Fingerprinting of chlorinated paraffins and their transformation products in plastic consumer products.

Chlorinated paraffins (CPs) can be classified according to their length as short-chain (SC, C10-C13), medium-chain (MC, C14-C17) and long-chain (LC, C ≥ 18) CPs. Technical CP-mixtures can contain a wide range of carbon- (C-, nC = 10-30) and chlorine- (Cl-, nCl = 3-19) homologues. CPs are high-production volume chemicals (>106 t/y). They are used as flame-retardants, plasticizers and coolant fluids. Due to the persistence, bioaccumulation, long-range environmental transport potential and adverse effects, SCCPs are regulated as persistent organic pollutants (POPs) by the Stockholm Convention. Transformation of CPs can lead to the formation of unsaturated compounds such as chlorinated mono- (CO), di- (CdiO) and tri-olefins (CtriO). Such transformation reactions can occur at different stages of CP manipulation providing characteristic C-/Cl-homologue distributions. All this results in unique patterns that collectively create a fingerprint, which can be distinguished from CP-containing samples. Therefore, CP-fingerprinting can develop into a promising tool for future source apportionment studies and with it, the reduction of environmental burden of CPs and hazards to humans. Herein, CP-containing plastics were studied to establish fingerprints and develop this method. We analyzed four household items by reverse-phase liquid-chromatography coupled with a mass spectrometer with an atmospheric pressure chemical ionization source and an Orbitrap mass analyzer (RP-LC-APCI-Orbitrap-MS) operated at a resolution of 120000 (FWHM at m/z 200). MS-data of different CP-, CO-, CdiO- and CtriO-homologues were efficiently processed with an R-based automatic mass spectra evaluation routine (RASER). From the 16720 ions searched for, up to 4300 ions per sample were assigned to 340 C-/Cl-homologues of CPs and their transformation products. Specific fingerprints were deduced from the C-/Cl-homologues distributions, the carbon- (nC) and chlorine- (nCl) numbers and saturation degree. These fingerprints were compared with the ones obtained by a GC-ECNI-Orbitrap-MS method.

Simultaneous quantification of progestogens in plasma and serum by UHPLC-HRMS employing multiplexed targeted single ion monitoring.

Progesterone is the predominant gestagen in most mammals studied so far. It plays a substantial role in the regulation of the female reproductive cycle and in providing support for pregnancy maintenance. Despite its known functions, gaps in knowledge are present regarding its reduced metabolites that potentially exert biological activity. Therefore, a new UHPLC-HRMS method based on a Q Exactive™ mass spectrometer was developed to detect and quantify simultaneously progesterone, its hormone precursor pregnenolone and 10 reduced progestogens (20α-DHP, 20ß-DHP, 3α,5α-THP, 3α,5ß-THP, 3ß,5α-THP, 3ß,5ß-THP, 3α-DHP, 3ß-DHP, 5α-DHP and 5ß-DHP) in plasma and serum samples. Purification was achieved by an optimized solid phase extraction (SPE) and the analysis was conducted in positive electrospray ionization (ESI) mode with the application of multiplexed selected ion monitoring (msx-t-SIM). The method validation included the study of sensitivity, selectivity, curve fitting, carry-over, accuracy, precision, recovery and matrix effects. Despite the poor ionization properties of underivatized steroids, a high sensitivity in the range of pg/mL was achieved.

Progestogen profiling in plasma during the estrous cycle in cattle using an LC-MS based approach.

