Nonalcoholic fatty liver disease is associated with coronary artery calcification

Nonalcoholic fatty liver disease (NAFLD) is related to risk factors of coronary artery disease, such as dyslipidemia, diabetes, and metabolic syndrome, which are closely linked with visceral adiposity. The aim of this study was to investigate whether NAFLD was associated with coronary artery calcification (CAC), which is used as a surrogate marker for coronary atherosclerosis independent of computed tomography (CT)-measured visceral adiposity. Out of 5,648 subjects who visited one of our health screening centers between 2003 and 2008, we enrolled 4,023 subjects (mean age, 56.9 ± 9.4 years; 60.7% males) without known liver disease or a history of ischemic heart disease. CAC score was evaluated using the Agatston method. On univariate analysis, the presence of CAC (score >0) was significantly associated with age, sex, body mass index, aspartate aminotransferase, alanine aminotransferase, high-density lipoprotein cholesterol, triglycerides, and increased risk of diabetes, hypertension, smoking, and NAFLD. Increasing CAC scores (0, <10, 10-100, ≥ 100) were associated with higher prevalence of NAFLD (odds ratio [OR], 1.84; 95% confidence interval [CI], 1.61-2.10; P<0.001). Multivariable ordinal regression analysis was adjusted for traditional risk factors, and CT-measured visceral adipose tissue area in a subgroup of subjects showed that the increased CAC scores were significantly associated with the presence of NAFLD (OR, 1.28, 95% CI, 1.04-1.59; P = 0.023) independent of visceral adiposity. CONCLUSION: Patients with NAFLD are at increased risk for coronary atherosclerosis independent of classical coronary risk factors, including visceral adiposity. These data suggest that NAFLD might be an independent risk factor for coronary artery disease.     

A comparison of vitamin D activity in paired non-malignant and malignant human breast tissues

Links between a low vitamin D status and an increased risk of breast cancer have been observed in epidemiological studies. These links have been investigated in human tissue homogenates and cultured cell lines. We have used non-malignant, malignant and normal reduction mammoplasty breast tissues to investigate the biological and metabolic consequences of the application of vitamin D to intact ex vivo human breast tissue. Tissues were exposed to 1α,25(OH)(2)D(3) (1,25D; active metabolite) and 25(OH)D (25D; pre-metabolite). Changes in mRNA expression and protein expression after vitamin D exposure were analysed. Results indicate that while responses in normal and non-malignant breast tissues are similar between individuals, different tumour tissues are highly variable with regards to their gene expression and biological response. Collectively, malignant breast tissue responds well to active 1,25D, but not to the inactive pre-metabolite 25D. This may have consequences for the recommendation of vitamin D supplementation in breast cancer patients.     

Glutamatergic activities in neonatal rat spinal cord heterogeneously regulate single-fiber splanchnic nerve discharge

Kynurenic acid (KYN) is a metabolite of tryptophan and is involved in various neurological disorders. Using whole-bundle nerve recording techniques, we previously observed that applications of KYN to block endogenous ionotropic glutamate receptor activities in neonatal rat spinal cords in vitro cause a reversible fluctuation of splanchnic sympathetic nerve discharge (SND). We hypothesized that the SND fluctuation was due to a heterogeneous single-fiber response. To detail individual fiber activities, we used the so-called ‘oligofiber recordings’. Spontaneous single-fiber activities were recorded from the collagenase-dissociated splanchnic nerve fascicles. Applications of KYN increased, decreased or did not change firing rates. The heterogeneous responses in spontaneous spiking activities were confirmed by applications of APV or CNQX, suggesting an effect mediated by endogenous NMDA- or non-NMDA receptor activities. In addition to changes in firing rates, apparent drug-induced changes in firing patterns were also observed in some fiber activities. Using the oligofiber recording techniques, we confirmed a differential role of endogenous ionotropic glutamate receptor activities in regulating sympathetic outflows from the spinal cord of neonatal rats. Fine-tuning of ionotropic glutamate receptor activities in the spinal cord may serve as a simple way for heterogeneous regulation of various sympathetic-targeting tissues.     

Are newborn rat-derived neural stem cells more sensitive to lead neurotoxicity?

Lead ion (Pb(2+) ) has been proven to be a neurotoxin due to its neurotoxicity on mammalian nervous system, especially for the developing brains of juveniles. However, many reported studies involved the negative effects of Pb(2+) on adult neural cells of humans or other mammals, only few of which have examined the effects of Pb(2+) on neural stem cells. The purpose of this study was to reveal the biological effects of Pb(2+) from lead acetate [Pb (CH 3 COO) 2 ] on viability, proliferation and differentiation of neural stem cells derived from the hippocampus of newborn rats aged 7 days and adult rats aged 90 days, respectively. This study was carried out in three parts. In the first part, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay (MTT viability assay) was used to detect the effects of Pb(2+) on the cell viability of passage 2 hippocampal neural stem cells after 48-hour exposure to 0-200 μM Pb(2+) . In the second part, 10 μM bromodeoxyuridine was added into the culture medium of passage 2 hippocampal neural stem cells after 48-hour exposure to 0- 200 μM Pb(2+) , followed by immunocytochemical staining with anti-bromodeoxyuridine to demonstrate the effects of Pb(2+) on cell proliferation. In the last part, passage 2 hippocampal neural stem cells were allowed to grow in the differentiation medium with 0-200 μM Pb(2+) . Immunocytochemical staining with anti-microtubule-associated protein 2 (a neuron marker), anti-glial fibrillary acidic protein (an astrocyte marker), and anti-RIP (an oligodendrocyte marker) was performed to detect the differentiation commitment of affected neural stem cells after 6 days. The data showed that Pb(2+) inhibited not only the viability and proliferation of rat hippocampal neural stem cells, but also their neuronal and oligodendrocyte differentiation in vitro. Moreover, increased activity of astrocyte differentiation of hippocampal neural stem cells from both newborn and adult rats was observed after exposure to high concentration of lead ion in vitro. These findings suggest that hippocampal neural stem cells of newborn rats were more sensitive than those from adult rats to Pb(2+) cytotoxicity.     

A Long-Term Survival Case of a Primary Malignant Intracerebral Nerve Sheath Tumor

We report a long-term survival case of a primary malignant intracerebral nerve sheath tumor (MINST) occurring in the right frontal lobe of a 13-year old boy. After the gross total resection (GTR), we have performed radiation therapy but it recurred 50 months after the surgery, so the second GTR was performed. Later, second tumor recurrence was found 4 months after the second surgery. Subsequently the third GTR, radiotherapy, and chemotherapy were carried out. At present, the patient has been remaining alive for 77 months without evidence of tumor recurrence. According to the previous reports, the primary MINST is very rare : there are only 8 cases reported. It is also a fast-growing, invasive tumor with poor outcome. This is the first case that had no recurrence for 50 months after the surgery among the reported cases that had been followed up for more than 5 years. It is supposed that a period of recurrence free survival after GTR and low mitotic activity are associated with the patient''s prognosis. A GTR followed by adjuvant radiation therapy and chemotherapy will be recommended to patients of MINST.