A single pretreatment with clofibric acid attenuates carbon tetrachloride-induced necrosis, but not steatosis, in rat liver.

The present study investigated whether a single pretreatment with clofibric acid suppresses liver injury in rats after CCl4 intoxication. Rats received a single pretreatment with clofibric acid (100 mg/kg, i.p.) 1 h prior to a CCl4 (1 mL/kg, p.o.) challenge, and were euthanized 24 h after the CCl4 administration. A single pretreatment with clofibric acid effectively suppressed increases in the serum aminotransferase activities and the severity of necrosis following the CCl4 challenge, whereas the pretreatment did not protect against CCl4-induced fatty liver. The clofibric acid pretreatment did not affect blood concentrations of CCl4 in the early stage after CCl4 dosing, or the level of the CCl4 reaching the liver 1 h after the CCl4 challenge. Moreover, the clofibric acid pretreatment did not affect the intensity of the covalent binding of the [14C]CCl4 metabolite to microsomal proteins and lipids. The clofibric acid pretreatment did not alter microsomal cytochrome P450 2E1 activity. Based on these results, we conclude that protection against CCl4-induced hepatocellular necrosis by a clofibric acid pretreatment does not require its repeated administration, and that a single and brief pre-exposure to clofibric acid prior to CCl4 dosing markedly suppresses necrosis without affecting the development and progression of steatosis.

Persistent reflux symptoms cause anxiety, depression, and mental health and sleep disorders in gastroesophageal reflux disease patients.

Some patients with gastroesophageal reflux disease experience persistent reflux symptoms despite proton pump inhibitor therapy. These symptoms reduce their health-related quality of life. Our aims were to evaluate the relationship between proton pump inhibitor efficacy and health-related quality of life and to evaluate predictive factors affecting treatment response in Japanese patients. Using the gastroesophageal reflux disease questionnaire, 145 gastroesophageal reflux disease patients undergoing proton pump inhibitor therapy were evaluated and classified as responders or partial-responders. Their health-related quality of life was then evaluated using the 8-item Short Form Health Survey, the Pittsburgh Sleep Quality Index, and the Hospital Anxiety and Depression Scale questionnaires. Sixty-nine patients (47.6%) were partial responders. These patients had significantly lower scores than responders in 5/8 subscales and in the mental health component summary of the 8-item Short Form Health Survey. Partial responders had significantly higher Pittsburgh Sleep Quality Index and Hospital Anxiety and Depression Scale scores, including anxiety and depression scores, than those of responders. Non-erosive reflux disease and double proton pump inhibitor doses were predictive factors of partial responders. Persistent reflux symptoms, despite proton pump inhibitor therapy, caused mental health disorders, sleep disorders, and psychological distress in Japanese gastroesophageal reflux disease patients.

Serum Levels of Albumin-ß-Amyloid Complex in Patients with Depression.

OBJECTIVE: Epidemiologic studies have demonstrated that suffering from depression may be a risk for Alzheimer disease (AD). As a possible biologic mechanism underlying the transition from depression to AD, it has been speculated that pathologic changes in ß-amyloid (Aß) metabolism are involved. To further understand the peripheral kinetics of amyloid in patients with depression, we investigated serum levels of free Aß and albumin-bound Aß. METHODS: Seventy inpatients with DSM-IV major depressive disorder (MDD) and 81 healthy individuals (the comparison group) were recruited between June 2012 and February 2014. Serum Aß40 and Aß42 levels, Aß40/Aß42 ratio, and serum levels of albumin-Aß complexes (SLAACs) were compared between the comparison group and patients in two age groups comprising younger (<60 years) and elderly (≥60 years) people. RESULTS: SLAAC was decreased in older patients with MDD but not in younger patients. The serum-free Aß40/Aß42 ratio was higher in patients with depression, even in younger patients. CONCLUSION: Our findings suggest that free Aß and the albumin-bound Aß reflect a different serum amyloid kinetics in depression. We speculate that serum-free Aß reflects changes in amyloid metabolism in patients suffering from depression and albumin-bound Aß reflects AD pathology and may be a potential predictor of the prodromal stage of AD.

Coexpression of organic anion-transporting polypeptides 1B3 and multidrug-resistant proteins 2 increases the enhancement effect of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid on hepatocellular carcinoma in magnetic resonance imaging.