In many mammalian species, corpus luteum derived progesterone (P4) is the main functional gestagen during the estrous cycle and pregnancy. P4 can be metabolized into various metabolites, of which some are biologically active. While some metabolites target the classical nuclear progesterone receptor (PR), neurosteroids bind the receptors of type A γ-aminobutyric acid (GABAA-r) in the brain. According to the position of reduction within the molecule, metabolites of P4 can be characterized into C20-reduced progestogens (20α-dihydroprogesterone (20α-DHP) and 20ß-dihydroprogesterone (20ß-DHP)), C3-reduced progestogens (3α-dihydroprogesterone (3α-DHP) and 3ß-dihydroprogesterone (3ß-DHP)), 5α-reduced progestogens (5α-dihydroprogesterone (5α-DHP), allopregnanolone and isopregnanolone) and 5ß-reduced progestogens (5ß-dihydroprogesterone (5ß-DHP), pregnanolone and epipregnanolone). We questioned whether the reduced progestogens are present in bovine plasma during the estrous cycle and whether their profiles differed from the profile of the common precursor P4 around the time of luteolysis. The analytes were monitored in plasma samples using liquid chromatography mass spectrometry (LC-MS). While progestogens lagged behind the drop of P4 at luteolysis, they followed the profile of P4 during the estrous cycle. The abundance of P4 was predominant followed by allopregnanolone, pregnanolone, epipregnanolone and 20ß-DHP. Further studies will need to focus particularly on the period around luteolysis.

Assessment of the ochratoxin A production ability of Aspergillus tubingensis.

Aspergillus tubingensis is a black Aspergillus frequently isolated from different agricultural products, including grapes. Conflicting results have been published in recent years about its ability to produce ochratoxin A (OTA), a potent nephrotoxic and carcinogenic mycotoxin. This study re-examined six A. tubingensis strains deposited in international culture collections for OTA production. OTA could not be detected in any A. tubingensis extract using HPLC coupled with a fluorescence detector (FLD), whereas it was easily detected in ochratoxigenic A. niger extracts used as positive control. The same outcome was obtained using LC-MS. The presence of other metabolites with retention times similar to the OTA signal in the A. tubingensis extracts or background noise of the growth media may be reasons for the misinterpretation of the chromatograms obtained by HPLC-FLD.

Effect of corn root exudates on the degradation of atrazine and its chlorinated metabolites in soils.

DIMBOA (3,4-dihydro-2,4-dihydroxy-7-methoxy-2H-1,4-benzoxazin-3-one), a major benzoxazinone of Poaceae plants, was isolated and purified from corn seedlings. The effect of isolated and purified DIMBOA on the degradation of atrazine [2-chloro-4-(ethylamino)-6-(isopropylamino)-s-triazine], and its toxic breakdown products, desethylatrazine [2-chloro-4-amino-6-(isopropylamino)-s-triazine; DEA] and desisopropylatrazine [2-chloro-4-(ethylamino)-6-amino-s-triazine; DIA], was studied in the absence of plants using batch experiments, while the effect of corn root exudates on these compounds was determined in hydroponic experiments. Degradation experiments were performed in the presence and absence of 50 microM, 1 mM, or 5 mM DIMBOA resulting in ratios of DIMBOA to pesticide of 1:1, 20:1, and 100:1. We observed a 100% degradation of atrazine to hydroxyatrazine within 48 h at a ratio of DIMBOA to atrazine of 100:1. DIMBOA had the largest effect on atrazine, while it was about three times less effective on DEA and DIA. Corn (Zea mays L. cv. LG 2185) was exposed to 10 mg L(-1) of either atrazine, DEA, or DIA for 11 d in a growth chamber experiment. Up to 4.3 micromol L(-1) d(-1) of hydroxyatrazine were formed in the nutrient solutions by plants exposed to atrazine, while the formation of hydroxylated metabolites from plants exposed to DEA and DIA was smaller and also delayed. The formation of hydroxylated metabolites increased in the solution with plant age in all atrazine, DEA, and DIA treatments. HMBOA (3,4-dihydro-2-hydroxy-7-methoxy-2H-1,4-benzoxazin-3-one), the lactam precursor of DIMBOA, and a tentatively identified derivative of MBOA (2,3-dihydro-6-methoxy-benzoxazol-2-one) were detected in the corn root exudates. Mass balance calculations revealed that up to 30% of the disappearance of atrazine and DEA, and up to 10% of DIA removal from the solution medium in our study could be explained by the formation of hydroxylated metabolites in the solution itself. Our results show that higher plants such as corn have the potential to promote the hydrolysis of triazine residues in soils by exudation of benzoxazinones.

