[Small duct primary sclerosing cholangitis diagnosed after fever and liver disorder: a case report].

A woman in her 10s presented to our hospital with persistent fever and liver disorder and was admitted. It was considered that her fever was due to infectious, hematological, and collagen diseases; however, these diseases were excluded. Upper and lower gastrointestinal endoscopy revealed gastritis and indicated inflammatory bowel disease involvement. Neither bile duct stricture nor bile duct wall thickening was observed in the imaging. Thus, liver biopsy was performed due to worsening liver disorder. A diagnosis of small duct primary sclerosing cholangitis was made based on the findings of edematous enlargement of the portal tracts, neutrophilic infiltration, and destruction of the interlobular bile ducts. Furthermore, liver biopsy is helpful in diagnosing unknown liver disorders, even if no abnormality in the bile duct is observed on imaging.

Chronic Active Epstein-Barr Virus Infection Indistinguishable from Autoimmune Hepatitis: A Case Report.

Chronic active Epstein-Barr virus (CAEBV) infection is a rare disease, mainly affecting children, typically characterized by persistent infectious mononucleosis (IM)-like symptoms. We describe an adult case of CAEBV without IM-like symptoms, which was indistinguishable from autoimmune hepatitis (AIH). A 60-year-old woman with liver damage was diagnosed with AIH (International Diagnostic Score: 16 points). She had been treated with prednisolone for three years; however, her transaminases had never normalized. She was admitted for another liver biopsy due to repeated high fevers and worsening of her liver damage over two months. Her EBV-DNA copy number was 2.9 × 104 copies/µg DNA, and EBV-encoded small RNA1-positive lymphocytic infiltration was observed in both the present and previously collected (three years ago) liver tissue samples. This case implies that hepatic involvement in a CAEBV without IM-like symptoms is difficult to distinguish from AIH and may be misdiagnosed. In some steroid resistant AIH cases, evaluating for CAEBV may be valuable.

A vein-viewing application enabled detecting abdominal wall varices related to the presence of non-treated gastroesophageal varices: a cross-sectional study.

BACKGROUND: Gastroesophageal varices (GOV) are a life-threatening complication in chronic liver disease. A method for non-invasively predicting GOV is crucial for management. This study aimed to determine whether a vein-viewing application can detect abdominal wall varices (AWV) and elucidate the relationship between AWV and GOV. METHODS: One-hundred patients with chronic liver diseases were prospectively enrolled. All the patients underwent esophagogastroduodenoscopy within three months of the enrollment. Unmanipulated images (UI) and vein-weighted images (VWI) were taken for assessing AWV by a vein-viewing application on iPhone. Two doctors independently evaluated both image types. We defined the grading of both UI and AWV as grade 0 (non-detectable), grade 1 (slightly detectable), and grade 2 (distinct). RESULTS: The causes of liver diseases among the 71 men and 29 women (median age, 70.5 yr) included Hepatitis B (n = 19), Hepatitis C (n = 21), alcoholism (n = 33), primary biliary cholangitis (n = 3), autoimmune hepatitis (n = 4) and others (n = 20). GOV was indicated in 60 patients, and half of them had not been treated previously (non-treated). VWI could significantly visualize AWV than UI (72% vs. 24%, p = 0.0005). The presence of cirrhosis (chronic hepatitis vs. cirrhosis = 64.6% vs. 91.4%, p = 0.004) and GOV (52.3% vs. 74.3%, p = 0.032) were significantly higher in the VWI-AWV grade 2 group. Multivariate analysis demonstrated that VWI-AWV grade 2 was an independent factor related to the presence of non-treated GOV [OR = 3.05 (1.24-7.53), p = 0.016]. CONCLUSIONS: The vein-viewing application non-invasively detected AWV related to the presence of cirrhosis and GOV, and VWI-AWV grade 2 was an independent factor related to the presence of non-treated GOV.

Newly Invented Micellized Vitamin K2 Recovered Prolonged Prothrombin Time under Obstructive Jaundice in Rats with Bile Duct Ligation.

