OBJECTIVE: Evaluation of importance of serum levels of basic fibroblast growth factor (bFGF) in patients with ovarian cancer, patients with border-line ovarian tumor, patients with benign ovarian cyst and women with normal ovarian tissue. DESIGN: Prospective clinical study. SETTING: Department of Gynecology and Obstetrics, Charles University, Faculty of Medicine in Hradec Kralove and University Hospital Hradec Kralove. METHODS: Measurement of serum levels of bFGF by ELISA using reagents of company R&D Systems prior to treatment in a total of 74 consecutive coming women. RESULTS: Serum level of bFGF from peripheral blood before treatment was significantly higher (p < 0.05) in patients with newly diagnosed ovarian cancer (n = 22), Med = 10.35 pg/ml (1.2-46.2 pg/ml) compared to patients with a border-line ovarian tumor (n = 9), Med = 5.4 pg/ml (1.6-6.8 pg/ml), patients with benign ovarian cyst (n = 24), Med = 5.2 pg/ml (0.1-67.2 pg/ml), and to women with normal ovarian tissue (n = 19) Med = 4.3 pg/ml (0.9-13.4 pg/ml). There isnt strong linear correlation (Spearmans rank correlation coefficient = 0.208791) between the serum level of bFGF and CA125 collected from peripheral blood before primary surgery or neoadjuvant chemotherapy in a group of patients with ovarian cancer (n = 14). We have not found significance correlation between age and serum levels of bFGF in patients with ovarian cancer, with border-line ovarian tumor, with benign ovarian cyst and in women with normal ovarian tissue. CONCLUSION: Serum levels of bFGF in patients with ovarian cancer are significantly higher than in patients with a border-line ovarian tumor, with benign ovarian cyst and in women with normal ovarian tissue regardless of age of patients.

• Klíčová slova
• angiogenesis, basic fibroblast growth factor (bFGF), basic fibroblast growth factor (bFGF) angiogenesis., ovarian cancer,
• MeSH
• fibroblastové růstové faktory krev   MeSH
• lidé MeSH
• nádory vaječníků krev   patologie   MeSH
• ovariální cysty krev   patologie   MeSH
• prospektivní studie MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• fibroblastové růstové faktory MeSH

BACKGROUND: Bile salts likely contribute to liver injury in patients with primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC). Fibroblast growth factor 19 (FGF19) is a bile salt-induced enterokine with hepatoprotective potential as it suppresses de novo bile salt synthesis. Here, we evaluated the bile salt receptor FXR/FGF19 gut-liver axis in PSC and PBC patients. METHODS: Fasted patients with PSC (n = 12) and PBC (n = 10), and healthy controls (HC; n = 10) were orally challenged with the natural FXR agonist chenodeoxycholic acid (CDCA 15 mg/kg). Blood was sampled hourly until 8 h afterwards. Serum FGF19 and bile salt excursions were determined. Serum levels of 7α-hydroxy-4-cholesten-3-one (C4), reflecting bile salt synthesis, were measured as a biomarker of FGF19 response. RESULTS: Baseline serum FGF19 levels were comparable between groups, while fasted bile salt levels in PSC patients were elevated. Upon CDCA challenge, HC and PBC patients showed a serum FGF19 peak after 4 h followed by a decline. PSC patients showed a prolonged and elevated serum FGF19 response up to 8 h, combined with a sustained serum elevation of CDCA and other bile salts. In general, C4 levels declined following FGF19 elevation. In PSC patients with less favorable prognosis, baseline C4 levels were drastically suppressed and did not further decline. CONCLUSION: Following an oral CDCA challenge, PSC patients showed an impaired clearance of CDCA and a prolonged serum FGF19 response. FXR agonist therapy in PSC could cause prolonged exposure to elevated levels of FGF19, and we propose careful monitoring for detrimental side effects in patient studies.

• Klíčová slova
• Chenodeoxycholic acid, Farnesoid X receptor, Fibroblast growth factor 19, Primary sclerosing cholangitis,
• MeSH
• aplikace orální MeSH
• cholestenony krev   MeSH
• dospělí MeSH
• fibroblastové růstové faktory krev   metabolismus   MeSH
• játra metabolismus   MeSH
• klinické protokoly MeSH
• kyselina chenodeoxycholová aplikace a dávkování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• purgativa aplikace a dávkování   MeSH
• senioři MeSH
• sklerozující cholangitida krev   farmakoterapie   metabolismus   MeSH
• střevní sliznice metabolismus   MeSH
• studie případů a kontrol MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• 7 alpha-hydroxy-4-cholesten-3-one MeSH Prohlížeč
• cholestenony MeSH
• FGF19 protein, human MeSH Prohlížeč
• fibroblastové růstové faktory MeSH
• kyselina chenodeoxycholová MeSH
• purgativa MeSH