The use of soluble, salivary c-erbB-2 for the detection and post-operative follow-up of breast cancer in women: the results of a five-year translational research study.

A surge of new technological developments, coupled with the limitations of existing disease-detection methodologies, is propelling the field of medical diagnostics forward at unprecedented rates. Advancements in proteomics and nanotechnology are paving the way for diagnostic tests that will be capable of rapid multi-analyte detection in both laboratory and non-laboratory settings. Technological advancements have also benefited biomarker research to the point where saliva is now recognized as an excellent diagnostic medium that can be collected simply and non-invasively. Salivary biomarkers have been identified that may provide diagnostic information about a variety of cancers and other diseases. In particular, proof-of-principle has been demonstrated for salivary c-erbB-2, whose elevation has been shown to correlate strongly with breast malignancy in women. The purpose of this manuscript is to review the past literature and present the current research focused on the use of saliva as a diagnostic medium for the detection of malignancies that are remote from the oral cavity.

Evaluation of tamoxifen in persistent or recurrent nonsquamous cell carcinoma of the cervix: a Gynecologic Oncology Group study.

This study was undertaken to estimate the antitumor activity of tamoxifen in patients with persistent or recurrent nonsquamous cell carcinoma of the cervix. Furthermore, the nature and degree of adverse effects from tamoxifen in this cohort of individuals was examined. Tamoxifen citrate was to be administered at a dose of 10 mg per orally twice a day until disease progression or unacceptable side effects prevented further therapy. A total of 34 patients (median age: 49 years) were registered to this trial; two were declared ineligible. Thirty-two patients were evaluable for adverse effects and 27 were evaluable for response. There were only six grades 3 and 4 adverse effects reported: leukopenia (in one patient), anemia (in two), emesis (in one), gastrointestinal distress (in one), and neuropathy (in one). The objective response rate was 11.1%, with one complete and two partial responses. In conclusion, tamoxifen appears to have minimal activity in nonsquamous cell carcinoma of the cervix.

N-nitrosylation potential of mono-N-desethylamiodarone at physiological pH.

Amiodarone (AMI) is frequently used for the treatment of supraventricular arrhythmias. The parent drug is rapidly dealkylated to mono-N-desethylamiodarone (MDEA) and the plasma concentrations of AMI and MDEA are comparable. MDEA is a secondary amine and may thus undergo formation to the corresponding N-nitrosamine in combination with coadministered nitrovasodilators. Previous studies have shown that nitrovasodilators release the vasoactive NO? which may nitrosylate thiol or secondary amine groups in aqueous solutions. Therefore, the nitrosylation potential of MDEA at physiological pH was investigated. N-Nitroso-monodesethylamiodarone (NO-MDEA) was synthesized, characterized and used as a reference product for the detection of the corresponding N-nitrosamine. HPLC and NMR results have shown that the NO-MDEA product is an equilibrium of two configurational isomers (syn and anti). NO-release was generated by sodium nitroprusside (SNP) which was exposed to light. The formation to NO-MDEA was assayed by HPLC-UV. It has been found that MDEA is nitrosylated in the higher nanomolar range and that varying oxygenation of the reaction mixture did not significantly affect the reaction yields. The addition of thiols such as serum albumin (0.6mM), l-cysteine (2.5mM) or N-acetylcysteine (2.5mM) inhibited the NO-MDEA formation indicating that they may prevent N-nitrosamine formation in vivo. However, as S-nitrosothiols may also release NO?, in long term exposure to elevated levels of nitric oxide the nitrosylation of secondary amines may be taken into account.

Biotransformation of 2-benzoxazolinone and 2-hydroxy-1,4-benzoxazin-3-one by endophytic fungi isolated from Aphelandra tetragona.

