Biomedical subjects

S Fujii

Publications and source records attributed to S Fujii.

At least 19 recordsLinked to original sources

PubMed2006

Intrauterine administration of autologous peripheral blood mononuclear cells promotes implantation rates in patients with repeated failure of IVF-embryo transfer.

BACKGROUND: There are few effective approaches to infertile patients with repeated failure in IVF-embryo transfer therapy. Since recent evidence suggests that some populations of maternal immune cells positively support embryo implantation, we have developed a new approach using peripheral blood mononuclear cells (PBMCs). METHODS: Patients who had not experienced successful pregnancy despite four or more IVF-embryo transfer sessions were enrolled in this study (n = 35, 35 cycles). PBMCs were obtained from patients on the day of oocyte retrieval and were cultured with HCG for 48 h. Two days later, PBMCs were freshly isolated from patients again, combined with cultured PBMC and then administered to the intrauterine cavity of the patients. Blastocyst transfer was performed on day 5, and the success of implantation in the PBMC-treated group was compared with that in the non-treated group. RESULTS: Clinical pregnancy rate, implantation rate and live birth rate in the PBMC-treated group (41.2, 23.4 and 35.3%; n = 17, 47 and 16, respectively) were significantly higher than those in the non-treated group (11.1, 4.1 and 5.5%; n = 18, 49 and 18, respectively). CONCLUSION: Intrauterine administration of autologous PBMC may be an effective approach to improve embryo implantation in patients with repeated IVF failures.

Adult↗

PubMed2006

Ovarian leukocyte distribution and cytokine/chemokine mRNA expression in follicular fluid cells in women with polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) affects 5-10% of reproductive-aged women and is commonly associated with anovulatory infertility. Leukocytes, together with granulosa cells, may contribute to the pathogenesis of PCOS via their ability to secrete an array of cytokines implicated in follicle growth. The aim of this study was to examine leukocyte subtypes in follicular phase ovaries and to quantify cytokine and chemokine mRNA expression in follicular fluid cells obtained at the time of oocyte retrieval before IVF in women with and without PCOS. METHODS: Ovaries were immunostained for various leukocyte markers [CD3, CD4, CD14, CD15, CD45, CD45RA, CD45RO, CD57 and major histocompatibility complex (MHC) class II]. In addition, follicular fluid cells were subjected to quantitative RT-PCR to evaluate colony-stimulating factor-1 (CSF-1), granulocyte-macrophage (GM)-CSF, interleukins (IL-1beta, IL-6, IL-8 and IL-10), monocyte chemotactic protein (MCP-1) and tumour necrosis factor (TNFalpha) mRNA expression relative to beta-actin. RESULTS: CD45RO+ cells (activated/memory T lymphocytes) were reduced by 60% in the theca layer of follicles from PCOS women. The relative abundance of macrophages and neutrophils was unchanged. Cytokine and chemokine mRNA transcripts examined were not affected by PCOS status. There was an association between high BMI and high TNFalpha and low IL-6 mRNA expression in follicular cells. IL-6 expression was higher in women who subsequently achieved pregnancy. CONCLUSIONS: T lymphocytes potentially play a role in the local pathological mechanisms of PCOS. Further studies are required to identify their contribution to the aetiology of this common condition.

Adult↗

PubMed2006

Aqueous particulate foams stabilized solely with polymer latex particles.

