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At least 1,009 records · Page 56Linked to original sources
PubMed2006

Exposure to 3,3',4,4',5-pentachlorobiphenyl during embryonic development has a minimal effect on the cytochrome P4501A response to 2,3,7,8-tetrachlorodibenzo-p-dioxin in cultured chicken embryo hepatocytes.

Concentrations of dioxin-like compounds in avian eggs can vary substantially between individuals, species, and collection sites. Although the inducibility of cytochrome P4501A (CYPIA) in hepatocyte cultures is commonly used to predict species sensitivity to environmental contaminants, it is not known how exposure to dioxin-like compounds during embryonic development might alter this biomarker response. To investigate this question, we injected vehicle or 0.4, 0.8, or 1.6 microg/kg of 3,3',4,4',5-pentachlorobiphenyl (PCB 126) into the air cell of fertilized chicken eggs before incubation, and we measured CYP1A endpoints in cultured hepatocytes of day-19 embryos from each treatment group. The CYP1A response to PCB 126 also was assessed in whole liver tissue. Embryonic exposure to the most environmentally relevant treatment, 0.4 microg/kg of PCB 126, increased CYPIA4 mRNA expression 29-fold compared to control values in whole liver tissue but only twofold compared to control values in cultured hepatocytes. The CYPIA response to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was not altered in hepatocytes cultured from embryos treated with 0.4 microg/kg of PCB 126, but at 0.8 and 1.6 microg/kg of PCB 126, several concentration-dependent effects were observed. For example, embryos exposed to higher concentrations of PCB 126 in ovo were more responsive to CYP1A mRNA induction by TCDD in vitro. These findings suggest that exposure to environmental levels of dioxin-like compounds during incubation is not likely to alter species-sensitivity estimates derived from in vitro CYP1A data.

Animals↗
PubMed2026

The Mediating Role of Immune Cells in the Genetically Predicted Relationship between Gut Microbiota and Puerperal Sepsis: A Mendelian Randomization Study.

INTRODUCTION: The causal relationship between gut microbiota and puerperal sepsis (PS) remains unclear, and there is a lack of in-depth research regarding the potential mediating role of immune cells in this context. OBJECTIVE: This study aims to investigate the causal relationship between gut microbiota and PS using Mendelian randomization (MR) analysis and to assess the mediating effects of immune cells on the risk of PS onset through mediation analysis. MATERIALS AND METHODS: We selected data from large-scale genome-wide association studies (GWAS) involving 473 gut microbiota species, 731 immune cell phenotypes, and PS datasets. Univariate MR (UVMR) analysis was employed to explore the causal relationship between gut microbiota and PS, with the primary statistical method being inverse variance weighting (IVW). Multiple statistical models were applied for sensitivity analysis to minimize the confounding effects of horizontal pleiotropy and heterogeneity. Subsequently, a two-step mediation MR analysis was conducted to evaluate whether immune cells mediate the relationship between gut microbiota and PS. RESULTS AND DISCUSSION: Analysis using various statistical models indicated that 11 gut microbiota species (e.g., Azorhizobium, Bacillus velezensis, CAG-245 sp000435175, Lentimicrobiaceae, and Providencia) exhibited a causal relationship with PS. Further reverse causal analysis between PS and gut microbiota ruled out the possibility of reverse causality. The two-step mediation MR analysis demonstrated that the percentage of IgD-CD27- B cells (10.26%) and CD62L- monocytes (17.29%) partially mediated the effect of CAG-245 sp000435175 on PS risk. CONCLUSION: This study provides evidence of a causal relationship between the abundance of certain gut microbiota species and PS, while also revealing a potential mediating role of immune cells. These findings offer valuable theoretical insights into personalized treatment strategies and the development of novel diagnostic biomarkers for PS.

Humans↗
PubMed2003

Gender differences in bone turnover in 2-year-old Thoroughbreds.