The biotransformation of the phytoanticipins 2-benzoxazolinone (BOA) and 2-hydroxy-1,4-benzoxazin-3-one (HBOA) by four endophytic fungi isolated from Aphelandra tetragona was studied. Using high-performance liquid chromatography-mass spectrometry, several new products of acylation, oxidation, reduction, hydrolysis, and nitration were identified. Fusarium sambucinum detoxified BOA and HBOA to N-(2-hydroxyphenyl)malonamic acid. Plectosporium tabacinum, Gliocladium cibotii, and Chaetosphaeria sp. transformed HBOA to 2-hydroxy-N-(2-hydroxyphenyl)acetamide, N-(2-hydroxyphenyl)acetamide, N-(2-hydroxy-5-nitrophenyl)acetamide, N-(2-hydroxy-3-nitrophenyl)acetamide, 2-amino-3H-phenoxazin-3-one, 2-acetylamino-3H-phenoxazin-3-one, and 2-(N-hydroxy)acetylamino-3H-phenoxazin-3-one. BOA was not degraded by these three fungal isolates. Using 2-hydroxy-N-(2-hydroxyphenyl)[(13)C(2)]acetamide, it was shown that the metabolic pathway for HBOA and BOA degradation leads to o-aminophenol as a key intermediate.

Saliva as a diagnostic fluid.

In the last 10 years, the use of saliva as a diagnostic fluid has become somewhat of a translational research success story. Technologies are now available enabling saliva to be used to diagnose disease and predict disease progression. This review describes some important recent advances in salivary diagnostics and barriers to application and advancement. This review will also stimulate future research activity.

Phenol oxidative coupling in the biogenesis of the macrocyclic spermine alkaloids aphelandrine and orantine in Aphelandra sp.

A crucial step in the biosynthesis of the spermine alkaloid aphelandrine and its diastereoisomer orantine is an intramolecular cyclization of the intermediate (S)-dihydroxyverbacine. In order to elucidate this step of the biosynthetic pathway, microsomes from the roots of Aphelandra squarrosa Nees were incubated with unlabeled and (D8)-labeled (S)-dihydroxyverbacine. It was shown that the microsomal fraction catalyzes the intramolecular coupling of (S)-dihydroxyverbacine to aphelandrine. This was proven by microsomal transformation of (D8)-labeled (S)-dihydroxyverbacine to (D8)-labeled aphelandrine. The reaction absolutely requires NAPDH and O2. The underlying reaction mechanism is probably an oxidative phenol coupling catalyzed by an aphelandrine synthase. This enzyme is proposed to be a cytochrome P-450 oxidase. The intramolecular cyclization of (S)-dihydroxyverbacine represents an important point in the biogenesis of the aphelandrine-type alkaloids.

Metabolism of amiodarone (Part III): identification of rabbit cytochrome P450 isoforms involved in the hydroxylation of mono-N-desethylamiodarone.

1. Amiodarone (AMI) is a potent anti-arrhythmic drug and mono-N-desethylamiodarone (MDEA) is its only known metabolite. It was found recently that in rabbit liver microsomes MDEA was biotransformed to n-3-hydroxybutyl-MDEA (3OH-MDEA). 2. In liver microsomes isolated from the untreated rabbit, the formation of 3OH-MDEA obeyed Michaelis-Menten enzyme kinetics with Km = 6.39 +/- 1.07 microM and Vmax = 0.56 +/- 0.21 nmolmin(-1) mg(-1) protein. 3. Furthermore, (1) among chemicals usually used as inhibitors of cytochrome P450, only midazolam (MDZ), cyclosporin A and ketoconazole inhibited the MDEA hydroxylase activity significantly (>60% inhibition), (2) MDZ, a substrate of CYP3A, inhibited the 30OH-MDEA formation competitively (Ki = 10 +/- 5 microM), (3) the formation rates of 3OH-MDEA correlated positively with those of 1'OH-MDZ (r = 0.81; n = 6), and (4) MDEA hydroxylase activity of microsomes isolated from rabbit rifampicin-induced cultured hepatocytes was 4-fold more active than the control. 4. Since CYP3A6 is mainly induced by rifampicin in rabbit-cultured hepatocytes, the data suggest that this isoform is involved in the biotransformation of MDEA to 3OH-MDEA. 5. Since alpha-naphthoflavone, cimetidine and quinidine also partially inhibited the MDEA hydroxylase activity, it is possible that other CYPs, such as 1A, 2C and 2D, may also be active in the metabolism of amiodarone.

