OBJECTIVES: The aim of this study was to develop limited sampling models for estimating the area under the concentration-versus-time curve (AUC) of carboplatin. METHODS: Based on pharmacokinetic analyses of 14 patients who received 300 mg x m2 of carboplatin over a 90-min infusion following irinotecan, we developed limited sampling models with stepwise multiple linear regression analysis. We validated these models to be unbiased and precise using pharmacokinetic data of a second group of 14 patients. We also compared the observed and the predicted AUC in the patients using Calvert's formula with the patients' renal function. RESULTS: We developed the following models: AUC (mg x ml(-1) x min) = 0.784 x C4 + 1.30 (r2=0.930) and AUC=0.100 x C0.25 + 0.597 x C4 + 0.140 (r=0.992), where C0.25 and C4 denote unbound plasma concentrations (microg x ml(-1)) of carboplatin at 0.25 h and 4 h after the end of infusion, respectively. These models were validated to be unbiased and precise: a mean prediction error (MPE) with standard deviation (SD) = 2.41 (9.45)% and a root mean squared error (RMSE) = 9.42% for the one-sample model, and MPE with (SD) = 1.22 (5.56)% and RMSE = 5.49% for the two-sample model. We also calculated predicted AUC in the patients using Calvert's formula: MPE with (SD)= -5.87 (21.5)% and RMSE = 21.5%. CONCLUSIONS: These estimations were, as expected, more accurate than the prediction using Calvert's formula based on patients' renal function. The result of this study confirmed the idea that the pharmacokinetic parameters derived from limited sampling models would be more suitable for pharmacokinetic analysis of carboplatin than those obtained using Calvert's formula.

Adult↗

PubMedDate not supplied

A new surgical procedure for the very severe inverted nipple.

Severe cases of inverted nipple usually cannot be corrected by a simple procedure, especially if the nipple cannot be pulled out above the areolar level by manipulation. We describe a new method for these cases and we classify the inverted nipple into 3 grades following the choice of their required operative procedure. Our classification for inverted nipple is as follows. Grade I: The inversion is corrected simply by manipulation; the nipple protrusion is long-lasting. Grade II: The inversion can be corrected by manipulation, but recurrence of the inversion is frequent. Grade III: The inversion cannot be corrected without a surgical procedure. Cases of Grades I and II can be corrected by conventional simple surgical procedures. But some cases of Grade II and almost all of Grade III cannot be corrected by conventional methods, in spite of the high frequency of relapse. Cutting of the lactiferous duct, such as the Pitanguy and Broadbent methods, can correct the very severely inverted nipple. But if we want to maintain the lactiferous function after correction, we had better not cut the lactiferous ducts. Our new procedure for correcting very severe cases can keep the lactiferous function after correction without any relapse. In order to avoid the recurrence of nipple retraction and to maintain the lactiferous function, the new surgical procedure that we performed makes an incision deeply and vertically on the nipple to free the lactiferous ducts from the contracted tissues surrounding them. After extension or resection of the restricting tissues, the nipple is raised easily. This procedure will preserve the feeding function and prevent the recurrence of nipple inversion. For very severe cases, using a dermal flap inserted into the base of the nipple may be necessary due to its role of interposing tissue to prevent reverting to inversion.

Adult↗

PubMedDate not supplied

Positional nystagmus and body sway after alcohol ingestion.

Positional nystagmus and body sway were measured for 8 hours following alcohol ingestion in 27 human volunteers. The intensity of positional alcohol nystagmus phase I (PAN-I) correlated well with blood alcohol concentration (BAC) along the time axis; the correlation coefficient between PAN-I and BAC 1 hour after alcohol ingestion was 0.62 (P less than .01). The minimum threshold BAC resulting in PAN-I was 0.23 mg/mL. Body sway was measured by stabilometry. The circumscribed area of posturography before and after alcohol ingestion was compared. Temporal changes in body sway and BAC were also closely correlated. The BAC threshold for increased body sway was estimated to be somewhere between 0.5 and 0.8 mg/mL, considerably higher than the threshold for PAN-I. Measurements of blood acetaldehyde, the dehydrated product of ethanol metabolism, showed no correlation with either the intensity of PAN or changes in body sway. The intensity of PAN and body sway measured at the time of peak BAC 1 hour after alcohol ingestion, however, showed significant positive correlation (r = .50, n = 25; P less than .01).