REASONS FOR PERFORMING STUDY: Injuries to the skeleton are a major cause of morbidity and mortality in racehorses and age, gender and season have all been shown to influence risk of injury. OBJECTIVES: To use biochemical markers of bone cell activity to establish to whether cellular processes in bone underlie these described effects. METHODS: Blood samples were collected monthly from 2-year-old horses in race training between November 1998 and September 1999. Mean age at the start of the study was 20 months (range 18-23 months), with no significant difference in average age between colts (n = 84) and fillies (n = 63). Three markers were measured; osteocalcin (OC, bone formation), the carboxyterminal cross-linked telopeptide of type I collagen (ICTP, bone resorption) and the carboxyterminal propeptide of type I collagen (PICP), which is less 'bone-specific' than the other 2 markers. RESULTS: Colts had, on average, 3.62 ng/ml higher OC concentrations (P = 0.044) and 0.68 mg/l higher ICTP concentrations (P = 0.01) than fillies. The effect of gender was not statistically significant for PICP. However, in May, PICP concentrations were on average 157 mg/l higher in fillies than colts. There was no effect of age or season on marker concentrations. CONCLUSIONS: This study has shown that there are gender differences in bone turnover markers in 2-year-old Thoroughbreds; however, age, within the limited range studied, did not have a significant effect on bone cell activity. Lower bone marker concentrations may reflect smaller bone size and/or earlier skeletal maturation in fillies. An increase in concentrations of PICP in fillies in spring and early summer may relect an influence of sex hormones on collagen turnover. POTENTIAL RELEVANCE: Gender differences in bone cell activity in 2-year-old colts and fillies may influence bone's adaptive responses to training and risk of injury.

Age Factors↗
PubMed2005

The molecular epidemiology of gliomas in adults.

In this paper the authors highlight recent findings from molecular epidemiology studies of glioma origin and prognosis and suggest promising paths for future research. The reasons for variation in glioma incidence according to time period of diagnosis, sex, age, ancestry and ethnicity, and geography are poorly understood, as are factors that affect prognosis. High-dose therapeutic ionizing irradiation and rare mutations in highly penetrant genes associated with certain rare syndromes--the only two established causes of glioma--can be called upon to explain few cases. Both familial aggregation of gliomas and the inverse association of allergies and immune-related conditions with gliomas have been shown consistently, but the explanations for these associations are inadequately developed or unknown. Several biomarkers do predict prognosis, but only evaluation of loss of 1p and 19q in oligodendroglial tumors are incorporated in clinical practice. Ongoing research focuses on classifying homogeneous groups of tumors on the basis of molecular markers and identifying inherited polymorphisms that may influence survival or risk. Because most cases of glioma have yet to furnish either an environmental or a genetic explanation, the greatest potential for discovery may lie in genomic studies in conjunction with continued evaluation of environmental and developmental factors. Large sample sizes and multidisciplinary teams with expertise in neuropathology, genetics, epidemiology, functional genomics, bioinformatics, biostatistics, immunology, and neurooncology are required for these studies to permit exploration of potentially relevant pathways and modifying effects of other genes or exposures, and to avoid false-positive findings. Improving survival rates for patients harboring astrocytic tumors will probably require many randomized clinical trials of novel treatment strategies.

Adult↗
PubMed1997

Dietary control of cancer.

Many laboratory studies and human epidemiological data suggest that most cancer deaths are attributable to lifestyle, including nutritional factors and tobacco and alcohol consumption. Tobacco consumption is causally related to cancer of the lung, mouth, larynx, esophagus, bladder, kidney, and pancreas. Nutrients and non-nutrient dietary components probably account for cancer of the colon, breast, prostate, and stomach. This report is based on literature and our own data pertaining to the role of dietary fat, calories, and fiber in the development of colon and breast cancer. We also discuss the evidence from epidemiological, mechanistic, and preclinical efficacy studies indicating a protective effect of micronutrients, non-nutrients, and certain antioxidants in food against oral and lung cancers. Given the continuing cancer burden and the relatively slow impact of proven cancer treatment strategies in reducing cancer mortality, it is essential to evaluate promising nutrients and non-nutrients in foods as chemopreventive agents in persons at increased risk for cancer. Development of reliable intermediate biomarkers is valuable for clinical chemoprevention intervention trials. The purpose of this report is to provide the reader with plausible approaches to cancer control.