Cytokine concentrations in stimulated whole saliva among patients with primary Sjögren's syndrome, secondary Sjögren's syndrome, and patients with primary Sjögren's syndrome receiving varying doses of interferon for symptomatic treatment of the condition: a preliminary study.

Sjögren's syndrome is an autoimmune disorder which causes diminished salivary flow due to autoimmune sialoadenitis. This decrease in saliva flow is the result of inflammation and atrophy of the salivary glands. Most treatment regimens are palliative in nature, but treatment with interferon (IFN) holds promise for Sjögren's syndrome sufferers. Several studies have investigated cytokine concentrations in the salivary glandular tissues from Sjögren's syndrome patients; however, there is little information concerning cytokine expression in saliva. This is especially true with respect to treatment modalities and their effects on local cytokines. A clinical study was conducted to determine salivary interleukin (IL)-6, IFN, and IL-2, concentrations among subjects diagnosed with primary and secondary Sjögren's syndrome and a healthy control group. The primary Sjögren's syndrome showed significantly higher salivary IL-2 and salivary IL-6 than the control and secondary Sjögren's groups. There were no between group differences for salivary IFN concentrations. In addition, the study assessed salivary IL-6, IFN, and IL-2 concentrations among 18 Sjögren's syndrome patients before and after administration of IFN via the oral mucosal route. The results of the study showed that the mean values for the pre- and post-treatment groups for stimulated whole saliva flow rates were 3.15 and 3.74 ml/5 min, respectively. The post-treatment group exhibited a 16.8% increase in stimulated whole saliva flow rates. The salivary IL-6 concentration was 53.3% lower for the post-treatment group (17.79) as compared to the baseline value (33.35). The values for salivary IFN and salivary total protein were virtually unchanged from their baseline values. Salivary IL-2 values, however, were 50% lower in the post-treatment group (3.07) when compared to their respective baseline values (6.10). The results of this study suggest that healthy individuals exhibit lower salivary IL-2 and IL-6 as compared to individuals suffering from primary and secondary Sjögren's syndrome. The results also suggest that administration of IFN via the oral mucosal route may increase salivary flow rates and depress certain cytokines (IL-2, IL-6) associated with inflammatory destruction of salivary glandular tissues in Sjögren's syndrome patients.

Influence of radiation sterilization on the stability of trifluorothymidine.

The influence of radiation sterilization on the stability of trifluorothymidine (TFT) was investigated. TFT was irradiated under ambient atmosphere with a 60Co-source and with an electron accelerator at 25, 50, and 100 kGy, respectively. The radiation-induced effects were determined by chromatographic and spectroscopic methods as well as potentiometrically with a fluoride selective electrode. TFT was moderately stable to ionizing radiation. The degradation induced by electron-beam irradiation was significantly (P=95%) smaller than by gamma-irradiation. The radiolysis products amounted to about 0.25% after electron-beam irradiation at 25 kGy, and to about 0.50% after gamma-irradiation, respectively. The main irradiation product was 5-trifluoromethyluracil (TFMU). In addition five further impurities were detected with HPLC. Identification of degradation products was performed using HPLC-ESI-MS. A degradation path of TFT after radiation sterilization was shown.

Metabolism of amiodarone. II. High-performance liquid chromatographic assay for mono-N-desethylamiodarone hydroxylation in liver microsomes.

