The effects of the cyclosporin A, a P-glycoprotein inhibitor, on the pharmacokinetics of baicalein in the rat: a microdialysis study.

1. Baicalein is a bioactive flavonoid isolated from the root of Scutellaria baicalensis Georgi, a medicinal herb that has been used since ancient times to treat bacterial infections. As little is known concerning its pharmacokinetics, this study focussed on its pharmacokinetics as well as the possible roles of the multidrug transporter P-glycoprotein on its distribution and disposition. 2. Three microdialysis probes were simultaneously inserted into the jugular vein, the hippocampus and the bile duct of male Sprague-Dawley rats for sampling in biological fluids following the administration of baicalein (10, 30 and 60 mg kg(-1)) through the femoral vein. The P-glycoprotein inhibitor cyclosporin A was used to help delineate its roles. 3. The study design consisted of two groups of six rats in parallel: control rats which received baicalein alone and the cyclosporin A treated-group in which the rats were injected cyclosporin A, a P-glycoprotein inhibitor, 10 min prior to baicalein administration. 4. Cyclosporin A treatment resulted in a significant increase in elimination half-life, mean residence time and area under the concentration versus time curve (AUC) of unbound baicalein in the brain. However, AUC in the bile was decreased. 5. The decline of baicalein in the hippocampus, blood and bile suggested that there was rapid exchange and equilibration between the peripheral compartment and the central nervous system. In addition, the results indicated that baicalein was able to penetrate the blood-brain barrier as well as undergoing hepatobiliary excretion. 6. Although no direct transport studies were undertaken and multiple factors may affect BBB penetration and hepatobiliary excretion, strong association of the involvement of P-glycoprotein in these processes is indicated.

Analysis of synthetic chemical drugs in adulterated Chinese medicines by capillary electrophoresis/electrospray ionization mass spectrometry.

Sixteen synthetic chemical drugs, often found in adulterated Chinese medicines, were studied by capillary electrophoresis/UV absorbance (CE/UV) and capillary electrophoresis/electrospray ionization mass spectrometry (CE/ESI-MS). Only nine peaks were detected with CZE/UV, but on-line CZE/MS provided clear identification for most compounds. For a real sample of a Chinese medicinal preparation, a few adulterants were identified by their migration times and protonated molecular ions. For coeluting compounds, more reliable identification was achieved by MS/MS in selected reaction monitoring mode. Micellar electrokinetic chromatography (MEKC) using sodium dodecyl sulfate (SDS) provided better separation than capillary zone electrophoresis (CZE), and, under optimal conditions, fourteen peaks were detected using UV detection. In ESI, the interference of SDS was less severe in positive ion mode than in negative ion mode. Up to 20 mM SDS could be used in direct coupling of MEKC with ESI-MS if the mass spectrometer was operated in positive ion mode. Because of better resolution in MEKC, adulterants can be identified without the use of MS/MS.

Optimizing separation conditions for polycyclic aromatic hydrocarbons in micellar electrokinetic chromatography.

We report the separation of polycyclic aromatic hydrocarbons (PAHs) using 0.1% poly(ethylene oxide) (PEO) in micellar electrokinetic chromatography (MEKC). In the presence of PEO, adsorption of PAHs on the capillary wall was reduced, leading to better resolution and reproducibility. Effects of tetrapentylammonium iodide (TPAI), dextran sulfate (DS), methanol, and sodium lauryl sulfate (SDS) on the separation of PAHs were elucidated. In terms of resolution and speed, DS, compared to TPAI, is a better additive for separation of PAHs. When using 0.1% PEO solution containing 45% methanol, 50 mM SDS, and 0.02% DS, separation of 10 PAHs containing 2 to 5 benzene rings was accomplished in less than 12 min at 15 kV in a commercial CE system. The method has also been tested for separating seven PAHs with high quantum yields when excited at 325 nm using a He-Cd laser. Unfortunately, separation of the seven PAHs was not achieved and sensitivity diminished under the same conditions. To optimize sensitivity, resolution and speed, a stepwise technique in MEKC has been proposed. The seven PAHs were resolved in 35 min at 15 kV when separation was performed in 0.1% PEO solution containing 35 mM SDS, 40% methanol and 0.02% DS for 2 min, and subsequently in 0.1% PEO solution containing 20 mM SDS, 50% methanol, and 0.02% DS.

Selective expression of different fucosylated epitopes on two distinct sets of Schistosoma mansoni cercarial O-glycans: identification of a novel core type and Lewis X structure.