In this article, a wide range of latexes are evaluated as possible foam stabilizers. These include near-monodisperse, poly(N-vinyl pyrrolidone)-stabilized polystyrene [PNVP-PS] latexes with diameters ranging from 170 nm to 1.62 microm, submicrometer-sized poly(ethylene glycol)-stabilized polystyrene [PEGMA-PS] latex particles, a PNVP-stabilized poly(4-bromostyrene) [PNVP-PBrS] latex with a mean diameter of 870 nm, two PNVP-stabilized poly(methyl methacrylate) [PNVP-PMMA] latexes with mean diameters of 730 nm and 1.20 microm, a PNVP-stabilized poly(2-hydroxypropyl methacrylate) [PNVP-PHPMA] latex with a mean diameter of 630 nm, and a charge-stabilized anionic PS latex of 220 nm diameter. The effect of varying the particle size, latex concentration, and latex surface composition on foam stability were studied in detail. The larger PNVP-PS latexes, the PNVP-PBrS, and the two PNVP-PMMA latexes gave highly stable foams, whereas PEGMA-PS, PNVP-PHPMA, and the charge-stabilized PS latex produced either no foams or foams with inferior long-term stabilities. Scanning electron microscopy studies revealed hexagonally close-packed latex arrays in the walls of the dried foam, which leads to localized moiré patterns being observed by optical microscopy. Moreover, these dried foams are highly iridescent in bright transmitted light.

Journal Article↗

PubMed2006

Stimulation of cAMP signalling allows isolation of clonal pancreatic precursor cells from adult mouse pancreas.

AIMS/HYPOTHESIS: Duct cells of the pancreas are thought to include latent progenitors of islet endocrine cells that can be induced to differentiate by appropriate morphogens. Here we developed a method for isolating pancreatic ductal epithelial cells from adult mice that overcomes the shortcomings of previous methods. MATERIALS AND METHODS: Pancreatic ductal cells were grown in serum-free DMEM/F12 medium in the presence of cholera toxin or 8-bromo-cyclic adenosine monophosphate, which is known to be an intracellular cAMP generator. Single cell cloning was performed by limiting dilution in serum-free medium. RESULTS: The isolated clonal cells expressed high levels of cytokeratin and Ipf1 (formerly known as Pdx-1). Adenovirus-mediated expression of ngn3 (also known as Neurog3) and Ptf1a in these cells induced expression of insulin and somatostatin, and of carboxypeptidase A, respectively. Furthermore, albumin production was induced by dexamethasone or by long-term culture in serum-containing medium. CONCLUSIONS/INTERPRETATION: Stimulation of the cAMP-dependent signalling allowed us to isolate clonal pancreatic ductal cells from adult mice. These cells are able to partially differentiate into endocrine cells, exocrine cells and hepatocyte-like cells and are therefore considered to have the characteristics of endodermal progenitor cells.

Animals↗

PubMed2006

Size and viscoelasticity of spatially confined multilamellar vesicles.

We studied viscoelastic properties and scaling behavior of multilamellar vesicles (MLVs) confined between two parallel plates as a function of the shear rate and sample thickness (gap size between parallel plates). The rheological properties are classified into two regimes; the shear-thinning regime at high shear rates and the shear-thickening regime at low shear rates. In the former, the MLV radius results from the mechanical balance between the effective surface tension sigma(eff) and viscous stress force. The MLV radius is independent of the gap size. sigmaeff estimated by van der Linden model is 2.1+/-0.15x10(-4) Nm-1 corresponding to the same value obtained by SANS measurement. Power law exponents for the steady state viscosity and yield stress against pre-shear rate ([see text], [see text]) well agree with prediction based on the layering of membranes. Therefore, viscoelastic properties in this regime could be modeled by assuming that the dynamics of MLVs are driven by layering of MLV polydomains, which could be accompanied by the viscous dissipation, i.e., the stress relaxation on the MLV, induced by continuous sequence of yields of MLVs. The flow curve is empirically explained by the assumption of a relaxation time for the MLV shape. In the latter, however, scaling laws observed in the shear-thinning regime break down. The MLV radius increases when the gap size is reduced below the threshold value and MLV is no longer formed at very small gap sizes. Different dynamics from the shear-thinning regime seem to dominate the viscoelasticity.

Colloids↗

PubMed2006

Biphasic clinical course and early white matter abnormalities may be indicators of neurological sequelae after status epilepticus in children.

