Nitroxide-Mediated Controlled Radical Copolymerization of α-Trifluoromethylstyrenes with Styrenes.

Fluorinated polymers are important materials in everyday life; however, most monomers of widely used fluoropolymers are gaseous, and their polymerization is difficult in an ordinary laboratory. Therefore, partially fluorinated polymers have recently been reported. As an easy-to-handle fluorine-containing monomer, α-trifluoromethylstyrene (TFMST) can be used to produce partially fluorinated polymers with trifluoromethyl groups in the main chain; however, TFMST does not homopolymerize, and there are limited reports on its copolymerization with styrene (ST). In this study, we applied the controlled radical polymerization method, which is effective for the polymerization of ST, to the copolymerization of TFMST and ST. We also showed that nitroxide-mediated polymerization is effective. The content ratio of TFMST in the TFMST-ST copolymer can be controlled between 10% and 40% by changing its monomer ratio. Additionally, the polymerization of TFMST and ST with substituents was performed to increase structural variations. The thermal stability as well as water and oil repellency of the synthesized polymers with different composition ratios and substituents were also evaluated.

Case report: therapeutic monitoring of vancomycin in an acute liver failure patient with anuria under high-flow continuous hemodiafiltration.

BACKGROUND: High-flow continuous hemodiafiltration (HF-CHDF) combines diffusive and convective solute removal and is employed for artificial liver adjuvant therapy. However, there is no report on dosage planning of vancomycin (VCM) in patients with acute liver failure under HF-CHDF. CASE PRESENTATION: A 20-year-old woman (154 cm tall, weighing 50 kg) was transferred to the intensive care unit (ICU) with acute liver failure associated with autoimmune liver disease. On the following day, HF-CHDF was started due to elevated plasma ammonia concentration. On ICU day 8, VCM was started for suspected pneumonia and meningitis (30 mg/kg loading dose, then 20 mg/kg every 12 hrs). However, on ICU day 10, VCM blood concentration was under the limit of detection (< 3.0 µg/mL) and the patient developed anuria. The VCM dose was increased to 20 mg/kg every 6 hrs. Calculation with a one-compartment model using the HF-CHDF blood flow rate as a surrogate for VCM clearance, together with hematocrit and protein binding ratio, predicted a trough VCM blood concentration of 15 µg/mL. The observed concentration was about 12 µg/mL. The difference may represent non-HF-CHDF clearance. Finally, living donor liver transplantation was performed. CONCLUSION: We report an acute liver failure patient with anuria under HF-CHDF in whom VCM administration failed to produce an effective blood concentration, likely due to HF-CHDF-enhanced clearance. VCM dosage adjustment proved successful, and was confirmed by calculation using a one-compartment model.

Effect of the Effortful Swallow on Pharyngeal Cavity Volume: Kinematic Analysis in Three Dimensions Using 320-Row Area Detector Computed Tomography.

This study evaluated the effects of the effortful swallow (ES) on pharyngeal cavity volume using three-dimensional kinematic analyses. Nine healthy volunteers (30.7 ± 7.8 years old) underwent a CT scan while swallowing 10 ml of honey thick liquid using no maneuvers (control) and during an ES. Upper and lower volumes (bordered by valleculae) of the pharyngeal air column and the bolus were measured at every frame and were compared between ES and control swallows. Duration of pharyngeal obliteration and the timing of swallowing events were also measured. Maximum volume and volume at the onset of hyoid anterosuperior movement using ES were significantly smaller than those in control swallows (p = 0.012, p = 0.015) in the upper pharynx but not significantly different in lower pharynx. Minimum pharyngeal volume was sustained for a longer time when ES was used compared to control swallows in both upper and lower pharynx (upper p = 0.016, lower p = 0.027). Onset of velopharyngeal closure was earlier when comparing ES and control swallows (p = 0.04). Termination of all events was significantly delayed when the ES was used (p < 0.05). Changes in the upper pharyngeal volume and in the onset of velopharyngeal closure suggest earlier pharyngeal constriction when using the ES. Longer pharyngeal obliteration and prolonged termination of velopharyngeal closure and epiglottis inversion suggest the prolonged pharyngeal constriction during the ES. These findings suggest the ES can be useful for improving the efficiency of swallowing.

Ceftriaxone-induced encephalopathy in a patient with a solitary kidney.

