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Results for “Biomarker variability”

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PubMed1996

Limited value of the urinary phenytoin metabolic ratio for the assessment of cytochrome P4502C9 activity in vivo.

Relationships between the ratio of p-hydroxyphenytoin (p-HPPH), the major metabolite of phenytoin, to unchanged phenytoin excreted in urine (the urinary metabolic ratio or MR) were compared with a number of indices of the metabolic clearances of phenytoin and tolbutamide published previously for seventeen subjects separately administered these known cytochrome P4502C9 (CYP2C9) substrates. Significant correlations (rs = 0.50-0.60, P < 0.05) were observed between the phenytoin MR, derived from either 0-24 or 24-48 h urine collections, and inverse areas under the plasma unbound concentration-time curves (measured over various time intervals) of phenytoin and with plasma unbound tolbutamide clearance. Significant correlations (rs = 0.59-0.74) were also observed between the phenytoin MRs and metabolic unbound clearances for p-hydroxyphenytoin formation. Despite the significant correlations, variability in tolbutamide and phenytoin metabolic clearance parameters tended to account for < 50% of the variability in phenytoin MR. Correlations between the renal clearance of phenytoin and the phenytoin MRs suggest that variability in the renal clearance of unchanged drug limits the usefulness of the phenytoin MR for the investigation of factors influencing CYP2C9 activity in vivo.

Adult↗

PubMed2004

Protein thiol oxidation and lipid peroxidation in patients with uraemia.

BACKGROUND: Patients with uraemia are exposed to increased oxidative stress. In this study, a series of oxidative stress markers were measured in patients with chronic renal failure (CRF) and patients with CRF on haemodialysis (HD) compared to normal controls to establish whether there is enhanced oxidative stress on HD therapy in uraemic subjects. METHODS: Protein thiol oxidation, lipid hydroperoxides, albumin and uric acid concentrations were estimated in patients receiving HD and patients with CRF and compared with those in healthy controls. RESULTS: There was a significant decrease in the level of protein thiols in CRF (p = 0.0001) and HD patients (p = 0.0001) compared with that in controls. Lipid hydroperoxides were significantly higher in CRF (p = 0.026) and HD patients (p = 0.003) than in controls. However, there was no significant difference in protein thiols and lipid hydroperoxides between CRF and HD patients. Serum protein thiols correlated negatively with lipid hydroperoxides and positively with serum albumin. CONCLUSIONS: These findings suggest that both CRF and HD patients have increased plasma protein oxidation and lipid peroxidation. However, HD therapy per se did not contribute to oxidative stress already present in uraemia. Owing to the variability in lipid peroxidation products as markers of oxidative stress and the vital role played by thiol antioxidants in the biological system, it is suggested that protein thiol oxidation may be a better marker of oxidative stress.

Adult↗

PubMed2001

Validity and public health implications of maternal perception of the onset of lactation: an international analytical overview.

The main objective of this analytical overview is to assess the validity of maternal perception of the onset of lactation (OL) as an indicator of lactogenesis stage II (LS-II). Prospective studies that assessed OL and/or LS-II [based on test-weighing milk volume (MV) and/or breast milk biomarkers (BMB)] were identified. OL is a clearly defined and easily identified event across cultures, with the overwhelming majority of women being able to report when they experience it. Mean OL ranges from 50 to 73 h postpartum across studies and from 1 to 148 h postpartum within studies. The wide range detected within samples is fully consistent with the wide within sample LS-II variability as determined by BMB or MV. Studies have identified similar risk factors for delayed LS-II, such as labor and delivery stress, primiparity and insulin-dependent diabetes mellitus, regardless of marker used (i.e., OL, MV or BMB). The correlation between OL and MV (r = -0.60) is of similar magnitude to that between OL and BMB (r = 0.50) and that between BMB and MV (r = 0.47-0.69). In conclusion, OL is a valid clinical indicator of LS-II. This has public health relevance because studies have identified delayed OL (i.e., >72 h postpartum) as a risk factor for shorter breastfeeding duration and for greater infant weight loss by d 3 postpartum. Multidisciplinary studies are needed to standardize the definition of OL and to confirm its validity in different sociocultural contexts.