Animals↗
PubMed1999

Effects of variations in live weight gain on bone growth and composition and on markers of bone turnover in lambs.

Growing lambs were fed the same diet at intakes supporting mean live weight gains of 0.1, 0.2 and 0.3 kg day-1, representing slow, intermediate and fast growth groups, respectively. The effects on bone growth and composition, and on blood and urinary bone marker concentrations or excretion rates were monitored. Compared with the slow-growing lambs, the higher intake group grew twice as fast, had higher rates of bone growth (indicated by external metatarsal length), and larger and heavier bones at slaughter. Bones from fast-growing animals had higher collagen and deoxypyridinoline concentrations, and lower Ca:collagen, Ca :P and pyridinoline : deoxypyridinoline ratios, indicating a less mature bone compared with the slow-growing lambs. Bone growth rate had no effect on plasma osteocalcin, bone-specific alkaline phosphatase or growth hormone concentrations, nor on the urinary excretion of pyridinoline and deoxypyridinoline. The results for plasma markers may be explained by an increase in blood volume linked with increased body weight.

Alkaline Phosphatase↗
PubMed1999

[PICP].

Explore the source record for details and available documents.

Adult↗
PubMed2001

Effects of statins on biomarkers of bone metabolism: a randomised trial.

BACKGROUND AND AIM: Recently, several studies have indicated there may be differences among statins regarding a possible association between therapy and a reduction in risk of fractures. No data from prospective randomised clinical trials designed to assess either biochemical or clinical effects on bone metabolism are yet available. We assayed levels of biochemical markers of bone formation in stored serum samples from a recently completed randomised clinical trial conducted to compare the effects of simvastatin and atorvastatin on the lipid profile of patients with hypercholesterolaemia. METHODS AND RESULTS: This 12-week, randomised, multicenter, open-label study was designed to compare the safety and lipid-lowering efficacy of simvastatin 40 mg or 80 mg with that of atorvastatin 20 mg or 40 mg in 846 hypercholesterolaemic patients. Stored serum samples from this study were analysed to compare the effects of simvastatin and atorvastatin on 2 biomarkers of bone turnover, bone-specific alkaline phosphatase (BSAP), a marker of bone formation, and C-teleopeptide of type 1 collagen (CTx), a marker of bone resorption. Treatment with simvastatin 40 and 80 mg/day, but not atorvastatin 20 and 40 mg/day, led to significant (p < 0.05) reductions in BSAP in both men (4.1-5.4% reduction) and women (4.2-7.4% reduction). In addition, there appeared to be a dose-dependent effect with greater reductions in BSAP seen with the 80 mg dose of simvastatin. Treatment with either 20 mg or 40 mg of atorvastatin had no significant effect on BSAP levels on the groups as a whole or in the gender-specific subgroups. CTx showed a small, but not statistically significant, decrease with simvastatin, again with an apparent dose-related trend. Atorvastatin treatment generally resulted in small, non significant increases in CTx. CONCLUSIONS: The present serum bone biomarker results show that treatment with simvastatin, but not atorvastatin, decreases BSAP and suggest that simvastatin may have a beneficial effect on bone turnover.

Adult↗
PubMed1998

Bone markers during a 6-month space flight: effects of vitamin K supplementation.