Amiodarone (AMI) is a potent antiarrhythmic drug. In vivo and in vitro, AMI is biotransformed to mono-N-desethylamiodarone (MDEA). Recently, it was observed that MDEA was further hydroxylated to n-3'-hydroxybutyl-MDEA (3'OH-MDEA). The performance of a HPLC-UV assay being developed for the quantification of the new compound was investigated. Liver microsomes isolated from rabbit, rat and human biotransformed MDEA to 3'OH-MDEA. Their estimates of Michaelis-Menten parameters were Km=6.39, 25.2, 19.4 microM; Vmax=560, 54, 17.3 pmol/mg protein/min), respectively. Thus, hydroxylase activity in mammals may be the origin of the species dependence observed in the AMI metabolism.

Reliability assessment of soluble c-erbB-2 concentrations in the saliva of healthy women and men.

BACKGROUND: The protein c-erb B-2, also known as Her2/neu, is a prognostic breast cancer marker assayed in tissue biopsy specimens from women diagnosed with malignant tumors. Current studies suggest that soluble fragments of the c-erb B-2 oncogene may be released from the cell surface and become detectable in patients with a carcinoma of the breast. Consequently, the purpose of this study is to assay soluble c-erb B-2 protein in the saliva of healthy men and women to determine the reliability of the assay. METHODS: To determine the diagnostic utility of this oncogene, we assayed the soluble form of the c-erb B-2 protein in the saliva with an enzyme-linked immunosorbent assay. The study population consisted of 10 healthy women and 9 healthy men who were serially sampled for saliva 3 times a day for a 5-day period. Saliva was collected from each subject at 9 AM, 4 PM, and 9 PM during the 5-day period. RESULTS: We found the presence of c-erb B-2 protein in the saliva of both groups of subjects. The salivary levels of c-erb B-2 were not significantly different when compared for gender differences. Likewise, the results suggest that sampling during various times of the day for salivary c-erb B-2 levels has no effect on marker concentration. Reliability analyses showed that supervised salivary collections were more reliable than unsupervised collections. CONCLUSIONS: The results of this pilot study suggest that the assay for salivary c-erb B-2 protein is reliable and might have potential use in the initial detection and follow-up screening for the recurrence of breast cancer in both men and women.

Metabolism of amiodarone (part I): identification of a new hydroxylated metabolite of amiodarone.

UNLABELLED: Amiodarone (AMI) is a potent antiarrhythmic drug, but its metabolism has not yet been fully documented. Mono-N-desethylamiodarone (MDEA) is its only known metabolite. Our preliminary investigations using rabbit liver microsomes had shown that in vitro AMI was biotransformed to MDEA, and the latter was rapidly further biodegraded to other unknown products. The aim of the present study was to investigate the chemical structure of the biotransformed compound of MDEA. Upon incubation of MDEA with rabbit liver microsomes and NADPH as cofactor, MDEA was biotransformed into three unknown products: X1, X2, and X3. The products were purified using chromatography. The chemical structure of the major product, X1, was investigated in detail. HPLC-ESI-MS revealed that MDEA had been oxygenated. Hydrogen-deuterium exchange experiments showed that the X1 molecule contained one exchangeable hydrogen atom more than its precursor MDEA, indicating that MDEA had been hydroxylated. Further results from ESI-MS/MS analysis indicated that the site of hydroxylation was the n-butyl side chain. NMR analysis (1H NMR, one-dimensional-total correlation spectroscopy, and heteronuclear multiple-bond correlation spectroscopy) established the 3-position (omega-1) of the butyl moiety as the specific carbon atom that is hydroxylated. Rat liver microsomes were also able to catalyze MDEA hydroxylation. Compound X1, as analyzed by HPLC-ESI-MS and ESI-MS/MS, was detected in the liver, heart, lung, and kidney tissue of four rats receiving AMI, suggesting that the hydroxylated MDEA was a secondary metabolite of AMI. CONCLUSION: in mammals, MDEA is hydroxylated to the secondary metabolite of AMI [2-(3-hydroxybutyl)-3-[4-(3-ethylamino-1-oxapropyl)-3,5-diiodobenzoyl]-benzofuran].