In cholestatic liver diseases, coagulopathy is induced by malabsorption of vitamin K. Supplementation of vitamin K has previously been shown to prevent coagulopathy. In this study, we tested the efficacy of a newly invented micellized vitamin K2 (m-vitK2) in treating coagulopathy, using a rat bile duct ligation (BDL) model. Experiment 1: m-vitK2 (0.3 mg/kg) or m-vitK2 (0.3 mg/kg) mixed with taurocholic acid (TA) (10 mg/body) was orally administrated every day for 7 d from the fourth day after BDL (n=6 for each). Experiment 2: To evaluate absorption, m-vitK2 (0.3 mg/kg) with or without TA (10 mg/body) was orally administered on the fourth day after BDL and compared with the untreated control BDL (n=2 for each). These data were compared with sham-operated (n=6) and untreated control BDL rats (n=6). The m-vitK2 recovered prothrombin time (PT) in Experiment 1 (control 42.7±5.7 s vs. m-vitK2 24.0±9.3 s, p<0.05). Experiment 2 demonstrated that the mixture of m-vitK2 and TA enhanced absorption compared to m-vitK2 alone. Moreover, in Experiment 1, m-vitK2 mixed with TA completely recovered PT (control 42.7±5.7 s vs. m-vitK2+TA 14.9±1.2 s, p<0.01). Micelle sizes decreased with the m-vitK2 and TA treatment (m-vitK2 86.3±5.6 nm vs. m-vitK2+TA 71.9±4.7 nm, p<0.05). Orally administered, newly invented m-vitK2 recovered coagulopathy even under obstructive jaundice. TA decreased the mean micelle size and improved m-vitK2 absorption.

Erratum for Ikeda et al., "Pemafibrate Dramatically Ameliorated the Values of Liver Function Tests and Fibrosis Marker in Patients with Non-Alcoholic Fatty Liver Disease".

[This corrects the article DOI: 10.33160/yam.2020.08.009.].

Preablation three-dimensional ultrasonography can predict therapeutic effect and local tumor progression after radiofrequency ablation for hepatocellular carcinoma.

PURPOSE: To assess the agreement between ablative margin (AM) predicted by preablation three-dimensional ultrasonography (3D-US) and AM measured on postablation computed tomography (CT)/magnetic resonance (MR) images. METHODS: Sixty patients with 73 hepatocellular carcinoma nodules were enrolled. 3D-US data were collected immediately after puncture by the electrode before ablation. The maximum distance from the electrode to the edge of the tumor in the plane perpendicular to the electrode (C-plane) was defined as "a" and the diameter of the ablation zone as "b". We classified predicted AM into "0.5b - a" ≥0 mm as AM(+) or <0 mm as AM(-), and "0.5b - a" ≥3 mm or <3 mm. RESULTS: Forty-eight nodules (66 %) were visualized in the C-plane. There was an agreement between the predicted and measured AMs for 39 (81 %) of the 48 nodules. Local tumor progression was observed in 3 (7%) of 43 nodules with predicted AM(+) and in 2 (40 %) of 5 nodules with predicted AM(-) but was not observed in any of 21 nodules with predicted AM ≥ 3 mm. The local tumor progression rate was significantly lower for nodules with predicted AM(+) compared with predicted AM(-)(p = 0.03), and for nodules with predicted AM ≥ 3 mm compared with predicted AM < 3 mm (p = 0.04). Local progression was detected in 2 (4.7 %) of 42 nodules with a sufficient AM (≥0 mm) on postablation CT/MR images and in 5 (83.3 %) of 6 nodules with an insufficient AM (<0 mm); the difference in progression rate was significant (p = 0.0008). CONCLUSION: 3D-US allows prediction of the AM before radiofrequency ablation.