Breast Feeding↗

PubMed2002

Serological markers in inflammatory bowel disease: the pros and cons.

Accurate serological assays are desirable for the diagnosis of inflammatory bowel disease. Among several serological markers anti-Saccharomyces cerevisiae mannan antibodies and perinuclear antineutrophil cytoplasmic autoantibodies are highly disease specific for Crohn's disease and ulcerative colitis, respectively. Combining the two improves their specificity. Sensitivity, however, is still low. Due to lack of standardization and vast interobserver variability, they cannot be used as the only diagnostic criteria but can assist clinicians in diagnosing and categorizing patients with inflammatory bowel disease as well as in helping them to take therapeutic decisions.

Antibodies, Anti-Idiotypic↗

PubMed2005

Methylation status of fragile histidine triad (FHIT) gene and its clinical impact on prognosis of patients with multiple myeloma.

Aberrant methylation of tumor suppressor genes (TSG) has been studied in multiple myeloma (MM). We determined the methylation status of the FHIT (fragile histidine triad) gene, a putative TSG, in 48 patients with MM. Clinical association with its methylation status was then analyzed. The FHIT gene methylation was observed in 21 of the 48 patients (44%). No association between FHIT gene methylation and clinical variables such as age, gender and clinical stage was found. However, the estimated 50% survival time of the methylated group was significantly shorter than that of the unmethylated group (18.2 vs. 45.1 months, P < 0.05). Univariate analysis revealed adverse prognostic factors: FHIT gene methylation (P = 0.028), poor performance status (I to IV, P = 0.002), anemia (< or =8.5 g/dL, P = 0.007), hypoalbuminemia (< or =3.5 g/dL, P < 0.002), high serum C-reactive protein levels (>0.5 mg/dL, P = 0.002), elevated beta-2-microglobulin serum levels (>6.5 mg/L, P < 0.001), and treatments not including autologous peripheral blood stem cell transplantation (auto-PBSCT) (P = 0.007). Multivariate analysis identified FHIT gene methylation [hazard ratio (HR) 1.722, 95% confidence interval (CI) 1.150-2.603, P = 0.009], elevated beta-2-microglobulin serum levels (>6.5 mg/L, HR 2.005, 95% CI 1.035-3.937, P = 0.004), and treatments not including auto-PBSCT are independent predictive variables. These findings indicate that aberrant methylation of the FHIT gene is an independent adverse prognostic factor in MM.

Acid Anhydride Hydrolases↗

PubMed2005

Irinotecan pharmacokinetic and pharmacogenomic alterations induced by methylselenocysteine in human head and neck xenograft tumors.

The combination of methylselenocysteine and irinotecan (CPT-11) is synergistic against FaDu and A253 xenografts. Methylselenocysteine/CPT-11 increased tumor cure rate to 100% in FaDu and to 60% in A253. In this study, the effect of methylselenocysteine on pharmacokinetic and pharmacogenetic profiles of genes relevant to CPT-11 metabolic pathway was evaluated to identify possible mechanisms associated with the observed combinational synergy. Nude mice bearing tumors (FaDu and A253) were treated with methylselenocysteine, CPT-11, and a combination of methylselenocysteine/CPT-11. Samples were collected and analyzed for plasma and intratumor concentration of CPT-11 and 7-ethyl-10-hydroxyl-camptothecin (SN-38) by high-performance liquid chromatography. The intratumor relative expression of genes related to the CPT-11 metabolic pathway was measured by real-time PCR. After methylselenocysteine treatment, the intratumor area under the concentration-time curve of SN-38 increased to a significantly higher level in A253 than in FaDu and was associated with increased expression of CES1 in both tumors. Methylselenocysteine/CPT-11 treatment, compared with CPT-11 alone, resulted in a significant decrease in levels of ABCC1 and DRG1 in FaDu tumors and an increase in levels of CYP3A5 and TNFSF6 in A253 tumors. No statistically significant changes induced by methylselenocysteine/CPT-11 were observed in the levels of other investigated variables. In conclusion, the significant increase in the cure rate after methylselenocysteine/CPT-11 could be related to increased drug delivery into both tumors (CES1), reduced resistance to SN-38 (ABCC1 and DRG1) in FaDu, and induced Fas ligand apoptosis (TNFSF6) in A253. No correlation was observed between cure rate and other investigated variables (transporters, degradation enzymes, DNA repair, and cell survival/death genes) in either tumor.

