Relationship between intestinal hyperpermeability and obesity / Összefüggés a bél-hiperpermeabilitás és az elhízás között

Obesity is a combination of genetic, environmental factors, and systemic inflammation of adipose tissue. In the last decade, more and more evidence suggests that intestinal microbiota is an environmental factor that plays a crucial role in obesity and associated metabolic disorders. Here, we review the association between intestinal microbiota and obesity based on the literature data available to us. The intestinal flora, in the equilibrium state of conventional bacteria, protects the health of the host and helps the development of the immune system. The genome, diet, lifestyle, and epigenetic changes of the host can pathologically alter the composition of the microbiota. In dysbiosis, the development of the gut-associated lymphoid tissue (GALT) associated with the intestinal tract is impaired and the integrity of the intestinal barrier is impaired. Due to the consequent intestinal hyperpermeability, components of pathogenic pathogens such as lipopolysaccharides enter the bloodstream. These components bind to receptors on adipose tissue immune cells as ligands for molecular samples with pathogenic properties and induce adipose tissue dysfunction. The secretion of inflammatory cytokines in adipose tissue is increased. This induces persistent low chronic inflammation, which is responsible for the development of obesity. The damage to health caused by the hyperpermeability of the intestinal barrier can be reduced by interventions, or restored early in the process. Knowing the relationships will help prevent and treat obesity.

Pregnancy in women with cystic fibrosis: 14 case reports and literature review / Cystás fibrosisban szenvedo nok várandóssága: 14 eset ismertetése és irodalmi áttekintés

Összefoglaló. A cystás fibrosisban szenvedo betegek várható élettartama jelentosen megnott az utóbbi évtizedben, egyre több beteg képes saját gyermeket vállalni. Célunk a cystás fibrosisban szenvedo várandós nok perinatalis és anyai történéseinek felmérése saját eseteink és az irodalmi adatok alapján. 14, cystás fibrosisban szenvedo no 16 várandósságáról számolunk be. Rögzítettük a várandósok életkorát, testtömegét, testmagasságát, testtömegindexét, légzésfunkciós értékeit a graviditás kezdetén és végén. Az anyai átlagéletkor szüléskor 21,6 (18-25) év volt. Az anyák graviditásának kezdetén a testmagasság átlaga 162 (150-175) cm, a testtömeg átlaga 57,6 (42-72) kg, a testtömegindex átlaga 21,4 (19,1-23,2) kg/m2 volt. A graviditás végén a testtömeg átlaga 62 (39-76) kg, a testtömegindex átlaga 23,6 (21,3-24,1) kg/m2 volt. A graviditás alatti súlygyarapodás átlaga 8 (1,5-21,5) kg volt. A légzésfunkciós értékek a graviditás kezdetén 2 betegnél voltak beszukültek. A graviditás alatt még 2 beteg légzésfunkciós értékei csökkentek. A sikeres graviditások száma 13 volt. 1 anya kétszer szült. A koraszülések száma 1 volt. A várandósság átlagosan a 38. (34-40.) gestatiós hét után 7 esetben császármetszéssel, 6 esetben hüvelyi szüléssel fejezodött be. A vetélések száma 3 volt. Az Apgar-pontszám minden esetben normális volt. 13 gyermek közül 11-nél a verejtékteszt nem volt emelkedett. 2 gyermeknél magas verejtékértékek voltak, egyikük c.1521_1523delCTT-heterozigóta, a másiknál génmutációt nem tudtunk igazolni. A cystás fibrosisban szenvedo nok általában jól tolerálják a várandósságot az esetek többségében. A kórosan beszukült tüdofunkcióval, alacsony tápláltsági állapottal és cukorbetegséggel rendelkezo nok nagyobb valószínuséggel számíthatnak káros következményekre. Az újszülöttek prognózisa általában jó, de számítani kell a koraszülés és a kis súllyal születés gyakoribb elofordulására. Ideális esetben a várandósságot elozetes tanácsadás útján kell megtervezni, és speciális cystás fibrosis csoportnak kell a várandósok ellátását figyelemmel kísérni, ideértve a cystás fibrosis kezelésében jártas szülészeket is. Kisszámú saját adatunk retrospektív elemzése megerosíti az irodalmi adatok tanúságait. Orv Hetil. 2021; 162(28): 1129-1136. Summary. The life expectancy of patients with cystic fibrosis has increased significantly in the last decade, with more and more patients being able to have their own children. The aim of our study was to assess the perinatal and maternal outcome of pregnant women with cystic fibrosis based on our own cases and literature data. We report 16 pregnancies in 14 women with cystic fibrosis. We recorded the age, body weight, height, body mass index, and respiratory function values of pregnant women at the beginning and end of pregnancy. The mean maternal age at childbirth was 21.6 (18-25) years. At the beginning of maternal pregnancy, the mean height was 162 (150-175) cm, the mean body weight was 57.6 (42-72) kg, and the mean body mass index was 21.4 (19.1-23.2) kg/m2. At the end of pregnancy, the mean body weight was 62 (39-76) kg and the mean body mass index was 23.6 (21.3-24.1) kg/m2. The weight gain under pregnancy was mean 8 (1.5-21.5) kg. The respiratory function values at the onset of pregnancy were narrowed in 2 patients. During pregnancy, the respiratory function values of 2 more patients decreased. The number of successful gestations was 13. A mother gave birth twice. The number of premature births was one. The pregnancy after the mean 38. (34-40.) gestational week was completed in 7 cases by cesarean section and in 6 cases by vaginal delivery. The number of miscarriages was 3. The Apgar score was normal in all cases. In 11 of 13 children, the sweat test was not elevated. 2 children had high sweat values, one of them is heterozygous with c.1521_1523delCTT, the other could not prove a gene mutation. Women with cystic fibrosis generally tolerate pregnancy well, in most cases. Women with poor lung function, low nutritional status, and diabetes are more likely to expect adverse consequences. The outcome of the newborns is good in general, but a common occurrence of premature birth and low birth weight is to be expected. Ideally, pregnancy should be planned through prior counseling and the care of pregnant women should be monitored by a specialized cystic fibrosis team, including obstetricians experienced in the treatment of cystic fibrosis. A retrospective analysis of our own small-number data confirms the evidence from the literature data. Orv Hetil. 2021; 162(28): 1129-1136.

