OBJECTIVES: Periodontitis is a common chronic inflammatory disease characterized by the destruction of the supporting structures of the teeth. The stages of menopause also worsen inflammatory condition. Biomarkers from biological fluids can be used as a diagnostic indicator to correlate these two conditions of present and future disease activity. The aim of the present study was to evaluate the neopterin levels in three biological fluids obtained from pre- and postmenopausal women with periodontitis following non-surgical periodontal therapy (NSPT, that is, scaling).METHODS: This was a cross-sectional interventional study. Thirty women, aged 40–60 years, with periodontitis were selected according to their menstrual history. They were divided into the pre- and postmenopausal groups, with each group including 15 participants. The neopterin levels were measured in both groups at baseline and 3 months after NSPT. Intergroup comparison and percentage decrement analysis were performed using the independent sample t test, and intragroup comparison was performed using the paired t test.RESULTS: There were statistically significant reductions in the mean values of saliva, urine, and plasma from baseline to 3 months after NSPT in the groups. Intergroup comparison showed no significant values in the postmenopausal group, and a significant reduction was seen in the mean values was seen in the mean values.CONCLUSIONS: Neopterin levels decreased at 3 months after NSPT in both the groups, suggesting that NSPT can be a gold standard therapy and that the neopterin level could be a indicator to identify periodontal destruction.
Biomarkers ; Female ; Humans ; Inflammation ; Menopause ; Neopterin ; Periodontitis ; Plasma ; Saliva ; Tooth

BACKGROUND: Although Th2 immune activation is predominant in allergic diseases, neopterinlevels and indoleamine 2,3-dioxygenase (IDO)-1 activity (kynurenine:tryptophan ratio), which reflect Th1 immune activity, increase with interferon-gamma (IFN-γ) stimulation. We investigated neopterin, tryptophan, and kynurenine levels as biomarkersof the Th1 immune system activation and changes in IDO-1 activityin children with asthma, allergic rhinitis, and atopic dermatitis, as well as the relationship between these biomarkers and the total IgE level, age, and disease severity. METHODS: We divided 205 children (80 girls and 125 boys, four months to 17 years old) into four groups: controls, patients with asthma, patients with allergic rhinitis, and patients with atopic dermatitis. Peripheral venous blood samples were collected. Neopterin levels were determined by an enzyme immunoassay. Tryptophan and kynurenine levels were analyzed using HPLC. IDO-1 enzyme activity was calculated using tryptophan and kynurenine levels. IgE levels were measured. The Mann-Whitney U test, Kruskal-Wallis test, and Conover post-hoc method were used for statistical analysis. RESULTS: Neopterin, tryptophan, and kynurenine levels were higher and IgE levels and IDO-1 enzyme activity were lower in patients with asthma and allergic rhinitis than in controls (P < 0.05). Patients with atopic dermatitis showed higher neopterin, tryptophan, and kynurenine levels, higher IDO-1 activity, and lower IgE levels thancontrols (P < 0.05). CONCLUSIONS: The Th1/Th2 balance is disrupted in children with allergic diseases, concomitant with increased Th1-mediated immune response activation and reduced IgEproduction, which is promoted by Th2-type cytokines.
Asthma ; Biomarkers ; Child ; Chromatography, High Pressure Liquid ; Cytokines ; Dermatitis, Atopic ; Female ; Humans ; Hypersensitivity ; Immune System ; Immunoenzyme Techniques ; Immunoglobulin E ; Indoleamine-Pyrrole 2,3,-Dioxygenase ; Interferon-gamma ; Kynurenine ; Methods ; Neopterin ; Rhinitis, Allergic ; Tryptophan