Clinical course and serial neuroimaging findings are not fully described in children who have had neurological sequelae following status epilepticus. We found four patients who had neurological sequelae out of 42 children with status epilepticus in 2004. MRI studies were reviewed with specific attention to diffusion-weighted images (DWI) and the apparent diffusion coefficient (ADC). Proinflammatory cytokines, including tumor necrosis factor-alpha and interleukin-6, were measured in the cerebrospinal fluid (CSF) (3 patients). The clinical course showed biphasic; initial status epilepticus and neurological exacerbation along with seizure recurrence four to five days after onset. Within three days after initial status epilepticus, CT (all patients) and MRI (2 patients) did not show any abnormalities. From four to ten days after onset, MRI demonstrated diffuse hyperintensity in the cerebral white matter on DWI and hypointensity on ADC maps in all patients. Diffuse brain atrophy progressed thereafter. Tumor necrosis factor-alpha or interleukin-6 was elevated in all patients. A biphasic clinical course may be a specific feature for neurological sequelae. The preferential white matter involvement on MRI and elevated CSF cytokines indicate that glial dysfunction may play an important role in the pathophysiology of status epilepticus-associated cerebral damage.

Brain Mapping↗

PubMed2006

Analysis of parameter variations in L-Q equations for river runoff processes from the viewpoint of spatial and temporal conditions.

This study aims to find out variation characteristics of the parameters of 'a' and 'b' in L = a x Q(b), an empirical equation for run-off loading (L) and flow rate (Q), by evaluating the effects of flow conditions and regional properties of the watersheds on the values. We selected the Kamo River basin (155 km2) as a study field, and conducted various kinds of investigations, such as 80 day high frequency observations, continuous monitoring for more than 2 years, storm event surveys, and simultaneous surveys of 39 stations. Then, we obtained 7-170 data in each of 39 sampling stations. The main results obtained are as follows: (1) L-Q equation with a range of 'a' can express L-Q relation in most of the WQIs (water quality indices); (2) 'a' receives temporal (flow condition) effects more in SS, VSS and Al, while it receives regional effect more in inorganic carbon, TN, Ca and Fe; (3) both of flow change in storm events, and base flow levels affect the L-Q relation, and their effects can classify the WQIs into several groups; (4) the effects of regional properties were obviously observed in 'a', and quantitatively evaluated, especially for density of population.

Algorithms↗

PubMed2005

Possible role of REG Ialpha protein in ulcerative colitis and colitic cancer.

BACKGROUND AND AIMS: Although regenerating gene (REG) Ialpha protein may be involved in the inflammation and carcinogenesis in the gastrointestinal tract, its pathophysiological role in ulcerative colitis (UC) and the resulting colitic cancer remains unclear. We investigated expression of the REG Ialpha gene and its protein in UC and colitic cancer tissues. We examined whether cytokines are responsible for REG Ialpha gene expression and whether REG Ialpha protein has a trophic and/or an antiapoptotic effect on colon cancer cells. METHODS: Expression of REG Ialpha mRNA and its gene product in UC tissues was analysed by real time reverse transcription-polymerase chain reaction and immunohistochemistry, respectively. The effects of cytokines on REG Ialpha promoter activity were examined in LoVo cells by luciferase reporter assay. The effects of REG Ialpha protein on growth and H(2)O(2) induced apoptosis were examined in LoVo cells by MTT and TUNEL assays, respectively. RESULTS: REG Ialpha protein was strongly expressed in inflamed epithelium and in dysplasias and cancerous lesions in UC tissues. The level of REG Ialpha mRNA expression in UC tissues correlated significantly with severity of inflammation and disease duration. REG Ialpha promoter activity was enhanced by stimulation with interferon gamma or interleukin 6. REG Ialpha protein promoted cell growth and conferred resistance to H(2)O(2) induced apoptosis in LoVo cells. REG Ialpha protein promoted Akt phosphorylation and enhanced Bcl-xL and Bcl-2 expression in LoVo cells. CONCLUSIONS: The REG Ialpha gene is inducible by cytokines and its gene product may function as a mitogenic and/or an antiapoptotic factor in the UC-colitic cancer sequence.