Pemafibrate Dramatically Ameliorated the Values of Liver Function Tests and Fibrosis Marker in Patients with Non-Alcoholic Fatty Liver Disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease related to metabolic syndrome, which can progress to liver cirrhosis. Standard medication has not been established. Pemafibrate is a selective peroxisome proliferator-activated receptor (PPAR) α modulator. We retrospectively evaluated the efficacy of pemafibrate in patients with NAFLD. METHODS: We retrospectively enrolled 17 patients (ten men, seven women; median age, 63 years; range, 27-81 years). They were all proven to have fatty liver through imaging and had little or no history of drinking (ethanol consumption of < 20 g/day for women and < 30 g/day for men). They were administered pemafibrate from October 2018 to June 2020. RESULTS: After administration, serum triglyceride (TG) tended to be decreased (300.5 ± 22.5 to 239.5 ± 34.3 mg/dL, P = 0.06). Serum high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL) cholesterol levels did not change. ALT was significantly decreased (-47.4%) for six months (57.5 ± 8.8 to 30.3 ± 5.8 U/L, P < 0.01). The values of serum GGT significantly decreased (-48.7%) for sixth months (63.9 ± 10.3 to 32.8 ± 6.6 U/L, P < 0.01). Aspartate aminotransferase (AST) to platelet ratio (APRI), a fibrosis marker, also was significantly decreased in the sixth month (0.7 ± 0.1 to 0.4 ± 0.1, P < 0.05). Body mass index (BMI) and hemoglobin A1c (HbA1c) showed no significant change. CONCLUSION: Pemafibrate dramatically ameliorated the values of liver function tests and APRI in patients with NAFLD.

Protective Effects of Ipragliflozin, a Sodium-glucose Cotransporter 2 Inhibitor, on a Non-alcoholic Steatohepatitis Mouse Model.

BACKGROUND: The options for the treatment of nonalcoholic steatohepatitis (NASH) are limited. We examined the effects of ipragliflozin, a sodium-glucose cotransporter 2 inhibitor, on the fatty liver Shionogi (FLS)-ob/ob mice, a non-alcoholic steatohepatitis mouse model. METHODS: FLS-ob/ob male mice were treated with vehicle (n = 10) and ipragliflozin (n = 8). Serum metabolic markers, histopathology of the liver, hepatic cholesterol and triglyceride levels and hepatic mRNA levels related to fibrosis, lipid metabolism and endoplasmic reticulum (ER) stress were compared between the two groups. RESULTS: The body weight and hepatic cholesterol and triglyceride levels were significantly decreased in the ipragliflozin group compared with the control group. Hepatic steatosis and fibrosis were significantly ameliorated by the treatment with ipragliflozin. Hepatic infiltration of macrophage, expression levels of 8-hydroxy-2-deoxyguanosine (8-OHdG) and hepatic mRNA levels of ER stress markers were not significantly modulated by the treatment with ipragliflozin. CONCLUSION: Ipragliflozin can be a therapeutic option for patients with NASH. The precise mechanisms of action need to be clarified in future studies.

Gene Expression Analysis of the Activating Factor 3/Nuclear Protein 1 Axis in a Non-alcoholic Steatohepatitis Mouse Model.

BACKGROUND: Nonalcoholic fatty liver disease/steatohepatitis (NAFLD/NASH) is a chronic liver disease related to metabolic syndrome that can progress to liver cirrhosis. The involvement of the endoplasmic reticulum (ER) stress response in NAFLD progression and the roles played by activating factor 3 (ATF3) and the downstream nuclear protein 1 (NUPR1) are poorly understood. The aim of this study was to determine the gene expression profiles around the ATF3/NUPR1 axis in relation to the development of NAFLD using novel mouse models. METHODS: Fatty liver Shionogi (FLS) mice (n = 12) as a NAFLD model and FLS-ob/ob mice (n = 28) as a NASH model were fed a standard diet. The FLS mice were sacrificed at 24 weeks of age as a control, whereas the FLS-ob/ob mice were sacrificed at 24, 36, and 48 weeks of age. Hepatic steatosis, inflammation, and fibrosis were evaluated by biochemical, histological, and gene expression analyses. The expression levels of the ER-stress related genes Jun proto-oncogene (C-jun), Atf3, Nupr1, and C/EBP homologous protein (Chop) were measured in liver tissue. Apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. RESULTS: Control mice demonstrated hepatic steatosis alone without apparent fibrosis. On the other hand, FLS-ob/ob mice showed severe steatohepatitis at both 24 and 36 weeks of age and severe fibrosis at both 36 and 48 weeks of age. The expression levels of Atf3, Nupr-1, and C-jun significantly increased from 24 to 48 weeks of age in FLS-ob/ob mice compared with control mice. The expression level of Chop was already high in FLS mice and maintained similar levels in FLS-ob/ob mice; the expression level was consistent with the percentage of TUNEL-positive cells. CONCLUSION: The ATF3/NUPR1 axis plays a pivotal role in NASH progression in association with C-jun and Chop and appears to induce apoptosis from early steatosis in the NASH model mice.