Animals↗

PubMed1992

Serum sialyl Tn as an independent predictor of poor prognosis in patients with epithelial ovarian cancer.

PURPOSE: Monoclonal antibody (moAB) TKH-2 directed to the tumor-associated O-linked sialyl 2-6-alpha-N-acetylgalactosaminyl (sialyl Tn; STN) epitope was generated by immunization with ovine submaxillary mucin (Kjeldsen et al, Cancer Res 48:2214-2220, 1988). We investigated whether circulating serum levels of STN antigen might influence the prognosis of patients with ovarian cancer. PATIENTS AND METHODS: Serum samples were obtained from 126 healthy nonpregnant women, 157 patients with benign gynecologic disease, and 89 patients with histologically proven epithelial ovarian cancer. Circulating serum STN-antigen concentrations (U/mL) were determined by a competitive radioimmunoassay kit (Otsuka Assay Laboratories, Tokushima, Japan) in a one-step procedure. RESULTS: Serum antigen levels were elevated in 48.3% of the patients. The levels of STN antigen were significantly higher in the sera of patients with cancer when compared with levels in benign and healthy controls (P less than .05). The 5-year survival rate for patients with STN-negative (serum STN levels less than 50.0 U/mL) versus STN-positive (greater than or equal to 50 U/mL) tumors was 76.9% versus 10.8%, respectively (P less than .05). The progression-free interval (PFI) at 5 years was 51.9% versus 5.4%, respectively (P less than .05). The overall survival probability and PFI were worse in patients with STN-positive sera. Multivariate regression analysis revealed that stage, residual tumor size, positive STN, performance status, and histologic grade were the five important variables for predicting overall survival. CONCLUSION: We conclude that a positive STN-antigen level in sera is an independent predictor of poor prognosis in ovarian cancer.

Adult↗

PubMed2004

Usefulness of basal cell cocktail (34betaE12 + p63) in the diagnosis of atypical prostate glandular proliferations.

We evaluated the diagnostic usefulness of the 34betaE12-p63 cocktail, compared with 34betaE12 and p63 used alone, in 34 prostate needle biopsy (NBXs) and 3 transurethral resection specimens containing atypical glandular proliferations and in 18 NBXs containing unequivocal prostate carcinoma (PCa). Staining intensity; percentage of basal cells staining in benign, atypical, and malignant glands; number of benign glands lacking basal cell staining; and staining variance were analyzed. All NBXs with unequivocal PCa were negative with all 3 markers. Diagnoses were as follows for the atypical cases after staining for the 3 markers: PCa, 9; postatrophic hyperplasia, 12; high-grade prostatic intraepithelial neoplasia (HGPIN), 5; atypical adenomatous hyperplasia, 6; benign atypical proliferations, 4; and HGPIN with adjacent small atypical acinar proliferation suggestive of PCa, 1. The cocktail demonstrated consistently strong staining intensity and improved basal cell staining in morphologically benign and benign atypical glands compared with p63 and 34betaE12 alone; it had the smallest staining variance compared with 34betaE12 (F < 0.0001) and p63 (F = 0.31), although its advantage for resolving individual atypical cases was limited compared with 34betaE12 and p63 alone. Of 37 atypical cases, 1 (3%) additionally was resolved as benign using the cocktail and p63. Because the diagnosis of PCa is supported by lack of basal cell staining, the immunohistochemical analysis with highest possible sensitivity and lowest possible variability is critical to ensure that a negative reaction is true. The cocktail provides a simple, cost-effective improvement in basal cell immunohistochemical analysis of difficult prostate lesions.