Adenoma↗

PubMed2005

Methylation of the oestrogen receptor gene in non-neoplastic epithelium as a marker of colorectal neoplasia risk in longstanding and extensive ulcerative colitis.

BACKGROUND: Surveillance colonoscopy is widely recommended in patients with longstanding and extensive ulcerative colitis (UC) in order to detect colorectal neoplasia at an early stage. However, it still remains questionable whether surveillance colonoscopy effectively enables early detection of UC associated neoplasia. There is a great need for sensitive markers to identify individuals at increased risk of neoplasia. The oestrogen receptor (OR) gene shows age related methylation in the colorectal epithelium and is methylated frequently in sporadic colorectal neoplasia, suggesting that OR methylation may predispose to colorectal neoplasia. AIM: To clarify whether analysis of methylation of the OR gene in non-neoplastic epithelium can contribute to prediction of increased neoplasia risk in UC patients. MATERIALS AND METHODS: A total of 165 non-neoplastic colorectal epithelia from 30 patients with longstanding and extensive UC, including 13 UC patients with neoplasia and 17 patients without, were evaluated. Methylation specific polymerase chain reaction was performed to determine the methylation status of the OR gene. RESULTS: Methylation of the OR gene was detected in 54 of 70 (77.1%) non-neoplastic colorectal epithelia in UC with neoplasia but in only 23 of 95 (24.2%) without neoplasia. Methylation of the OR gene was significantly more frequent in non-neoplastic epithelium from UC with neoplasia than in chronic colitic epithelium from UC without neoplasia. Furthermore, in UC with neoplasia, the OR gene was extensively methylated in non-neoplastic epithelia throughout the colorectum compared with those in UC without neoplasia. CONCLUSION: These results suggest that analysis of OR gene methylation may have potential as a useful marker for identifying individuals at increased risk of neoplasia among those with longstanding and extensive UC.

Aged↗

PubMed2005

Direct evidence for mutual interactions between perineuronal astrocytes and interneurons in the CA1 region of the rat hippocampus.

Recent studies have demonstrated that astrocytes express a variety of ion channels and neurotransmitter receptors and can modulate the activity of neurons. Since a single astrocyte makes tight contacts with many neighboring neuronal cells, they can provide efficient and wide modulation of neuronal networks. Here, we provide direct evidence for mutual interactions between perineuronal astrocytes and interneurons in the stratum radiatum of the rat hippocampus. Direct depolarization of a perineuronal astrocyte suppressed the excitatory postsynaptic currents in an adjacent interneuron and increased the paired-pulse ratio, indicating that perineuronal astrocytes have a suppressive effect on presynaptic elements. Moreover, perineuronal astrocyte activation modulated the directly induced firing pattern of the interneuron, with initial facilitation and subsequent suppression. Conversely, direct firing of the interneuron depolarized the membrane potential and reduced the input resistance of the perineuronal astrocyte. These results directly demonstrate the existence of bidirectional interactions between neurons and perineuronal astrocytes.

4-Aminopyridine↗

PubMed2005

Coronary arterial calcification is associated with albuminuria in type 2 diabetic patient.

