The potential prognostic novel markers PIV and PILE score to predict survival outcomes at hepatocellular cancer.

OBJECTIVE: We aimed at investigating the prognostic significance of a novel immune marker, PIV and PILE score (a score composite from PIV, LDH and ECOG PS), in patients with HCC in a single center. PATIENTS AND METHODS: 120 patients who met the criteria were included. PIV and PILE at the time of diagnosis were computed retrospectively. For PIV, the median value of 286.15 was taken as the cut-off. While <286.15 was considered low, ≥286.15 was considered high PIV. The PILE score included PIV (< median vs. ≥ median), lactate dehydrogenase level (

Association of serum proprotein convertase Subtilisin/Kexin Type 9 (PCSK9) level with thyroid function disorders.

OBJECTIVE: We aimed at demonstrating the effect of thyroid function status on proprotein convertase subtilisin kexin type 9 (PCSK9) and determining the effect of thyroid hormones on lipid metabolism by comparing the PCSK9 levels of patients with subclinical hypothyroidism, overt hypothyroidism, and hyperthyroidism. PATIENTS AND METHODS: 124 patients with thyroid disorders, aged between 18 and 65 years, were included in this study. The participants were divided into 3 groups. Group 1 comprised 52 patients with subclinical hypothyroidism, Group 2 comprised 40 patients with overt hypothyroidism, and Group 3 comprised 32 patients with hyperthyroidism. In all of these groups, the thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, total cholesterol, fasting serum glucose, antithyroid peroxidase antibody, antithyroglobulin antibody, and PCSK9 levels were measured. RESULTS: No significant difference was found between the 3 groups in terms of age, gender, and body mass indices. Median PCSK9 measurements were 14.55 ng/mL in Group 1, 14.895 ng/mL in Group 2, and 9.775 ng/mL in Group 3. There was a significant difference in the PCSK9 levels between Group 1-Group 3 and Group 2-Group 3 (p <0.0001 and p <0.0001, respectively). A positive correlation between PCSK9 and the TSH levels (r = 0.211, p= 0.019), and a negative correlation (r = -0,239, p = 0.009 and r = -, 0.218, p = 0.015) between the fT3 and fT4 levels were found. CONCLUSIONS: The serum PCSK9 levels were shown to be associated with thyroid dysfunction. However, no relationship was observed between the serum PCSK9 level and thyroid autoantibody positivity, and obesity in this study.

Effects of umbelliferone isolated from the Ferulago pauciradiata Boiss. & Heldr. Plant on cecal ligation and puncture-induced sepsis model in rats.

Sepsis is a pathophysiological event involving systemic inflammatory response syndrome, multiple organ failure syndromes, and tissue damage. Overproduction of free radicals as a result of tissue damage during sepsis contributes to cellular toxicity, organ failure, and even mortality. Antioxidants, which scavenge free radicals, play a protective role against various diseases. Previous studies have shown that umbelliferone (UF) has antioxidant and anti-inflammatory effects. Since oxidative stress is naturally associated with sepsis-induced organ dysfunction, the application of antioxidant compounds could potentially illuminate the pathophysiology of sepsis, which does not yet have an effective treatment. The sepsis model induced by cecal ligation and puncture (CLP) was applied to rats. Different doses of UF (10░mg/kg, 20░mg/kg, and 40░mg/kg) on oxidant-antioxidant in septic rats, mRNA of inflammatory mediators such as tumor necrosis factor- α (TNF-α) and interleukin (IL)-1 its effects on expression levels were evaluated in lung, kidney, and liver tissues. When the lung, kidney, and liver tissues of septic rats were compared with those of the control group, it was found that UF administration increased dose-dependent superoxide dismutase activity and glutathione levels and significantly decreased malondialdehyde levels. The effects of UF administration on oxidative parameters were dose-dependent. The 40░mg/kg UF dose showed greater anti-oxidative properties than the 20░mg/kg and 10░mg/kg doses for all the evaluated parameters. Further, the TNF- α mRNA expression of the CLP +40░mg/kg group was reduced to a level comparable to that of the control group. UF has been found to be an effective molecule in reducing oxidative stress by supporting endogenous antioxidants and enhancing the scavenging effects of free radicals. The potent antioxidant property of UF may also be related to the suppression of the cytokine cascade during sepsis. The results suggest that UF administration may represent a new treatment for the prevention of lung, kidney and liver damage caused by septic conditions.