OBJECTIVE: Since fibroblast growth factor 19 (FGF-19) is a potent metabolic regulator that influences glucose and lipid homeostasis, our aim was to develop an ELISA assay for measuring FGF-19 in human serum and to investigate its concentrations in healthy volunteers and patients suffering from metabolic syndrome. MATERIAL AND METHODS: A sandwich ELISA method was developed for quantitative determination of human FGF-19 in serum samples. Blood pressure, waist circumference, FGF-21 serum levels, serum cholesterol, triacylglycerols, HDL-cholesterol, LDL-cholesterol, insulin, glucose, adiponectin, uric acid, creatinine, hs-CRP and calculated BMI and Quicki insulin sensitivity index were measured in 153 healthy volunteers and 66 persons with metabolic syndrome. RESULTS: Neither sex nor age influenced FGF-19 serum concentration in the healthy volunteers. Probands with metabolic syndrome had 65 % lower FGF-19 serum values than the healthy ones (medians 158.6 versus 242.4 ng/L; p<0.01). FGF-19 correlated with glucose (r = -0.35, p<0.01), HDL (r = 0.24, p = 0.045), triacylglycerols (r = -0.19, p = 0.05) and with a number of other risk factors for metabolic syndrome (r = -0.28, p = 0.01). When adjusted to the concentrations of triacylglycerols, BMI and glucose, and finally to all data pertinent to FGF-19 (according to correlation analysis), our data indicate that FGF-19 is an independent marker of metabolic syndrome. CONCLUSIONS: The present study demonstrates the analytical properties of the ELISA FGF-19 assay and its usefulness when studying the metabolic syndrome. Serum concentrations of FGF-19 could be new key predictors of metabolic syndrome and thereby even a new negative risk factor of atherosclerosis.

• MeSH
• diabetes mellitus 2. typu krev   MeSH
• ELISA metody   MeSH
• fibroblastové růstové faktory analýza   MeSH
• lidé MeSH
• metabolický syndrom krev   MeSH
• rekombinantní proteiny analýza   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• FGF19 protein, human MeSH Prohlížeč
• fibroblastové růstové faktory MeSH
• rekombinantní proteiny MeSH

Critical illness is associated with a disturbed regulation of gastrointestinal hormones resulting in functional and metabolic anomalies. Fibroblast growth factor 19 (FGF19) is an ileum-derived metabolic hormone induced by bile salts upon gallbladder emptying after enteral nutrient stimulation. Our aim was to study the nutrient-stimulated FGF19 response in 24 patients admitted to the intensive care unit (ICU) compared with 12 healthy controls. All subjects received intraduodenal high-lipid nutrient infusion for 120 minutes. Blood was collected every 30 minutes until 1 hour after infusion, and gallbladder emptying was studied by ultrasound. Serum levels of bile salts and FGF19 were assessed. ICU patients had significantly higher fasting bile salt serum levels compared with controls, whereas FGF19 serum levels were similar. In both groups, nutrient infusion elicited substantial bile salt elevations (P < 0.001), peaking at 90 minutes, albeit with a significantly lower peak in the ICU patients (P = 0.029). In controls, FGF19 was significantly elevated relative to baseline from 120 minutes onward (P < 0.001). In ICU patients, the FGF19 response was blunted, as reflected by significantly lower FGF19 elevations at 120, 150, and 180 minutes (P < 0.05) and significantly lower area under the curve (AUC) values compared with controls (P < 0.001). Gallbladder dysmotility was associated with the impaired FGF19 response in critical illness. The gallbladder ejection fraction correlated positively with FGF19 AUC values (ρ = +0.34, P = 0.045). In 10 of 24 ICU patients, gallbladder emptying was disturbed. These patients had significantly lower FGF19 AUC values (P < 0.001). Gallbladder emptying and the FGF19 response were respectively disturbed or absent in patients receiving norepinephrine. Conclusion: The nutrient-stimulated FGF19 response is impaired in ICU patients, which is mechanistically linked to gallbladder dysmotility in critical illness. This may contribute to disturbed liver metabolism in these patients and has potential as a nutritional biomarker.