AIM: Although microalbuminuria has been suggested as an independent risk factor for ischemic heart disease, the relationship between diabetic nephropathy and macroangiopathy remains unclear. Previously, we reported that coronary artery calcification detected by electron beam computed tomography (EBCT) could indicate the degree of coronary atherosclerosis in type 2 diabetic patients. In this study, we examine the association between coronary arterial calcification and microalbuminuria and aortic calcification and microalbuminuria. METHODS: Two hundred and fifty-six patients, including 177 type 2 diabetic patients (106 patients with normoalbuminuria, 71 with microalbuminuria) and 79 non-diabetic patients were evaluated by assessing the urinary albumin excretion rate and using EBCT to determine a coronary calcification score (CCS) and an aortic calcification score (ACS). RESULTS: No differences were observed regarding age, smoking index or BMI. Diabetic patients exhibited a greater CCS than non-diabetic subjects (non-diabetes 33 +/- 75 vs. diabetes 203 +/- 467, p < 0.05). Diabetic patients with microalbuminuria exhibited the most advanced CCS (253 +/- 491, p < 0.05). In contrast, no difference was observed in ACS among three groups. Multiple regression analysis showed that CCS is significantly associated with urinary albumin excretion rate as well as age, duration of diabetes and serum creatinine (R(2) = 0.31), while ACS is strongly associated with age, smoking, serum creatinine, systolic blood pressure and low-density lipoprotein cholesterol level (R(2) = 0.29). CONCLUSION: Increased urinary albumin excretion is associated with coronary arterial calcification in diabetic patients.

Age Factors↗

PubMed2005

Novel quantitative assessment of myocardial perfusion by harmonic power Doppler imaging during myocardial contrast echocardiography.

OBJECTIVE: To test the hypothesis that the power of the received signal of harmonic power Doppler imaging (HPDI) is proportional to the bubble concentration under conditions of constant applied acoustic pressure, and to determine whether a new quantitative method can overcome the acoustic field inhomogeneity during myocardial contrast echocardiography (MCE) and identify perfusion abnormalities caused by myocardial infarction. METHODS: The relation between Levovist concentration and contrast signal intensity (CI) of HPDI was investigated in vitro under conditions of constant acoustic pressure. MCE was performed during continuous infusion of Levovist with intermittent HPDI every sixth cardiac cycle in 11 healthy subjects and 25 patients with previous myocardial infarction. In the apical views myocardial CI (CI(myo)) was quantified in five myocardial segments. The CI from the left ventricular blood pool adjacent to the segment was also measured in dB and subtracted from the CI(myo) (relative CI (RelCI)). RESULTS: CI had a logarithmic correlation and the calculated signal power a strong linear correlation with Levovist concentration in vitro. Thus, a difference in CI of X dB indicates a microbubble concentration ratio of 10(X/10). In normal control subjects, CI(myo) differed between the five segments (p < 0.0001), with a lower CI(myo) in deeper segments. However, RelCI did not differ significantly between segments (p = 0.083). RelCI was lower (p < 0.0001) in the 39 infarct segments (mean (SD) -18.6 (2.8) dB) than in the 55 normal segments (mean (SD) -15.1 (1.6) dB). RelCI differed more than CI(myo) between groups. CONCLUSIONS: The new quantitative method described can overcome the acoustic field inhomogeneity in evaluation of myocardial perfusion during MCE. RelCI represents the ratio of myocardium to blood microbubble concentrations and may correctly reflect myocardial blood volume fraction.

Adult↗

PubMed2005

Development of an integrated analysis procedure for three-ways layout field surveys data in lakes.

Lake water quality systems are extremely complex and every lake is characterized by many complicated interactions between biological, chemical and physical variables. One of the most important tasks of lake mechanism analysis is to examine the relations among important water quality variables and to describe such complicated relationships quantitatively, simply and practically. Lake Biwa was chosen as a target lake, where a periodic water quality investigation was conducted every month from 1979 at 50 sampling sites. The objective of this study is to establish an application procedure of three-ways layout data and to present a vision including its practical result, expecting that this vision may also provide a direction for further research. The results showed that (1) cluster analysis following the three-ways layout ANOVA method is very effective in presenting water quality variation, (2) correlation analysis of water quality indices in each effect of parameters and their interaction between two items verifies that their relationships in parameters are different due to different mechanisms. (3) An integrated analysis procedure was derived, potentially describing those data in forms which convey their important characteristics and reveal their significant relationship. The same approach of this analysis procedure could be possibly applied for other water quality indices in other lakes.