Progesterone inhibits glucocorticoid-induced murine thymocyte apoptosis.

Sex and sex hormones modulate immune development and responses. A primary target of their effects is the structure and cellularity of the thymus; therefore, we examined the effects of sex and sex steroids on thymocyte apoptosis. We demonstrate initially that male DBA mice have a significantly higher percentage of glucocorticoid-induced apoptotic thymocytes (46.1+/-3.8%) than their female counterparts (31.6+/-3.1%; P=0.012). We postulated that this gender difference was due to differential modulation of glucocorticoid-induced apoptosis by sex hormones such as estrogen, testosterone or progesterone. Both estrogen and testosterone increased in vitro thymocyte apoptosis. In contrast, progesterone not only inhibited spontaneous in vitro thymocyte apoptosis, but also prevented in vitro glucocorticoid-induced apoptosis. Progesterone administration also suppressed glucocorticoid-induced in vivo thymocyte apoptosis. These results suggest that anti-apoptotic effects of progesterone may influence T cell development and subsequent immune responses.

Transradial coronary angioplasty and stent implantation in acute myocardial infarction: initial experience.

Transradial coronary angioplasty and stent implantation in have been associated with reduced complications, length of stay and hospital costs when compared to the transfemoral approach. Fourteen high-risk patients with acute myocardial infarction underwent transradial coronary angioplasty and stent placement. All diagnostic and interventional procedures were successfully completed using 6 French guide catheters and ACS Tristar stents (Guidant Corporation, Santa Clara, California) up to 4 mm in diameter. Thirteen patients received glycoprotein IIb/IIIa inhibitors. There were no procedural or access site complications. The mean length of stay was 3.5 days and the mean time interval from initial radial cannulation compared favorably with 14 acute myocardial infarction patients undergoing transfemoral angioplasty and stent placement. Transradial angioplasty in acute myocardial infarction appears to be a safe and feasible option. The procedure time is not increased in experienced hands, and the combination of rare access site complications and early ambulation may lead to decreased morbidity and lower costs. Transradial angioplasty in acute myocardial infarction may be an attractive option in thrombolytic therapy patients (facilitated percutaneous coronary intervention) or those who require aggressive anticoagulation or antiplatelet therapy.

The presence of soluble c-erbB-2 in saliva and serum among women with breast carcinoma: a preliminary study.

The protein c-erbB-2, also known as Her2/neu, is a prognostic breast cancer marker assayed in tissue biopsies from women diagnosed with malignant tumors. Present studies suggest that soluble fragments of the c-erbB-2 oncogene may be released from the cell surface and become detectable in patients with carcinoma of the breast. Consequently, the purpose of this study was to assay the c-erbB-2 protein in the saliva and serum of women with and without carcinoma of the breast and to determine whether the protein possesses any diagnostic value. To determine the diagnostic utility of this oncogene, the soluble form of the c-erbB-2 protein was assayed in the saliva and serum using ELISA in three different groups of women. The three groups consisted of 57 healthy women, 41 women with benign breast lesions, and 30 women diagnosed with breast cancer. To compare the relative diagnostic utility of the c-erbB-2 protein, CA 15-3 was also measured. The CA 15-3 measurements served as a "gold standard" by which to compare the c-erbB-2 protein's diagnostic effectiveness. We found c-erbB-2 protein in the saliva and serum of all three groups of women. The salivary and serological levels of c-erbB-2 in the cancer patients, however, were significantly higher (P < 0.001) than the salivary and serum levels of healthy controls and benign tumor patients. Additionally, the c-erbB-2 protein was found to be equal to or to surpass the ability of CA 15-3 to detect patients with carcinoma. The results of the pilot study suggest that the c-erbB-2 protein may have potential use in the initial detection and/or follow-up screening for the recurrence of breast cancer in women.