Biomarkers, Tumor↗

PubMed2002

Malignant melanoma of the oral mucosa in a 17-year-old adolescent girl.

Mucosal melanomas of the oral cavity are rarely seen in the United States. The hard palate is the most common intraoral site. This unusual case occurred in the oral cavity of a 17-year-old Asian girl, who presented to her dentist with complaints of pain and swelling in the upper jaw. The lesion was distal and palatal to the maxillary left second molar, which was vital. Interestingly, the clinical presentation was a hyperplastic, tender lesion that bled when probed. Histopathologically, the biopsy demonstrated a sheet of spindle-shaped cells arranged in nests and fascicles. The nuclei were vesicular, oval to spindle-shaped, and some contained nucleoli that were distinguishable but not prominent. No melanin pigment was observed in the lesion. Tumor cells strongly expressed S100 protein, gp100 (HMB-45), and microphthalmia transcription factor, and variably expressed MART1, but not cytokeratins, CD34, or muscle-specific actin. The histopathologic features and immunohistochemical findings are consistent with a diagnosis of malignant melanoma.

Adolescent↗

PubMed1999

[Sensitivity of sputum eosinophil cationic protein level for monitoring asthmatic patients with normal peak expiratory flow].

Previous studies have shown that eosinophils and eosinophil cationic protein (ECP) levels in the sputum of patients with asthma closely reflect inflammatory activity of the bronchial mucosa. We examined whether the ECP level or eosinophil count in induced sputum provides information useful in determining whether to taper the dose of medications or to terminate treatment especially with inhaled corticosteroids in patients with well controlled asthma. We studied 15 adults with asthma who consistently maintained a peak expiratory flow (PEF) value within 80% or more of their predicted value (green zone) for at least 4 weeks with no asthmatic symptoms. All patients underwent at least two hypretonic saline inhalation tests. Forty sputum samples were obtained for evaluation of cell count and ECP level. Before the tests, patients were requested to record asthmatic symptoms, medications received, and morning and evening PEF values in a diary for more than 3 months. The relations among clinical and laboratory variables, including symptoms scores, medication scores, asthma scores (= symptom scores + medication scores). PEF values, forced expiratory volume (FEV1.0) during the test, and sputum eosinophil count or sputum ECP, were analyzed. The sputum ECP level correlated significantly with the percentage of eosinophils in the sputum (rs = 0.783). There were also significant correlations between the sputum ECP level and the mean weekly symptom scores (rs = 0.500-0.510), medication scores (rs = 0.510-0.540), and asthma scores (rs = 0.509-0.548). However, there were no significant correlations among sputum ECP level, mean morning PEF or evening PEF, daily variation in PEF, and FEV1.0. We conclude that the sputum ECP level is a sensitive laboratory variable useful in monitoring the presence of eosinophilic inflammation in the bronchial mucosa of patients with bronchial asthma, especially those who have mild or no symptoms with normal PEF.

Adult↗

PubMedDate not supplied

Cardiovascular function of African women with different BMIs and blood pressures: the POWIRS study.

