Impact of overweight on left ventricular function in type 2 diabetes mellitus

Background

Coexistence of left ventricular (LV) longitudinal myocardial systolic dysfunction with LV diastolic dysfunction could lead to heart failure with preserved ejection fraction (HFpEF). Diabetes mellitus (DM) is known as a significant factor associated with HFpEF. Although the mechanisms of DM-related LV myocardial injury are complex, it has been postulated that overweight contributes to the development of LV myocardial injury in type 2 diabetes mellitus (T2DM) patients. However, the precise impact of overweight on LV longitudinal myocardial systolic function in T2DM patients remains unclear.

Methods

We studied 145 asymptomatic T2DM patients with preserved LV ejection fraction (LVEF) without coronary artery disease. LV longitudinal myocardial systolic function was assessed by global longitudinal strain (GLS), which was defined as the average peak strain of 18-segments obtained from standard apical views. Overweight was defined as body mass index (BMI) ≥ 25 kg/m². Ninety age-, gender- and LVEF-matched healthy volunteers served as controls.

Results

GLS of overweight T2DM patients was significantly lower than that of non-overweight patients (17.9 ± 2.4% vs. 18.9 ± 2.6%, p < 0.05), whereas GLS of both overweight and non-overweight controls was similar (19.8 ± 1.3% vs. 20.4 ± 2.1%, p = 0.38). Furthermore, multiple regression analysis revealed that for T2DM patients, BMI was the independent determinant parameters for GLS as well as LV mass index.

Conclusions

Overweight has a greater effect on LV longitudinal myocardial systolic function in T2DM patients than on that in non-DM healthy subjects. Our finding further suggests that the strict control of overweight in T2DM patients may be associated with prevention of the development of HFpEF.

     

Deoxyribonucleoside triphosphate imbalance. 5-Fluorodeoxyuridine-induced DNA double strand breaks in mouse FM3A cells and the mechanism of cell death

The mechanism of cytotoxic action of 5-fluorodeoxyuridine (FdUrd) in mouse FM3A cells was investigated. We observed the FdUrd-induced imbalance of intracellular deoxyribonucleoside triphosphate (dNTP) pools and subsequent double strand breaks in mature DNA, accompanied by cell death. The imbalance of dNTP pools was maximal at 8 h after 1 microM FdUrd treatment; a depletion of dTTP and dGTP pools and an increase in the dATP pool were observed. The addition of FdUrd in culture medium induced strand breaks in DNA, giving rise to a 90 S peak by alkaline sucrose gradient sedimentation. The loss of cell viability and colony-forming ability occurred at about 10 h. DNA double strand breaks as measured by the neutral elution method were also observed in FdUrd-treated cells about 10 h after the addition. These results lead us to propose that DNA double strand breaks play an important role in the mechanism of FdUrd-mediated cell death. A comparison of the ratio of single and double strand breaks induced by FdUrd to that observed following radiation suggested that FdUrd produced double strand breaks exclusively. Cycloheximide inhibited both the production of DNA double strand breaks and the FdUrd-induced cell death. An activity that can induce DNA double strand breaks was detected in the lysate of FdUrd-treated FM3A cells but not in the untreated cells. This suggests that FdUrd induces the cellular DNA double strand breaking activity. The FdUrd-induced DNA strand breaks and cell death appear to occur in the S phase. Our results indicate that imbalance of the dNTP pools is a trigger for double strand DNA break and cell death.     

Receptive field mechanisms of ganglion cells in the cat retina

On the basis of anatomical and physiological results of the vertebrate retina, a method is proposed for analysing the respective fields of ganglion cells in the cat retina. In the model, we assume the following: (a) Ganglion cells receive their input from bipolar and/or amacrine cells. (b) The nonlinearity of ganglion cell responses is due to the activities of transient type amacrine cells. The method has been proved to be effective. According to the results of this investigation, the receptive field properties of X type and Y type ganglion cells are heterogeneous. Thus, it may be considered that their receptive fields consist of center and surround mechanisms. The receptive field properties of X-cells are almost linear and the X-cells seem to receive most of their input from bipolar cells. On the other hand, the ones of Y-cells are highly nonlinear. Consequently, it is conceivable that the Y-cells receive their input mainly from transient type amacrine cells.     

An application of optimal diving models to diving behaviour of Brünnich's guillemots

Although theoretical models predict that the quality of foraging patches has little effect on optimal dive time with increasing depth, many empirical studies show that dive time at a given depth may vary. We developed a model that incorporated patch quality as a parameter of energy intake as a nonlinear function of time, and applied it to the diving behaviour of Brünnich's guillemots, Uria lomvia. The model indicated that optimal dive time can vary widely depending on the parameter. It also explained the convergence of observed dive times with travel time. Assuming the birds dived optimally, this parameter can be estimated from travel time and dive time for each dive. Foraging patches with larger estimated parameter values were favoured by the birds, suggesting that the parameter indicated patch quality. We used this parameter to test an optimal patch use model in divers. The results indicate that Brünnich's guillemots adjust their diving behaviour adaptively depending on patch quality, and that the optimal diving model is valid for prediction of observed dive patterns if patch quality is incorporated appropriately. Copyright 2002 The Association for the Study of Animal Behaviour. Published by Elsevier Science Ltd. All rights reserved.     