Most attempts at rational development of new analgesics have failed, in part because chronic pain involves multiple processes that remain poorly understood. To improve translational success, one strategy is to select novel targets for which there is proof of clinical relevance, either genetically through heritable traits, or pharmacologically. Such an approach by definition yields targets with high clinical validity. The biology of these targets can be elucidated in animal models before returning to the patients with a refined therapeutic. For optimal treatment, having biomarkers of drug action available is also a plus. Here we describe a case study in rational drug design: the use of controlled inhibition of peripheral tetrahydrobiopterin (BH4) synthesis to reduce abnormal chronic pain states without altering nociceptive-protective pain. Initially identified in a population of patients with low back pain, the association between BH4 production and chronic pain has been confirmed in more than 12 independent cohorts, through a common haplotype (present in 25% of Caucasians) of the rate-limiting enzyme for BH4 synthesis, GTP cyclohydrolase 1 (GCH1). Genetic tools in mice have demonstrated that both injured sensory neurons and activated macrophages engage increased BH4 synthesis to cause chronic pain. GCH1 is an obligate enzyme for de novo BH4 production. Therefore, inhibiting GCH1 activity eliminates all BH4 production, affecting the synthesis of multiple neurotransmitters and signaling molecules and interfering with physiological function. In contrast, targeting the last enzyme of the BH4 synthesis pathway, sepiapterin reductase (SPR), allows reduction of pathological BH4 production without completely blocking physiological BH4 synthesis. Systemic SPR inhibition in mice has not revealed any safety concerns to date, and available genetic and pharmacologic data suggest similar responses in humans. Finally, because it is present in vivo only when SPR is inhibited, sepiapterin serves as a reliable biomarker of target engagement, allowing potential quantification of drug efficacy. The emerging development of therapeutics that target BH4 synthesis to treat chronic pain illustrates the power of combining human and mouse genetics: human genetic studies for clinical selection of relevant targets, coupled with causality studies in mice, allowing the rational engineering of new analgesics.
Analgesics ; therapeutic use ; Animals ; Biopterin ; analogs & derivatives ; metabolism ; Chronic Pain ; drug therapy ; genetics ; Disease Models, Animal ; Drug Discovery ; GTP Cyclohydrolase ; genetics ; metabolism ; Humans ; Rodentia ; Signal Transduction ; drug effects ; genetics

OBJECTIVES: Neopterin is a valuable diagnostic biomarker, which is elevated in inflammatory conditions like periodontitis, that is characterized by destruction of the supporting structures of the teeth. Among the biomarkers, neopterin occurs in body fluids, and acts as a diagnostic marker for present and future disease activity. METHODS: Thirty female subjects with chronic periodontitis, mean age 50 years (40-60 years) were included in this study. Depending upon their menstrual history, subjects were categorized into two groups of fifteen each. Group I 15 pre-menopausal women, and Group II 15 post-menopausal women. Saliva was collected, and neopterin levels were assessed by enzyme-linked immunosorbent assay in both the groups, at base line and after three months of nonsurgical periodontal therapy (NSPT). Periodontal parameters like pocket probing depth (PD) and Russell's periodontal disease index (PDI) were assessed before treatment as well as after three months of scaling and root planning. RESULTS: Intra group analysis showed significant markdown in the mean values of all the parameters from baseline to three months (P < 0.001), for all patients. The intergroup comparison, from baseline to 3 months also showed no significant change in PD and PDI values, but there was a statistically significant difference in the salivary neopterin levels (P = 0.04). CONCLUSIONS: Neopterin levels were found to be reduced in three months after NSPT in both the groups, suggesting that the NSPT is the gold standard therapy, and also that neopterin levels in saliva can be used as an indicator to identify periodontal inflammation and destruction.
Biomarkers ; Body Fluids ; Chronic Periodontitis ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Inflammation ; Neopterin* ; Periodontal Diseases ; Periodontitis ; Reactive Oxygen Species ; Root Planing ; Saliva ; Tooth ; Women's Health

BACKGROUNDTetrahydrobiopterin (BH4) is an essential cofactor of nitric oxide synthases (NOSs) for the synthesis of nitric oxide (NO). BH4 therapy can reverse the disease-related redox disequilibrium observed with BH4 deficiency. However, whether BH4 exerts a protective effect against radiation-induced damage to cardiomyocytes remains unknown.

