Dietary curcuminoids prevent high-fat diet-induced lipid accumulation in rat liver and epididymal adipose tissue.

Curcumin and its structurally related compounds (curcuminoids), the phenolic yellowish pigments of turmeric, display antioxidative, anticarcinogenic and hypocholesterolemic activities. In this study, we investigated the effects of dietary supplemented curcuminoids [commercial grade curcumin: a mixture of curcumin (73.4%), demethoxycurcumin (16.1%) and bisdemethoxycurcumin (10.5%)] on lipid metabolism in rats. Male Sprague-Dawley rats were assigned to three diet groups (n = 6) and fed a moderately high-fat diet (15 g soybean oil/100 g diet) for 2 wk. One diet group did not receive supplements (CONT), while the others were supplemented with 0.2 g curcuminoids/100 g diet (CUR0.2) or 1.0 g curcuminoids/100 g diet (CUR1.0). Liver triacylglycerol and cholesterol concentrations were significantly lower in CUR1.0 rats than in CONT rats. Plasma triacylglycerols in the VLDL fraction were also lower in CUR1.0 rats than in CONT rats (P < 0.05). Hepatic acyl-CoA oxidase activity of both the CUR0.2 and CUR1.0 rats was significantly higher than that of CONT rats. Furthermore, epididymal adipose tissue weight was significantly reduced with curcuminoid intake in a dose-dependent manner. These results indicate that dietary curcuminoids have lipid-lowering potency in vivo, probably due to alterations in fatty acid metabolism.

Adenovirus-mediated transfer of p53 augments hyperthermia-induced apoptosis in U251 glioma cells.

PURPOSE: Hyperthermia kills glioma cells by inducing apoptosis and is thereby an effective therapeutic modality for the treatment of malignant gliomas. However, cells harboring mutated p53 are refractory to hyperthermia-induced apoptosis. In this study, we assessed whether or not adenovirus (Adv)-mediated transduction of p53 overrides this resistant mechanism. METHODS AND MATERIALS: We transduced the p53 wild-type tumor suppressor gene into U251 glioma cells harboring mutated p53 using Adv vectors in combination with hyperthermia (43, 44.5 degrees C), and evaluated the degree of cell death and apoptosis. RESULTS: The percentage of cells that had died, as measured by trypan blue staining, among U251 cells infected with the Adv for p53 (Adv-p53) and treated with hyperthermia, was significantly higher than the percentage of cells that had died among U251 cells infected with Adv-p53 and not treated with hyperthermia, or those infected with the control Adv for dE (Adv-dE) and treated with hyperthermia. The degree of apoptosis, measured at 24 h after treatment, in hyperthermia-treated U251 cells infected with Adv-p53 (43 degrees C, 73%; 44.5 degrees C, 92%) was much higher than that infected with Adv-p53 (41%), or that infected with control Adv-dE and treated with hyperthermia (43 degrees C, 1.3%; 44.5 degrees C, 19%). Treatment with combined hyperthermia and Adv-p53 infection induced cleavage of caspase-3 in U251 cells. CONCLUSION: These results indicate that Adv-mediated transduction of p53 would render glioma cells highly sensitive to hyperthermia.

Antioxidative effects of turmeric, rosemary and capsicum extracts on membrane phospholipid peroxidation and liver lipid metabolism in mice.

Phospholipid hydroperoxides (PLOOH) in the plasma, red blood cells (RBC) and liver of mice were measured after dietary supplementation for one week (1% w/w of diet) with a turmeric extract (curcuminoid), hexane extract of rosemary, and supercritical CO2-extracted capsicum pigment (supplemented with alpha-tocopherol to prevent fading). A lower PLOOH level was found in RBC of the spice extract-fed mice (65-74% of the non-supplemented control mice). The liver lipid peroxidizability induced with Fe2+/ascorbic acid was effectively suppressed by dietary supplementation with the turmeric and capsicum extracts to mice. While no difference in the plasma lipids was observed, the liver triacylglycerol concentration of the turmeric extract-fed mice was markedly reduced to one-half of the level in the control mice. These findings suggest that these spice extracts could act antioxidatively in vivo by food supplementation, and that the turmeric extract has the ability to prevent the deposition of triacylglycerols in the liver.

