3H-Spiroperidol (Spiperone) Binding Sites in Rat Adrenal Glomerulosa Cells

3H-spiperone, a dopaminergic antagonist, was used to study binding sites in rat adrenal glomerulosa membrane. The equilibrium dissociation constant (Kd) and binding capacity for 3H-spiperone binding were 2.2 nM and 268 fmol/mg protein, respectively. Determination of the Kd by kinetic studies provided a value of 2.6 nM, which corresponded closely to the Kd estimated by equilibrium studies. In a study of the subcellular distribution of dopamine receptors in adrenal glomerulosa cells, 3H-spiperone binding activity at the interface of density 1.14 to 1.16 accounted for 60% of the total activity in all fractions. These dopaminergic binding sites in adrenal glomerulosa cells may modulate aldosterone secretion induced by antidopaminergic agents

Theracurmin inhibits intestinal polyp development in Apc‐mutant mice by inhibiting inflammation‐related factors

Colorectal cancer (CRC) is the second leading cause of cancer death worldwide. Therefore, it is important to establish useful methods for preventing CRC. One prevention strategy involves the use of cancer chemopreventive agents, including functional foods. We focused on the well‐known cancer chemopreventive agent curcumin, which is derived from turmeric. However, curcumin has the disadvantage of being poorly soluble in water due to its high hydrophobicity. To overcome this problem, the formation of submicron particles with surface controlled technology has been applied to curcumin to give it remarkably improved water solubility, and this derived compound is named Theracurmin. To date, the preventive effects of Theracurmin on hereditary intestinal carcinogenesis have not been elucidated. Thus, we used Apc‐mutant mice, a model of familial adenomatous polyposis, to evaluate the effects of Theracurmin. First, we showed that treatment with 10‐20 µM Theracurmin for 24 hours reduced nuclear factor‐κB (NF‐κB) transcriptional activity in human colon cancer DLD‐1 and HCT116 cells. However, treatment with curcumin mixed in water did not change the NF‐κB promoter transcriptional activity. As NF‐κB is a regulator of inflammation‐related factors, we next investigated the downstream targets of NF‐κB: monocyte chemoattractant protein‐1 (MCP‐1) and interleukin (IL)‐6. We found that treatment with 500 ppm Theracurmin for 8 weeks inhibited intestinal polyp development and suppressed MCP‐1 and IL‐6 mRNA expression levels in the parts of the intestine with polyps. This report provides a proof of concept for the ongoing Theracurmin human trial (J‐CAP‐C study)

Aclarubicin in the treatment of elderly patients with acute nonlymphocytic leukemia.

Thirteen previously untreated patients aged 70 and above with acute nonlymphocytic leukemia were treated with aclarubicin (ACR) alone. Among 10 cases (3, acute myelocytic leukemia; 4, acute myelomonocytic leukemia; 2, acute monocytic leukemia; and one, acute erythroleukemia) in which an evaluation was possible, 5 cases (3, acute myelomonocytic leukemia; and 2, acute monocytic leukemia) obtained complete remission (CR). The CR rate was 83% in 6 patients with acute myelomonocytic leukemia or acute monocytic leukemia. The median CR duration and survival was 7.5 and 10 + months, respectively. Although side effects of the drug on digestive system such as nausea, vomiting and anorexia were observed in all patients, they were controllable by conventional treatments. The results suggest that ACR is effective for the clinical management of elderly patients with acute nonlymphocytic leukemia, especially those with acute myelomonocytic leukemia or acute monocytic leukemia.</p

Effects of Non-Essential Amino Acids on Knee Joint Conditions in Adults: A Randomised, Double-Blind, Placebo-Controlled Trial

Joint problems impair performance during exercise and daily activities and influence quality of life. The present study aimed to examine the effects of a combination of six non-essential amino acids (6AA) on joint conditions in an adult population. A total of 50 participants aged between 20 and 64 years with joint discomfort but no diagnosed joint disorder were randomly and blindly assigned to a control or 6AA group. The 6AA group took 12 g of the non-essential amino acid formulation orally (4 g three times a day) and the control group took equivalent doses of a placebo. Each group maintained the daily dose for 12 weeks. Primary outcome measures were evaluated with the visual analogue scale (VAS), the Japanese Knee Osteoarthritis Measure (JKOM), and the Japanese Orthopaedic Association score (JOA). These tests were taken before the experiment began at 4 weeks and 12 weeks after the intervention. The results of the VAS indicated that 6AA improved joint pain, discomfort, and stiffness both during a resting state and during normal activity. Participants’ scores on the JKOM and JOA also showed significant improvements in the group that had taken the 6AA supplement. These results demonstrate that 6AA improves symptoms of joint problems, such as pain, discomfort, stiffness, and difficulty in performing daily activities after 4 weeks of daily consumption