The glycobiology of Schistosoma mansoni is dominated by developmentally regulated expression of various fucosylated structures, most notably the Lewis X epitope and a multifucosylated sequence, Fuc alpha1-->2Fuc alpha1-->, in its various forms. For the infective cercarial stage, Lewis X has been structurally identified on glycosphingolipids and N-glycans of total glycoprotein extracts, and a population of multifucosylated glycoproteins were found to carry a unique terminal sequence, +/-Fuc alpha1-->2Fuc alpha1-->[3GalNAc beta1-->4(Fuc alpha1-->2Fuc alpha1--> 2Fuc alpha1-->3) GlcNAc beta1-->3Gal alpha1-->](n), on their O-glycans. Using a mass spectrometry approach coupled with chromatographic separation, sequential exoglycosidase digestion, periodate oxidation, and other chemical derivatization, we demonstrate that Lewis X could also be carried on the cercarial O-glycans, but the two distinctive sets of fucosylated epitopes were conjugated to two different core structures. Lewis X, lacNAc, or single GlcNAc was found to attach directly to the -->3Gal beta1-->3GalNAc core and indirectly via another beta-Gal residue branching off from C6 of the reducing end GalNAc to give a biantennary-like structure. The -->3(+/-Gal beta1-->6)Gal beta1-->3(-->3Gal beta1-->6)GalNAc core thus characterized represents a novel core type for O-glycans. In contrast, the previously characterized multifucosylated terminal sequences were carried on conventional type 1 and 2 cores. The smallest structures of the reductively released O-glycans were defined as GalNAc beta1-->4GlcNAc beta1-->3Gal beta1-->3GalNAcitol with a total of two to four fucoses attached to the terminal lacdiNAc. alpha-Galactosylation of the nonreducing terminal beta-GalNAc instead of fucose capping leads to further elongation with another lacdiNAc unit that could also extend directly from C6 of the reducing end GalNAc and similarly elongated or terminated.

Analysis of a commercial preparation of erythromycin estolates by tandem mass spectrometry and high performance liquid chromatography/electrospray ionization tandem mass spectrometry using an ion trap mass spectrometer.

Because of the lack of a UV chromophore and their much smaller abundances in comparison with the major component, the minor components in erythromycin estolate preparations are difficult to analyze by high performance liquid chromatography ultraviolet (HPLC-UV). Tentative assignment of the major and minor components can be achieved with the combination of full scan and ZoomScan using an ion trap mass spectrometer. Tandem mass spectrometry (MS/MS) provided an effective method to quickly identify most components without chromatographic separation, and all the related compounds, except the isobaric pair ECE and PdMeEA, could be identified in this way. The best result was obtained by using liquid chromatography/tandem mass spectrometry (LC/MS/MS) operated in selected reaction monitoring mode. The major compound, the estolate of erythromycin A (EAE), and seven other minor components, could be separated and identified, with semiquantitative estimates of relative concentrations.

Analysis of referral initiatives, severity of illness and return to care of older women with cervical cancer.

BACKGROUND: Cervical cancer is a worldwide malignancy particularly prevalent in older women. Due to the increasing population ratio of older women and their more complicated illnesses, doctors in Taiwan are concerned about the care of older patients with cervical cancer. Few studies have been performed on the association between referral initiative and illness severity upon referral as well as the tendency of older patients with cervical cancer to return to the referring doctor and to the consultant at the medical center for follow-up. The purpose of this study was to investigate the referral association by adjusting for confounding variables. METHODS: This study included 214 women aged 65 years and over with cervical cancer diagnosed between 1987 and 1995. Patients were referred to a tertiary teaching hospital by 71 primary care gynecologists. The International Federation of Gynecology and Obstetrics clinical stage and clinical severity were assessed in each patient. Histopathologic results were reviewed to confirm the diagnosis. RESULTS: Of all the cervical cancer referrals, 20.2% were initiated by patients or families and 79.8% were initiated by primary care doctors. No statistically significant differences were found in the Basic Activities of Daily Living or Instrumental Activities of Daily Living between doctor- and patient-initiated referrals. High Geriatric Depression Scale and low Mini-Mental State Examination were associated with doctor-initiated referrals. Higher cancer stage and greater clinical severity of patients with cervical cancer was found in patient- rather than doctor-initiated referrals. After adjusting for marriage, family type, medical payment, mental status, cancer stage and clinical severity, the data showed that, if the referral was initiated by a primary care doctor, older patients with cervical cancer had a similar likelihood to return to both the primary care doctor and the tertiary teaching hospital for follow-up. CONCLUSIONS: If a referral was initiated by a doctor, older women with cervical cancer were not only likely to return to their consulting physician at the medical center, but also likely to return to their primary care doctor. Continuous care is more likely to occur when the primary care doctor initiated the referral.

Ethnic dental analysis of shovel and Carabelli's traits in a Chinese population.

Chinese populations differ from Caucasoids by having a high prevalence of shovel trait and a low prevalence of Carabelli's trait. This study was conducted to investigate the association between the shovel and the Carabelli's traits in a Chinese population. The research design investigated a Chinese population that resides in southern Taiwan. The ancestors of this Chinese population migrated to Taiwan from mainland China, mainly from Fukien and Kwangtung. The effects of sex and age on Carabelli's trait were controlled in this investigation, as was the association between tooth size and Carabelli's trait. Results show that males were more likely to have Carabelli's trait expressed on teeth than females. The buccolingual diameter of Carabelli's trait teeth was larger than that of teeth without the trait. After controlling for sex, age, and tooth size, the existence of the shovel trait increased the likelihood of having Carabelli's trait by a factor of five and a half, which is a significant effect.