INTRODUCTION: The aim of this study was to investigate the cardiovascular profiles of a group of African women with different body mass indices and blood pressures. MATERIALS AND METHODS: The study included a sample of 98 apparently healthy African women. The subjects were divided into three groups: lean normotensive (lean NT), overweight/obese normotensive (OW/OB NT), and overweight/obese hypertensive (OW/OB HT). The Finometer apparatus was used to obtain a more elaborate cardiovascular profile. The lipid profile and subcutaneous fat distributions were also determined. RESULTS: A positive correlation between blood pressure and increased adiposity was obtained. Cardiac output (CO) was elevated in both OW/OB groups. Arterial compliance (CW) was significantly decreased and total peripheral resistance (TPR) significantly increased in the OW/OB HT group compared to the OW/OB NT group. In the total group, systolic and diastolic blood pressure could be explained best by the abdominal skinfold, which showed a direct positive association with TPR and a negative association with CW . In the OW/OB HT group, the increased TPR could best be explained by the abdominal skinfold. CONCLUSIONS: In the OW/OB HT group, an increase in CO and decrease in vascular function led to the hypertensivity of this group. This seems to be related to a truncal, especially abdominal subcutaneous fat distribution. The decreased vascular function was reaffirmed by the pulse pressure (PP) exceeding 63 mmHg, indicating that this group was at high risk for the development of further cardiovascular complications. Lack of significant differences between the OW/OB groups for the anthropometric and lipid profile variables and the difference in age may indicate that the younger OW/OB NT group was at high risk and should be followed up in ensuing years.

Adult↗

PubMed1995

[Serum hepatitis B markers: atypical patterns detected at the Hospital Insular de Gran Canaria].

Two atypical serological markers of hepatitis B virus (HBV) infection were detected in 19 patients during a 18-month period study. Pattern 1 (10 patients) was consistent with HBV-2 infection. Reactivity of HbsAG was confirmed by neutralization tests; the absence of other markers was also verified, included anti-HBcIgM. Three of the patients were classified in high risk groups and seven in the low risk groups for hepatitis B; in none of them was co-infection with hepatitis A virus (HAV) detected. Pattern 2 (9 patients) was characterized by the detection of HBsAg and HBeAg and the absence of other hepatitis B markers. Six of these patients were HIV-positive patients and had increased and persistent levels (for longer than 12 weeks) of these markers. In the three remaining patients (with no underlying immunological disorders) there was a loss of these markers within a variable time (2 days to 16 weeks). Nevertheless, DNA-VHB was detected in one of these serum samples once all markers of virus B had disappeared.

Adolescent↗

PubMed1996

Human immunodeficiency virus (HIV) phenotype and interleukin-2/ interleukin-10 ratio are associated markers of protection and progression in HIV infection.

Human immunodeficiency virus (HIV) isolability, rate of viral replication, HIV phenotype, type 1 and type 2 cytokine production, and CD4 counts were cross sectionally analyzed in 63 HIV seropositive (HIV+) individuals to establish possible correlations between virologic and immunologic markers of protection and progression. We observed that these markers are tightly correlated. Thus, lack or low prevalence of HIV isolability and the presence of nonsyncitium inducing strains are associated with the strongest type 1 cytokine production, the weakest type 2 cytokine production, and highest CD4 counts. Conversely, the isolation of highly replicating, syncitium-inducing HIV strains is associated with the weakest type 1 cytokine production, the strongest type 2 cytokine production, and lowest CD4 counts. Additionally, it was determined that the interleukin (IL)-10/IL-2 ratio best discriminates among different virologic scenarios. These data suggest that the virologic and immunologic correlates of disease protection and progression might be associated variables that define two different subsets of HIV+ individuals and lend support to a viro-immunologic hypothesis of HIV infection.

Biomarkers↗

PubMed1998

[Immunohistochemical study on keratin no. 8, 18 and 19 expression of carcinoid tumors].