Data Collection↗

PubMed2004

Synthesis of polystyrene/poly[2-(dimethylamino)ethyl methacrylate-stat-ethylene glycol dimethacrylate] core-shell latex particles by seeded emulsion polymerization and their application as stimulus-responsive particulate emulsifiers for oil-in-water emulsions.

Surfactant-stabilized polystyrene (PS) latex particles with a mean hydrodynamic diameter of 155 nm were prepared by aqueous emulsion polymerization using 2,2'-azobis(2-amidinopropane) hydrochloride as a cationic radical initiator. Seeded aqueous emulsion copolymerizations of 2-(dimethylamino)ethyl methacrylate (DMA) and ethylene glycol dimethacrylate (EGDMA) were conducted in the presence of these PS particles to produce two batches of colloidally stable core-shell latex particles, in which the shell comprised a cross-linked P(DMA-stat-EGDMA) overlayer. Both the PS and PS/P(DMA-stat-EGDMA) latexes were characterized in terms of their particle size, morphology, and composition using dynamic light scattering, electron microscopy, and FT-IR spectroscopy, respectively. Using the PS/P(DMA-stat-EGDMA) latex particles as a pH-responsive particulate ('Pickering'-type) emulsifier, polydisperse n-dodecane-in-water emulsions were prepared at pH 8 that could be partially broken (demulsified) on lowering the solution pH to 3. These emulsions were characterized in terms of their emulsion type, mean droplet diameter, and morphology using electrical conductivity and Mastersizer measurements, optical microscopy, and scanning electron microscopy (using critical point drying for sample preparation).

Journal Article↗

PubMed2004

Experimental transplantation study for possible transformation of bone marrow cells in the mouse placenta.

The aim of the present study is to establish a mouse model of the transplantation of bone marrow cells into the placenta in mid-gestation. The mononuclear fraction of bone marrow cells was isolated by Ficoll gradient centrifugation from the femur bones of C57BL/6 green fluorescent protein (GFP) gene transgenic (Tg) mice. After intraperitoneal injection of pentobarbital sodium, the abdominal cavities of pregnant non-Tg (C57BL/6 or ICR) mice were opened at 9.5 days postcoitum (dpc). The mononuclear fraction of bone marrow cells from Tg mice (3-5 x 10(5)cells/3 microl) was directly injected into the placental portion of the pregnant uterus, at a depth of approximately 3 mm, using a 31-gauge injector. The placenta was sampled at 14.5 dpc. Confocal laser scanning microscopic analysis of the serial sections of the sampled placenta (150-250 sections/placenta) was carried out to detect GFP-positive cells and to assess immunostaining for cytokeratin, CD34, p57(Kip2) and prolactin. Most pregnant mice survived until sampling of the placenta at 14.5-18.5 dpc (88.9% for C57BL6 and 100% for ICR). The survival rate of fetuses from mice in which the placenta was transplanted with GFP-positive bone marrow cells was approximately 50%. A small population (0.154%) of injected bone marrow cells was retained in the placental tissue. Immunohistochemically, cytokeratin, CD34 and p57(Kip2) were positively stained in 0.062%, 4.5% and 2.1% of GFP-positive cells, respectively, while prolactin was not positive in any of the cells examined. GFP-positive bone marrow cells were successfully transplanted to the murine placenta. Future investigations of the specific antigens in bone marrow cells retained in the placenta may enable a better understanding of the local regulation of placental development.

Animals↗

PubMed2004

Effect of varying the oil phase on the behavior of pH-responsive latex-based emulsifiers: demulsification versus transitional phase inversion.