• MeSH
• dospělí MeSH
• dyskineze žlučových cest krev   MeSH
• fibroblastové růstové faktory krev   MeSH
• kritický stav MeSH
• lidé středního věku MeSH
• lidé MeSH
• postprandiální období * MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• žlučové kyseliny a soli krev   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• FGF19 protein, human MeSH Prohlížeč
• fibroblastové růstové faktory MeSH
• žlučové kyseliny a soli MeSH

The objective of this study was to measure plasma fibroblast growth factor 21 and 19 (FGF21 and FGF19) levels in patients with Cushing's syndrome (CS) and to compare it with those of lean control subjects (C) and patients with obesity (OB). Fourteen untreated patients with CS, 19 patients with OB and 36 controls were included in the study. Plasma FGF21 and FGF19 levels were measured by ELISA kits, other hormonal and biochemical parameters were measured by standard laboratory methods. Plasma FGF19 did not significantly differ among the studied groups. Plasma FGF21 levels were significantly higher in both CS and OB groups relative to C group but they did not differ between CS and OB groups. In a combined population of all three groups FGF21 levels positively correlated with BMI, waist circumference and percentage of total and truncal fat mass. Less prominent inverse relationship with these parameters was found for FGF19. Neither FGF21 nor FGF19 were significantly related to cortisol concentrations. Increased FGF21 concentrations in both patients with CS and OB relative to lean subjects suggest that excessive body fat and/or related metabolic abnormalities rather than direct effects of cortisol are responsible. In contrast neither obesity nor hypercortisolism significantly affected FGF19 concentrations.

• MeSH
• adipozita MeSH
• biologické markery krev   MeSH
• Cushingův syndrom krev   patofyziologie   MeSH
• dospělí MeSH
• ELISA MeSH
• fibroblastové růstové faktory krev   MeSH
• hydrokortison krev   MeSH
• index tělesné hmotnosti MeSH
• lidé středního věku MeSH
• lidé MeSH
• obezita krev   patofyziologie   MeSH
• obvod pasu MeSH
• studie případů a kontrol MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• biologické markery MeSH
• FGF19 protein, human MeSH Prohlížeč
• fibroblast growth factor 21 MeSH Prohlížeč
• fibroblastové růstové faktory MeSH
• hydrokortison MeSH

CONTEXT: Fibroblast growth factor 19 (FGF19) and FGF21 are novel metabolic regulators that improve insulin sensitivity and decrease adiposity in mice. However, little is known about the nutritional regulation of these factors in humans. OBJECTIVE: The objective of this study was to measure plasma FGF19 and FGF21 levels in patients with anorexia nervosa (AN) and to explore its relationship with anthropometric and endocrine parameters. DESIGN: This was a single-center cross-sectional study. SETTING: The study was performed in a university hospital. PATIENTS: Seventeen untreated women with a restrictive type of AN and 17 healthy women (control group) were included. MAIN OUTCOME MEASURES: Fasting plasma FGF19 and FGF21, serum insulin, leptin, soluble leptin receptor, adiponectin, resistin, and C-reactive protein were the main outcome measures. RESULTS: Plasma FGF19 levels did not significantly differ between the groups studied, whereas plasma FGF21 levels were significantly reduced in AN relative to the control group. Plasma FGF21 positively correlated with body mass index and serum leptin and insulin and was inversely related to serum adiponectin in both groups. In contrast, plasma FGF19 was not related to any of parameters studied. Partial realimentation significantly reduced plasma FGF21 levels in AN. CONCLUSION: Circulating levels of FGF21 but not FGF19 are strongly related to body weight and serum levels of leptin, adiponectin, and insulin in both anorectic and normal-weight women. We suggest that reduced plasma FGF21 levels could be involved in the pathophysiology of AN or in a complex adaptive response to this disease.

• MeSH
• adiponektin krev   MeSH
• biologická adaptace fyziologie   MeSH
• dospělí MeSH
• fibroblastové růstové faktory krev   fyziologie   MeSH
• index tělesné hmotnosti MeSH
• inzulin krev   MeSH
• leptin krev   MeSH
• lidé MeSH
• mentální anorexie krev   etiologie   MeSH
• přijímání potravy fyziologie   MeSH
• průřezové studie MeSH
• studie případů a kontrol MeSH
• tělesná hmotnost fyziologie   MeSH
• trijodthyronin krev   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adiponektin MeSH
• ADIPOQ protein, human MeSH Prohlížeč
• FGF19 protein, human MeSH Prohlížeč
• fibroblast growth factor 21 MeSH Prohlížeč
• fibroblastové růstové faktory MeSH
• inzulin MeSH
• leptin MeSH
• trijodthyronin MeSH