Ceftriaxone (CRO) is a long-acting third-generation cephalosporin antibiotic. We present a case of CRO-induced encephalopathy in an 84-year-old male patient with a solitary right kidney, admitted with bilateral pneumonia and right pyelonephritis. Intravenous CRO (2 g, every 24 hours) was started for the infection, but tonic-clonic seizures of the left face and left upper extremity appeared on the eighth day. To examine the relationship between CRO administration and the seizures, we measured CRO concentrations in the patients' plasma/serum and cerebrospinal fluid. The CRO concentration in blood at the onset of encephalopathy was estimated to have been approximately 60 µg/ml based on a simulation curve. We also calculated the pharmacokinetic parameters after CRO administration. The patient had about one-tenth of the total body clearance and one-third of the volume of distribution compared with healthy adults, and the elimination half-life was about three times longer.

The effect of bolus consistency on pharyngeal volume during swallowing: Kinematic analysis in three dimensions using dynamic Area Detector CT.

OBJECTIVE: This study investigated the effects of bolus consistency on pharyngeal volume during swallowing using three-dimensional kinematic analysis. METHODS: Eight subjects (2 males and 6 females, mean ± SD 44 ± 10 years old) underwent a 320-row area detector scan during swallows of 10 mL of honey-thick liquid and thin liquid. Critical event timing (hyoid, soft palate, UES) and volume of pharyngeal cavity and bolus were measured and compared between two swallows. RESULTS: The pharynx is almost completely obliterated by pharyngeal constriction against the tongue base for both consistencies. There were no significant differences in maximum volume, minimum volume and pharyngeal volume constriction ratio values between thick and thin liquids. However, the pattern of pharyngeal volume change (decrease) was different. For thick liquids, the air volume started to decrease before the onset of hyoid anterosuperior movement and decreased rapidly after onset of hyoid anterosuperior movement. During thin liquid swallowing, air volume remained relatively large throughout the swallow and started to decrease later when compared to swallowing thick liquids. At onset of UES opening, the bolus volume was not significantly different between thin and thick liquids; however, air volume was significantly larger when swallowing thin liquids, which made the total volume of the pharyngeal cavity larger. CONCLUSION: This difference between the two consistencies is associated with differences in tongue motion to propel the bolus and clear the pharynx from possible residue.

Protein Sensing Device with Multi-Recognition Ability Composed of Self-Organized Glycopeptide Bundle.

We designed and synthesized amphiphilic glycopeptides with glucose or galactose at the C-terminals. We observed the protein-induced structural changes of the amphiphilic glycopeptide assembly in the lipid bilayer membrane using transmission electron microscopy (TEM) and Fourier transform infrared reflection-absorption spectra (FTIR-RAS) measurements. The glycopeptides re-arranged to form a bundle that acted as an ion channel due to the interaction among the target protein and the terminal sugar groups of the glycopeptides. The bundle in the lipid bilayer membrane was fixed on a gold-deposited quartz crystal microbalance (QCM) electrode by the membrane fusion method. The protein-induced re-arrangement of the terminal sugar groups formed a binding site that acted as a receptor, and the re-binding of the target protein to the binding site induced the closing of the channel. We monitored the detection of target proteins by the changes of the electrochemical properties of the membrane. The response current of the membrane induced by the target protein recognition was expressed by an equivalent circuit consisting of resistors and capacitors when a triangular voltage was applied. We used peanut lectin (PNA) and concanavalin A (ConA) as target proteins. The sensing membrane induced by PNA shows the specific response to PNA, and the ConA-induced membrane responded selectively to ConA. Furthermore, PNA-induced sensing membranes showed relatively low recognition ability for lectin from Ricinus Agglutinin (RCA120) and mushroom lectin (ABA), which have galactose binding sites. The protein-induced self-organization formed the spatial arrangement of the sugar chains specific to the binding site of the target protein. These findings demonstrate the possibility of fabricating a sensing device with multi-recognition ability that can recognize proteins even if the structure is unknown, by the protein-induced self-organization process.

The Association of 3-D Volume and 2-D Area of Post-swallow Pharyngeal Residue on CT Imaging.

