The effects of postprandial glucose and insulin levels on postprandial endothelial function in subjects with normal glucose tolerance

Background

Type 2 diabetes mellitus (T2DM) patients are at increased risk of developing cardiovascular events. Unfortunately traditional risk assessment scores, including the Framingham Risk Score (FRS), have only modest accuracy in cardiovascular risk prediction in these patients.

Methods

We sought to determine the prognostic values of different non-invasive markers of atherosclerosis, including brachial artery endothelial function, carotid artery atheroma burden, ankle-brachial index, arterial stiffness and computed tomography coronary artery calcium score (CACS) in 151 T2DM Chinese patients that were identified low-intermediate risk from the FRS recalibrated for Chinese (<20% risk in 10?years). Patients were prospectively followed-up and presence of atherosclerotic events documented for a mean duration of 61?±?16?months.

Results

A total of 17 atherosclerotic events in 16 patients (11%) occurred during the follow-up period. The mean FRS of the study population was 5.0?±?4.6% and area under curve (AUC) from receiver operating characteristic curve analysis for prediction of atherosclerotic events was 0.59?±?0.07 (P?=?0.21). Among different vascular assessments, CACS?>?40 had the best prognostic value (AUC 0.81?±?0.06, P?<?0.01) and offered significantly better accuracy in prediction compared with FRS (P?=?0.038 for AUC comparisons). Combination of FRS with CACS or other surrogate vascular markers did not further improve the prognostic values over CACS alone. Multivariate Cox regression analysis identified CACS?>?40 as an independent predictor of atherosclerotic events in T2DM patients (Hazards Ratio 27.11, 95% Confidence Interval 3.36-218.81, P?=?0.002).

Conclusions

In T2DM patients identified as low-intermediate risk by the FRS, a raised CACS?>?40 was an independent predictor for atherosclerotic events.     

Structure-antibacterial activity relationship for 9-O,9'-O-demethyl (+)-virgatusin

The relationship between the antibacterial activity and structure of 9-O,9'-O-demethyl (+)-virgatusin (Virg 3) was examined. The conversion of hydroxy groups on the 9 and 9' positions to amino groups increased the activity. It was found that the 3'-methoxy group was more important for higher activity than the 4'-methoxy group on the 7'-phenyl group, and that the 3,4-methylenedioxy group on the 7-phenyl group was necessary for activity.     

Cellular redox state protects acetaldehyde-induced alteration in cardiomyocyte function by modifying Ca2+ release from sarcoplasmic reticulum

Recent studies indicate that low concentrations of acetaldehyde may function as the primary factor in alcoholic cardiomyopathy by disrupting Ca(2+) handling or disturbing cardiac excitation-contraction coupling. By producing reactive oxygen species, acetaldehyde shifts the intracellular redox potential from a reduced state to an oxidized state. We examined whether the redox state modulates acetaldehyde-induced Ca(2+) handling by measuring Ca(2+) transient using a confocal imaging system and single ryanodine receptor type 2 (RyR2) channel activity using the planar lipid bilayer method. Ca(2+) transient was recorded in isolated rat ventricular myocytes with incorporated fluo 3. Intracellular reduced glutathione level was estimated using the monochlorobimane fluorometric method. Acetaldehyde at 1 and 10 microM increased Ca(2+) transient amplitude and its relative area in intact myocytes, but acetaldehyde at 100 microM decreased Ca(2+) transient area significantly. Acetaldehyde showed a minor effect on Ca(2+) transient in myocytes in which intracellular reduced glutathione content had been decreased against challenge of diethylmaleate to a level comparable to that induced by exposure to approximately 50 microM acetaldehyde. Channel activity of the RyR2 with slightly reduced cytoplasmic redox potential from near resting state (-213 mV) or without redox fixation was augmented by all concentrations of acetaldehyde (1-100 microM) used here. However, acetaldehyde failed to activate the RyR2 channel, when the cytoplasmic redox potential was kept with a reduced (-230 mV) or markedly oxidized (-180 mV) state. This result was similar to effects of acetaldehyde on Ca(2+) transient in diethylmaleate-treated myocytes, probably being in oxidized redox potential. The present results suggest that acetaldehyde acts as an RyR2 activator to disturb cardiac muscle function, and redox potential protects the heart from acetaldehyde-induced alterations in myocytes.     