Rapid bone loss is a serious health problem for astronauts during long lasting missions in space. We have recorded the changes of biochemical markers for bone metabolism in one of the astronauts during the 6-month space flight of the EUROMIR-95 mission. Immediately after launch both bone resorption markers and urinary calcium excretion increased about two fold, whereas bone formation markers remained unchanged. After 12 1/2 weeks the astronaut received vitamin K1 (10 mg/day for 6 weeks). Vitamin K is known to be involved in the formation of gamma-carboxyglutamate (Gla) in proteins, such as the calcium-binding bone Gla-proteins osteocalcin and matrix Gla-protein. Concomitant with the start of vitamin K treatment, the calcium-binding capacity of osteocalcin increased, and so did the urinary excretion of free Gla. This is suggestive for a subclinical vitamin K-deficiency in the astronaut before vitamin K-supplementation. During periods of high vitamin K status markers for bone formation (osteocalcin and bone alkaline phosphatase) had increased as compared to the first part of the flight. The mean increases were 14 and 23%, respectively. Our data suggest that increased intake of vitamin K may contribute to counteracting microgravity-induced loss of bone mass during long lasting space missions, but need confirmation in more astronauts.

1-Carboxyglutamic Acid↗
PubMedDate not supplied

[Serum osteocalcin and bone alkaline phosphatase in healthy children in relation to age and gender].

Biochemical markers of bone formation are important in the study of growth and skeletal metabolism. However, interpretation of their values for children and adolescents is difficult because they depend on many factors such as age, gender, pubertal stage, race, nutritional and health status, specificity of assays and others. Therefore, age and sex specific reference ranges for bone formation markers must be established in a defined paediatric population. The purpose of this study was the investigation of normal serum concentration of osteocalcin (OC) and bone alkaline phosphatase (BALP) in Polish children aged 2-18 years. We studied 121 healthy children (56 girls, 65 boys) divided into 3 age groups of both genders: prepubertal, pubertal and postpubertal. The level of OC was determined by N-MID Osteocalcin One Step ELISA kit (Osteometer Bio Tech, Denmark) and the activity of BALP was measured using an enzyme immunoassay Alkphase-B kit (Metra Biosystems, USA). We observed, that both formation markers showed sigmoid regression curves with increasing age. The peak values of OC and BALP occurred during puberty in girls aged 9-13 years (115.6 +/- 21.3 ng/ml; 108.8 +/- 23.6 U/L) and in boys aged 10-15 years (117.8 +/- 22.3 ng/ml; 118.4 +/- 24.5 U/L). In all children after puberty, we observed a gradual lowering of both markers. However, girls showed decreased postpubertal values of OC and BALP 2-3 years earlier than boys, indicating the earlier completion of puberty in girls. The correlation between OC and BALP was statistically significant (r=0.612; p<0.001) in tested children. The results of this study may establish the reference values for bone turnover markers in Polish healthy children, which will be useful in the diagnosis and monitoring of therapy in bone diseases.

Adolescent↗
PubMed2004

Health effects of exposure to waste incinerator emissions:a review of epidemiological studies.

This review evaluates the epidemiological literature on health effects in relation to incineration facilities. Several adverse health effects have been reported. Significant exposure-disease associations are reported by two thirds of the papers focusing on cancer (lung and larynx cancer, non-Hodgkin's lymphoma). Positive associations were found for congenital malformations and residence near incinerators. Exposure to PCB and heavy metals were associated with several health outcomes and in particular with reduction of thyroid hormones. Findings on non-carcinogen pathologies are inconclusive. Effect of biases and confounding factors must be considered in the explanation of findings. Methodological problems and insufficient exposure information generate difficulties on study results. Research needs include a better definition of exposure in qualitative and quantitative terms in particular by developing the use of biomarkers and by implementing environmental measurements.

Carcinogens↗
PubMedDate not supplied

ProteinChip Array analysis of microdissected colorectal carcinoma and associated tumor stroma shows specific protein bands in the 3.4 to 3.6 kDa range.