Pharyngeal residue, the material that remains in the pharynx after swallowing, is an important marker of impairments in swallowing and prandial aspiration risk. The goals of this study were to determine whether the 2D area of post-swallow residue accurately represents its 3D volume, and if the laterality of residue would affect this association. Thirteen patients with dysphagia due to brainstem stroke completed dynamic 320-detector row computed tomography while swallowing a trial of 10 ml honey-thick barium. 3D volumes of pharyngeal residue were compared to 2D lateral and anterior-posterior areas, and a laterality index for residue location was computed. Although the anteroposterior area of residue was larger than the lateral area, the two measures were positively correlated with one another and with residue volume. On separate bivariate regression analyses, residue volume was accurately predicted by both lateral (R2 = 0.91) and anteroposterior (R2 = 0.88) residue areas, with limited incidence of high residuals. Half of the sample demonstrated a majority of pharyngeal residue lateralized to one side of the pharynx, with no effect of laterality on the association between areas and volume. In conclusion, the area of post-swallow pharyngeal residue was associated with volume, with limitations in specific cases. Direct measurement of pharyngeal residue volume and swallowing physiology with 3D-CT can be used to validate results from standard 2D instrumentation.

An autopsy case of progressive multifocal leukoencephalopathy after rituximab therapy for malignant lymphoma.

Progressive multifocal leukoencephalopathy (PML) is a rare fatal demyelinating disease of the central nervous system caused by reactivation of the JC virus (JCV), which is named after the initials of the patient from whom the virus was first isolated. JCV is highly prevalent worldwide, infects humans in early childhood, and the infection persists throughout the course of life in latent form. The present paper deals with the second autopsy case report of rituximab-associated PML in Japan. A 63-year-old woman who had undergone chemotherapy for non-Hodgkin lymphoma developed progressive dysarthria and cerebellar ataxia. Head magnetic resonance imaging (MRI) revealed small, scattered, hyperintense areas in the midbrain, pons and thalamus, and the patient was first diagnosed as having cerebral infarction. Follow-up MRI showed tendency toward cerebellar atrophy and multiple system atrophy cerebellar type was suggested, which we concluded must have coincidentally occurred. It was challenging to perform biopsy due to the location of the foci and the patient's condition. Twelve months later she died of aspiration pneumonia caused by the bulbar lesion. At autopsy, the histological examination suggested the presence of demyelinating foci with numerous foamy macrophages. In the foci, oligodendrocytes with enlarged ground-glass like nuclei were found in a scattered manner and astrocytes with bizarre nuclei were also detected. These findings verified the case as PML. The first diagnosis of cerebral infarction was later withdrawn, although appropriate disorders were not recalled even after testing with various antibodies. The rate of PML development tends to increase after treatment with molecular-targeted therapies, which directly or indirectly attenuate the cellular-mediated immune system. Various novel molecular-targeted and immunosuppressive drugs have been released on the market; the cases of PML have consequently increased. Accordingly, pathologists should keep this disease in mind in the differential diagnosis when neural symptoms newly emerge in patients who are treated with these drugs.

The Mendelsohn Maneuver and its Effects on Swallowing: Kinematic Analysis in Three Dimensions Using Dynamic Area Detector CT.

This study investigated the effects of Mendelsohn maneuver with three-dimensional kinematic analysis. Nine female speech-language pathologists (nine females, mean ± SD 27.1 ± 3.5 years old) underwent 320-row area detector scan during swallows of 4-ml nectar-thick liquid using with no maneuvers (control) and with Mendelsohn maneuver (MM). Critical event timing (hyoid, soft palate, epiglottis, laryngeal vestibule, true vocal cords (TVC), UES), hyoid and laryngeal excursion, cross-sectional area of UES, and volume of pharyngeal cavity and bolus were measured and compared between two swallows. In MM, all the events were significantly prolonged with delayed termination time (p < 0.05) except UES opening. The onset, termination, and duration of UES opening were not significantly affected by MM nor was timing of bolus transport. The hyoid bone was positioned significantly higher at maximum displacement (p = 0.011). Pharyngeal constriction ratio was 95.1% in control and 100% of all subjects in MM. Duration of minimum pharyngeal volume was significantly longer in MM than in control (p = 0.007). The MM produces several distinct changes in the kinematics of swallowing in healthy subjects with no dysphagia. The changes in the timing and magnitude of hyoid displacements and prolonged closure of the pharynx during swallowing suggest the utility of MM for improving the safety and efficiency of swallowing in selected cases.

Phase II study of cetuximab with irinotecan for KRAS wild-type colorectal cancer in Japanese patients.