Colonic Hydrogen Generated from Fructan Diffuses into the Abdominal Cavity and Reduces Adipose mRNA Abundance of Cytokines in Rats.

Hydrogen (H2) protects against inflammation-induced oxidative stress. Nondigestible saccharides (NDSs) enhance colonic H2 production. We examined whether colonic H2 transfers to tissues in the abdominal cavity and whether it affects expression of proinflammatory cytokines. In Expts. 1 and 2, rats were fed diets containing fructooligosaccharides [FOSs; 25 (Expt. 1) and 50 g/kg (Expts. 1 and 2)] for 7 and 14 d, respectively. The no-FOS diet was used as the control diet. At the end of the experiment, H2 excretion and the portal H2 concentration were significantly greater in the FOS group than in the control group. In the FOS group, the arterial H2 concentration was no more than 1.5% of the portal H2 concentration (P = 0.03). The H2 concentration in abdominal cavity tissues, especially adipose tissue, in the FOS group was 5.6- to 43-fold of that in the control group (P < 0.05). The H2 content in the abdominal cavity in the FOS group was 11-fold of that in the control group (P < 0.05). In Expt. 3, rats were fed a high-fat diet containing FOS and inulin (50 g/kg) for 28 d. The area under the curve for H2 excretion between 0 and 28 d and portal and adipose H2 concentrations were significantly higher in the FOS and inulin groups than in the high-fat control group. Adipose mRNA abundance of nuclear factor kappa-light-chain-enhancer of activated B cells 1 was lower in the FOS group than in the control group (P = 0.02) and those of interleukin-6 and chemokine (C-C motif) ligand 2 tended to be lower (P < 0.11). Colonic H2 generated from NDS diffuses to the abdominal cavity before transferring to abdominal tissues. Reduced cytokine expression by FOS feeding might be dependent on increased colonic H2. Colonic H2 may have important implications in the suppressive effect on metabolic syndrome via oxidative stress.Hydrogen (H2) protects against inflammation-induced oxidative stress. Nondigestible saccharides (NDSs) enhance colonic H2 production. We examined whether colonic H2 transfers to tissues in the abdominal cavity and whether it affects expression of proinflammatory cytokines. In Expts. 1 and 2, rats were fed diets containing fructooligosaccharides [FOSs; 25 (Expt. 1) and 50 g/kg (Expts. 1 and 2)] for 7 and 14 d, respectively. The no-FOS diet was used as the control diet. At the end of the experiment, H2 excretion and the portal H2 concentration were significantly greater in the FOS group than in the control group. In the FOS group, the arterial H2 concentration was no more than 1.5% of the portal H2 concentration (P = 0.03). The H2 concentration in abdominal cavity tissues, especially adipose tissue, in the FOS group was 5.6- to 43-fold of that in the control group (P < 0.05). The H2 content in the abdominal cavity in the FOS group was 11-fold of that in the control group (P < 0.05). In Expt. 3, rats were fed a high-fat diet containing FOS and inulin (50 g/kg) for 28 d. The area under the curve for H2 excretion between 0 and 28 d and portal and adipose H2 concentrations were significantly higher in the FOS and inulin groups than in the high-fat control group. Adipose mRNA abundance of nuclear factor kappa-light-chain-enhancer of activated B cells 1 was lower in the FOS group than in the control group (P = 0.02) and those of interleukin-6 and chemokine (C-C motif) ligand 2 tended to be lower (P < 0.11). Colonic H2 generated from NDS diffuses to the abdominal cavity before transferring to abdominal tissues. Reduced cytokine expression by FOS feeding might be dependent on increased colonic H2. Colonic H2 may have important implications in the suppressive effect on metabolic syndrome via oxidative stress