ABSTRACT
This study was to investigate the time course of changes to the antioxidant activity of milk from cows fed a trehalose‐supplemented diet, and to determine possible underlying mechanisms for ...observed changes. Six Holstein cows were used, and subjected to two experimental feeding periods consisting of a 1% trehalose‐supplemented diet for 10 days, followed by a basal diet only (no trehalose) for 10 days. 1,1‐Diphenyl‐2‐picrylhydrazyl (DPPH) radical scavenging activities in milk were gradually increased during the trehalose supplementation period and were highest at the end of the second period. However, trehalose was not detected in the milk and plasma of dairy cows fed a diet supplemented with trehalose for 10 days, indicating that the increased antioxidant activity in the milk of trehalose‐fed cows is not due to the direct transfer of trehalose to the milk. Plasma DPPH activities exhibited a similar time course to that seen for milk. Relative superoxide dismutase (SOD) activities in the rumen were higher 3 days after the end of trehalose supplementation than at any other time during the experimental periods. These results suggested that the improved antioxidant activity in milk and plasma of cows fed a trehalose‐supplemented diet was due to improved ruminal relative SOD activity.
19 in 19: A convergent total synthesis of 19‐hydroxysarmentogenin has been achieved, starting from three simple fragments. The desired product was synthesized in 19 steps from the AB ring system with ...the installation of six stereocenters and the formation of three CC bonds.
Cardenolides comprise an important family of natural steroids with a wide spectrum of biological activities. Although 19-hydroxysarmentogenin-3-O-α-l-rhamnoside (1a) and trewianin (1b) were ...structurally determined to have cardenolide structures, their biological activities have not been evaluated. The 6/6/6/5-membered ABCD-ring systems of both 1a and 1b are decorated by a β-oriented C17-butenolide, three C11,14,19-hydroxy groups, and a C3–O-l-rhamnoside moiety. On the other hand, 1a and 1b are epimeric at the C5-position. The structures of 1a and 1b were assembled from four simple fragments by applying a convergent and unified strategy. The AB-ring 10a/b and the D-ring 8/9 were tentatively tethered at the acetal moiety, and a subsequent stereoselective 6-exo radical reaction linked the two fragments. Next, an aldol reaction enabled simultaneous introduction of three new stereocenters of the C-rings of 5aa and 54. Attachment of the C17-butenolide led to aglycons 2a and 2b. l-Rhamnose was then installed into 2a and 2b to yield the targets 1a and 1b, respectively. Finally, the growth inhibitory activity of 1a, 1b, 2a, and 2b was assessed against MCF-7 human breast carcinoma cells. The significantly higher activities of 1a and 1b in comparison to 2a and 2b demonstrated the biological importance of the monosaccharide substructure.
Summary
Recent investigations have revealed the crucial role of von Willebrand factor (vWF) in platelet thrombus formation under flow conditions. The plasma concentrations of vWF were measured ...together with various hemodynamic and hemostatic parameters in 51 cases of acute myocardial infarction. In 10 randomly selected cases, the plasma concentrations and distribution of multimers vWF were serially determined after reperfusion therapy by percutaneous transluminal coronary angioplasty (PTCA). The vWF concentration at the onset of the acute myocardial infarction was significantly higher than in an age-matched control group (vWF AG: 18.7 ± 1.2 µg/ml vs. 10.3 ± 0.5 µg/ml, p = 8.43×10
−
(12), mean ± SE). Simultaneous determination of hemodynamic and hemostatic parameters revealed that the only two parameters that were significantly correlated with the patients` plasma vWF concentrations were their pulmonary capillary wedge pressure (PCWP) and heart rate, suggesting a relationship between hemodynamic changes induced by the onset of myocardial infarction and the vWF plasma concentrations. Serial determinations revealed that the vWF concentrations had not changed 1 h after reperfusion therapy, but that they significantly increased by 24 to 72 h. The distribution of the larger multimers of vWF also increased in the acute and subacute phase. The vWF concentration and multimer distribution normalized 14 days after the onset of the myocardial infarction. Our findings suggest that the vWF concentration increased in acute myocardial infarction patients, possibly in association with the hemodynamic deterioration that occurs in acute myocardial infarction.
Mutations in p53 gene exons 5–9 were studied in 44 non‐Hodgkin's lymphomas (NHL) consisting of 35 B‐NHL and 9 T‐NHL. Missense mutations were found in two diffuse large B‐cell lymphomas (DLBL) and one ...peripheral T‐cell lymphoma (unspecified). Double transversion missense and nonsense mutations were detected in one DLBL and one adult T‐cell leukemia/lymphoma. Silent mutations were found in two DLBL. Detailed histomorphological study showed that cases harboring p53 missense mutation with/without nonsense mutation tended to have larger nuclei with much more prominent nucleoli. Cytomorphometric analysis was therefore conducted by measuring the gross area of 100 lymphoma cell nuclei in 44 cases and the results were compared between lymphomas harboring p53 missense mutation with/without nonsense mutation and lymphomas harboring p53 silent mutation or lacking mutation. It was found that the lymphomas harboring p53 missense mutation with/without nonsense mutation had a highly significantly larger nuclear gross area than lymphomas with silent p53 mutation or lacking mutation (two‐sample t‐test, P < 0.00001; Exact Wilcoxon rank–sum test, P < 0.00001). This result suggests that p53 mutation might induce enlargement of neoplastic cell nuclei by some molecular mechanism.