The role of insulin - like growth factor - 1 on steatohepatitis.

PURPOSE: Recent studies have revealed that growth hormone and STAT5 were related to hepatosteatosis in mice. Loss of signal transducer and activator of transcription factor-5 leads to hepatosteatosis and impaired liver regeneration. We aimed to investigate the role of IGF-1 in steatosis with normal (SNLFT) and disturbed liver function tests (SDLFT) in humans. METHODS: We included 272 NAFLD patients and 110 age, sex and body mass index (BMI)-matched healty controls. We measured routine blood biochemistry and complete blood count, IGF-1, insulin, c-peptide, ferritin, hsCRP, ESR and HOMA-IR. We subdivided NAFLD patients into SNLFT and SDLFT subgroups. RESULTS: ge, sex and BMI were similar between NAFLD and controls. IGF-1 levels were significantly lower in NAFLD patients (120,6±48,2) than controls (148,9±53,8), (<0,0001). IGF-1 levels were also lower in SDLFT subgroup (93,4±27,8) than SNLFT subgroup (123,1±49,0), (p:0,032). Waist circumference, fasting blood glucose, HbA1c, uric acid, hsCRP, AST, ALT, GGT, WBC, hemoglobin, hematocrit, ferritin, insulin, c-peptid and HOMA-IR measurements were significantly higher in NAFLD patients than controls (for all values: p<0,0001).Cholesterol (p:0,026), triglycerides (p<0,0001), ESR (p:0,006) were significantly higher in NAFLD patients than controls. HDL-chelesterol levels were significantly lower (p:0,002) in NAFLD patients than controls. CONCLUSION: This study supported previous findings of experi-mental studies in that, IGF-1 levels were lower in SNLFT and SDLFT. Growth hormone-IGF-1 system may be involved in the pathogenesis of NAFLD.

A standardised static in vitro digestion method suitable for food - an international consensus.

Simulated gastro-intestinal digestion is widely employed in many fields of food and nutritional sciences, as conducting human trials are often costly, resource intensive, and ethically disputable. As a consequence, in vitro alternatives that determine endpoints such as the bioaccessibility of nutrients and non-nutrients or the digestibility of macronutrients (e.g. lipids, proteins and carbohydrates) are used for screening and building new hypotheses. Various digestion models have been proposed, often impeding the possibility to compare results across research teams. For example, a large variety of enzymes from different sources such as of porcine, rabbit or human origin have been used, differing in their activity and characterization. Differences in pH, mineral type, ionic strength and digestion time, which alter enzyme activity and other phenomena, may also considerably alter results. Other parameters such as the presence of phospholipids, individual enzymes such as gastric lipase and digestive emulsifiers vs. their mixtures (e.g. pancreatin and bile salts), and the ratio of food bolus to digestive fluids, have also been discussed at length. In the present consensus paper, within the COST Infogest network, we propose a general standardised and practical static digestion method based on physiologically relevant conditions that can be applied for various endpoints, which may be amended to accommodate further specific requirements. A frameset of parameters including the oral, gastric and small intestinal digestion are outlined and their relevance discussed in relation to available in vivo data and enzymes. This consensus paper will give a detailed protocol and a line-by-line, guidance, recommendations and justifications but also limitation of the proposed model. This harmonised static, in vitro digestion method for food should aid the production of more comparable data in the future.

In Vitro Models for Studying Secondary Plant Metabolite Digestion and Bioaccessibility.