Multiple pathways of carcinogenesis have been associated with colorectal carcinomas, including the adenoma-carcinoma sequence. The non polyposis coli gene has also been implicated in the pathogenesis of these tumors. Identification of the epithelial-mesenchymal interaction may help in understanding the pathways of invasion and may lead to the development of new, non-invasive tools for the diagnosis and prognosis of colon carcinomas. A ProteinChip Array technology (SELDI=Surface Enhanced Laser Desorption Ionization) has been developed enabling analysis and profiling of complex protein mixtures from a few cells. This study describes the protein analysis of approximately 500-1000 freshly obtained cells from normal and malignant colonic epithelium and its associated stroma by SELDI-TOF-MS (Surface Enhanced Laser Desorption Ionization Time-of-Flight Mass Spectrometry). Pure cell populations of normal and malignant epithelium as well as stroma (without tumor cells) were selected by microdissection from 9 patients. A pattern of 3 peptides of 3.48, 3.55 and 3.6 kDa, which were increased in the colon tumor epithelium and stroma compared to associated normal colon and stroma in all 9 patients, was observed. Coupling microdissection with SELDI represents a powerful tool to identify cell and tumor specific proteins and to understand molecular events underlying the invasive event in colorectal carcinomas. The presence of certain proteins in invasive carcinomas may lead to the development of non invasive biomarkers for the identification or detection of recurrence of colorectal malignancies.

Adenocarcinoma↗
PubMed2005

[Some bone turnover markers in serum of healthy children and adolescents in relation to age and gender].

The purpose of this study was the investigation of serum concentration of serum C-telopeptide of type I collagen (s-CTX) and bone alkaline phosphatase (BALP) in Polish healthy children aged 2-18 years. We studied 141 healthy children (64 girls, 77 boys) divided into 3 age groups of both genders: prebubertal, pubertal and postpubertal. The level of s-CTX was determined by Serum CrossLaps One Step ELISA kit (Osteometer Bio Tech, Denmark) and the activity of BALP was measured using an enzyme immunoassay Alkphase-B kit (Metra Biosystems, USA). We observed that both markers of bone turnover showed sigmoid regression curves with increasing age. The peak values of s-CTX and BALP occurred during puberty in the girls aged 8-13 years (2266 +/- 368 ng/ml; 113.4 +/- 21.9 U/L) and in the boys aged 10-15 years (2139 +/- 489 ng/ml; 117.8 +/- 24.7 U/L). In all children after puberty, we observed a gradual lowering of both markers. However, girls showed decreased postpubertal values of s-CTX and BALP 2-3 years earlier than boys, reflecting the earlier completion of puberty in girls. The correlation between s-CTX and BALP was statistically significant (r = 0.578; p < 0.0001) in tested children. The results of this study will be useful in the diagnosis and monitoring of therapy in bone diseases.

Adolescent↗
PubMedDate not supplied

[Use of biochemical markers of bone metabolism in veterinary medicine].

Effective, non-invasive bone assessment methods for screening, diagnosis and follow-up of the skeleton are more and more requested in veterinary medicine. In contrast to clinical parameters, invasive methods and imaging techniques, indices of bone turnover is a tool for bone metabolism evaluation of the whole skeleton. Biochemical bone markers therefore provide a more real-time assessment of the bone status with simple blood- or urine-analysis. This article surveys currently available biochemical marker of bone metabolism used in veterinary medicine. Additionally, information is provided about physiological and pathological, as well as therapeutic variations of biochemical bone marker concentrations in various species.

Animal Diseases↗
PubMed1991

Progress in chemoprevention of gastrointestinal cancers.