FGF2 is secreted from cells by an unconventional secretory pathway. This process is mediated by direct translocation across the plasma membrane. Here, we define the minimal molecular machinery required for FGF2 membrane translocation in a fully reconstituted inside-out vesicle system. FGF2 membrane translocation is thermodynamically driven by PI(4,5)P2-induced membrane insertion of FGF2 oligomers. The latter serve as dynamic translocation intermediates of FGF2 with a subunit number in the range of 8-12 FGF2 molecules. Vectorial translocation of FGF2 across the membrane is governed by sequential and mutually exclusive interactions with PI(4,5)P2 and heparan sulfates on opposing sides of the membrane. Based on atomistic molecular dynamics simulations, we propose a mechanism that drives PI(4,5)P2 dependent oligomerization of FGF2. Our combined findings establish a novel type of self-sustained protein translocation across membranes revealing the molecular basis of the unconventional secretory pathway of FGF2.

• Klíčová slova
• Fibroblast Growth Factor 2, Unconventional protein secretion, biochemistry, biophysics, human, oligomerization, phosphoinositide, protein translocation across membranes, reconstitution with purified components, structural biology,
• MeSH
• fibroblastový růstový faktor 2 metabolismus   MeSH
• fosfatidylinositol-4,5-difosfát metabolismus   MeSH
• heparitinsulfát metabolismus   MeSH
• membránové transportní proteiny metabolismus   MeSH
• multimerizace proteinu * MeSH
• sekreční vezikuly metabolismus   MeSH
• simulace molekulární dynamiky MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• fibroblastový růstový faktor 2 MeSH
• fosfatidylinositol-4,5-difosfát MeSH
• heparitinsulfát MeSH
• membránové transportní proteiny MeSH

BACKGROUND: High cardiovascular risk in patients with chronic kidney disease (CKD) may be related to mineral disorder and microinflammation. Fibroblast growth factor 23 (FGF-23) is a phosphatonin and inhibitor of calcitriol synthesis, which is associated with poor prognosis in CKD patients starting dialysis. Matrix-metalloproteinases (MMP-2, MMP-9) contribute to myocardial remodeling and arterial calcification. FGF-23 and MMPs levels are altered in CKD, however, little is known about their association and relation to cardiovascular (CV) disease. METHODS: Standard laboratory parameters, plasma levels of MMP-2, MMP-9, FGF-23, PAPP-A and CV disease history were assessed in 80 patients with CKD 1-5 and 44 healthy control subjects. RESULTS: FGF-23 and MMP-2 (assessed by ELISA) were higher in CKD patients compared to controls. FGF-23 increased from CKD 3, whereas MMP-2 increased only in CKD 5. FGF-23 was positively associated with MMP-2, adjusted to age, eGFR, phosphatemia, calcitriol and parathormone. FGF-23 independently correlated with parathormone and inversely with calcitriol, whereas MMP-2 was related to phosphatemia. FGF-23 was higher in subjects with a history of CV disease compared to those free of such history (559.0 vs.184.0 RU/ml), adjusted to age and eGFR. CONCLUSION: Our data suggest a possible relationship between FGF-23, MMP-2 and CV disease in CKD. Potential causality of this association remains to be elucidated.

• MeSH
• biologické markery MeSH
• chronické selhání ledvin komplikace   metabolismus   MeSH
• cytokiny krev   MeSH
• ELISA MeSH
• fibroblastové růstové faktory metabolismus   MeSH
• fibroblastový růstový faktor 23 MeSH
• kalcitriol krev   MeSH
• kardiovaskulární nemoci komplikace   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lipidy krev   MeSH
• matrixové metaloproteinasy metabolismus   MeSH
• parathormon krev   MeSH
• pohlavní dimorfismus MeSH
• progrese nemoci MeSH
• senioři MeSH
• sérový albumin metabolismus   MeSH
• stárnutí fyziologie   MeSH
• vitamin D terapeutické užití   MeSH
• vitaminy terapeutické užití   MeSH
• vyšetření funkce ledvin MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• biologické markery MeSH
• cytokiny MeSH
• FGF23 protein, human MeSH Prohlížeč
• fibroblastové růstové faktory MeSH
• fibroblastový růstový faktor 23 MeSH
• kalcitriol MeSH
• lipidy MeSH
• matrixové metaloproteinasy MeSH
• parathormon MeSH
• sérový albumin MeSH
• vitamin D MeSH
• vitaminy MeSH