Application of antisense ribonucleic acid complementary to O6-methylguanine-deoxyribonucleic acid methyltransferase messenger ribonucleic acid for therapy of malignant gliomas.

OBJECTIVE: A derivative of chloroethylnitrosoureas, 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU), is a drug of choice for the chemotherapy of human malignant brain tumors. However, the cytocidal effect of ACNU is effectively repressed through repair of ACNU-mediated deoxyribonucleic acid lesions by O6-methylguanine-deoxyribonucleic acid methyltransferase (MGMT). Because a variety of human tumors, including brain tumors, contain high levels of MGMT activity, we investigated the effect of antisense ribonucleic acid (RNA) complementary to MGMT messenger RNA on ACNU resistance in tumor cells. METHODS: We established a stable ACNU-resistant clone, C6AR, from the rat glioma cell line C6 exposed to a stepwise increasing concentration of ACNU. We transfected a plasmid deoxyribonucleic acid-encoding antisense MGMT RNA under the control of the human metallothionein promoter into C6AR cells and determined the effect of the antisense RNA on ACNU resistance of tumor cells by a colony-forming efficiency assay. RESULTS: C6AR cells expressed abundant MGMT messenger RNA, although the transcription level of the MGMT gene in parental C6 cells was below the lower limits of detection under the same assay conditions. ACNU resistance of C6AR cells was significantly repressed by transfected gene-dependent antisense MGMT RNA expression that resulted in decreased survival of the tumor cells. CONCLUSION: ACNU resistance resulting from the expression of MGMT in rat glioma cells is significantly overcome by the expression of antisense MGMT RNA. This result suggests that the antisense MGMT RNA system might be a useful strategy for overcoming ACNU resistance in the treatment of intractable malignant gliomas.

Pharmacotherapeutic effects of toki-shakuyaku-san on leukorrhagia in young women.

Toki-shakuyaku-san is a traditional Chinese herbal prescriptions that is composed of 6 herbal plants, i.e., peony root, atractylodes lancea rhizome, alisma rhizome, hoelen, cnidium rhizome and Japanese angelica root. Administration with Toki-shakuyaku-san normalized irregular menstrual cycle, healed cervical pseudo-erosion and reduced leukorrhagia in young women who had insufficient luteal function.

[Central alveolar hypoventilation as a complication of massive intracerebellar hemorrhage: report of a case treated by diaphragm pacing].

The author reported a case of central alveolar hypoventilation (Ondine's curse) which was treated by diaphragm pacing. A 59-year-old man was admitted because of sudden deep coma and tetraparesis. Neurological examination on admission showed miotic pupils with absent light reaction, no oculocephalic reflex, no corneal reflex and tetraparesis. Glasgow scale was evaluated to be E-1 V-1, and M-3 with total of 5 points. Computed tomography confirmed a large hematoma in the cerebellum with ventricular rupture. Immediately, a suboccipital craniectomy was performed and the hematoma was evacuated. His neurological condition was improved gradually within a month after the operation. He responded to verbal orders and moved all his limbs against gravity. His respiration, however, was irregular with a pattern of so-called "cluster breathing" followed by prolonged apnea, that was more pronounced in night. He was suffered from hypoxic hypercapnea and recurrent pneumonia. Therefore, authors decided to employ diaphragm pacing for management of central alveolar hypoventilation. A diaphragm pacemaker (radiofrequency induction) was implanted. A cuff electrode was put around the right phrenic nerve in the right thorax, and the receiver installed subcutaneously in the right anterior chest. Postoperative respiratory study showed ventilation on pacing with satisfactory blood gas and he became able to move around using a wheel chair. In 1966 Glenn demonstrated a new technique to move the diaphragm paced by a receiver through the phrenic nerve, triggered by radio wave from external device.(ABSTRACT TRUNCATED AT 250 WORDS)