Sterically stabilized polystyrene latexes (previously described by Amalvy, J. I.; et al. Chem. Commun. 2003, 1826) were evaluated as pH-responsive particulate emulsifiers for the preparation of both oil-in-water and water-in-oil emulsions. The steric stabilizer was a well-defined AB diblock copolymer where A is poly(2-(dimethylamino)ethyl methacrylate) and B is poly(methyl methacrylate). Several parameters were varied during the emulsion preparation, including the polarity of the oil phase, the latex concentration, surface concentration of copolymer stabilizer, and solution pH. Nonpolar oils such as n-dodecane gave oil-in-water emulsions, and polar oils such as 1-undecanol produced water-in-oil emulsions. In both cases, these emulsions proved to be stimulus-responsive: demulsification occurred rapidly on adjusting the solution pH. Oils of intermediate polarity such as methyl myristate or cineole led to emulsions that underwent transitional inversion on adjusting the solution pH. All emulsions were polydisperse and typically ranged from 40 to 400 microm diameter, as judged by optical microscopy and Malvern Mastersizer measurements. Critical point drying of the emulsion droplets, followed by scanning electron microscopy studies, confirmed that the latex particles were adsorbed as a single monolayer at the oil/water interface, as anticipated.

Journal Article↗

PubMed2004

Hyperlipidaemia is positively correlated with lymph node metastasis in men with early gastric cancer.

BACKGROUND: Although increased dietary fat or cholesterol has been reported to be a risk factor for the development of certain cancers, the effect of serum lipid levels on tumour metastasis is not clearly understood. METHODS: The association between lymph node metastasis and preoperative serum levels of total cholesterol (TC) and triglyceride (TG) as well as various pathological findings for tumours was examined in 353 patients with early gastric cancer who underwent gastrectomy with classical lymphadenectomy. RESULTS: The rate of lymph node metastasis was significantly higher in patients with early gastric cancer who had hypercholesterolaemia (TC 220 mg/dl or greater) or hypertriglyceridaemia (TG 150 mg/dl or greater). The tendency was more prominent in men, and multivariate analysis showed that hypertriglyceridaemia was an independent risk factor for nodal metastasis in men, in addition to pathological invasion to the submucosal layer or to lymphatic vessels. In contrast, neither hypercholesterolaemia nor hypertriglyceridaemia showed a significant association with nodal status in women with early gastric cancer. CONCLUSION: Raised serum lipid levels might favour the development of lymph node metastasis in men with early-stage gastric cancer. In patients with early gastric cancer serum lipid levels should be checked before operation, and the use of minimal local treatments must be considered carefully in male patients with hyperlipidaemia.

Adult↗

PubMed2004

Evaluation of developmental toxicity of beta-thujaplicin (hinokitiol) following oral administration during organogenesis in rats.

The objective of this study was to evaluate the developmental toxicity of beta-thujaplicin (TP) in rats. Pregnant rats were given TP by gastric intubation at 15, 45, or 135 mg/kg on days 6-15 of pregnancy. The maternal body weight gain during administration at 45 and 135 mg/kg and after administration at 136 mg/kg and adjusted weight gain at 45 and 135 mg/kg were significantly reduced. A significant decrease in food consumption during and after administration was found at 45 and 135 mg/kg. A significant increase in the incidence of postimplantation loss was found in pregnant rats given TP at 135 mg/kg. A significantly lower weight was found in female fetuses at 45 and 135 mg/kg and in male fetuses at 135 mg/kg. Although a significantly increased incidence of fetuses with skeletal variations and decreased degree of ossification were found at 135 mg/kg, no significant increase in external, skeletal and internal malformations was detected after administration of TP. The data demonstrated that TP had adverse effects on embryonic/fetal survival and growth only at maternal toxic doses. No adverse effects on morphological development were found in rats fetuses. Based on the significant decreases in maternal body weight gain and weight of female fetuses at 45 mg/kg and higher, it is concluded that the no-observed-adverse-effect levels (NOAELs) of TP for both dams and fetuses are considered to be 15 mg/kg in rats.

Abnormalities, Drug-Induced↗