Interaction of dimeric horse cytochrome c with cyanide ion

We have previously shown that methionine–heme iron coordination is perturbed in domain-swapped dimeric horse cytochrome c. To gain insight into the effect of methionine dissociation in dimeric cytochrome c, we investigated its interaction with cyanide ion. We found that the Soret and Q bands of oxidized dimeric cytochrome c at 406.5 and 529 nm redshift to 413 and 536 nm, respectively, on addition of 1 mM cyanide ion. The binding constant of dimeric cytochrome c and cyanide ion was obtained as 2.5 × 10⁴ M^?1. The Fe–CN and C–N stretching (ν _Fe–CN and ν _CN) resonance Raman bands of CN^?-bound dimeric cytochrome c were observed at 443 and 2,126 cm^?1, respectively. The ν _Fe–CN frequency of dimeric cytochrome c was relatively low compared with that of other CN^?-bound heme proteins, and a relatively strong coupling between the Fe–C–N bending and porphyrin vibrations was observed in the 350–450-cm^?1 region. The low ν _Fe–CN frequency suggests weaker binding of the cyanide ion to dimeric cytochrome c compared with other heme proteins possessing a distal heme cavity. Although the secondary structure of dimeric cytochrome c did not change on addition of cyanide ion according to circular dichroism measurements, the dimer dissociation rate at 45 °C increased from (8.9 ± 0.7) × 10^?6 to (3.8 ± 0.2) × 10^?5 s^?1, with a decrease of about 2 °C in its dissociation temperature obtained with differential scanning calorimetry. The results show that diatomic ligands may bind to the heme iron of dimeric cytochrome c and affect its stability.     

Effect of Caffeine-Containing Beverage Consumption on Serum Alanine Aminotransferase Levels in Patients with Chronic Hepatitis C Virus Infection: A Hospital-Based Cohort Study

Introduction

To date, there have been no prospective studies examining the effect of coffee consumption on serum alanine aminotransferase (ALT) level among individuals infected with the hepatitis C virus (HCV). We conducted a hospital-based cohort study among patients with chronic HCV infection to assess an association between baseline coffee consumption and subsequent ALT levels for 12 months.

Materials and Methods

From 1 August 2005 to 31 July 2006, total 376 HCV-RNA positive patients were recruited. A baseline questionnaire elicited information on the frequency of coffee consumption and other caffeine-containing beverages. ALT level as a study outcome was followed through the patients’ medical records during 12 months. The association between baseline beverage consumption and subsequent ALT levels was evaluated separately among patients with baseline ALT levels within normal range (≤45 IU/L) and among those with higher ALT levels (>45 IU/L).

Results

Among 229 patients with baseline ALT levels within normal range, 186 (81%) retained normal ALT levels at 12 months after recruitment. Daily drinkers of filtered coffee were three times more likely to preserve a normal ALT level than non-drinkers (OR=2.74; P=0.037). However, decaffeinated coffee drinkers had a somewhat inverse effect for sustained normal ALT levels, with marginal significance (OR=0.26; P=0.076). In addition, among 147 patients with higher baseline ALT levels, 39 patients (27%) had ALT reductions of ≥20 IU/L at 12 months after recruitment. Daily drinkers of filtered coffee had a significantly increased OR for ALT reduction (OR=3.79; P=0.034). However, in decaffeinated coffee drinkers, OR could not be calculated because no patients had ALT reduction.

Conclusion

Among patients with chronic HCV infection, daily consumption of filtered coffee may have a beneficial effect on the stabilization of ALT levels.     

Presenilin-1 mutation activates the signaling pathway of caspase-4 in endoplasmic reticulum stress-induced apoptosis

In the previous reports, we showed that the familial Alzheimer's disease (AD)-linked presenilin-1 (PS1) mutation induced the fragility to the endoplasmic reticulum (ER) stress and that caspase-4 mediates ER stress-induced- and beta-amyloid induced-apoptotic signaling in human cells. These results suggest the involvement of ER stress and caspase-4 in the cell death observed in AD. In this report, we studied the activation of caspase-4 in the familial AD-linked PS1 mutation (DeltaE9). Cleavage of caspase-4 under ER stress was enhanced by the overexpression of the familial AD-linked mutation (DeltaE9), showing that caspase-4 is a key caspase involved in the apoptotic signaling of AD. We also showed that the overexpression of caspase-4 induced cleavage of caspase-9 and caspase-3 without releasing cytochrome-c from the mitochondria. Thus, caspase-4 activates downstream caspases independently of mitochondrial apoptotic signaling and this might contribute to the pathogenesis of AD. To sum up our data, the familial AD-linked PS1 mutation accelerates the cleavage of caspase-4 under the ER stress and results in the activation of caspase-9 and caspase-3, apoptosis signal, without releasing cytochrome-c.     

Two novel steroidal alkaloid glycosides from the seeds of Lycium barbarum

Two novel steroidal alkaloid glycosides, lycioside A (1) and lycioside B (2) were isolated from the seeds of Lycium barbarum. Their structures were determined by various spectroscopic analyses. Compounds 1 and 2 showed inhibitory activities with the IC(50) values of 75.3 and 72.8 μM against rat intestinal sucrase, and 63.4 and 59.1 μM against rat intestinal maltase.     

The inhibitory effects of mushroom extracts on sucrose-dependent oral biofilm formation

Mushrooms contain large quantities of α-glucans. Shiitake (Lentinula edodes), Japan’s most popular edible mushroom, has been reported to contain about 6% (weight/dried weight) of α-(1,3)-glucan. This glucan is one of the major components of oral biofilm formed by the cariogenic bacteria Streptococcus mutans and Streptococcus sobrinus. We found that extracts from shiitake and other edible mushrooms could reduce preformed biofilms of S. mutans and S. sobrinus in the presence of dextranase. We also investigated the α-glucanase activities of shiitake mushroom extracts and their effects on biofilm formation. The extracts possessed α-glucanase activity and degraded water-insoluble glucans from mutans streptococci. The extracts strongly inhibited the sucrose-dependent formation of biofilms by S. mutans and S. sobrinus in the presence of dextranase. Our results suggest that some components of mushrooms, including α-glucanases, might inhibit the sucrose-induced formation of oral biofilms.