[Metabolic complications of obesity during adolescence, particularly regarding elevated uric acid levels]. / Az elhízás anyagcsere-szövodményei serdülokorban, különös tekintettel az emelkedett húgysavszintek elofordulására.

INTRODUCTION: Obesity is a social problem worldwide that leads to several diseases, including metabolic syndrome, hypertension and cardiovascular diseases. It is known that hyperuricemia in adults may be associated with these disorders. AIM: The aim of the authors was to investigate the frequency of metabolic syndrome and hyperuricemia and their relationship among obese adolescents. METHOD: This was a cross-sectional study. The authors analysed the data of 162 overweight or obese adolescents (100 boys and 62 girls) who were previously investigated in a paediatric endocrinology consultation. Anthropometric and metabolic parameters were evaluated in all subjects. Healthy, age-matched, non obese girls (n = 20) and boys (n = 26) were used as controls. The age of overweight or obese boys was: 12 ± 2.1 and overweight or obese girls was 11 ± 2.5 years. In the control group the age of boys was 12.9 ± 2.5 years and the age of girls was 13.2 ± 1.6 years. Linear regression was used to evaluate associations between uric acid and clinical and laboratory findings associated with metabolic syndrome. RESULTS: Obese or overweight subjects had greater BMI SDS (boys, 3.4 ± 1.3 vs 0.05 ± 0.4 in controls, p<0.0001; girls, 3.75 ± 1.4 vs 0.72 ± 0.9 in controls, p = 0.0001), waist circumference (boys, 90.1 ± 9.2 vs 82.3 ± 6.4 cm in controls; girls, 90.2 ± 8.6 vs 78.1 ± 7.2 cm in controls, p<0.001), higher systolic blood pressure (boys, 125 ± 14.3 vs 118.2 ± 10.8 mmHg in controls, p = 0.02; girls, 125.8 ± 11.8 vs 119.8 ± 8.8 mmHg in controls, p<0.01), diastolic blood pressure (boys, 78.4 ± 9.1 vs 71.2 ± 8.0 mmHg in controls, p = 0.0003; girls, 76.45 ± 7.2 vs 73.2 ± 6.3 mmHg in controls, p = 0.0453). The prevalence of metabolic syndrome was 45/162 (27.8%) and the prevalence of hyperuricemia was 62/162 (38.3%). Of the 45 subjects with metabolic syndrome, 30 (66.7%) had hyperuricemia. CONCLUSIONS: It can be concluded that hyperuricemia is strongly associated with metabolic syndrome. The high concentration of uric acid predicts cardiovascular risk in adulthood. It is important for paediatricians to determine and assess uric acid levels in overweight or obese adolescents.