Correction: Effects of resource-dependent cannibalism on population size distribution and individual life history in a case-bearing caddisfly.

[This corrects the article DOI: 10.1371/journal.pone.0191925.].

Effects of resource-dependent cannibalism on population size distribution and individual life history in a case-bearing caddisfly.

Resource availability often determines the intensity of cannibalism, which has a considerable effect on population size distribution and individual life history. Larvae of the caddisfly Psilotreta kisoensis build portable cases from sedimentary sands and often display cannibalism. For this species, the availability of preferable case material is a critical factor that affects larval fitness, and material is locally variable depending on the underlying geology. In this study, we investigated how sand quality as a case material determines cannibalism frequency among larvae and, in turn, how the differential cannibalism frequency affects the body-size distribution and voltinism. Rearing experiments within a cohort revealed that a bimodal size distribution developed regardless of material quality. However, as the preferable material became abundant, the proportion of larger to smaller individuals increased. Consecutive experiments suggested that smaller larvae were more frequently cannibalized by larger ones and excluded from the population when preferable smooth material was abundant. This frequent cannibalism resulted in a bimodal size distribution with a significantly higher proportion of larger compared to smaller individuals. The size-dependent cannibalism was significantly suppressed when the larvae were raised in an environment with a scarcity of the preferable case material. This is probably because larvae cannot enjoy the benefit of rapid growth by cannibalism due to the difficulties in enlarging their case. At low cannibalism the growth of smaller individuals was stunted, and this was probably due to risk of cannibalism by larger individuals. This growth reduction in small individuals led to a bimodal size-distribution but with a lower proportion of larger to smaller individuals compared to at high cannibalism. A field study in two streams showed a similar size distribution of larvae as was found in the rearing experiment. The bimodal ratio has consequences for life history, since a size-bimodal population causes a cohort splitting: only larvae that were fully grown at 1 year had a univoltine life cycle, whereas larvae with a stunted growth continued their larval life for another year (semivoltine). This study suggests that availability of preferable case building material is an important factor that affects cannibalism, which in turn affects larval population size structure and cohort splitting.

Differential Responses of Two Ecologically Similar Case-Bearing Caddisfly Species to a Fish Chemical Cue: Implications for a Coexistence Mechanism.

The mechanisms for the coexistence of multiple species occupying the same ecological niche are often puzzling. Predator effects on competitively superior species is one possible mechanism. In this study, we tested whether the presence of size-selective predators (fishes) acts as a mechanism for the coexistence of two species of case-bearing caddisfly larvae, Perissoneura paradoxa and Psilotreta kisoensis (Odontoceridae, Trichoptera). The larvae of these two species have similar ecological and life history traits except their body size, and they have been found to coexist only in habitats shared with predatory fishes. Experiments on intra and interspecific competition revealed that the larger Pe. paradoxa always outcompeted the smaller Ps. kisoensis in the absence of predatory fishes, suggesting that Pe. paradoxa performed intra-guild predation on Ps. kisoensis. We also conducted experiments to examine how strongly each of these species responded in terms of case repair with/without a predator chemical cue after their cases were partly dismantled. Perissoneura paradoxa exhibited a stronger case repair response in the presence of a predator chemical cue than that exhibited by Ps. kisoensis, suggesting that Pe. paradoxa is more vulnerable to fish predation, probably because their body size is in the preferred prey range of fishes. We suggest that the presence of predators works in the favor of smaller, subordinate species through size-selective predator effects, enabling these two competitive species to coexist in the same habitat.