METHODSClonogenic assays were performed to determine the effects of X-ray on H9c2 cells with or without BH4 treatment. The contents of lactate dehydrogenase (LDH), superoxide dismutase (SOD), and malondialdehyde (MDA) in H9c2 cells were measured to investigate oxidative stress levels. The cell cycle undergoing radiation with or without BH4 treatment was detected using flow cytometry. The expression levels of proteins in the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT)/P53 signaling pathway, inducible NOS (iNOS), and endothelial NOS (eNOS) were examined using Western blotting.

RESULTSX-ray radiation significantly inhibited the growth of H9c2 cells in a dose-dependent manner, whereas BH4 treatment significantly reduced the X-ray radiation-induced growth inhibition (control group vs. X-ray groups, respectively, P< 0.01). X-ray radiation induced LDH release, apoptosis, and G0/G1 peak accumulation, significantly increasing the level of MDA and the production of NO, and decreased the level of SOD (control group vs. X-ray groups, respectively, P < 0.05 or P < 0.01). By contrast, BH4 treatment can significantly reverse these processes (BH4 treatment groups vs. X-ray groups, P < 0.05 or P < 0.01). BH4 reversed the X-ray radiation-induced expression alterations of apoptosis-related molecules, including B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein, and caspase-3, and molecules of the PI3K/Akt/P53 signaling pathway. BH4 enhanced the production of NO in 2 Gy and 4 Gy radiated groups by upregulating eNOS protein expression and downregulating iNOS protein expression.

CONCLUSIONSBH4 treatment can protect against X-ray-induced cardiomyocyte injury, possibly by recoupling eNOS rather than iNOS. BH4 treatment also decreased oxidative stress in radiated H9c2 cells.

Animals ; Antioxidants ; metabolism ; Apoptosis ; drug effects ; Biopterin ; analogs & derivatives ; pharmacology ; Cell Cycle ; drug effects ; Cell Line ; Enzyme-Linked Immunosorbent Assay ; L-Lactate Dehydrogenase ; metabolism ; Myocytes, Cardiac ; cytology ; drug effects ; radiation effects ; Rats ; Signal Transduction

OBJECTIVETo study the diagnostic values of cerebrospinal concentrations of neopterin (NPT) and S100b for central nervous system infections in children.

METHODSEnzyme-linked immunosorbent assay was used to determinate the cerebrospinal concentrations of NPT and S100b in children with central nervous system infections and control children. The two groups of children were compared in terms of the two indicators, and the diagnostic values of the two indicators were evaluated by ROC curve analysis.

RESULTSChildren with viral encephalitis had significantly increased cerebrospinal concentrations of NPT and S100b compared with the control group and children with purulent meningitis (P<0.01); there was no difference in the cerebrospinal concentration of NPT between children with purulent meningitis and the control group, while the concentration of S100b in the purulent meningitis group was significantly higher than in the control group (P<0.01). According to the ROC curves, S100b was more valuable than NPT in the diagnosis of viral encephalitis; when cerebrospinal concentration was more than 0.384 ng/mL, S100b had a sensitivity of 93.3% and a specificity of 97.9%; a combination of the two indicators had a higher diagnostic value for viral encephalitis, with a sensitivity of 96.7% and a specificity of 97.9%.

CONCLUSIONSBoth NPT and S100b have certain values in the diagnosis of central nervous system infections in children, and S100b is better than NPT.

