics. Bone age refers to the individuals biological development which can differ within a relatively wide range for the same chronological age. Therefore, accurate assessment of skeletal maturity and pubertal growth plays an important role in establishing a diagnosis for certain diseases. In addition, it is essential for proper timing and success of treatments in many cases. Currently, there are many methods available to determine skeletal age and pubertal growth spurt. During growth, bones undergo significant changes, the sequence of which is strongly determined. These changes can be measured by various methods including radiological examinations. More specifically, these classical methods are often based on the radiological evaluation of morphological changes in the hand bones and cervical vertebrae. Methods based on dental development also exist to assess the biologic maturity of an individual. However, thanks to three-dimensional imaging techniques and molecular diagnostic methods, even more accurate tests can be performed to determine biological maturity. These modern methods rely on the information obtained from the cone-beam computer tomograph records and on the measurements of biomarkers present in different circulatory or other body fluids. The purpose of this summary is to provide an overview of the various classical and modern methods for the assessment of skeletal age that could aid us in many fields of science. Orv Hetil. 2018; 159(35): 1423-1432.

Defense mechanisms against acid exposure by dental enamel formation, saliva and pancreatic juice production

The pancreas, the salivary glands and the dental enamel producing ameloblasts have marked developmental, structural and functional similarities. One of the most striking similarities is their bicarbonate-rich secretory product, serving acid neutralization. An important difference between them is that while pancreatic juice and saliva are delivered into a lumen where they can be collected and analyzed, ameloblasts produce locally precipitating hydroxyapatite which cannot be easily studied. Interestingly, the ion and protein secretion by the pancreas, the salivary glands, and maturation ameloblasts are all two-step processes, of course with significant differences too. As they all have to defend against acid exposure by producing extremely large quantities of bicarbonate, the failure of this function leads to deteriorating consequences. The aim of the present review is to describe and characterize the defense mechanisms of the pancreas, the salivary glands and enamel-producing ameloblasts against acid exposure and to compare their functional capabilities to do this by producing bicarbonate.

A fogászati ellátás finanszírozása Németországban, az Egyesült Királyságban, Magyarországon és Lengyelországban

Absztrakt Bevezetes: Az egeszsegugyi ellatasok kozul a fogaszati beavatkozasok szama a legmagasabb, es a finanszirozasa is jelentős kiadasokat jelent. Celkitűzes: A vizsgalat celja negy europai orszag egeszsegugyi rendszerenek osszehasonlitasa a kozossegi fogaszati ellatas oldalarol. Modszer: A fogaszati ellatasra forditott osszegek es modszerek osszehasonlitasanak alapjat az egeszsegbiztositok altal biztositott adatok kepeztek. A vizsgalatban a kovetkező indikatorokat ertekeltek: a kozossegi fogaszat aranyszamait es a legfontosabb, szajegeszseghez kapcsolodo indexeket. Az altalanos fogaszati ellatasok kozul a prevencios, konzervalo fogaszati, endodonciai es szajsebeszeti beavatkozasokat valasztottak. Eredmenyek: Az egy aktiv fogorvosra juto lakosok szama Nemetorszagban (1247 lakos/fogorvos) a legkedvezőbb, mig Magyarorszagon (2020 lakos/fogorvos) a legrosszabb. A szajegeszseghez kapcsolt indikatorok szignifikans kulonbseget mutatnak a nyugat- es kelet-europai orszagok kozott. Ezzel ellentetben a teljes f...