The purpose of this study is to evaluate keratin expression in neuroendocrine cells and carcinoid tumor of the gastrointestinal tract and lung. Neuroendocrine cells in the lung and the gastrointestinal tract reacted with low-molecular keratin strongly, but not with high-molecular keratin. The low-molecular keratin expression of carcinoid tumor in the lung and the gastrointestinal tract, which varied in degree, were identical to that of neuroendocrine cells. Keratin 8 and 18 were found abundantly in neuroendocrine tumor and carcinoid tumor of the gastrointestinal tract, and in a lesser amount in carcinoid tumor of the lung, whereas keratin 19 was found in all cases with variable amounts. Based on these results, the combination of antibodies for several types of keratin is useful for examining keratin expression as a marker of epithelium in carcinoid tumor.

Adult↗

PubMed2006

Method validation and preliminary qualification of pharmacodynamic biomarkers employed to evaluate the clinical efficacy of an antisense compound (AEG35156) targeted to the X-linked inhibitor of apoptosis protein XIAP.

Data are presented on pharmacodynamic (PD) method validation and preliminary clinical qualification of three PD biomarker assays. M65 Elisa, which quantitates different forms of circulating cytokeratin 18 (CK18) as putative surrogate markers of both apoptotic and nonapoptotic tumour cell death, was shown to be highly reproducible: calibration curve linearity r2 = 0.996, mean accuracy > 91% and mean precision < 3%, n = 27. Employing recombinant (r) CK18 and caspase cleaved CK18 (CK18 Asp396 neo-epitope) as external standards, kit to kit reproducibly was < 6% (n = 19). rCK18 was stable in plasma for 4 months at -20 degrees C and -80 degrees C, for 4 weeks at 4 degrees C and had a half-life of 2.3 days at 37 degrees C. Cytokeratin 18 Asp396 NE, the M30 Apoptosense Elisa assay antigen, was stable in plasma for 6 months at -20 degrees C and -80 degrees C, for 3 months at 4 degrees C, while its half-life at 37 degrees C was 3.8 days. Within-day variations in endogenous plasma concentrations of the M30 and M65 antigens were assessed in two predose blood samples collected from a cohort of 15 ovarian cancer patients receiving carboplatin chemotherapy and were shown to be no greater than the variability associated with methods themselves. Between-day fluctuations in circulating levels of the M30 and M65 antigens and in XIAP mRNA levels measured in peripheral blood mononuclear cells by quantitative (q) RT-PCR were evaluated in two predose blood samples collected with a 5- to 7-day gap from 23 patients with advanced cancer enrolled in a phase I trial. The mean variation between the two pretreatment values ranged from 13 to 14 to 25%, respectively, for M65, M30 and qRT-PCR. These data suggest that the M30 and M65 Elisa's and qRT-PCR as PD biomarker assays have favourable performance characteristics for further investigation in clinical trials of anticancer agents which induce tumour apoptosis/necrosis or knockdown of the anti-apoptotic protein XIAP.

Apoptosis↗

PubMed2004

CDC/AHA Workshop on Markers of Inflammation and Cardiovascular Disease: Application to Clinical and Public Health Practice: laboratory tests available to assess inflammation--performance and standardization: a background paper.

Inflammation plays a key role in atherosclerosis. A number of different biomarkers of inflammation are measurable in blood. These include cytokines, chemokines, soluble adhesion molecules, and acute-phase reactants. The first 3 groups of molecules are not routinely measured in clinical laboratories. The acute-phase reactants include C-reactive protein (CRP). This analyte is stable and is readily measured by several commercial high-sensitivity (hs) assays, and numerous clinical studies have demonstrated its usefulness as an atherosclerotic risk marker. For these reasons, CRP is currently the inflammatory marker of choice. Comparison of commercial hsCRP assays has demonstrated that many are capable of imprecision of <7% at a CRP concentration of <1 mg/L. Method comparability studies have shown good agreement among some commercial hsCRP assays in terms of quartile assignments, whereas additional standardization efforts are necessary for others. The first goal of standardization is to develop a secondary reference material with a CRP of approximately 4 mg/L. This material can be used to assist diagnostic vendors in calibrator value assignment and assay harmonization. Another project is to define clearly what performance characteristics are necessary for hsCRP assays. Preliminary estimates based on the biological variability of CRP indicate that the total allowable analytical error is between 15% and 32%. The former requirement can be met with accuracy and imprecision of <5% and the latter requirement with accuracy and imprecision of <11%. If 2 hsCRP results are averaged, then the imprecision requirements are relaxed slightly. Clinical validation of these performance requirements is also required.