Constituents and bioactive principles of Polygonum chinensis.

Isolation and characterization of the chemical constituents of Polygonum chinensis L. gave the new 25R-spirost-4-ene-3,12-dione. The known compounds stigmast-4-ene-3,6-dione, stigmastane-3,6-dione, hecogenin and aurantiamide acetate were also isolated from for the first time from this species. Their anti-inflammatory and anti-allergic properties are described.

Influence of referral source on return compliance of adolescents.

PURPOSE: To determine the effect of the source of referral on appointment compliance of adolescents to referring doctors or to consultants at tertiary medical centers. METHODS: This analysis included 421 adolescent patients aged 10-18 years who were referred to the tertiary teaching hospital in Taiwan by 75 primary care doctors, including 56 pediatricians and 19 general practitioners in 1987-1996. Medical records were abstracted to determine clinical severity and demography. Data of compliance with return appointments were collected by an independently trained interviewer. RESULTS: A total of 18.07% of referrals were initiated by patients or families and 81.93% were initiated by primary care doctors. More severe illness was found in patient-initiated referrals than in doctor-initiated referrals. After controlling for demographic, family features, medical payment, and doctor specialty, this study showed that if the referral were initiated by patients or families, adolescent patients were less likely to return to either the primary care doctors or tertiary teaching hospitals. CONCLUSIONS: Although in a competitive environment, follow-up care is more likely to occur for both primary care doctors and consultants at tertiary teaching hospitals when the referral was initiated by primary care doctors.

The effect of shovel trait on Carabelli's trait in Taiwan Chinese and Aboriginal populations.

Chinese and other Mongoloid populations differ from Caucasoids by having a high prevalence of shovel trait and a low prevalence of Carabelli's trait. This study was conducted to compare the association between the shovel and the Carabelli's traits between Chinese and aboriginal Mongoloid populations. The research is designed to sample randomly a Chinese population and an aboriginal population having low admixture with neighboring populations. The Mongoloid aboriginal group was from the Bunun tribe who resides in an isolated alpine area in Taiwan. The effects of sex and age on Carabelli's trait were controlled in this study, as was the association between tooth size and Carabelli's trait. Our results show that males had more Carabelli's trait expressed on teeth than females in both of these two Mongoloid populations. The buccolingual diameter of Carabelli's trait teeth was larger than that of teeth without the trait. After controlling for sex, age, and tooth size, the existence of the shovel trait significantly increased the likelihood of having Carabelli's trait, especially in Chinese, which implies another significant ethnic feature for Mongoloid identification.

Logistic analysis of the effects of shovel trait on Carabelli's trait in a Mongoloid population.

Mongoloid populations differ from Caucasoids by having a high prevalence of shovel trait and a low prevalence of Carabelli's trait. This study was conducted to investigate the effects of the shovel trait on Carabelli's trait in a Mongoloid population. The research design sought a population that resides in an isolated area and exhibits low admixture with neighboring populations. The Mongoloid group selected for study was the Bunun tribe of aborigines who inhabit an alpine area in Taiwan. The effects of sex and age on Carabelli's trait were controlled in this investigation, as was the association between tooth size and Carabelli's trait. Results show that males were more likely to have Carabelli's trait expressed on teeth than females. The buccolingual diameter of Carabelli's trait teeth was larger than that of teeth without the trait. After adjusting for sex, age, and tooth size, the existence of the shovel trait increased the likelihood of having Carabelli's trait by a factor of three, an effect that is significant.

Inhibition of in vitro enzymatic DNA amplification reaction by ultra-violet light irradiation.

Ultra-violet light irradiation of containers and components used in in vitro DNA amplification reactions catalyse by Taq DNA polymerase is a simple and effective method to reduce carry-over contamination and can reduce false-positive results. However, we found that prolonged exposure of water in polypropylene microcentrifuge tubes to u.v. light can result in reduction of amplification efficiency by at least two orders of magnitude when these water specimens are used in amplification reaction mixtures. Although the mechanism that causes this inhibition of DNA amplification is unclear now, the results seem to suggest that u.v. irradiation for routine anti-contamination purposes should be used with caution.

Possible non-sexual transmission of genital human papillomavirus infections in young women.

Human papillomaviruses were detected by an in vitro enzymatic DNA amplification method in cells obtained from vulvar swabs of 9 of 61 (14.8%) young women without prior experience of sexual intercourse and in 7 of 57 (12.3%) young women with prior experience. The prevalence of human papillomavirus DNA in these two groups of women was not significantly different (x2 = 0.16, p > 0.5; 95% confidence interval -0.165 to 0.215). These results suggest that genital human papillomavirus is not sexually transmitted in all cases and that it may be acquired by modes other than sexual contact.