Hydroxysafflor yellow A acutely attenuates blood-brain barrier permeability, oxidative stress, inflammation and apoptosis in traumatic brain injury in rats1.

PURPOSE: To investigate the therapeutic benefits of Hydroxysafflor yellow A (HSYA) on blood-brain barrier (BBB) vulnerability after traumatic brain injury (TBI) and identify its potential action of mechanisms on TBIinduced injuries. METHODS: The rat TBI model was performed by using a controlled cortical impact device. The BBB permeability induced by TBI was measured through Evans Blue dye superflux and western blotting or polymerase chain reaction (PCR) for tight junctional proteins (TJPs). The post-TBI changes in oxidative stress markers, inflammatory response and neuron apoptosis in brain tissue were also tested. RESULTS: Herein, the results showed that HSYA acutely attenuated BBB permeability via increasing the production of the TJPs, including occludin, claudin-1 and zonula occludens protein 24 h after TBI. Additionally, HSYA could suppress the secretion of proinflammatory factors, such as interleukin-1ß, interleukin-6, and tumor necrosis factor-α (IL-1ß, IL-6, and TNF-α), and also concurrently down-regulate the expression of inflammation-related Toll-like receptor 4/nuclear factor kappa-B (TLR4/NF-kB) protein. These HSYA challenged changes were accompanied by the decreased TBI induced oxidative stress markers and inhibited the expression of apoptosis proteins Bax, caspase-3 and caspase-9. CONCLUSIONS: Taken together, all findings suggested that HSYA (30 mg/kg) are against TBI through improving the integrity in BBB, which are associated with the antioxidant, anti-inflammation and antiapoptosis via the probable mechanism of down-regulation of the TLR4/NF-kB pathway, and its in-detail protective mechanisms are under study.

Hydroxysafflor yellow A acutely attenuates blood-brain barrier permeability, oxidative stress, inflammation and apoptosis in traumatic brain injury in rats1

Abstract Purpose: To investigate the therapeutic benefits of Hydroxysafflor yellow A (HSYA) on blood-brain barrier (BBB) vulnerability after traumatic brain injury (TBI) and identify its potential action of mechanisms on TBIinduced injuries. Methods: The rat TBI model was performed by using a controlled cortical impact device. The BBB permeability induced by TBI was measured through Evans Blue dye superflux and western blotting or polymerase chain reaction (PCR) for tight junctional proteins (TJPs). The post-TBI changes in oxidative stress markers, inflammatory response and neuron apoptosis in brain tissue were also tested. Results: Herein, the results showed that HSYA acutely attenuated BBB permeability via increasing the production of the TJPs, including occludin, claudin-1 and zonula occludens protein 24 h after TBI. Additionally, HSYA could suppress the secretion of proinflammatory factors, such as interleukin-1β, interleukin-6, and tumor necrosis factor-α (IL-1β, IL-6, and TNF-α), and also concurrently down-regulate the expression of inflammation-related Toll-like receptor 4/nuclear factor kappa-B (TLR4/NF-kB) protein. These HSYA challenged changes were accompanied by the decreased TBI induced oxidative stress markers and inhibited the expression of apoptosis proteins Bax, caspase-3 and caspase-9. Conclusions: Taken together, all findings suggested that HSYA (30 mg/kg) are against TBI through improving the integrity in BBB, which are associated with the antioxidant, anti-inflammation and antiapoptosis via the probable mechanism of down-regulation of the TLR4/NF-kB pathway, and its in-detail protective mechanisms are under study.

Melandrium firmum Extract Promotes Hair Growth by Modulating 5α-Reductase Activity and Gene Expression in C57BL/6J Mice.

BACKGROUND: In our preliminary study, we screened for their potential to inhibit 5α-reductase, and Melandrium firmum (MF) extract showed the most potent activity as confirmed by high-performance liquid chromatography (HPLC). OBJECTIVE: This study aimed to investigate the effects of MF extract on 5α-reductase activity and its mechanisms of action in the prevention or treatment of androgenetic alopecia. METHODS: HPLC was used to measure 5α-reductase activity. The hair growth-promoting effect of MF extract in the shaved dorsal skin of C57BL/6J mice was studied for 30 days. Hair follicles were examined by histological examination. Protein and mRNA levels of growth factors involved in hair growth were determined by western blotting, and reverse transcription-polymerase chain reaction (RT-PCR) and qPCR, respectively. Cell proliferation was measured by (3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay. RESULTS: MF extract at 0.5 mg/ml showed 43.5% inhibition of 5α-reductase. MF extract promoted hair growth by inducing anagen phase reflected by skin color, hair density, and the number and size of hair follicles. It not only reduces the expression of transforming growth factor-beta 1 (TGF-ß1) and Dickkopf-1 (DKK-1), but also markedly upregulated insulin-like growth factor 1 and keratinocyte growth factor in the dorsal dermal tissue. Ursolic acid, ecdcysteron, and ergosterol peroxide were identified as active constituents by activity-guided fractionation to inhibit 5α-reductase. They decreased the gene expression of TGF-ß1 and DKK-1 in human hair dermal papilla cells. CONCLUSION: In summary, these finding indicate that MF extract might be a good drug candidate for hair growth promotion.