[Effect of treatment with gonadotropin releasing hormone analogues in girls with idiopathic central precocious puberty]. / Az idiopathiás centrális pubertas praecox gonadotropin releasing hormon analóg terápiájának hosszú távú hatása leányoknál.

UNLABELLED: It has been proven for more than two decades that gonadotropin releasing hormone analogue therapy is the only choice of treatment in patients with central precocious puberty. AIMS: The aim of the authors was to assess the effect of gonadotropin releasing hormone analogue treatment on final height, body mass index, bone mineral density and ovarian function in girls with idiopathic central precocious puberty. METHODS: Predicted adult height, target height and achieved height due to therapy was assessed in 15 girls with idiopathic precocious puberty treated with gonadotropin releasing hormone analogue. At the beginning of the treatment, the age of the girls was 7.0±0.8 years (mean±SD) and at the end of the treatment 12±0.8 years. The duration of gonadotropin-releasing hormone analogue treatment was 4.48±0.8 years. At the time of achieving final height, the age of the patients was 18.2±2.0 years and the height was 160.4±7.1 cm. When final height was reached, the authors evaluated bone mineral density Z-score values, levels of bone markers and the function of the hypothalamic-pituitary-gonadal axis. 15 healthy prepubertal girls, 15 pubertal girls and 15 girls who reached final height matched for chronological age were selected as control groups. RESULTS: The majority of the gonadotropin releasing hormone-treated girls reached or almost reached their expected height predicted on the basis of the heights of their parents, but the therapy resulted only in a modest beneficial effect on height gain. Despite the fact that the body weight of patients increased during the treatment, there was no significant difference in their body mass index when they reached their final height as compared to controls. As compared to controls, patients had a decreased bone mineral density at the time when they reached their final height (lumbar spine 2-4 Z score, -0.27±1.2 vs. 0.5±0.7 in controls; p = 0.0377), which could be explained by their overweight that already existed before treatment, lack of exercise and poor calcium uptake. Their menarche occurred 12±4.6 months after discontinuing the treatment. CONCLUSIONS: Gonadotropin releasing hormone analogue therapy exerts a modest beneficial effect on final height gain. There are no detrimental effects on body mass index, bone mineral density and ovarian function after treatment. Side-effects are of minor severity and they are tolerable.

Epidermal growth factor receptor (EGFR) high gene copy number and activating mutations in lung adenocarcinomas are not consistently accompanied by positivity for EGFR protein by standard immunohistochemistry.

The purpose of this study was to investigate whether detectable protein biomarker overexpression is a prerequisite for the presence of increased gene copy number or activating mutations and responsiveness to the epidermal growth factor receptor (EGFR) inhibitors gefitinib and erlotinib in patients with lung adenocarcinomas. EGFR status was prospectively analyzed in tumor biopsy samples by three methods: protein expression (n = 117) by standardized immunohistochemistry (IHC), gene copy number (n = 97) by fluorescent in situ hybridization (FISH), and mutation analysis by sequencing (n = 126). Fifty-nine percent of the samples were positive by IHC, 40% were positive by FISH, and 13.5% contained activating kinase domain mutations. Thirty-four percent of the FISH-positive and 27% of the mutant samples were also IHC-negative. All EGFR mutant patients had major clinical responses (five complete response and five partial response) to gefitinib or erlotinib treatment, although three of these tumors were IHC-negative and four were FISH-negative. In a retrospective analysis of samples from nine patients with excellent therapeutic responses (three complete response, five partial response, one stable disease) to erlotinib or gefitinib, mutations were identified in eight cases, but IHC was negative in four of these tumors. These results indicate that molecular diagnostic methods appear to be most important for the identification of lung adenocarcinoma patients who may benefit from EGFR inhibitor treatments.

