[Assessment of serum interleukin-6 with a rapid test. The diagnosis of neonatal sepsis can be established or ruled out]. / Szérum-interleukin-6-meghatározás gyorsteszt segítségével. Az újszülöttkori szepszis korai diagnózisa, kizárása.

INTRODUCTION: The mortality rate from sepsis is high and the risk of sepsis increases in prematurity in proportion to the decrease in birth weight. MATERIAL AND METHOD: The authors report the assessment of serum interleukin-6 levels in 12 term, at-risk newborn infants after birth and 60 VLBW neonates after detection of non-specific signs of infection or sepsis, treated in NICU at the Semmelweis University, 1st Department of Obstetrics and Gynecology in 2005-2006. The serum IL-6 level with a rapid test (Milenia Quickline IL-6 and PicoScan system) was investigated. The simultaneous assessment of C-reactive protein levels was analysed as well. RESULTS: The assessment of serum interleukin-6 and CRP levels for the early diagnosis of sepsis can be established or ruled out. The sensitivity of serum IL-6 level assessment was 100%. There were no false negative cases. The positive predictive value was 93%. There was a significant difference between the sepsis and infection group of VLBW infants in the serum Il-6 levels ( p = 0.048), and between the infection and non-infection groups in the interleukin-6 levels ( p < 0.005). CONCLUSIONS: In comparing the diagnostic value of IL-6 measurement in VLBW infants with signs of infection to the diagnostic methods currently in use, results showed that a combination of early assessment of IL-6 and CRP seems to increase diagnostic accuracy in attempting to differentiate between septic and nonseptic patients. Such increased accuracy will decrease neonatal morbidity as well as the financial cost of treatment.

HtrA1 is a novel mast cell serine protease of mice and men.

Mast cells are rich sources of proteases, such as tryptases and chymases that control many physiological and pathological processes, for example vascular permeability, smooth muscle cell proliferation or extracellular matrix remodeling. Murine mucosal mast cells mature under the influence of TGF-beta and play a role in asthmatic and anti-helminthic immune responses. In an attempt to identify novel genes that are highly upregulated during mucosal mast cell differentiation, we detected HtrA1 protease as a novel protein in mast cells by microarray experiments. HtrA1 level was much higher in murine mucosal than in connective tissue-type mast cells. Furthermore, HtrA1 is not localized in the secretory granules and is constitutively secreted by human mast cells. Although HtrA1 has been attributed a TGF-beta-inhibitory activity, it did not show any influence on TGF-beta-induced mucosal mast cell differentiation. As many extracellular target proteins have been suggested for HtrA1, this protease may participate in the mast cell-induced extracellular remodeling.

TIM-3 is expressed in melanoma cells and is upregulated in TGF-beta stimulated mast cells.

Many studies detect elevated numbers of mast cells in tumors, but it is still controversial whether they are beneficial or detrimental for tumor cells. Furthermore, many tumors, such as melanomas, produce large quantities of transforming growth factor (TGF)-beta and during tumorigenesis the apoptotic and growth-inhibitory effects of TGF-betas are lost. Based on these data we investigated the gene expression changes in TGF-betaI-treated human mast cells with DNA microarray and detected 45 differentially regulated genes, among them T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3). As the major sources of TIM-3 ligand galectin-9 are not tumor cells, but rather mast cells, this raises the possibility of an autocrine mechanism resulting in local immunosuppression through the elevated TIM-3 expression by TGF-betaI. Interestingly, not only melanoma tissue sections contained TIM-3-positive mast cells, but we detected this protein also in melanoma cells. Furthermore, TIM-3 was expressed in both WM35 and HT168-M1 melanoma cell lines at a higher level than in isolated epidermal melanocytes, which can contribute to the lower adhering capacity of tumor cells. In conclusion, the immunoregulatory molecule TIM-3 in TGF-beta-stimulated mast cells and melanoma cells may support the survival of this tumor type.

[The combined effect of prenatal steroid prophylaxis, neonatal surfactant therapy and reduction of risk of complications from respiratory life support on survival rate of very low birthweight infants]. / Az antenatalis szteroid profilaxis bevezetésének, a neonatalis surfactant terápia alkalmazásának és a respirációs szövodmények csökkentésének együttes hatása az igen kis súlyú újszülöttek túlélésére.

INTRODUCTION: Retrospective analysis on some factors possibly influencing survival rate of very low birthweight infants on respiratory life support has been carried out. AIM: The aim was to find out about roles played by prenatal steroid prophylaxis, neonatal surfactant therapy and methods of reduction of complication risk emanating from respiratory life support in the outcome of treatment. METHOD: The frequency rate of pneumothorax, pneumomediastinum and bronchopulmonary dysplasia was comparatively examined for all very low birthweight (less than 1500 g) neonates treated by respiratory life support in the I. Department of Obstetrics and Gynecology, Semmelweis University in 1999 (n = 178) and in 1989 (n = 78). Corresponding data were compared using t-tests. RESULTS: In 100% of the 1999 patients in the focus of the current investigation (178 newborn infants) have received prenatal steroid prophylaxis and 55% of them (98 neonates) have received neonatal surfactant therapy. Respiratory life support resulted in pneumothorax in 7.8% of them (14 patients) and bronchopulmonary dysplasia in 12.3% of them (22 neonates). Frequency rate of complications for the neonates under investigation attributable to respiratory support or initial illness decreased from 38.6% in 1989 to 19.6% in 1999, a difference proven significant by t-test (p < 0.05). Survival rate increased from 34.6% in 1989 to 63.5% in 1999, which is again a significant difference indicated by t-test (p < 0.05). The differences are especially consequential considering that the average gestation age of the infants in the 1999 group was lower than that of the infants in the 1989 group. CONCLUSION: Decrease in complication rate emanating from respiratory support and increase in survival rate over the 10 year period between 1989 and 1999 can be attributed to the combined effect of improvement in respiratory support therapy applied (aiming to minimise its adverse effects like barotrauma and volutrauma more effectively by refined technological means) and of the introduction of administering prenatal steroid prophylaxis and (if judged necessary) neonatal surfactant therapy. A considerable limitation of this study is the lack of separation of independent variables (the separate effects due to the separate treatments applied), but it is reasonable to believe that improvement was due to a combined effect of all changes in treatments indicated above. It is deemed probable that results can be further improved by finding ways to decrease barotrauma and volutrauma even more effectively than now.