CircRNA_0109291 regulates cell growth and migration in oral squamous cell carcinoma and its clinical significance.

OBJECTIVES: Circular RNAs (circRNAs), a new class of non-coding RNAs, have emerged as important regulators during tumorigenesis. However, the functions of circRNAs have not been completely clarified in the progression of cancers. In our study, a novel circRNA hsa_circ_0109291 was investigated in oral squamous cell carcinoma (OSCC) tissues and cell lines. MATERIALS AND METHODS: The expression profile of circRNAs in OSCC tumor tissues was performed by high-throughput sequencing. The CCK-8 wound healing and apoptosis assay were measured in OSCC cell lines after transfection with si-0109291 or si-NC. RESULTS: We discovered that hsa_circ_0109291 was significantly increased in OSCC tissues and cell lines compared with their corresponding control group. Knockdown of hsa_circ_0109291 inhibited proliferation and migration of OSCC cell lines in vitro. In addition, inhibition of hsa_circ_0109291 dramatically induced apoptosis of OSCC cells. We further found that high hsa_circ_0109291 levels in OSCC patients resulted in a poorer prognosis than in patients with low hsa_circ_0109291 levels. CONCLUSION: These findings indicated that hsa_circ_0109291 correlated with the progression of OSCC and might be a new therapeutic target for the treatment of OSCC.

Antiobesity Effect of Astilbe chinensis Franch. et Savet. Extract through Regulation of Adipogenesis and AMP-Activated Protein Kinase Pathways in 3T3-L1 Adipocyte and High-Fat Diet-Induced C57BL/6N Obese Mice.

Astilbe chinensis Franch. et Savat. (AC) has been used in traditional medicine for the treatment of chronic bronchitis, arthralgia, and gastralgia. In this study, we investigated the antiobesity effect of AC extract on 3T3-L1 preadipocytes and high-fat-diet-fed C57BL/6N obese mice. We found that AC extracts dramatically decreased the lipid content of 3T3-L1 cells in a concentration-dependent manner without cytotoxicity. The action mechanism of AC extract was demonstrated to be the inhibition of lipid accumulation and dose-dependent decrease in the expression of CCAAT/enhancer-binding protein α (C/EBPα), peroxisome proliferator-activated receptor-γ (PPAR-γ), and sterol regulatory element-binding protein 1 (SREBP1). Furthermore, AC extract increased the mitochondrial phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC), mitochondrial biogenesis, and lipolysis-related factors. In amice model of high-fat-diet-induced obesity, the mice administered AC extract experienced significant decrease of 64% in weight gain, 55% in insulin resistance index, 22% in plasma triglycerides (TG), 56% in total cholesterol (TC), and 21% in nonesterified fatty acid (NEFA) levels compared with those in the high-fat diet-fed control mice. Collectively, these results indicated that AC extract exerted antiobesogenic activity through the modulation of the AMPK signaling pathway, inhibition of adipogenesis, decreased lipid content, and reduced adipocyte size.

[The role of food-specific IgG antibody test in diagnosis and treatment of mild recurrent aphthous ulcer].

PURPOSE: To evaluate the role of food-specific IgG antibody test in the treatment of mild recurrent aphthous ulcer. METHODS: Seven hundred and ninety nine mild recurrent aphthous ulcer patients and 762 normal persons were enrolled in the experimental and control group respectively, based on the criteria for inclusion and exclusion. The blood serum samples of them were obtained to detect food-specific IgG antibody by enzyme-linked immunosorbent assay. The positive rates were then compared by Chi-square test between 2 groups using SPSS 17.0 software package. The experimental group was further analyzed based on age, gender, course, interval period, number of ulcer, allergy history, etc. Food rotation was applied in strong positive patients for food-specific IgG antibody. RESULTS: The positive rate was 45.2% in the experimental group and 40.9% in the control group(P=0.101). The positive rate was significantly higher in young patients (51.3%) and patients with short interval (83.9%). Food rotation could prolong the interval period from 13.00 days to 14.77 days in general but did not reduce the ulcer number significantly. CONCLUSIONS: Food-specific IgG antibody test may be helpful for the treatment of young or frequent patients with mild recurrent aphthous ulcer.