[Significance of metal ion metabolism and oxidative stress in male patients with porphyria cutanea tarda]. / A fémion-metabolizmus és az oxidatív stressz jelentôsége porphyria cutanea tarda betegségben szenvedô férfiakban.

In the last decades, the role of oxidative stress and trace elements was proven to play an important role in the pathogenesis of more and more diseases. This is why a great importance is attributed lately to the antioxidant therapy, and lots of studies are dealing with this issue. In porphyria cutanea tarda (PCT) the biosynthesis of hem is damaged, because of the reduced activity of uroporphyrinogen-decarboxylase enzyme. The hem precursors are accumulating in blood, liver and skin. The hem precursors and porphyrin are eliminated with urine and stool. The enzyme defect is autosomal dominant. The skin symptoms are intensified by sun exposure. This is because the accumulation of uroporphyrins and heptacarboxylporphyrin in the skin causes photosensitivity, and the accumulated iron has a lipid-peroxidation effect. Besides the genetical origin, the alcohol consumption, the hepatotoxic drugs, estrogen and viral infections can also determine the development of the disease. The applied treatment is phlebotomy. In the case of PCT that appears in the field of liver damage, the accumulation of iron is responsible for the development of oxidative stress. The patient's redox homeostasis is changed, and the level of antioxidants is decreased. The redox state of liver and the effects of additional antioxidant treatment in phlebotomized PCT patients were determined by biochemical and trace element analytical methods. According to the clinical data, phlebotomy proved to be an effective treatment in PCT patients. Phlebotomy improved the phototoxic skin symptoms, but it did not improve the ratios of trace elements to each other in the blood of the patients.

Hemorheological status and redox homeostasis of phlebotomised porphyria cutanea tarda patients with diabetes mellitus and in moderate alcohol consumer.

Increase in porphyrin concentration is caused by the decreased activity of uroporphyrinogen decarboxylase in porphyria cutanea tarda (PCT). Iron overload, alcohol consumption and diabetes mellitus play role in the development of PCT. We investigated the hemorheological and redox-parameters from the blood of 34 male PCT patients and 10 male volunteers. The disfunctions were investigated by pathological amounts of iron and lipid metabolism. Routine laboratory and hemorheological parameters, plasma free SH-group concentration, H-donating ability and reducing power were measured by spectrophotometry. Free radical activity was determined by chemiluminometry method. The hemorheological parameters were significantly increased in all three groups of PCT patients compared to the controls. Negative correlations were observed between blood viscosity and antioxidant defence of PCT patients and in PCT patients with alcohol consumption. Plasma and erythrocyte chemiluminescent intensity was higher in PCT patients than in controls, which indicated the decrease of antioxidant defence. Hemorheological parameters were highest in patients with diabetes and in alcohol consumers. Iron overload increased free radical reactions in PCT patients, leading to pathological viscosity. Increased free radical reactions and high blood viscosity increase the risk of cardiovascular diseases.

[Epidermal growth factor receptor (EGFR): therapeutic target in the treatment of lung adenocarcinoma]. / Epidermális növekedési faktor receptor (EGFR): célpont a tüdo adenocarcinomájának kezelésében.

Revolution in biotechnology made possible to identify those gene errors, which via their encoded proteins (mostly kinase enzymes) are key players in tumor development, growth and progression, and could be considered as molecular targets in tumor diagnosis and therapy. Activity of EGFR (epidermal growth factor receptor), an outstanding representative of the regulatory cell surface receptors, can be inhibited by drugs proved for clinical use. In the past year many groups observed that those lung adenocarcinoma cells, which contain activating mutation in the tyrosine kinase domain of EGFR show remarkable sensitivity to anti-EGFR compounds. The basis of the effective therapy is the identification of the mutations. The clinical advantage of EGFR is an example from the coming age of tumor chemotherapy, when the presence of molecular targets will guide the therapeutic choice.