Non-contact determination of parasympathetic activation induced by a full stomach using microwave radar

In order to evaluate parasympathetic activation which causes driving errors, without placing any burden on the monitored individuals, we conducted a non-contact parasympathetic activation monitoring through the back of a chair using a compact 24-GHz microwave-radar. We measured the high-frequency (HF, 0.15–0.4 Hz) power spectrum of heart rate variability (HRV) which reflects parasympathetic activation, induced by a full stomach. All participants had a large all-you-can-eat meal with beverages for lunch within 20 min. Before and after the large meals for durations of 10 min, the non-contact measurement was conducted for seven healthy male volunteers (mean age: 23 ± 1-year-old). In both non-contact (microwave radar) and contact (ECG as a reference) measurement, HF shows similar variations before and after large meal. Large meal significantly (p < 0.05) increased non-contact-derived HF from 1,026 ± 510 to 1,893 ± 613 ms² (922 ± 628 to 1,861 ± 940 ms², p < 0.05). This technique allows parasympathetic activation monitoring for safety precautions.     

Cell type-specific, topoisomerase II-dependent inhibition of hypoxia-inducible factor-1alpha protein accumulation by NSC 644221.

PURPOSE: The discovery and development of small-molecule inhibitors of hypoxia-inducible factor-1 (HIF-1) is an attractive, yet challenging, strategy for the development of new cancer therapeutic agents. Here, we report on a novel tricyclic carboxamide inhibitor of HIF-1alpha, NSC 644221. EXPERIMENTAL DESIGN: We investigated the mechanism by which the novel compound NSC 644221 inhibited HIF-1alpha. RESULTS: NSC 644221 inhibited HIF-1-dependent, but not constitutive, luciferase expression in U251-HRE and U251-pGL3 cells, respectively, as well as hypoxic induction of vascular endothelial growth factor mRNA expression in U251 cells. HIF-1alpha, but not HIF-1beta, protein expression was inhibited by NSC 644221 in a time- and dose-dependent fashion. Interestingly, NSC 644221 was unable to inhibit HIF-1alpha protein accumulation in the presence of the proteasome inhibitors MG132 or PS341, yet it did not directly affect the degradation of HIF-1alpha as shown by experiments done in the presence of cyclohexamide or pulse-chase labeling using [35S]methionine. In contrast, NSC 644221 decreased the rate of HIF-1alpha translation relative to untreated controls. Silencing of topoisomerase (topo) IIalpha, but not topo I, by specific small interfering RNA completely blocked the ability of NSC 644221 to inhibit HIF-1alpha. The data presented show that topo II is required for the inhibition of HIF-1alpha by NSC 644221. Furthermore, although NSC 644221 induced p21 expression, gammaH2A.X, and G2-M arrest in the majority of cell lines tested, it only inhibited HIF-1alpha in a distinct subset of cells, raising the possibility of pathway-specific "resistance" to HIF-1 inhibition in cancer cells. CONCLUSIONS: NSC 644221 is a novel HIF-1 inhibitor with potential for use as both an analytic tool and a therapeutic agent. Our data provide a strong rationale for pursuing the preclinical development of NSC 644221 as a HIF-1 inhibitor.     

Screening for primary angle closure in Mongolia: a randomised controlled trial to determine whether screening and prophylactic treatment will reduce the incidence of primary angle closure glaucoma in an east Asian population

AIM: To describe the methods used and initial results of a prospective study designed to determine whether screening and prophylactic treatment will reduce the incidence of primary angle closure glaucoma (PACG) in Mongolia. METHODS: A total of 4725 individuals aged 50 years and above were recruited to the study and randomised to intervention or control groups. All subjects had non-mydriatic optic disc examination. The intervention arm had measurement of anterior chamber depth (ACD) by A-scan ultrasound and intraocular pressure (IOP) with Tonopen. Gonioscopy was performed on test positive cases (ACD <2.53 mm or IOP >or=24 mm Hg either eye). Those with occludable angles were offered laser iridotomy. Primary outcome will be incidence of PACG at 5 year follow up. RESULTS: Glaucoma was diagnosed in 128 (2.7%) subjects. Of the remaining 4597, 2293 were randomised to intervention. Intervention as allocated was received by 2280 (99.4%) individuals. 160 (23.4%) of 685 test positive cases had occludable angles, of which 156 were treated with iridotomy. CONCLUSIONS: This trial is a further step in determining whether screening and prophylactic treatment for primary angle closure in east Asian populations will reduce the incidence of glaucoma.     

Individual differences on immunostimulatory activity of raw and black garlic extract in human primary immune cells

The immunostimulatory activities of garlic extract using a cell line or animal models have been reported; however, no previous studies have evaluated individual differences in regards to the immunostimulatory activities. The immunostimulatory activities such as cell proliferation, tumor necrosis factor (TNF-α) and nitric oxides (NO) production of raw garlic and black garlic extracts on individual primary lymphocytes or macrophages isolated from the blood of 21 volunteers were evaluated. The antioxidant and anticancer effects of raw garlic and black garlic ethanol extract was measured to determine the optimum conditions for extraction. The 70% ethanol black garlic extracts at 70°C for 12?h (70% BGE) showed the strongest antioxidant and anticancer activities. Immunostimulatory activities of garlic extracts extracted under optimal condition on primary immune cells obtained from 21 volunteers were analyzed. Results showed that the cell proliferation, TNF-α and NO production of primary immune cells treated with 70% raw garlic extract (70% RGE) were significantly different; however, little difference was observed for the 70% BGE treatment. BGE showed stronger immunostimulatory activities than RGE. These results indicate that the immunostimulatory activities of RGE and BGE can be strongly correlated with the antioxidant and anticancer activities. Determination of immunostimulatory activities of different types of garlic using immune cells isolated from volunteers was dependent on the individual constituents due to changes in the composition of garlic during processing. Individual primary immune cells might be used as important tools to determine individual differences in all food ingredients for the development of personalized immunostimulatory active foods.     

Schedule-dependent inhibition of hypoxia-inducible factor-1alpha protein accumulation, angiogenesis, and tumor growth by topotecan in U251-HRE glioblastoma xenografts

We have previously shown that topotecan, a topoisomerase I poison, inhibits hypoxia-inducible factor (HIF)-1alpha protein accumulation by a DNA damage-independent mechanism. Here, we report that daily administration of topotecan inhibits HIF-1alpha protein expression in U251-HRE glioblastoma xenografts. Concomitant with HIF-1alpha inhibition, topotecan caused a significant tumor growth inhibition associated with a marked decrease of angiogenesis and expression of HIF-1 target genes in tumor tissue. These results provide a compelling rationale for testing topotecan in clinical trials to target HIF-1 in cancer patients.