AIM: We aimed to elucidate the relationship between the contrast enhancement effect of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) on magnetic resonance imaging (MRI) of hepatocellular carcinomas (HCC) and the expressions of hepatocyte transporters (i.e. organic anion-transporting polypeptide [OATP]1B3, multidrug-resistant protein [MRP]2 and MRP3) and to clarify the characteristics of HCC with an MRI high-contrast enhancement effect. METHODS: We retrospectively examined the relationship between the relative enhancement ratio (RER) of HCC, absolute and relative immunohistochemical staining scores of hepatocyte transporters, and histological differentiation of 22 HCC from 21 patients who had undergone preoperative Gd-EOB-DTPA-enhanced MRI. RESULTS: RER had a significant correlation with OATP1B3 expression according to the absolute and relative scores (P = 0.016 vs 0.0006). The RER of HCC with high OATP1B3 and MRP2 expression levels was higher than that of HCC with low OATP1B3 or MRP2 expression levels (P = 0.0003). The RER of HCC with higher OATP1B3 rates was greater than that of HCC with lower OATP1B3 rates (P = 0.0005). HCC histological differentiation showed a significant correlation with OATP1B3 expression and RER (P = 0.023 vs 0.0095). CONCLUSION: We found that coexpression of OATP1B3 and MRP2 influenced the high contrast enhancement of HCC on MRI.

Cerebral infarction in the left hemisphere compared with the right hemisphere increases the risk of aspiration pneumonia.

BACKGROUND: Aspiration pneumonia (AP) following cerebral infarction (CI) has been considered as one of its most serious complications. Nevertheless, there are no reports on the association between the type or location of CI and the incidence of AP. In addition, the association between dysphagia, which leads to aspiration, and the type or location of CI has never been investigated. Therefore we hypothesized that the laterality of CI affects the development of both dysphagia and AP. METHODS: We performed a retrospective cohort study to examine the association between the laterality of CI and the incidence of dysphagia and AP in 133 patients. RESULTS: AP was found in 6.0% of the group with left CI and in 0.8% of the group with right CI. A univariate logistic regression analysis revealed that left CI was a significant predictor of AP (hazard ratio, 8.81; 95% confidence interval, 1.07-72.59; p = 0.043). Left CI was a significant predictor of AP even after adjusting for age, sex, CI type, or presence of diabetes mellitus. In addition, although the frequency of dysphagia as the direct cause of AP did not differ according to laterality, the frequency of AP that ensued from dysphagia in the left CI group was greater than that observed in the right CI group. CONCLUSIONS: The group with left CI from the motor cortex to the internal capsule complicated by dysphagia exhibited a high risk of AP.

Reduced interhemispheric inhibition in mild cognitive impairment.

In mild cognitive impairment (MCI), the corpus callosum is known to be affected structurally. We evaluated callosal function by interhemispheric inhibition (IHI) using transcranial magnetic stimulation (TMS) in MCI patients. We investigated 12 amnestic MCI patients and 16 healthy age-matched control subjects. The IHI was studied with a paired-pulse TMS technique. The conditioning TMS was given over the right primary motor cortex (M1) and the test TMS over the left M1. Motor evoked potentials were recorded from the relaxed first dorsal interosseous muscle. We also studied other motor cortical circuit functions; short-latency afferent inhibition (SAI), short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF). Both the amount of IHI and SAI were significantly reduced in MCI patients as compared with control subjects, whereas SICI or ICF did not differ between them. The degree of IHI significantly correlated with neither the mini-mental state examination score nor the degree of SAI. Our results suggest that transcallosal connection between bilateral M1 is primarily involved in MCI, regardless of SAI dysfunction.

Two cases of dementias with motor neuron disease evaluated by Pittsburgh compound B-positron emission tomography.

We described the cases of two patients with dementia associated with motor neuron disease, the former with frontotemporal dementia (FTD) and the latter with Alzheimer's disease (AD), studied by the Pittsburgh compound B-positron emission tomography (PIB-PET). In the FTD patient, the PIB-PET revealed no amyloid accumulation in the cortex, whilst in the AD patient showed amyloid accumulation mainly in the frontal, parietal and lateral temporal lobes, besides the posterior cingulate gyrus and the precuneus. Thus, PIB-PET might facilitate the discrimination of different proteinopathies that cause neurodegenerative diseases, as dementia associated with ALS.

[A case of malignant tumor of the ascending part of duodenum with osteoclast-like giant cells].