Acetaldehyde↗

PubMedDate not supplied

Analysis of transcriptional control elements in the 5'-upstream region of ovine interferon-tau gene using feeder-independent caprine trophoblast cell line, HTS-1.

Interferon-tau (IFNtau) is a protein secreted from the embryonic trophectoderm of ruminant ungulates during peri-implantation period. This protein acts on the uterine endometrium, which indirectly maintains corpus luteum function, and is therefore considered essential for the process of maternal recognition of pregnancy. Transcriptional regulation of IFNtau genes had been examined using human choriocarcinoma cell lines, JEG-3 or JAR, however, molecular mechanisms by which cell and term specific IFNtau expression are regulated have not been elucidated. Recently, a feeder cell free-trophoblast cell line derived from Shiba-goat placenta, termed HTS-1, was established. In the present investigation, the 5'-upstream region of ovine IFNtau (oIFNtau) gene was analysed using this cell line, which would provide a more suitable system for studies of the ovine trophoblast specific gene than human choriocarcinoma cells. Variously modified 5'-upstream sequences of the oIFNtau gene fused to a luciferase reporter gene were transiently transfected into HTS-1 cells, and human JEG-3 cells were used as a control. These results and co-transfection with expression vectors revealed that Ets-2 binding site in the promoter region was important in HTS-1, whereas AP-1 that binds to the enhancer region was a major activator in JEG-3. By electrophoretic mobility shift assay, a nuclear protein from HTS-1 cells was confirmed to bind specifically to the Ets-2 site of oIFNtau promoter region. Differences in amounts of AP-1 and Ets-2 protein were demonstrated in nuclear extracts from HTS-1, JEG-3 and ovine conceptuses. Substantial differences on oIFNtau gene transcriptions found between caprine HTS-1 and human JEG-3 cells suggest that this cell line could be valuable in the elucidation of a molecular mechanism(s) by which oIFNtau gene expression is regulated in a cell specific manner.

5' Flanking Region↗

PubMedDate not supplied

Combustion of brominated flame retardants and behavior of its byproducts.

The substance flow rate of PBDDs/DFs into flue gas and incineration residues from incineration of three types of waste samples containing brominated flame retardants were examined. The samples used consisted of PBDEs (a typical retardant), used TV casing materials (actual waste materials), and waste printed circuit boards. PBDDs/DFs concentrations in the experimental samples of PBDEs/PE, waste TV casing materials and printed circuit boards ranged between 3000 and 130,000 ng/g. These values are very high when compared to other investigations. The increase of chlorine concentration in input sample reduced the ratio of PBDDs/DFs in flue gas and raised the ratio of PCDDs/DFs. With adequate combustion control and flue gas treatment, the amount of PBDDs/DFs released from the incineration of resin containing brominated flame retardants was lower than the input amount. The presence of PBDDs/DFs in incineration residues dominated the total amount of dioxins released. When PBDDs/DFs, PCDDs/DFs and PXDDs/DFs were considered as a total, the total amount released was lower than the total amount input.

Journal Article↗

PubMedDate not supplied

Large-scale fires and time trends of PCDDS/DFs in sediments.