There is an increased interest in secondary plant metabolites, such as polyphenols and carotenoids, due to their proposed health benefits. Much attention has focused on their bioavailability, a prerequisite for further physiological functions. As human studies are time consuming, costly, and restricted by ethical concerns, in vitro models for investigating the effects of digestion on these compounds have been developed and employed to predict their release from the food matrix, bioaccessibility, and assess changes in their profiles prior to absorption. Most typically, models simulate digestion in the oral cavity, the stomach, the small intestine, and, occasionally, the large intestine. A plethora of models have been reported, the choice mostly driven by the type of phytochemical studied, whether the purpose is screening or studying under close physiological conditions, and the availability of the model systems. Unfortunately, the diversity of model conditions has hampered the ability to compare results across different studies. For example, there is substantial variability in the time of digestion, concentrations of salts, enzymes, and bile acids used, pH, the inclusion of various digestion stages; and whether chosen conditions are static (with fixed concentrations of enzymes, bile salts, digesta, and so on) or dynamic (varying concentrations of these constituents). This review presents an overview of models that have been employed to study the digestion of both lipophilic and hydrophilic phytochemicals, comparing digestive conditions in vitro and in vivo and, finally, suggests a set of parameters for static models that resemble physiological conditions.

Oestrogen and progesterone reduce lipopolysaccharide-induced expression of tumour necrosis factor-alpha and interleukin-18 in midbrain astrocytes.

Besides microglia, astrocytes exert an important regulatory function in the initiation and control of neuro-inflammatory processes in the central nervous system. Clinical and experimental data suggest that sex steroids are neuroprotective and that neurological/neurodegenerative disorders display sex-specific characteristics. Astroglia is known to respond to toxic stimuli by secretion of distinct pro-inflammatory/apoptotic cytokines. In the present study, we investigated the influence of oestrogen and progesterone on the expression of the cytokines tumour necrosis factor (TNF)-alpha and interleukin (IL)-18 in primary astrocytes obtained from neonatal mouse midbrain and cerebral cortex after the stimulation with lipopolysaccharides (LPS). LPS strongly induced the expression of TNF-alpha in astrocytes from both brain regions and IL-18 in those from midbrain. Oestrogen significantly attenuated LPS-induced TNF-alpha expression in the midbrain glia but not in the cortex glia. Combined treatment with oestrogen and progesterone together diminished LPS-induced IL-18 expression in the midbrain completely. Both steroid effects could be specifically antagonised by the steroid hormone receptor antagonists ICI 182 780 and mifepristone. We conclude that neuroprotective oestrogen and progesterone effects in the midbrain might be in part the consequence of a reduced pro-inflammatory response of astroglia.

Oestrogen regulates the expression and function of dopamine transporters in astrocytes of the nigrostriatal system.

Dopamine is actively and specifically eliminated from the extracellular space by astrocytes and neurones through dopamine transporters (DAT) and, afterwards, either recycled into vesicles or metabolised. The availability of dopamine reflects a critical point in the regulation of dopamine activity within the nigrostriatal circuit under normal and pathological conditions. From previous studies, we know that oestrogen regulates the efficacy of dopaminergic neurones at the synaptic level and improves dopamine function during Parkinson's disease. Accordingly, we investigated the contribution of local astroglial for extracellular dopamine elimination and the impact of oestrogen on DAT expression and activity. Using neonatal striatal and midbrain astrocyte cultures, we could demonstrate that astrocytes possess a specific dopamine uptake machinery and express DAT at considerable levels. The application of 17beta-oestradiol decreased the expression of DAT by 80% and 60% in midbrain and striatal astroglia cultures, respectively. The unspecific dopamine transporters (OCT3, VMAT2) were not detected in astroglia. Functionally, oestrogen exposure inhibited the clearance of dopamine from the extracellular space by 45% and 35% compared to controls in midbrain and striatal astroglia, respectively. The effect on DAT expression and activity was completely antagonised by the oestrogen receptor antagonist ICI 182 780. In conclusion, our data suggest that the positive reinforcement of dopamine transmission under physiological conditions and the alleviative impact of oestrogen under pathological conditions may be the result of a decline in DAT expression and therefore delayed dopamine uptake by astroglia.

Antibacterial activities of MDPB and fluoride in dentin bonding agents.