[Changes of cementum endotoxin levels in different teeth with periodontitis treated with root conditioning].

PURPOSE: To observe the changes of endotoxin levels after different teeth with periodontitis were treated with different methods. METHODS： Six healthy premolars extracted for orthodontic reasons and 36 posterior teeth extracted due to severe periodontitis were selected. Each tooth was processed from two 4 mm×4 mm×1 mm cementum pieces 2 mm under the cementum-enamel junction, each tooth with periodontitis was numbered. Healthy teeth served as negative control group, one of the two tablets from each tooth with periodontitis was selected in the periodontitis group, which was not treated with root surface treatment. The remaining 36 teeth with periodontitis were randomly divided into 6 groups: SRP group, SRP + antimicrobial peptide A group , SRP + antimicrobial peptide B group, SRP + EDTA group, SRP + Er:YAG laser group and SRP + Nd:YAG laser group. Endotoxin concentration in each tooth was determined by chromogenic substrate limulus reagent. The endotoxin concentration in each tooth was recorded according to the serial number, and the changes of endotoxin concentration were calculated before and after treatment. SPSS17.0 software package was used to analyze the data. RESULTS: Compared with the teeth with periodontitis, endotoxin concentration decreased to varying degrees, there were significant differences in each treatment group(P<0.01). Compared with SRP group, endotoxin levels in SRP + antimicrobial peptide A group, SRP + antimicrobial peptide B group, SRP + Er:YAG laser group were significantly decreased(P<0.01). No significant difference decreased was from between SRP + EDTA group and SRP + Nd:YAG laser group(P>0.05). CONCLUSIONS: Treatment of teeth with periodontitis using different methods can decrease the level of endotoxin, and the treatment of periodontitis root surface with antimicrobial peptide A + SRP may be more effective.

Mechanisms of TET protein-mediated DNA demethylation and its role in the regulation of mouse development.

TET (ten-eleven translocation) protein family includes three members TET1, TET2 and TET3, which belong to alpha-ketoglutaric acid ( α-KG )- and Fe(2+)-dependent dioxygenase superfamily, and have the capacity to convert 5-methylcytosine (5 mC) to 5-hydroxymethylcytosine (5 hmC), 5-formylcytosine (5 fC) and 5-carboxylcytosine (5 caC). At present, growing lines of evidence indicate that TET proteins are involved in the control of active or passive DNA demethylation via different mechanisms; moreover, their activities may be regulated by some cellular factors. TET proteins play vital roles in modulating mammal development, including primordial germ cell formation, embryonic development, stem cells pluripotency, nerve and brain development, etc. The identification of biological roles of TET proteins will open a new field in epigenetic research, and these studies on TET proteins are of great significance to life science research. Here, we review TET proteins from their structure, molecular mechanisms of DNA demethylation and function in the regulation of mouse development, which may provide the basis for understanding the functions of TET proteins.

Metformin decreases meal size and number and increases c-Fos expression in the nucleus tractus solitarius of obese mice.

Metformin is widely used to treat obese diabetics because of its beneficial effects on body weight, energy intake, and glucose regulation. However, it has not been investigated how oral metformin affects meal patterns, or whether the reduced food intake is associated with neuronal activation in the hindbrain. Accordingly, we investigated how orally administered metformin (150 or 300 mg/kg daily for 4 or 7 days) reduces body weight in obese mice on a high-fat diet by continuously measuring meal patterns, energy expenditure, and locomotor activity, and whether oral metformin (300 mg/kg daily for 3 days) increases c-Fos expression in the nucleus tractus solitarius (NTS) and area postrema. Furthermore, we determined whether oral metformin produces a conditioned taste aversion (CTA) in obese mice administered a single dose of metformin (75, 150, or 300 mg/kg, p.o.). Metformin (300 mg/kg daily for 7 days) reduced body weight and adiposity by decreasing nocturnal energy intake but did not significantly change energy expenditure or locomotor activity relative to vehicle, and it transiently decreased nocturnal meal size and reduced meal number throughout the experiments. Furthermore, metformin significantly increased c-Fos immunoreactivity within the NTS of obese mice compared to that in controls and pair-fed group, and induced a CTA at doses of 150 or 300 mg/kg. These results indicate that metformin-induced weight loss is associated with a sustained reduction in energy intake maintained by a reduction in meal size and number, and that oral administration of metformin causes visceral illness and neuronal activation in the NTS.