Drastic increases in PCDDs/DFs concentrations were identified in the uppermost layers of a sediment core sample taken from the coastal area of Kobe City. As large-scale fires caused by the Great Hanshin-Awaji earthquake were deemed to be a possible cause, we performed additional sampling of sediment cores and surface sediment samples, estimating the total amount of PCDDs/DFs released from fires and presuming the load to sediments by individual transport routes, such as air and water, using an air diffusion model to investigate the influence of fires. The total amount of PCDDs/DFs released from fires was estimated at 2000 g-total PCDDs/DFs, 22 g-TEQ. Increases in PCDDs/DFs generated in fires were principally transported through water rather than air. If 20% of the total PCDDs/DFs formed in fires had entered water, it would correspond to the entire increase of PCDDs/DFs concentration in sediment cores.

Air Movements↗

PubMedDate not supplied

Estrogenic and dioxin-like potency in each step of a controlled landfill leachate treatment plant in Japan.

The estrogenic activity (by E-screen bioassay), the concentrations of PCBs, PCDDs/PCDFs (and their resulting toxicity equivalents, TEQ) and several endocrine disrupting chemicals (EDCs: e.g., bisphenol A, nonylphenol, Butyl benzylpthalate (BBP), di-n-butylphthalate (DBP), 17alpha-ethynyl-estradiol or 4-octylphenol) have been analyzed from leachates of each step (before treatment, after biodegradation/sedimentation and after charcoal treatment) of a controlled landfill leachate treatment plant. The comparison of the effluent of the examined landfill leachate treatment plant with water from a nearby river in this study indicated no additional dioxin-like (e.g., TEQ: 0.027 compared to 1.01 pg TEQ/l; PCBs: 1.2 compared to 3.9 ng/l) or estrogenic impact (2.8 compared to 3.5 ng estradiol equivalents EE/l; analyzed by E-screen bioassay) from the leachate treatment plant into the surrounding water environment. The impact of dioxin-like compounds from uncleaned leachates into the final cleaned effluents could be sufficiently reduced by the leachate treatment plant for PCDDs (75%), PCDFs (62%), dioxin-like PCBs (97%), and the sum of TEQ (78%). The leachate treatment plant also achieved a reduction of the estrogenic activity as determined by E-screen (from 4.8 to 2.8 ng EE/l = 42%), by GC/MS for bisphenol A (>96% and nonylphenol (>98%) or by ELISA for estradiol (>80%). Additionally, for the validation of the E-screen, five known endocrine disrupting chemicals (EDCs: bisphenol A, BBP, DBP, 17 alpha-ethynyl-estradiol, 4-octylphenol) were analyzed. The EC50 values and estradiol equivalents factors (EEFs) for the five EDCs determined in this study were comparable to previously published data. The combined biological and chemical trace analysis data have provided valuable information on the relative contribution of natural, synthetic, and non-steroidal anthropogenic chemicals to the estrogenic and dioxin-like activity in leachates from a wastewater treatment plant, and water from a nearby river.

Benzofurans↗

PubMedDate not supplied

Leaching behavior of persistent organic pollutants (POPs) in shredder residues.

It is well known that some kinds of waste contain persistent organic pollutants (POPs) such as PCDD/DFs and PCBs. Leaching behaviors of these chemicals, however, have not been focused so much because of their low leachability. On the other hand, shredder residues originated from automobiles and electric appliances consist mainly of plastics, such as PVC, which contain additives including DEHP. In this study, contents analyses and leaching tests with and without surfactant-like substances for shredder residues were conducted. As a result, shredder residues from automobile and electric appliance contained PCBs in ppm level and a quantity of PCDD/DFs. Surfactant-like substances increase the leaching concentration of POPs. DEHP also leached out considerably even though using distilled water.

Benzofurans↗

PubMedDate not supplied

Full-scale plant study on low temperature thermal dechlorination of PCDDs/PCDFs in fly ash.

The low temperature thermal dechlorination process is an effective technology of dioxins decomposition in fly ash of municipal solid waste incinerators(MSWI). A full-scale dechlorination process was designed and constructed in Matsudo city, Japan. It was confirmed that PCDDs/PCDFs decomposition ratio was more than 99% with temperature of 350 degrees C and retention time of 1 hour, and thermal dechlorination moved on from PCDDs/PCDFs having more chlorine atoms to those of less chlorine atoms.