The aim of this study was to compare in vitro antibacterial activity of MDPB containing bonding system ABF with activities of three Fluoride containing bonding systems (Fuji Bond LC (FBLC), Prime&Bond NT (PBNT), and FluoroBond (FLB). Two bacterial strains were tested: Streptococcus mutans and Lactobacillus acidophilus. The study was performed on Muller Hinton Agar by Agar Well Technique. The bacterial agar was evenly distributed over the surface of petri dishes. Standard wells were punched into the agar. The test materials were placed in the wells of Muller Hinton agar plates, inoculated with Streptococcus mutans NCTC10449 and Lactobacillus acidophilus. The diameters of inhibition zones produced around the materials were measured after 24 h of incubation at 37 +/- 1 degrees C. For statistical analysis, Duncan's multiple range test was used. The primers of bonding agents were highly effective against to Streptococcus mutans. The MDPB containing primer of ABF Bond produced the greatest inhibition zones against to Lactobacillus acidophilus. It was followed by FLB primer. Lactobacillus acidophilus was resistant to FBLC primer and bonding, ABF, PBNT and FLB bonding agents. The results of this study indicated that, incorporation of MDPB in primer of self-etch system increased its antibacterial activity especially against to Lactobacillus acidophilus. However, all bonding systems except for bonding agent of ABF showed some antibacterial activity against to Streptococcus mutans.

Evaluation of internal adaptation in ceramic and composite resin inlays by silicon replica technique.

This study was aimed at investigating the internal adaptation of a ceramic (Ceramco II) and two composite resin inlay materials (SureFil and 3M Filtek Z 250) using silicon replica technique as an indicator. Forty-five standard mesial-occlusal-distal (MOD) cavities were prepared into brass moulds by using computer numerically controlled system. Inlays were prepared according to manufacturers' instructions with indirect methods. Replicas of the prepared cavities and inlays were produced with a polyvinyl siloxane material (Elite H-D). The spaces between inlays and cavities were filled by different coloured light-body polyvinyl siloxane material. Two parallel slices (mesio-distally) were obtained from the replicas with a sharp blade. Different coloured polyvinyl siloxane material thickness between cavity and inlay was measured at seven points (mesial, occlusal and distal). The data were evaluated with anova and Tukey's honestly significantly different (HSD) statistical tests. In the SureFil and Ceramco II groups, the sizes of the contraction gaps at mesial and distal gingival floors were greater than that of the occlusal marginal walls. In comparison of gap formation at occlusal regions, while the 3M composite group showed highest gap values (204.33 +/- 75.45 microm), the Ceramco II group revealed the lowest (141.17 +/- 23.66 microm) (P < 0.05). At the gingival floors, gap formation of Ceramco II group was the highest (227.08 +/- 51.95 microm). Neither the 3M Filtek Z250 nor SureFil group showed any statistical difference between gap values of their self-occlusal and gingival floors (P > 0.05). In conclusion, our results showed that ceramic inlays did not confer any big advantage for internal adaptation over the composite inlays.

Comparison of antibacterial activity of two dentin bonding systems using agar well technique and tooth cavity model.

OBJECTIVE: This study compared the antibacterial activities of two dentin bonding systems (ABF, Kuraray and Reactmer Bond, Shofu) by a conventional agar well technique and a newly designed in vitro test using tooth model. METHODS: In the agar well technique, the test materials were filled in the wells of Muller Hinton agar plates inoculated with Streptococcus mutans NCTC10449, and the diameters of inhibition zones produced around the materials were measured after 24h of incubation. For the tooth model test, three cavities (diameter 1mm, depth 2mm) were prepared in the flat occlusal dentin of human extracted molar. After sterilization, the teeth were left in broth culture of 1.56 x 10(8)CFU/ml of S. mutans at 37 degrees C for 72h for allowing bacteria to invade the cavity. The dentin bonding systems were applied separately to each of the two infected cavities, and the third cavity was left unapplied for control. After sealing the occlusal surfaces, the teeth were kept in physiologic saline solution at 37 degrees C for 72h. The standardized amounts of dentin chips (120+/-5mg) were obtained from the cavity walls and the number of bacteria recovered was determined. The results were analyzed by One Way ANOVA, Kruskal Wallis and Mann-Whitney's U tests. RESULTS: The primer of ABF and Reactmer Bond produced inhibition zones with similar sizes (p>0.05), but the bonding resin of ABF did not produce any inhibition. When tested by the model cavity method, the application of ABF resulted in significantly less bacterial recovery than Reactmer Bond (p<0.05), demonstrating substantial antibacterial effects. CONCLUSIONS: The tooth model method used in this study was effective for evaluating the substantial antibacterial effects of dentin bonding agents, and the experimental dentin bonding system ABF was demonstrated to be able to inactivate the bacteria in the cavity effectively in comparison with little antibacterial activity shown by Reactmer Bond.