Anti-obesity effect of resveratrol-amplified grape skin extracts on 3T3-L1 adipocytes differentiation.

Resveratrol (3,4,5-trihydroxy-trans-stilbene), a phytoalexin found in grape skin, grape products, and peanuts as well as red wine, has been reported to have various biological and pharmacological properties. The purpose of this study was to investigate the anti-obesity effect of resveratrol-amplified grape skin extracts on adipocytes. The anti-obesity effects of grape skin extracts were investigated by measuring proliferation and differentiation in 3T3-L1 cells. The effect of grape skin ethanol extracts on cell proliferation was detected by the MTS assay. The morphological changes and degree of adipogenesis of preadipocyte 3T3-L1 cells were measured by Oil Red-O staining assay. Treatment with extracts of resveratrol-amplified grape skin decreased lipid accumulation and glycerol-3-phosphate dehydrogenase activity without affecting 3T3-L1 cell viability. Grape skin extract treatment resulted in significantly attenuated expression of key adipogenic transcription factors, including peroxisome proliferator-activated receptor, CCAAT/enhancer-binding proteins, and their target genes (FAS, aP2, SCD-1, and LPL). These results indicate that resveratrol-amplified grape skin extracts may be useful for preventing obesity by regulating lipid metabolism.

Suppression of oxidative stress by grape seed supplementation in rats.

Polyphenol-rich grape seeds have a beneficial effect on human health. The present study was performed to investigate the effects of grape seeds on antioxidant activities in rats. Male Sprague-Dawley rats were randomly divided into a control diet group (C), a high-fat diet group (HF), a 5% grape seed-supplemented control diet group (G), and a 5% grape seed-supplemented high-fat diet group (HG). Dietary supplementation with grape seeds reduced serum concentrations of lipid peroxides compared with those in the C and HF groups. The hepatic level of lipid peroxides decreased significantly in the grape seed groups compared with that in the C and HF groups. Superoxide dismutase activity in the G group increased significantly compared with that in the C group. Catalase activity tended to be higher by feeding grape seeds. The grape seed diet increased glutathione peroxidase activity in the C group. Glutathione-S-transferase activity increased significantly in the G group compared with that in the C group. Hepatic content of total glutathione increased significantly in the HG group but decreased significantly in the HF group. The ratio of reduced glutathione and oxidized glutathione increased by feeding the grape seed diet. Total vitamin A concentration was significantly higher in HG group than in other groups. Liver tocopherol content of the G and HG groups was significantly higher than that of the control groups. These results suggest that dietary supplementation with grape seeds is beneficial for suppressing lipid peroxidation in high fat-fed rats.

Designing biomaterials for in situ periodontal tissue regeneration.

The regeneration of periodontal tissue poses a significant challenge to biomaterial scientists, tissue engineers and periodontal clinicians. Recent advances in this field have shifted the focus from the attempt to recreate tissue replacements/constructs ex vivo to the development of biofunctionalized biomaterials that incorporate and release regulatory signals in a precise and near-physiological fashion to achieve in situ regeneration. The molecular and physical information coded within the biomaterials define a local biochemical and mechanical niche with complex and dynamic regulation that establishes key interactions with host endogenous cells and, hence, may help to unlock latent regenerative pathways in the body by instructing cell homing and regulating cell proliferation/differentiation. In the future, these innovative principles and biomaterial devices promise to have a profound impact on periodontal reconstructive therapy and are also likely to reconcile the clinical and commercial pressures on other tissue engineering endeavors.

Low cytotoxicity porous Nd(2)(SiO(4))(3) nanoparticles with near infrared excitation and emission.

Porous Nd(2)(SiO(4))(3) nanoparticles were successfully synthesized by a controlled route. This kind of silicate nanoparticle could be excited by near-infrared (NIR) radiation (808 nm) and triggered a NIR emission (1066 nm) at room temperature. By monitoring the 1066 nm emission, the long-lived luminescent lifetime was determined to be 19.5 µs. These NIR nanoparticles with appropriate diameters (<100 nm) were suitable for cell assays. MTT assays showed that the cytotoxicity of the porous Nd(2)(SiO(4))(3) nanoparticles was very low. Therefore, these porous silicate nanoparticles are potential biosafe high-performance NIR biolabeling materials.