AIM: Cetuximab improves the prognosis for wild-type KRAS metastatic colorectal cancer (MCRC). We evaluated the safety and efficacy of cetuximab in combination with irinotecan in Japanese patients with wild-type KRAS MCRC refractory to irinotecan, oxaliplatin and fluoropyrimidines. METHODS: Cetuximab was administered initially at a dose of 400 mg/m2 , followed by weekly infusions at 250 mg/m2 . Irinotecan was administered every 2 weeks at 150 mg/m2 . Primary endpoint was the incidence of grade 3/4 adverse events; secondary endpoints included overall survival (OS), progression-free survival (PFS), response rate (RR), time to treatment failure (TTF), and TTF for irinotecan. RESULTS: Thirty-four patients were enrolled. Grade 3 or 4 toxicities were leucopenia (11.8%), neutropenia (23.5%), anemia (11.8%), fatigue (2.9%), anorexia (2.9%), diarrhea (14.7%) and hypomagnesemia (5.9%). Skin toxicities were as follows (any grade/grade 3): acne (94.2/8.8%), rash (55.9/0%), nail changes (75.5/8.8%) and hand-foot syndrome (55.9/5.9%). Median PFS was 6.0 months (95%CI; 4.7-7.4). Median OS was 12.9 months (95%CI; 10.0-15.9). RR was 26.4%. Median TTF was 5.1 months and median TTF for irinotecan was 5.0 months (95%CI; 4.3-5.6). CONCLUSION: Cetuximab with irinotecan therapy was well tolerated in Japanese patients with wild-type KRAS colorectal cancer refractory to irinotecan, oxaliplatin and fluoropyrimidine, thus demonstrating the feasibility of their usage.

EGFR L2 domain mutation is not correlated with resistance to cetuximab in metastatic colorectal cancer patients.

BACKGROUND: The KRAS mutation has been associated with resistance to cetuximab, an anti-epidermal growth factor receptor (EGFR) monoclonal antibody, in metastatic colorectal cancer (mCRC). However, the predictive biomarkers of cetuximab resistance in KRAS wild-type mCRC remain unknown except BRAF, NRAS, and PIK3CA exon 20. The objective of the study is to study the impact of EGFR L2 mutations on resistance to cetuximab in KRAS wild-type patients. PATIENTS AND METHODS: A total of 247 mCRC patients were screened for KRAS status at the National Cancer Center Hospital between September 2008 and April 2010. We analyzed the EGFR L2 domain mutation status in KRAS wild type and in the patients treated with cetuximab-based therapy. RESULTS: There were 136 patients with wild-type KRAS (55%). Sixty-five patients were analyzed for the L2 domain mutation status, and all patients received cetuximab-based therapy. One patient who had a mutation at exon 9 showed a partial response to cetuximab plus irinotecan. CONCLUSION: Mutation of the EGFR L2 domain was analyzed in mCRC patients. Our findings do not provide sufficient evidence that EGFR L2 domain mutation is correlated with resistance to cetuximab.

Successful control of intractable hypoglycemia using radiopharmaceutical therapy with strontium-89 in a case with malignant insulinoma and bone metastases.

This report describes the case of a 57-year-old woman with liver and bone metastases from malignant insulinoma, who was afflicted with severe hypoglycemia. Treatment of the liver metastases using octreotide, diazoxide and transarterial embolization failed to raise her blood glucose level and she required constant glucose infusion (about 1000 kcal/day) and oral feeding (about 2200 kcal/day) to avoid a hypoglycemic attack. Subsequently, 110 MBq (2.0 MBq/kg) of strontium-89 were administered by intravenous injection. Three weeks after the strontium-89 injection, we could reduce the dose of constant glucose infusion while maintaining a euglycemic status. Six weeks after the injection, the constant glucose infusion was discontinued. Although strontium-89 therapy is indicated for patients with multiple painful bone metastases, it was also useful as a means of inhibiting tumor activity and controlling hypoglycemia in this case. To our knowledge, this is the first report to provide evidence that strontium-89 can be useful in controlling intractable hypoglycemia in patients with malignant insulinoma with bone metastases.

Efficient myogenic differentiation of murine dermal Sca-1 (−) cells via initial aggregation culture.

Stem cells from various organs have been shown to regenerate muscle cells. Among them, skin-derived cells are promising because of their easy accessibility. We separated murine dermal cells into Sca-1 (+) and (−) fractions and investigated which of them could differentiate into muscle cells. After the cells were aggregated for 4 days and cultured on a collagen type I-coated plate for 7­10 days, the Sca-1 (−) fraction had expanded into many myoblastic cells, but the Sca-1 (+) fraction had not. Initial commitment to the myogenic lineage appeared to start during the aggregation. Sca-1 (−) cells proliferated exponentially and maintained their ability to differentiate into skeletal muscle cells within 7­10 days. About 60% of the cells showed positive staining for skeletal fast myosin heavy chain. Transplantation experiments revealed that the myoblastic cells arising after several passages were successfully engrafted into damaged host muscle. In conclusion, we have found that murine dermal Sca-1 (−) cells differentiate into muscle cells in vitro and in vivo after using an initial aggregation procedure. Their high differentiation efficiency and proliferation ability will offer substantial advantages for stem cell research.