Air Pollution↗

PubMedDate not supplied

Suppressive effect of mitragynine on the 5-methoxy-N,N-dimethyltryptamine-induced head-twitch response in mice.

We investigated the effects of mitragynine, a major alkaloid isolated from the leaves of Mitragyna speciosa Korth (Rubiaceae), on the 5-HT2A receptor-mediated head-twitch response in mice. Intraperitoneal injection of mitragynine (5-30 mg/kg), as well as intraperitoneal injection of 5-HT2A receptor antagonist ritanserin, inhibited the 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT: 16 mg/kg, IP)-induced head-twitch response in a dose-dependent manner. In contrast, mitragynine affected neither head-weaving caused by 5-MeO-DMT, nor drug-free spontaneous motor activity. Pretreatment of mice with reserpine (5 mg/kg, IP), p-chlorophenylalanine (p-CPA, 300 mg/kg x 3 times, IP), or 6-hydroxydopamine (6-OHDA, 50 micrograms/mouse, ICV) plus nomifensine (5 mg/kg, IP) did not change the suppressant effect of mitragynine on the head-twitch response caused by 5-MeO-DMT. On the other hand, the alpha 2-adrenoceptor antagonists yohimbine (0.5 mg/kg, IP), and idazoxan (0.2 mg/kg, IP), significantly attenuated the suppressant effect of mitragynine. Lesion of central noradrenergic systems by 6-OHDA plus nomifensine did not alter the effect of idazoxan (0.2 mg/kg) on mitragynine-induced suppression of the head-twitch response. These results indicate that stimulation of postsynaptic alpha 2-adrenoceptor, blockade of 5-HT2A receptors, or both, are involved in suppression of 5-HT2A receptor-mediated head-twitch response by mitragynine.

Adrenergic alpha-Antagonists↗

PubMedDate not supplied

Lyngbyatoxins B and C, two new irritants from Lyngbya majuscula.

Explore the source record for details and available documents.

Animals↗

PubMedDate not supplied

Detection of transforming growth factor-alpha and epidermal growth factor receptor mRNA and immunohistochemical localization of their proteins in the ovine uterus during the early implantation period.

Accumulated evidence suggests that growth factors of the epidermal growth factor (EGF) family play an important role in the murine implantation process. In the sheep, however, the uterine distribution of these factors and their receptor, EGF receptor (EGF-R), during implantation is not known. This study examined the presence of mRNA transcripts and immunohistochemical localization for transforming growth factor-alpha (TGF-alpha), the potent EGF-family member, and EGF-R in the ovine uterus during the early implantation period. By reverse transcriptase-polymerase chain reaction and sequencing of the products, the presence of TGF-alpha and EGF-R mRNA transcripts were detected in the endometrium on Days 14, 16 and 20 (Day 0 = day of mating). Immunohistochemical analysis revealed that the luminal and glandular epithelial cells and some stromal cells of the endometrium and the trophectoderm were positive for TGF-alpha and EGF-R on Days 14 and 15. Distinct staining for TGF-alpha was observed in the glandular epithelium of deep endometrial areas and strong immunoreactivity for EGF-R was found in the trophectoderm. On Days 16, 18 and 20, although the staining pattern for TGF-alpha was similar to that on the previous days, the immunoreactivity for EGF-R in the stromal cells increased and that in the gland decreased. A distinct immunoreactivity for EGF-R was found in the trophectoderm throughout the days examined. These results suggest that TGF-alpha expressed in the endometrium and trophectoderm may exert effects locally on these tissues during implantation in sheep. Furthermore, it is speculated that the temporal changes in the uterine EGF-R distribution may be related to the endometrial microvascular development.

Animals↗