Fabrication of apatite-type La(9.33)(SiO4)6O2 hollow nanoshells as energy-saving oxidative catalysts.

Apatite-type La(9.33)(SiO(4))(6)O(2) hollow nanoshells were successfully synthesized by a controlled route. These oxide-ion-conducting hollow nanoshells were used to catalyze oxidative coupling of methane, and an enhanced catalytic performance at relatively low temperature was realized. The high-activity and energy-saving features were attributed to their hollow nanostructures and oxide ion conductivity.

[Correlation of ornidazole concentration in saliva and serum of healthy volunteers].

OBJECTIVE: To investigate the distribution of ornidazole in the salivary and serum of healthy adults and explore the feasibility of monitoring serum drug concentration with salivary. METHODS: Six volunteers received a single dose of 0.6 g ornidazole via intravenous infusion. The concentrations of ornidazole in the saliva and serum were assayed by high-performance liquid chomatography, and the correlation of the drug concentrations in saliva to that in serum was analyzed. RESULTS: The concentration of ornidazole in the saliva was strongly associated with that in the serum (r = 0.825-0.969), and the ratio of saliva-to-serum concentration (S/P) of ornidazole was 0.99 ± 0.13. CONCLUSION: Detection of saliva ornidazole concentration is feasible for monitoring the therapeutic concentration of ornidazole.

Hydrothermal microemulsion synthesis of oxidatively stable cobalt nanocrystals encapsulated in surfactant/polymer complex shells.

Air-stable magnetic cobalt nanocrystals have been conveniently prepared via a reverse micellar synthesis, followed by a hydrothermal treatment. The synthesis was carried out by first mixing an aqueous solution containing cobalt chloride and poly(sodium 4-styrenesulfonate) (PSS) with an organic mixture containing cetyltrimethylammonium bromide (CTAB) to form reverse micelles, followed by reducing cobalt ions with sodium borohydride. The resultant nanoparticles were then undergone a hydrothermal treatment at 165 degrees C for 8 h to generate well-dispersed CTAB/PSS-encapsulated cobalt nanocrystals with an average diameter of 3.5 +/- 0.5 nm. The nanoparticles were highly crystalline with a hexagonal close-packed crystal phase. The presence of CTAB/PSS complex coatings was identified by FT-IR and UV-vis spectroscopies as well as thermogravimetry analyses. The nanocrystals exhibited superparamagnetic property at room temperature with a saturation magnetization (M(s)) of 95 emu/g. The magnetization could be largely preserved after storage at room temperature for 4 months as the M(s) value only slightly decreased to 88 emu/g (measured at 300 K). Thus, the polymer encapsulation could not only improve thermal stability of the micelles for the growth and nucleation of Co atoms but also protect the resulting cobalt nanocrystals from oxidation through forming an oxygen impermeable sheath.

[Portal vein flow rate used as a early predictor of portal vein thrombosis after periesophagastric devascularization].

OBJECTIVE: To evaluate the predictive value of portal vein flow rate preoperative for portal vein thrombosis (PVT) after periesophagastric devascularization in hepatitis B cirrhosis-related portal hypertension. METHODS: From January 2007 to July 2008, 45 patients with portal hypertension caused by hepatitis B cirrhosis were performed splenectomy with peri-esophagogastric devascularization in the same medical group in West China Hospital of Sichuan University. The portal vein flow rate and the diameter of portal vein were measured with doppler sonography respectively before and after the operation. At the same time, the level of PT and PLT were detected. The weight of spleens were measured after operation. RESULTS: Thirteen cases suffered from PVT postoperatively. Portal vein flow rate was significantly lower in patients with PVT postoperation than that in patients without PVT (P < 0.01). In patients with PVT (n = 13) postoperation, the preoperative portal vein flow rate was (19.5 +/- 5.3) cm/s. Among the 13 cases, there were 12 cases whose flow rate were lower than 25 cm/s, and 1 case whose flow rate was 32. 3 cm/s; In patients without PVT (n = 32), the preoperative portal vein flow rate was (9.6 +/- 8.0) cm/s. In patients with lower rate (n = 17), the incidence rate of PVT was 70.6%; in patients with higher rate (n = 28), the incidence rate of PVT was 3.6%. The incidence rate of PVT in patients with lower rate was significantly lower than patients with higher rate (P < 0.01). The diameter of portal vein in patients with PVT was significantly wider than patients without PVT. The diameter of portal vein was negative correlative with the portal vein flow rate. The value 25 cm/s was of diagnostic efficiency, the sensitivity was 92.3%, and specificity was 70.6%. CONCLUSIONS: The portal vein flow rate preoperative can be used as an early predictor of portal vein thrombosis after periesophagastric devascularization in hepatitis B cirrhosis-related portal hypertension to give a guide to clinical work.