Polychlorinated biphenyl-mediated decrease in serum thyroxine level in rodents.

Effects of Kanechlor-500 (KC500), a commercial polychlorinated biphenyl mixture, on the levels of serum thyroid hormones such as total thyroxine (T(4)) and triiodothyronine were examined in male mice, hamsters, rats, and guinea pigs. Four days after a single intraperitoneal injection of KC500, significant decreases in the levels of the serum total T(4) and free T(4) occurred in all the animals examined, whereas a significant decrease in the level of serum triiodothyronine was observed only in guinea pigs among the animals examined. In addition, no significant change in the level of serum thyroid-stimulating hormone was observed in any of the rodents examined. A significant increase in the activity of hepatic T(4)-UDP-glucuronosyltransferase after the KC500 administration occurred only in guinea pigs, whereas the increase in the amount of biliary [(125)I]T(4) glucuronide after an intravenous injection of [(125)I]T(4) to the KC500-pretreated animals occurred only in rats. On the other hand, in all the rodents examined, KC500-pretreatment promoted the clearance of [(125)I]T(4) from the serum and led to a significant increase in the steady-state distribution volumes of [(125)I]T(4). Likewise, its pretreatment raised the concentration ratio (K(p) value) of the liver to serum and the liver distribution of [(125)I]T(4) in all the rodents tested. The present findings indicate that for the first time the KC500-mediated decrease in the serum T(4) level in mice, hamsters, rats and guinea pigs occurs mainly through an increase in the accumulation level of T(4) in the liver.

Isolation of murine hair-inducing cells using the cell surface marker prominin-1/CD133.

Hair is a mini-organ in which dermal papilla (DP) cells play important roles in hair follicle morphogenesis and formation via interactions with epithelial cells. DP cells have previously been difficult to analyze because of the lack of a specific surface marker. We have demonstrated that prominin-1/CD133 (CD133) is a useful marker for murine DP cells. DP cells express CD133 during the early anagen stage (active growth phase) not only during hair morphogenesis, but also during the growth phase of hairs after birth. Gene expression and flow cytometric analysis revealed that CD133-positive (+) cells in the skin possess the characteristics of DP cells. The CD133(+) cells isolated from embryonic or adult skin-induced new hair follicles in vivo when they were transplanted into nude mice mixed with embryonic epithelial cells, but CD133-negative (-) cells could not. We propose that the CD133 is a novel surface marker useful for collecting DP cells in the anagen stage and for analyzing the function of DP.

Sedative effects of the jasmine tea odor and (R)-(-)-linalool, one of its major odor components, on autonomic nerve activity and mood states.

We investigated the effects of the odor of jasmine tea on autonomic nerve activity and mood states in a total of 24 healthy volunteers. We used the odor of jasmine tea at the lowest concentration that could be detected by each subject but that did not elicit any psychological effects. R-R intervals and the POMS test were measured before and after inhalation of the odors for 5 min. Both jasmine tea and lavender odors at perceived similar intensity caused significant decreases in heart rate and significant increases in spectral integrated values at high-frequency component in comparison with the control (P < 0.05). In the POMS tests, these odors produced calm and vigorous mood states. We also examined the effects of (R)-(-)-linalool, one of its major odor components, at the same concentration as in the tea, and (S)-(+)-linalool. Only (R)-(-)-linalool elicited a significant decrease in heart rate (P < 0.05) and an increase in high-frequency component in comparison with the controls, and produced calm and vigorous mood states. Thus, the low intensity of jasmine tea odor has sedative effects on both autonomic nerve activity and mood states, and (R)-(-)-linalool, one of its components, can mimic these effects.

Characterization and localization of side population cells in mouse skin.