Compliance and problems with the surveillance program for HCC diagnosis.

We conducted a multicenter retrospective study for evaluating the background of and diagnostic opportunity for 651 patients with primary hepatocellular carcinoma (HCC). The etiologies were hepatitis B virus (HBV) in 20.0% of patients, hepatitis C virus (HCV) in 36.3%, and non-B non-C (NBNC) in 43.5%. The characteristics of non-alcoholic NBNC HCC patients included low frequency of liver cirrhosis and high frequency of life style-related diseases. The mean diameter of HCC was approximately 4cm. Most patients were diagnosed using ultrasonography and dynamic computed tomography (CT). However, 18.6% of patients were diagnosed using conventional contrast-enhanced CT. Compliance with the surveillance program for HCC diagnosis was 35.4% in HBV carriers and 49.2% in HCV carriers. The main causes of deviation from the program included undiagnosed HBV and HCV carriers, non-compliance with the surveillance program by physicians, and no medical care for HBV and HCV carriers. For an early diagnosis of HCC, it is essential to improve the diagnoses of HBV and HCV carriers, promote the follow-ups of HBV and HCV carriers in hospitals, re-educate physicians, and identify the risk factors of NBNC HCC.

Integrated trophic position decreases in more diverse communities of stream food webs.

The relationship between biodiversity and ecosystem functioning is an important theme in environmental sciences. We propose a new index for configuration of the biomass pyramid in an ecosystem, named integrated trophic position (iTP). The iTP is defined as a sum of trophic positions (i.e. the average number of steps involved in biomass transfer) of all the animals in a food web integrated by their individual biomass. The observed iTP for stream macroinvertebrates ranged from 2.39 to 2.79 and was negatively correlated with the species density and the Shannon-Wiener diversity index of the local community. The results indicate a lower efficiency of biomass transfer in more diverse communities, which may be explained by the variance in edibility hypothesis and/or the trophic omnivory hypothesis. We found a negative effect of biodiversity on ecosystem functioning.

Falsely Elevated Serum Vitamin B12 Levels Were Associated with the Severity and Prognosis of Chronic Viral Liver Disease.

BACKGROUND: Vitamin B12 is stored primarily in the liver, and highly elevated serum vitamin B12 levels occur in acute hepatitis and severe alcoholic liver disease. We evaluated the relationship between vitamin B12 levels and liver disease severity and long term prognosis in patients with chronic viral hepatitis and cirrhosis. METHODS: We enrolled 90 patients (57 men, 33 women) with chronic viral hepatitis and cirrhosis who admitted to our hospital as a prospective cohort study. Overall, 37 patients had chronic hepatitis and 53 had cirrhosis (Child-Pugh A 33, B 13, and C 7); 57 patients had primary liver cancer. Serum vitamin B12 concentration and holotranscobalamin (holoTC) II (active form of vitamin B12) were determined and followed prospectively for at least 5 years. RESULTS: Mean total serum vitamin B12 concentration was significantly higher in Child-Pugh C (1308 ± 599 pg/mL) compared to those with chronic hepatitis (655 ± 551 pg/mL), Child-Pugh A (784 ± 559 pg/mL), and Child-Pugh B (660 ± 464 pg/mL) (P = 0.036) Presence of primary liver cancer also influenced serum vitamin B12 levels [657 (167-2956) vs. 432 (189-2956); P = 0.015]. Patients were divided into quartiles by vitamin B12 level. Patients without primary liver cancer in quartile 4 (≥ 880 pg/mL) demonstrated significantly poorer prognosis than those in quartiles 1-3 (< 880 pg/mL) (P = 0.023). The percentage of holohaptocorrin (holoHC) [(total vitamin B12 - holoTC II) × 100] was significantly higher in Child-Pugh B and C 86 (80-87)% than chronic hepatitis and Child-Pugh A 77 (31-89)% (P = 0.006) Multivariate analysis indicated serum vitamin B12 levels (HR = 1.001, P = 0.029) as a prognostic factor. CONCLUSION: Falsely elevated serum vitamin B12 levels mainly composed of increased holoHC were associated with severity (Child-Pugh C and primary liver cancer) and prognosis in chronic viral liver disease.