Risks faced by donors of right lobe for living donor liver transplantation.

BACKGROUND: Because of the shortage of deceased donors with livers fit for transplantation, living donor liver transplantation (LDLT) is becoming an attractive alternative. Attention should be paid to the donors, especially to those of the right lobe. In this study, we evaluated the risks faced by donors of the right lobe for adult-to-adult LDLT. METHODS: The perioperative data from 105 consecutive living donors of the right lobe performed in West China Hospital from January 2002 to December 2007 were retrospectively studied. Preoperative evaluation included CT, MRCP, and intraoperative cholangiography, showing liver volume, hepatic vasculature and the biliary system. The standard liver volume (SLV) and the ratio of left lobe volume to SLV were calculated. The right lobe grafts were obtained by transecting the liver on the right side of the middle hepatic vein without inflow vascular occlusion, using an ultrasonic dissector. After operation the donors were monitored in the Intensive Care Unit for about three days. Each donor was followed up for at least 6 months. RESULTS: There was no donor mortality. Major complications occurred in 14 donors (13.3%), of whom 3 received conservative treatment, 8 required invasive paracentesis, and 3 required further surgery. All donors were recovered well and resumed their previous occupations. CONCLUSIONS: Donors of the right lobe face low risks. The preoperative evaluation, especially evaluation of the volume of the remnant liver, should be exact. During the operation, the patency of the remnant hepatic vasculature and bile duct must be preserved, and the extent of injury to the remnant liver should be limited as much as possible. The detection and treatment of postoperative complications should be diligently performed.

A hierarchical lattice structure and formation mechanism of ZnO nano-tetrapods.

The existence of characteristic longitudinal optical and transverse optical phonons of cubic ZnO in ZnO nano-tetrapods is determined by Raman spectroscopy and first-principles calculations. Stacking sequence change at the boundary of the core and legs is also identified by high-resolution transmission electron microscopy. Based on this experimental and theoretical evidence, we demonstrate that the lattice structure of ZnO nano-tetrapods is hierarchical with a zinc blende core connecting to four wurtzite legs. Furthermore, we establish the atomic configuration and propose a formation mechanism induced by Laplace pressure in the initial growth stage of ZnO nano-tetrapods.

Population pharmacokinetics of remifentanil in patients undergoing orthotopic liver transplantation.

BACKGROUND: Little is known about the influence of liver transplantation on the pharmacokinetics of most anesthetic drugs. The goal of this study was to study the population pharmacokinetics of remifentanil in the different phases of orthotopic liver transplantation (OLT) and the influence of relevant factors. METHODS: Thirteen adult patients undergoing OLT were enrolled. A single bolus infusion of remifentanil 5 microg/kg was administered during the preanhepatic, anhepatic and neohepatic phases of OLT. Arterial blood samples of 1.5 ml were collected at 0 (baseline), 1, 2, 3, 5, 7, 10, 15, 20, 25, 30, 45, 60 and 90 minutes after drug administration. Remifentanil concentration was assayed by high-performance liquid chromatography/mass spectrometry/mass spectrometry (HPLC/MS/MS). Population pharmacokinetic modeling was performed using nonlinear mixed-effects modeling (NONMEM). RESULTS: The pharmacokinetics of remifentanil in patients undergoing OLT was best described by a two-compartment open model. The pharmacokinetic parameters were not influenced by age, gender, operative phase, blood temperature, rehydration volume, or blood loss volume during sampling. The volume of distribution in the central compartment (V(1)) and the volume of distribution in the peripheral compartment (V(2)) were influenced by body weight. CONCLUSIONS: The population pharmacokinetics of remifentanil in patients undergoing OLT can be well described by a two-compartment open model. The functional status of the liver does not significantly affect the pharmacokinetics of remifentanil, but the body weight is an influential factor of V(1) and V(2).