Angiotensin II and tumor necrosis factor-alpha synergistically promote monocyte chemoattractant protein-1 expression: roles of NF-kappaB, p38, and reactive oxygen species

We examined whether ANG II and TNF-alpha cooperatively induce vascular inflammation using the expression of monocyte chemoattractant protein (MCP)-1 as a marker of vascular inflammation. ANG II and TNF-alpha stimulated MCP-1 expression in a synergistic manner in vascular smooth muscle cells. ANG II-induced MCP-1 expression was potently inhibited to a nonstimulated basal level by blockade of the p38-dependent pathway but only partially inhibited by blockade of the NF-kappaB-dependent pathway. In contrast, TNF-alpha-induced MCP-1 expression was potently suppressed by blockade of NF-kappaB activation but only modestly suppressed by blockade of p38 activation. ANG II- and TNF-alpha-induced activation of NF-kappaB- and p38-dependent pathways was partially inhibited by pharmacological inhibitors of ROS production. Furthermore, ANG II- and TNF-alpha-stimulated MCP-1 expression was partially suppressed by ROS inhibitors. We also examined whether endogenous ANG II and TNF-alpha cooperatively promote vascular inflammation in vivo using a wire injury model of the rat femoral artery. Blockade of both ANG II and TNF-alpha further suppressed neointimal formation, macrophage infiltration, and MCP-1 expression in an additive manner compared with blockade of ANG II or TNF-alpha alone. These results suggested that ANG II and TNF-alpha synergistically stimulate MCP-1 expression via the utilization of distinct intracellular signaling pathways (p38- and NFkappaB-dependent pathways) and that these pathways are activated in ROS-dependent and -independent manners. These results also suggest that ANG II and TNF-alpha cooperatively stimulate vascular inflammation in vivo as well as in vitro.     

Nematocyst composition of the cubomedusan Chiropsalmus quadrigatuschanges with growth

The nematocysts of Chiropsalmus quadrigatus (Cubozoa; Cubomedusa; Chirodropidae) were examined to determine if their composition changes with an increase in body size. Fixed tentacles of specimens collected in Okinawa, Japan, were homogenized and their nematocysts were observed under a differential interference contrast microscope. Six nematocyst types were observed in medusae of all sizes microbasic mastigophores (MM), large and small trirhopaloids (lTR and sTR), holotrichous isorhizas (HI), ellipsoidal isorhizas (eI), and ovoid isorhizas (oI). Two other nematocysts, large ovoid isorhizas (loI) and microbasic euryteles (ME), were observed only in small individuals. There was also marked difference in proportion of tentacular nematocysts between small and large individuals. HI was the dominant type in small specimens, while MM and eI were predominant in large specimens. Nematocyst composition in the bell and pedalia also differed between small and large individuals. Bells of small medusae contained oI and sTR, while only oI were observed in most large individuals. The pedalia of small medusae had clusters of MM, ME, sTR, and oI. Such single clusters on pedalium bases were characteristic of small individuals. The pedalia of large individuals contained scattered oI. Tentacles of medusae are used for prey capture, so the changes in the major type of nematocysts in tentacles may reflect changes in prey type.     

Use of indigenous ecological knowledge of the Maasai pastoralists for assessing rangeland biodiversity in Tanzania

This paper incorporates the indigenous ecological knowledge (IEK) of the Maasai pastoralists and ecological methods to assess effects of grazing and cropping on rangeland biodiversity at macro‐ and micro‐landscape scales in northern Tanzania. The joint surveys with pastoralists identified indicator plant species and their associations with micro‐landscapes and livestock grazing suitability (i.e. for cattle and small ruminant grazing), while traditional calf‐pasture reserves (alalili pl. alalilia) were evaluated for preservation of rangeland biodiversity. The macro‐landscapes comprising the cool high plateau (osupuko pl. isipuki) and montane forest highland (endim) were included in the survey. At micro‐landscape scales, the osupuko was classified into uplands (orkung'u), slopes (andamata) and dry valley bottomlands (ayarata). The micro‐landscapes were assessed in terms of herbaceous plant species and woody species richness and risks of soil erosion. Biodiversity varied at both the macro‐ and micro‐landscape scales and in accordance with the land‐use types. Greater plant species diversity and less erosion risks were found in the pastoral landscapes than in the agro‐pastoral landscapes. The calf‐grazing pastures had greater herbaceous species richness than the non‐calf pastures, which in turn had more woody species. The study concludes that the indigenous systems of landscape classification provides a valuable basis for assessing rangeland biodiversity, which ecologists should incorporate into ecological surveys of the rangelands in East Africa in the future.     