Serum Procalcitonin in Patients with Acute Liver Failure.

BACKGROUND: Procalcitonin (PCT) is a known diagnostic marker of bacterial infection. There are no previous reports of PCT concerning acute liver failure (ALF). We evaluated the clinical value of serum PCT levels in patients with ALF. METHODS: Forty-four patients with acute hepatitis (19 men and 25 women; median age, 40 years; range, 20-79 years) were retrospectively enrolled from January 2001 and June 2015. PCT levels were measured by saved serum samples obtained within 3 days after admission. ALF was defined as prothrombin time (PT) < 40% regardless of hepatic encephalopathy. RESULTS: Serum PCT levels were significantly higher in the patients with ALF (n = 16) than in those with non-ALF (n = 28) [0.25 (0.13-2.66) ng/mL vs. 0.165 (0.03-1.08), P = 0.00967]. Creatinine, total bilirubin, and direct bilirubin were positively correlated, and PT was negatively correlated with PCT. Receiver operating characteristic curve analysis showed an area under the curve of 0.74 for detecting ALF. With a PCT cut-off value of 0.5 ng/mL, the presence of ALF could be demonstrated with low sensitivity (37.5%) and high specificity (96.5%) with high positive (85.7%) and negative (72.9%) predictive value. Multivariate analysis showed that PCT was an independent factor associated with the presence of ALF. The cumulative survival rate was also significantly lower in patients with PCT ≥ 0.5 ng/mL (P = 0.0314), but it was not an independent prognostic factor. CONCLUSION: Serum PCT level was significantly higher in patients with ALF.

Antifibrotic effects of ambrisentan, an endothelin-A receptor antagonist, in a non-alcoholic steatohepatitis mouse model.

AIM: To examine the effects of the endothelin type A receptor antagonist ambrisentan on hepatic steatosis and fibrosis in a steatohepatitis mouse model. METHODS: Fatty liver shionogi (FLS) FLS-ob/ob mice (male, 12 wk old) received ambrisentan (2.5 mg/kg orally per day; n = 8) or water as a control (n = 5) for 4 wk. Factors were compared between the two groups, including steatosis, fibrosis, inflammation, and endothelin-related gene expression in the liver. RESULTS: In the ambrisentan group, hepatic hydroxyproline content was significantly lower than in the control group (18.0 µg/g ± 6.1 µg/g vs 33.9 µg/g ± 13.5 µg/g liver, respectively, P = 0.014). Hepatic fibrosis estimated by Sirius red staining and areas positive for α-smooth muscle actin, indicative of activated hepatic stellate cells, were also significantly lower in the ambrisentan group (0.46% ± 0.18% vs 1.11% ± 0.28%, respectively, P = 0.0003; and 0.12% ± 0.08% vs 0.25% ± 0.11%, respectively, P = 0.047). Moreover, hepatic RNA expression levels of procollagen-1 and tissue inhibitor of metalloproteinase-1 (TIMP-1) were significantly lower by 60% and 45%, respectively, in the ambrisentan group. Inflammation, steatosis, and endothelin-related mRNA expression in the liver were not significantly different between the groups. CONCLUSION: Ambrisentan attenuated the progression of hepatic fibrosis by inhibiting hepatic stellate cell activation and reducing procollagen-1 and TIMP-1 gene expression. Ambrisentan did not affect inflammation or steatosis.

[Corrigendum] Preventive effect of caffeine and curcumin on hepato-carcinogenesis in diethylnitrosamine-induced rats.