Extraskeletal neoplasms with osteoclast-like giant cells are very rare. These tumors are most frequently reported in the breast and pancreas, and but rarely in other sites. We report a case of duodenal malignant tumor with osteoclast-like giant cells. The patient was a 76-year-old man who presented with vomiting. Computed tomography, magnetic resonance imaging, and gastrointestinal endoscopy revealed a giant tumor in the ascending part of duodenum. Biopsy specimens showed an undifferentiated malignant tumor with benign multinucleated giant cells. Immunohistochemical staining indicated that the tumor cells were reactive with vimentin, but not with epithelial markers or the other mesenchymal markers, and the multinucleated giant cells were reactive with CD68. Thus, we diagnosed a malignant tumor of the ascending part of duodenum with osteoclast-like giant cells. To the best of our knowledge, this is the first case of duodenal malignant tumor with osteoclast-like giant cells in Japan.

Primary squamous cell carcinoma associated with ovarian endometriosis: a case report and literature review.

Primary squamous cell carcinoma (SCC) associated with ovarian endometriosis is extremely rare and has a poor prognosis due to insufficient information on the optimal postoperative treatment. Here, we describe the response of this tumor to the administration of paclitaxel-carboplatin. A 45-year-old woman diagnosed with stage IIIc primary SCC of the ovary associated with endometriosis underwent optimal surgery followed by six courses of chemotherapy at 3-week intervals with paclitaxel and carboplatin. She tolerated the chemotherapy well and remained without evidence of disease during first-line chemotherapy. Two months later, she was readmitted with recurrence of a pelvic tumor. Although she was treated with chemotherapy (weekly paclitaxel and chemotherapeutic regimen of irinotecan + mitomycin C), the tumor was resistant to second-line and third-line chemotherapy and she died 15 months after surgery. Paclitaxel-carboplatin administration may be an effective treatment for primary SCC of the ovary but further studies are required to investigate it true efficacy in the treatment of this disease.

[A case of recurrent high-grade endometrial stromal sarcoma controlled by a combination of Ifosfamide, adriamycin, and cisplatin].

A 52-year-old woman with recurrent high-grade endometrial stromal sarcoma presented with left hypochondralgia. She had undergone total hysterectomy and bilateral salpingo-oophorectomy for the disease over the past six months, and preferred not to receive additional treatment. The following regimen of chemotherapy was given: each course consisted of ifosfamide (1,000 mg/m²) on days 1-5, adriamycin (60 mg/m²) on day 1, and cisplatin (15 mg/m²) on days 1-5. After 4 courses of the chemotherapy, the intraabdominal mass and multiple pulmonary nodules were reduced 45. 1% from the beginning. This case suggests that IAP might be effective chemotherapy for patients with high-grade endometrial stromal sarcoma.

[Efficacy and safety of S-1 plus docetaxel combination therapy for patients with advanced gastric cancer].

Recently, the significant efficacy of S-1 monotherapy or S-1 plus CDDP combination therapy has been reported. Docetaxel also has been reported to have favorable efficacy in gastric cancer. In addition, docetaxel can be administered in outpatient clinics. We investigated the efficacy and safety of S-1 plus docetaxel combination therapy for 35 naive patients with advanced gastric cancer. Docetaxel was administered at a dose of 40 mg/m(2) on day 1, and oral S-1 was administered at the full dose of 80 mg/m(2) twice daily for two weeks followed by one week rest. MST was 300 days, and the response rate was 42. 9%. Although leucopenia was observed in 31%, all patients were able to be continue this therapy. In conclusion, we considered that this S-1 plus docetaxel combination therapy was effective and safe in advanced gastric cancer, and convenient for outpatients.

Exaggerated placental site reaction following an elective abortion.

We encountered a case of exaggerated placental site (EPS) reaction following an elective abortion. EPS is a miscellaneous trophoblastic lesion. There have been few reports describing its clinical course, and the ultrasonogram and magnetic resonance imaging characteristics have not been reported previously. We present the ultrasonogram and magnetic resonance imaging findings of EPS together with histopathological observations.

Delivery by cesarean section after embolization for vaginal arteriovenous malformation.

Vaginal arteriovenous malformation (AVM) can lead to life-threatening complications on delivery. No deliveries have been reported after selective embolization for a vaginal AVM. A 34-year-old nulliparous woman was found to have an arterial pulsatile mass on the left vaginal wall. The findings of magnetic resonance imaging and magnetic resonance angiography were consistent with an AVM. Selective transcatheter embolization for the AVM was done and, afterwards, the patient was found to be pregnant. The prenatal course was uneventful and the patient underwent elective cesarean delivery at term. Vaginal AVM can be successfully treated with selective embolization, with a good obstetric outcome.