Isotopic composition and morphology of living Globorotalia scitula: a new proxy of sub-intermediate ocean carbonate chemistry?

Abundance, isotopic composition and morphological imprints of the planktonic foraminifera Globorotalia scitula (Brady) were closely examined for possible use as a novel reconstruction tool of chemical environments in sub-intermediate depth seawater in the past. Based on the MOCNES plankton tow observation of dwelling depths of G. scitula and the isotopic compositions together with hydrochemistry data, the empirical relations between isotopic disequilibria in carbon (Δδ¹³C=δ¹³C_{G. scitula}−δ¹³C_DIC) and oxygen (Δδ¹⁸O=δ¹⁸O_{G. scitula}−δ¹⁸O_w) isotopes in the carbonate tests and the seawater δ¹⁸O and δ¹³C of dissolved inorganic carbon (DIC), respectively, are introduced. The morphological information such as pore density and porosity is also examined for significant relations to carbonate chemistry. Shell porosity is strongly correlated saturation state of calcite. The dissolution of living G. scitula tests may promote the observed isotopic differences as well as the increases in porosity. Δδ¹⁸O of G. scitula is found effectively to be linear function of both water temperature and calcite saturation state (Ω), and thereby temperature equation for G. scitula is provided, while Δδ¹³C of G. scitula is a linear function of only calcite saturation state.The equation was validated by using Globorotalia scitula collected by a sediment trap in intermediate water depths. Satisfactory agreements were found between observed and calculated Δδ¹⁸O from the empirical equations based on temperature and hydrochemistry data at sediment trap deployment site, indicating that the equation may be useful in paleo-environmental reconstruction of sub-intermediate water. The sediment trap observation further suggests that the abundance of G. scitula does not necessarily correspond to surface water productivity and to POC flux, but instead, it correlates well with the supply of fine organic matter, which appears to be a result of water convection. Thus, G. scitula may be an unambiguous and excellent paleo-environmental recorder for carbonate chemistry and for fine organic matter transport to the depths, if isotopic and morphological observations are combined.     

A simple method for production of arachidonic acid byMortierella alpina

Summary A filamentous fungus,Mortierella alpina was incubated aerobically on a medium made from potato paste and dextrose at 20 °C for 20 days. The yield of arachidonic acid reached 11.8 g/kg medium, which is more than 10 times higher than that by any other method reported previously. The highest content of the acid was 67.4% of the total fatty acids.     

Lanthanum-Induced Mucosal Alterations in the Stomach (Lanthanum Gastropathy): a Comparative Study Using an Animal Model

Lanthanum (La) carbonate (LC) is one of the most potent phosphate binders that prevents the elevation of serum phosphate levels in patients with end-stage renal diseases undergoing dialysis. LC binds strongly to dietary phosphate and forms insoluble complexes that pass through the gastrointestinal tract. La deposition in patients treated with LC is a recently documented finding particularly observed in gastric mucosa. We herein describe the detailed gastric mucosal lesions in 45 LC-treated patients and address the potential underlying pathologic mechanism using oral LC administration in rats. Microscopically, La deposition, as shown by subepithelial collections of plump eosinophilic histiocytes or small foreign body granulomas containing coarse granular or amorphous inclusion bodies, was found in the gastric mucosa of 44 (97.8%) of the 45 dialysis patients in the study cohort, which was most frequently associated with foveolar hyperplasia (37.8%). Using oral administration of rats with 1000 mg/day LC for 2 or more weeks, La deposition was consistently detectable in the gastric mucosa but not in other organs examined. In addition, various histologic alterations such as glandular atrophy, stromal fibrosis, proliferation of mucous neck cells, intestinal metaplasia, squamous cell papilloma, erosion, and ulcer were demonstrated in the rat model. Thus, orally administered LC can induce mucosal injury, designated here as La gastropathy, which may alter the local environment and result in La deposition in the gastric mucosa, thereby potentially inducing abnormal cell proliferation or neoplastic lesions.