Following the publication of this article, an interested reader drew to our attention an anomaly associated with the presentation of Figs. 3 and 4; essentially, there was the direct duplication of a panel between Fig. 3B, upper left­hand panel (the G1-10W data) and Fig. 4B, also the upper left-hand panel (the G1-14W data). In the upper-left panels of Fig. 3B and 4B, we wanted to demon-strate microscopic features of the control liver at 10 weeks and 14 weeks, respectively. After having re-examined our original data, we note that we inadvertently duplicated the picture of the control liver at 14 weeks in the upper­left panel of Fig. 3B. A corrected version of Fig. 3 is presented below, in which the G1-10W data in Fig. 3B are now correctly shown. Since G1-10W and G1-14W are control images of the liver, exhibiting a normal appearance, this error did not affect the findings in the study. We sincerely apologize for this mistake, and thank the reader of our article who drew this matter to our attention. Furthermore, we regret any inconvenience this mistake has caused. [the original article was published in the International Journal of Oncology 40: 1779-1788, 2012; DOI: 10.3892/ijo.2012.1343].

Preventive Effect of Geraniol on Diethylnitrosamine-Induced Hepatocarcinogenesis in Rats.

BACKGROUND: Geraniol is a plant-derived phytochemical possessing anti-cancer action. The anti-carcinogenic effect of geraniol was investigated in the diethylnitrosamine (DEN)-induced hepatocarcinogenic rat model. METHODS: Male Wistar rats were intraperitoneally injected with 300 µL of phosphate-buffered saline (PBS) (G1; n = 4) or DEN (100 mg/kg body weight) dissolved in PBS (G2; n = 8) every 2 weeks on experimental weeks 2, 4 and 6. The rats were treated with a low concentration (0.07%) of geraniol (G3; n = 9) and high concentration (0.35%) of geraniol (G4; n = 7) for 12 weeks. To evaluate the effects of geraniol on the DEN-induced hepatocarcinogenesis, we compared the relative liver weight, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) levels and expression levels of proliferating cell nuclear antigen (PCNA) and glutathione S transferase-P (GST-P) by immunohistochemical analyses among each group. RESULTS: Relative liver weight was significantly higher in G2 than in G1 (P < 0.01). Both serum AST and ALT levels were significantly higher in G2 than in G3 and in G4 (P < 0.05). Serum ALP levels did not show a significant difference among each group. Percentages of both PCNA- and GST-P- positive area were significantly decreased in G3 and in G4 compared to in G2 (P < 0.001, respectively), suggesting anti-hepatocarcinogenic effects of geraniol. CONCLUSION: Geraniol is a promising compound useful for suppression of hepatocellular carcinoma. The mechanisms of action are required to be clarified in the future intensive study.

Left Renal Cortical Thickness Measured by Ultrasound Can Predict Early Progression of Chronic Kidney Disease.

AIMS: The kidney becomes atrophic in advanced chronic kidney disease, and renal size and parenchymal volume correlate with renal function. However, alterations in renal parenchymal volume have not been adequately studied in terms of the renal cortex and medulla. We investigated the relationship between the changes in the renal cortex and medulla and renal function. METHODS: Renal ultrasound (US) parameters including renal length, parenchymal thickness, cortical thickness and medullary thickness were assessed in 176 subjects, who were categorized into 4 groups based on the estimated glomerular filtration rate (ml/min/1.73 m2): group 1, ≥ 90; group 2, ≥ 60 but < 90; group 3, ≥ 30 but < 60; and group 4, < 30. Renal US parameters in both kidneys were compared among the 4 groups. RESULTS: We found stepwise associations in renal length, cortical thickness and parenchymal thickness with decreased renal function. Medullary thickness showed no changes among groups 1-3. Multiple linear regression analysis including sex, age and renal US parameters showed that only renal length was an independent predictor of renal function. When analyzed in groups 1-3, cortical thickness was the strongest associated parameter. Lower cortical left/right ratio (left cortical thickness/right cortical thickness) showed a stepwise association with a decrease in renal function. CONCLUSION: Renal length and cortical thickness measured by US were correlated with renal function. In particular, left cortical thickness could help to detect early changes in renal function.