Recently, the detection of side population (SP) cells, which have the ability to strongly efflux Hoechst 33342 fluorescence dye, has attracted attention as a method of stem cell isolation. We identified SP cells from mouse skin using the same method as from bone marrow. This population almost completely disappeared after treatment with the calcium channel blocker verapamil. SP cells were mainly localized in the epidermis, with a few in the dermis. The ratio of SP cells decreased as the mouse became older. Surface marker analysis revealed that the sorted SP cells expressed alpha6-integrin, beta1-integrin, Sca-1, keratin 14, and keratin 19, which are proliferating and progenitor cell markers, at levels higher than in non-SP cells, while they expressed E-cadherin, CD34, and CD71 at lower levels. The expression of breast cancer resistance protein 1 (BCRP1), which participates in dye efflux, was expressed at high levels at both the protein and mRNA level in sorted SP cells. Immunohistochemical analysis showed that BCRP1 was expressed in the basal layers and hair bulge regions of mouse skin. BCRP1 mRNA was found in basal layers and hair follicles of newborn skin by in situ hybridization. These results indicate that the localization of BCRP1-positive cells is compatible with that of keratinocyte stem cells. Based on the close relationship between BCRP1 and the SP cell phenotype, we conclude that keratinocyte stem cells are closely related to the SP- or BCRP1-positive cells.

Sensory evaluation of the synergism among odorants present in concentrations below their odor threshold in a Chinese jasmine green tea infusion.

The mechanism for the contribution of subthreshold aroma constituents to the overall jasmine tea odor impression was studied on the basis of a sensory evaluation. Binary model aqueous solutions containing the authentic odorants of a jasmine tea infusion, (E)-2-hexenyl hexanoate (I), (Z)-3-hexenol (II), and indole (III), were each prepared in a concentration below the odor threshold. Each solution had no aroma, but when 4-hexanolide replaced only 5% of each odorant, the odor intensity of each model solution was significantly strengthened. An astringent note and heavy note were recognized for each solution as the commonly perceived characteristics from the sensory evaluation. The concentration of 4-hexanolide added was also at the subthreshold level. The results suggest mutual interaction between odorants I, II, or III and 4-hexanolide. The effect on the overall odor sensation of a jasmine tea infusion by adding 4-hexanolide at a concentration below its odor threshold was also studied. In this case, the intensity of both the sweet and astringent notes was significantly strengthened in comparison with the odor impression of the original jasmine tea infusion. This phenomenon is considered to have been a synergistic effect between subthreshold odor compounds in the jasmine tea infusion. The results of this study clarify for the first time that the subthreshold aroma constituents play an important role in the characteristic flavor of a jasmine tea infusion.

A possible mechanism for decrease in serum thyroxine level by polychlorinated biphenyls in Wistar and Gunn rats.

We have previously demonstrated that in mice, the decrease in serum thyroxine (T(4)) level by polychlorinated biphenyls (PCBs) occurs without an increase in the UDP-glucuronosyltransferase (T(4)-UDP-GT) for T(4) glucuronidation, although the PCB-induced decrease in rats is generally thought to occur through induction of T(4)-UDP-GT, UGT1A1, and UGT1A6. In the present study, to further clarify the relationship between the decrease in serum T(4) level and the increase in UGT1A activity by PCB in rats, we examined the relationship using Wistar rats and Gunn rats, a mutant strain of Wistar rats deficient in UGT1A isoforms. The serum total T(4) level was markedly decreased not only in the Wistar rats but also in the Gunn rats 4 days after treatment with a PCB, Kanechlor-500 (KC500, 100 mg/kg) or 2,2',4,5,5'-pentachlorobiphenyl (PentaCB, 112 mg/kg), and there was no significant difference in magnitude of the decrease between the two rat strains. At the same time, the level and activity of T(4)-UDP-GT were significantly increased by treatment with either KC500 or PentaCB in Wistar rats but not in Gunn rats. In addition, no significant change in the level of serum total triiodothyronine (T(3)) and thyroid-stimulating hormone by the KC500 treatment was observed in either Wistar or Gunn rats. Furthermore, significant decrease in the activity of hepatic type-I deiodinase, which mediates the deiodization of T(4) and T(3), by treatment with KC500 or PentaCB was observed in both Wistar and Gunn rats. From the serum of KC500- or PentaCB-treated Wistar and Gunn rats, mono- and di-hydroxylated PCB metabolites, which would bind to T(4) binding serum protein (transthyretin), were detected. In conclusion, the present results suggest that the decrease in serum total T(4) level by either KC500 or PentaCB in Gunn rats was not dependent on the increase in hepatic T(4)-UDP-GT activity. The findings further suggest that the PCB-mediated decrease in serum T(4) level might occur, at least in part, through formation of the hydroxylated PCB metabolites. Furthermore, even in Wistar rats, the PCB-mediated decrease in serum T(4) level might occur not only through the increase in hepatic T(4)-UDP-GT but also via formation of hydroxylated PCB metabolites.