[Advanced ovarian cancer with Sister Mary Joseph's nodule--a case report].

A metastatic umbilical tumor,which we call Sister Mary Joseph's nodule (SMJN), is a sign of poor prognosis despite the primary site of malignant tumor. We describe here a patient with an advanced ovarian cancer and SMJN. A 51-year-old woman was referred to our department for evaluation of an umbilical tumor. As a result of systemic examination, the patient was diagnosed as stage IV ovarian cancer and rapidly underwent an optimal operation. Postoperatively, the chemotherapy for advanced ovarian tumors was begun (paclitaxel 180 mg/m(2) and carboplatin AUC 5, 10 courses every 3 weeks). The patient is well without signs of tumor recurrence or metastasis 10 months after the operation. Forty percent of all navel neoplasms are malignant tumors. It is important to perform a pathological examination of a navel neoplasm or a systemic examination as fast as possible.

Evaluation of effectiveness of prophylactic cerclage of a short cervix according to interleukin-8 in cervical mucus.

OBJECTIVE: This study was undertaken to compare rates of preterm delivery according to cervical mucus interleukin-8 (IL-8) among women who underwent cerclage because of a short cervix. STUDY DESIGN: This retrospective study included 16,508 patients whose cervical length and cervical mucus IL-8 concentrations were measured between 20 and 24 weeks. A short cervix was defined by a length of 25 mm or less, whereas IL-8 concentrations exceeding 360 ng/mL were considered high. Whether to perform cerclage was decided by clinicians without consideration of IL-8 concentrations. RESULTS: Among all subjects, a significantly smaller percentage of subjects avoided delivery before 37 weeks when cervical mucus IL-8 was elevated (P = .0302) or the cervix was short (P < .0001). Among patients with a short cervix, preterm delivery was more likely when cervical mucus IL-8 was elevated. Overall, risk of preterm delivery in patients with a short cervix did not differ between those undergoing and not undergoing cerclage. However, among patients with a short cervix, those with normal IL-8 concentrations in cervical mucus were less likely to have preterm delivery if they underwent cerclage (before 37 weeks, 33% vs 54.5%, P = .01; before 34 weeks, 4% vs 13.6%, P = .03). In contrast, when cervical mucus IL-8 was high, delivery before 37 weeks was more likely with than without cerclage (78% vs 54.1%, P = .03). CONCLUSION: With normal cervical mucus IL-8, cerclage treatment for cervical shortening may reduce the rate of preterm delivery, but with elevated cervical mucus IL-8 cerclage may be harmful.

Induction of hepatic peroxisome proliferation by 8-2 telomer alcohol feeding in mice: formation of perfluorooctanoic acid in the liver.

The effects of dietary administration of 1H, 1H, 2H, 2H-perfluorodecanol (8-2 telomer alcohol), on peroxisome proliferation in the liver of mice were studied. Male ddY mice were fed on a diet containing 8-2 telomer alcohol at concentrations of 0, 0.025, 0.05, 0.1, and 0.2% (w/w) for 7, 14, 21, and 28 days. These treatments with 8-2 telomer alcohol caused liver enlargement in a dose- and duration-dependent manner. Peroxisome proliferation in the liver of mice was confirmed by electron microscopic examination. Peroxisomal acyl-CoA oxidase was induced by these treatments with 8-2 telomer alcohol in a dose- and time-dependent manner. The concentration of perfluorooctanoic acid (PFOA) and related compounds were determined in the liver and plasma, since PFOA had been shown to be a possible metabolite of 8-2 telomer alcohol and to cause significant peroxisome proliferation in rodents. Five metabolites, namely, perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), 2H, 2H-perfluorodecanoic acid (8-2 telomer acid), and two unidentified metabolites, were present in the liver and serum. PFOA was confirmed to be accumulated in the liver of mice following the administration of 8-2 telomer alcohol in a dose- and duration-dependent manner. A linear relationship was observed between the concentration of PFOA and the activity of peroxisomal acyl-CoA oxidase in the liver of mice. These results strongly suggest that PFOA, but not 8-2 telomer alcohol itself, caused peroxisome proliferation in the liver. The present study provided evidence that 8-2 telomer alcohol is converted into PFOA in vivo and that the PFOA formed produces biological effects in the liver of mice.