Antioxidant activity of some foods containing phenolic compounds.

This study was designed to determine the total phenols (TP) and total antioxidant activity (TAA) of some liquid and solid plant foods that are commonly consumed in Turkey. Total phenols were analysed according to the Folin-Ciocalteu method and antioxidant activities of these compounds in aqueous phase were assessed by measuring their direct ABTS.- radical scavenging abilities. Total phenols varied from 68 to 4162 mg/l for liquid foods and from 735 to 3994 mg/kg for solid foods. TAA of liquid and solid foods ranged between 0.61-6.78 mM and 0.63-8.62 mM, respectively. Total antioxidant activities of foods were well correlated with total phenols (r2 = 0.95). According to content of total phenols per serving, liquid foods were in the order of black tea > instant coffee > coke > red wine > violet carrot juice > apricot nectar > Turkish coffee > grape molasses > sage > white wine > linden flower, and solid foods were in the order of red grape > raisins > tarhana > dried black plum > dried apricot > grape > fresh paprika > fresh black plum > Urtica sp. > cherry > fresh apricot > paprika pickle > paprika paste.

Adsorption of direct-acting and indirect-acting mutagens by various dietary fibers.

The protective effect of dietary fiber on human cancer has received great attention during the last decades. Because dietary fiber constitutes a large group of complex polysaccharides with various solubilities, degrees of lignification, chemical compositions and structural arrangements, several mechanisms for their effects have been proposed. In this study, in vitro binding capacities of various dietary fibers (potato fiber and glucomannan) and dietary fiber constituents (pectic acid and cellulose) against indirect mutagen 2-amino-3-methyl-3H-imidazo (4,5-f) quinoline (IQ) and direct-acting mutagen sodium azide were investigated. Direct-acting mutagen sodium azide was not adsorbed to the dietary fiber and dietary fiber constituents of 0 degree C, pH 4.5 and 37 degrees C, pH 7.0. However, indirect-acting mutagen 2-amino-3-methyl-3H-imidazo (4,5-f) quinoline (IQ) were sorbed by them in variable ratios at 0 degree C, pH 4.5 and 37 degrees C, pH 7.0. The differences between the in vitro binding capacities of the samples at two experimental conditions were found to be statiscially significant (P < 0.01). IQ was not released from the dietary fibers and constituents in distilled water.

Polycystic ovaries in association with müllerian anomalies.

The polycystic ovary syndrome, whose etiopathogenesis is not clearly understood, has a wide spectrum of clinical presentations, and may co-exist with other pathologic conditions. In this study, we evaluated the prevalence of ultrasound-defined polycystic ovaries (PCO) in patients with müllerian anomalies (n = 167), and those without müllerian anomalies (n = 3165) from 1990 to 1994, in a population markedly composed of infertility patients. PCO were found in 50 (29.9%) patients in the study group, compared to 637 (20.1%) patients in controls (P < 0.01). Müllerian anomalies were further grouped according to the American Fertility Society (AFS) classification and it was found that patients with the septate uteri and bicornuate uteri malformations had a higher prevalence of PCO than the controls (P < 0.001, P < 0.05, respectively). Although a difference existed in the percentage of PCO in patients with unicornuate uteri and didelphic uteri compared to controls, this difference did not reach statistical significance (P > 0.05). We conclude that, as PCO are more prevalent in certain müllerian anomalies, an embryogenetic defect may also be involved in the etiopathogenesis of PCO.