Alkyl p-hydroxybenzoates such as isobutyl p-hydroxybenzoate (PHBA-iBu), butyl p-hydroxybenzoate (PHBA-nBu), isopropyl p-hydroxybenzoate (PHBA-iPr), propyl p-hydroxybenzoate (PHBA-nPr), ethyl ...p-hydroxybenzoate (PHBA-Et), and methyl p-hydroxybenzoate (PHBA-Me) are widely used as preservatives, stabilizers and antiseptics for medical supplies, cosmetics, foodstuffs etc. We determined the binding affinity of alkyl p-hydroxybenzoates to human estrogen receptor α (ERα) and β (ERβ) by non-RI receptor binding assays. PHBA-iBu had a high binding affinity for ERα (IC50 : 6.0×10-6M, the relative binding affinity (RBA) : 0.267) and ERβ (IC50 : 5.0×10-6M, RBA : 0.340). These IC50 values and RBA were almost the same as those of bisphenol A. The ranking of the estrogenic potency of alkyl p-hydroxybenzoates for both ERs is different; that is, PHBA-iBu>PHBA-nBu≒PHBA-iPr≒PHBA-nPr>PHBA-Et»PHBA-Me. Alkyl p-hydroxybenzoates bound with equal relative affinity to both ERα and β proteins. Alkyl p-hydroxybenzoate having a long alkyl side-chain showed a high affinity for ERα and β. These findings suggest that p-hydroxybenzoates may be endocrine disruptors.
We determined the binding affinities of some chemicals suspected of having endocrine-disrupting effects for androgen and/or estrogen receptors (ADR and ERα) by a non-radioisotope (RI) receptor ...binding assay. Tributyltin had the highest binding affinity for ADR with an IC50 of 7.6 × 10-6 M, but no affinity for ERα. Bisphenol A and 4-nonylphenol strongly bound to both ADR (IC50 values of 7.9 × 10-6 and 1.3 × 10-5 M, respectively) and ERα (IC50 values of 7.8 × 10-6 and 7.2 × 10-7 M, respectively). Octachlorostyrene had affinity for both receptors (IC50 for ADR, 2.7 × 10-5 M; and for ERα, 7.0 × 10-5 M). Although 4-octylphenol had a low affinity for ADR, it had a high affinity for ERα (IC50 of 9.8 × 10-6 M). Di-n-butyl phthalate, dicyclohexyl phthalate, and di(2-ethylhexyl)phthalate had low affinities for both ADR and ERα. The affinity of benzophenone was low for both receptors and n-butylbenzene had no affinity for either. Styrene trimers such as 1a-phenyl-4a-(1'-phenylethyl)tetralin (ST-2), 1a-phenyl-4e-(1'-phenylethyl)tetralin (ST-3), 1e-phenyl-4a-(1'-phenylethyl)tetralin (ST-4), and 1e-phenyl-4e-(1'-phenylethyl)tetralin (ST-5) had relatively high affinities, with IC50 values of 1.2-3.1 × 10-5 M. Styrene dimers showed lower affinities for ADR than the trimers. Some styrene oligomers have been previously reported to have binding affinities for ERα. These findings suggest that some chemicals possess binding affinities for ADR and ERα. It is necessary to examine the effects of substances on various hormone receptors to elucidate their endocrine-disrupting activities.
Purpose: We evaluated the surgical outcomes of non-renorrhaphy, mini-incision partial nephrectomy using a soft-coagulation system. Methods: Non-renorrhaphy mini-incision, partial nephrectomy was ...performed in 33 consecutive patients with small renal tumors between April 2016 and March 2019. After tumor resection, the soft-coagulation system was used to achieve hemostasis. A TachoSilⓇ or BOLHEALⓇ was used on the resection bed. The urinary collecting system was only sutured if it was opened. The surgical outcomes of each patient were retrospectively evaluated. Results: The patients’ mean age was 66.8 (36–83) years. The mean tumor size, operative time, and amount of intraoperative blood loss were 25.7 mm, 230 (140–357) min, and 292.2 (0–1332) mL, respectively. In 8 patients, the renal artery was clamped during the operation (mean warm ischemia time: 7.4 2–18 min). The urinary collecting system was sutured in 18 patients. Two complications of Clavien-Dindo grade III or worse occurred: postoperative bleeding, which required a blood transfusion, and complete atrioventricular block (A-V block), which required temporary cardiac pacing. The A-V block spontaneously resolved a few days after the operation, and cardiac pacing was not required thereafter. The surgical margins were negative in all cases, and no tumor recurrence was observed during the observational period (681.8 16–1126 days). The mean (range) rate of change in the estimated glomerular filtration rate at one year after surgery was −9.0% (−21.8–14.3%). Conclusion: Non-renorrhaphy partial nephrectomy using a soft-coagulation system is safe and produces acceptable oncological outcomes.
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