Carcinogenesis is a complex and multistep process. Numerous inhibitors (either naturally occurring or synthetic) have been identified that can interfere with various phases of carcinogenesis, including the endogenous formation of carcinogens, the activation or detoxification of carcinogens, or events in tumor promotion. Many of these compounds have survived a complex screening program and are currently in or ready for clinical application. In gastrointestinal malignancies, colon neoplasia has been a popular target for chemoprevention. The identification of preneoplastic events in colon mucosa or in the progression of malignancy from adenomas to adenocarcinomas has permitted the study of numerous compounds such as calcium salts, difluoromethylornithine, and prostaglandin synthesis inhibitors on intermediate biomarkers or on the development of recurrent adenomas or cancers. A variety of other compounds with general efficacy in other tumor models have also been shown to be effective inhibitors of tumorigenesis in preclinical models of esophageal, gastric, pancreatic, and hepatic carcinogenesis. This review provides an overview of carcinogenesis and principles of chemoprevention and highlights certain developments in the past year that exemplify the experience and progress in this area.

Gastrointestinal Neoplasms↗
PubMed1994

Clinical usefulness of serum carboxyterminal propeptide of procollagen I and tartrate-resistant acid phosphatase determinations to evaluate bone turnover in patients with chronic renal failure.

We have studied the levels of the biochemical markers of bone formation total serum alkaline phosphatase, osteocalcin (BGP) and carboxyterminal propeptide of type I procollagen (PICP), the levels of the biochemical marker of bone resorption serum tartrate-resistant acid phosphatase (TRAP) and those of intact immunoreactive PTH (iPTH) in 30 patients at different stages of chronic renal failure (CRF), all of them without verifiable hepatopathy, and in 9 patients in hemodialysis with hepatopathy measured by the Knodell index. Sixteen control subjects were also studied. In the group of patients with CRF with or without hepatopathy, the levels of biochemical markers of bone turnover were significantly elevated with respect to those of control patients. We did not find any significant difference in the levels of these parameters between the groups with and without liver damage, in spite of the fact that TRAP and PICP are cleared mainly by the liver. Levels of TRAP and PICP correlated significantly with the other biochemical markers of bone turnover studied. The good relation observed between PICP, TRAP and the biochemical indexes of bone activity and iPTH levels suggests the clinical value of these markers in the follow-up of bone involvement in patients with CRF. On the other hand, the frequent hepatopathy found in patients with CRF does not seem to affect to a significant extent the diagnostic value of PICP and TRAP in this pathology.

Acid Phosphatase↗
PubMed1993

Usefulness of biochemical markers of bone turnover in rats after clodronate administration.

Dichloromethylene bisphosphonate (clodronate), an inhibitor of bone resorption, has been administered subcutaneously (1.25 mg/day, 3 consecutive days) to control male albino Wistar rats (n = 8). Variations in the levels of serum alkaline phosphatase (AP) and osteocalcin (BGP), biochemical markers of bone formation, and in urinary hydroxyproline (OH-Prol) and serum tartrate-resistant acid phosphatase (TRAP), markers of bone resorption, have been analyzed. A significant decrease was observed in OH-Prol/creatinine and TRAP. We found a positive correlation between the percentage of decrease, with respect to basal values, of TRAP and OH-Prol/creatinine (p < 0.05). These results suggest that TRAP could be a useful marker to evaluate the changes of bone resorption induced by bisphosphonates in the rat together with the classical marker OH-Prol. A significant decrease was observed in AP. BGP also decreased significantly, but the decrease was relatively small compared to the coefficient of variation of the method. We suggest the preferential use of AP determination, instead of BGP, in the study of the effects produced by bisphosphonates on bone formation in rats, if hepatic function is maintained.

Acid Phosphatase↗
PubMed1993

Skeletal growth after oral administration of demineralized bone matrix.

Oral administration of bone extracts obtained from bovine demineralized bone matrix to rats has a direct effect on bone metabolism, affecting bone proportions and some markers of bone formation such as bone malate dehydrogenase, serum alkaline phosphatase and serum osteocalcin. Furthermore collagen deposition, bone protein synthesis and nucleic acids content were significantly increased by the treatment.

Administration, Oral↗