The aim of our study was to measure serum concentrations of fibroblast growth factor 19 (FGF-19) in patients with obesity (OB), obesity and type 2 diabetes mellitus (T2DM) and healthy subjects (C) at baseline and after selected interventions. We measured serum FGF-19 levels and other biochemical and hormonal parameters in 29 OB and 19 T2DM females and 30 sex- and age-matched control subjects. The interventions were acute hyperinsulinemia during isoglycemic-hyperinsulinemic clamp (n=11 for T2DM and 10 for C), very-low calorie diet (VLCD, n=12 for OB) and 3 months treatment with PPAR-alpha agonist fenofibrate (n=11 for T2DM). Baseline serum FGF-19 levels were significantly lower in OB relative to C group (132.1+/-12.7 vs. 202.2+/-16.7 pg/ml, p<0.05), while no significant difference was observed between T2DM and OB or control group. Acute hyperinsulinemia tended to decrease FGF-19 levels in both healthy and T2DM subjects. Three weeks of VLCD in OB group had no significant effect on FGF-19, whereas three months of fenofibrate treatment markedly reduced FGF-19 levels in T2DM patients (194.58+/-26.2 vs. 107.47+/-25.0 pg/ml, p<0.05). We conclude that FGF-19 levels in our study were at least partially dependent upon nutritional status, but were not related to parameters of glucose metabolism or insulin sensitivity.

• MeSH
• akutní nemoc MeSH
• biologické markery krev   MeSH
• diabetes mellitus 2. typu krev   terapie   MeSH
• dospělí MeSH
• fenofibrát farmakologie   terapeutické užití   MeSH
• fibroblastové růstové faktory krev   MeSH
• hyperinzulinismus krev   terapie   MeSH
• inzulinová rezistence MeSH
• kalorická restrikce * metody   MeSH
• krevní glukóza metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• obezita krev   MeSH
• PPAR alfa agonisté   fyziologie   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• biologické markery MeSH
• fenofibrát MeSH
• FGF19 protein, human MeSH Prohlížeč
• fibroblastové růstové faktory MeSH
• krevní glukóza MeSH
• PPAR alfa MeSH

BACKGROUND: The ileal-derived hormone, fibroblast growth factor 19 (FGF-19), may promote weight loss and facilitate type-2 diabetes mellitus remission in bariatric surgical patients. We investigated the effect of different bariatric procedures on circulating FGF-19 levels and the resulting impact on mitochondrial health in white adipose tissue (AT). METHODS: Obese and type-2 diabetic women (n = 39, BMI > 35 kg/m2) undergoing either biliopancreatic diversion (BPD), laparoscopic greater curvature plication (LGCP), or laparoscopic adjustable gastric banding (LAGB) participated in this ethics approved study. Anthropometry, biochemical, clinical data, serum, and AT biopsies were collected before and 6 months after surgery. Mitochondrial gene expression in adipose biopsies and serum FGF-19 levels were then assessed. RESULTS: All surgeries led to metabolic improvements with BPD producing the greatest benefits on weight loss (↓30%), HbA1c (↓28%), and cholesterol (↓25%) reduction, whilst LGCP resulted in similar HbA1c improvements (adjusted for BMI). Circulating FGF-19 increased in both BPD and LGCP (χ2(2) = 8.088; P = 0.018), whilst, in LAGB, FGF-19 serum levels decreased (P = 0.028). Interestingly, circulating FGF-19 was inversely correlated with mitochondrial number in AT across all surgeries (n = 39). In contrast to LGCP and LAGB, mitochondrial number in BPD patients corresponded directly with changes in 12 of 14 mitochondrial genes assayed (P < 0.01). CONCLUSIONS: Elevated serum FGF-19 levels post-surgery were associated with improved mitochondrial health in AT and overall diabetic remission. Changes in circulating FGF-19 levels were surgery-specific, with BPD producing the best metabolic outcomes among the study procedures (BPD > LGCP > LAGB), and highlighting mitochondria in AT as a potential target of FGF-19 during diabetes remission.

• Klíčová slova
• Bariatric surgery, FGF-19, Gut hormone, Mitochondria, Obesity, Type-2 diabetes recovery,
• MeSH
• bariatrická chirurgie metody   MeSH
• diabetes mellitus 2. typu metabolismus   patologie   MeSH
• dospělí MeSH
• fibroblastové růstové faktory metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mitochondrie metabolismus   MeSH
• obezita metabolismus   patologie   terapie   MeSH
• prospektivní studie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• FGF19 protein, human MeSH Prohlížeč
• fibroblastové růstové faktory MeSH