Acute-Phase Proteins↗

PubMed1995

Biological monitoring of exposure to benzene: a comparison between S-phenylmercapturic acid, trans,trans-muconic acid, and phenol.

OBJECTIVES: Comparison of the suitability of two minor urinary metabolites of benzene, trans,trans-muconic acid (tt-MA) and S-phenylmercapturic acid (S-PMA), as biomarkers for low levels of benzene exposure. METHODS: The sensitivity of analytical methods of measuring tt-MA and S-PMA were improved and applied to 434 urine samples collected from 188 workers in 12 studies in different petrochemical industries and from 52 control workers with no occupational exposure to benzene. In nine studies airborne benzene concentrations were assessed by personal air monitoring. RESULTS: Strong correlations were found between tt-MA and S-PMA concentrations in samples from the end of the shift and between either of these variables and airborne benzene concentrations. It was calculated that exposure to 1 ppm (8 hour time weighted average (TWA)) benzene leads to an average concentration of 1.7 mg tt-MA and 47 micrograms S-PMA/g creatinine in samples from the end of the shift. It was estimated that, on average, 3.9% (range 1.9%-7.3%) of an inhaled dose of benzene was excreted as tt-MA with an apparent elimination half life of 5.0 (SD 2.3) hours and 0.11% (range 0.05%-0.26%) as S-PMA with a half life of 9.1 (SD 3.7) hours. The mean urinary S-PMA in 14 moderate smokers and 38 non-smokers was 3.61 and 1.99 micrograms/g creatinine, respectively and the mean urinary tt-MA was 0.058 and 0.037 mg/g creatinine, respectively. S-PMA proved to be more specific and more sensitive (P = 0.030, Fisher's exact test) than tt-MA. S-PMA, but not tt-MA, was always detectable in the urine of smokers who were not occupationally exposed. S-PMA was also detectable in 20 of the 38 non-smokers from the control group whereas tt-MA was detectable in only nine of these samples. The inferior specificity of tt-MA is due to relatively high background values (up to 0.71 mg/g creatinine in this study) that may be found in non-occupationally exposed people. CONCLUSIONS: Although both tt-MA and S-PMA are sensitive biomarkers, only S-PMA allows reliable determination of benzene exposures down to 0.3 ppm (8 h TWA) due to its superior specificity. Because it has a longer elimination half life S-PMA is also a more reliable biomarker than tt-MA for benzene exposures during 12 hour shifts. For biological monitoring of exposure to benzene concentrations higher than 1 ppm (8 h TWA) tt-MA is also suitable and may even be preferred due to its greater ease of measurement.

Acetylcysteine↗

PubMed2005

Immunological markers in multiple sclerosis: tackling the missing elements.

Multiple sclerosis (MS) is a complex disease in which several pathophysiological mechanisms are involved: inflammation, demyelination, axonal damage and repairing. Further complicating the picture, such processes are variably represented in MS patient populations, thus accounting for the heterogeneity in phenotypic expression of the disease, its prognosis and response to therapies. In the last decade a huge effort has been made in the attempt to "capture" the gold fish, i. e., biological markers either specific for the disease and/or capable to predict, in newly diagnosed MS patients, disease course and response to therapy. Moreover, these biomarkers would be extremely useful in the development of new process-specific therapies. Unfortunately such markers are far from being "fished", but recent studies have pointed out new interesting candidates, driving new energies and hopes in the MS research community. In this review we briefly discuss the latest news on immune markers in MS.

Autoantibodies↗