Adolescent ; Central Nervous System Infections ; cerebrospinal fluid ; diagnosis ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Neopterin ; cerebrospinal fluid ; ROC Curve ; S100 Calcium Binding Protein beta Subunit ; cerebrospinal fluid

Biopterin ; analogs & derivatives ; deficiency ; genetics ; Child ; Consensus ; Diagnosis, Differential ; Humans ; Infant ; Infant, Newborn ; Neonatal Screening ; methods ; Phenylalanine ; blood ; Phenylalanine Hydroxylase ; deficiency ; genetics ; Phenylketonurias ; classification ; diagnosis ; therapy ; Practice Guidelines as Topic ; Severity of Illness Index ; Tyrosine ; blood

Biopterin ; analogs & derivatives ; deficiency ; genetics ; Child ; Consensus ; Diagnosis, Differential ; Humans ; Infant ; Infant, Newborn ; Neonatal Screening ; Phenylalanine ; blood ; Phenylalanine Hydroxylase ; deficiency ; genetics ; Phenylketonurias ; diagnosis ; etiology ; therapy ; Practice Guidelines as Topic ; Societies, Medical

BACKGROUND: The aim of this study was to investigate the effects of anesthetic techniques used during general anesthesia (GA) and spinal anesthesia (SA) on endothelial adhesion molecules in the fetal circulation of healthy parturients undergoing elective cesarean section. METHODS: Patients were randomly assigned to either the general anesthesia (n = 20) or spinal anesthesia (n = 20) group. Maternal and cord blood neopterin, sE-selectin, and sL-selectin levels were measured in both groups. RESULTS: Cord blood neopterin concentrations in the SA group were not different from those in the GA group, but maternal neopterin levels in the SA group were different from those in the GA group. Maternal blood levels of sE-selectin and sL-selectin were not different between the two groups. Similarly, the cord blood levels of sE-selectin and sL-selectin were not different between the two groups. We found an increased inflammatory process in the fetal circulation depending on the anesthetic method used. CONCLUSIONS: These results indicate the effects of general and spinal anesthetic techniques on serum sL-selectin, sE-selectin, and neopterin levels in neonates and parturients undergoing elective cesarean section. sE-selectin and neopterin concentrations and leukocyte counts were higher in the fetal circulation than in the maternal circulation during both GA and SA.
Anesthesia, General ; Anesthesia, Spinal ; Cesarean Section* ; Female ; Fetal Blood ; Humans ; Infant, Newborn ; Leukocyte Count ; Neopterin ; Pregnancy

Tetrahydrobiopterin (BH4) is an essential cofactor in NO synthesis by endothelial nitric oxide synthase (eNOS) enzymes. It has been previously suggested that reduced intrahepatic BH4 results in a decrease in intrahepatic NO and contributes to increased hepatic vascular resistance and portal pressure in animal models of cirrhosis. The main aim of the present study was to evaluate the relationship between BH4 and portal hypertension (PHT). One hundred ninety-three consecutive patients with chronic liver disease were included in the study. Liver biopsy, measurement of BH4 and hepatic venous pressure gradient (HVPG) were performed. Hepatic fibrosis was classified using the Laennec fibrosis scoring system. BH4 levels were determined in homogenized liver tissues of patients using a high performance liquid chromatography (HPLC) system. Statistical analysis was performed to evaluate the relationship between BH4 and HVPG, grade of hepatic fibrosis, clinical stage of cirrhosis, Child-Pugh class. A positive relationship between HVPG and hepatic fibrosis grade, clinical stage of cirrhosis and Child-Pugh class was observed. However, the BH4 level showed no significant correlation with HVPG or clinical features of cirrhosis. BH4 concentration in liver tissue has little relation to the severity of portal hypertension in patients with chronic liver disease.
Adult ; Aged ; Biopterin/*analogs & derivatives/analysis ; *Chromatography, High Pressure Liquid ; Chronic Disease ; Elasticity Imaging Techniques ; Female ; Hepatic Veins/physiology ; Humans ; Hypertension, Portal/complications/*diagnosis/metabolism ; Liver/pathology ; Liver Cirrhosis/ultrasonography ; Liver Diseases/complications/*diagnosis/metabolism ; Male ; Middle Aged ; Nitric Oxide/metabolism ; Portal Pressure ; Regression Analysis ; Severity of Illness Index