Cognitive decline is associated with nutritional risk in subjects with small head circumference (HC)

Nutrition has been found to be associated with cognitive impairment, but it has not been established whether these associations are present solely in later life or whether they are present in younger age as well. HC is a good indicator of brain development and the most sensitive anthropometric indicator of prolonged malnutrition during early life. This study examined the interaction between early HC and later (nutrition screening initiative) nutritional factors on the risk of cognitive decline in the elderly. The longitudinal factorial design had the mini-mental state examination (MMSE) score as the dependent variable, with HC as one factor and nutritional risk as another. We studied a sample of 495 not cognitively impaired Korean participants with 2 years follow-up data. After multivariable adjustment, interactive effect between HC and nutritional risk was significantly associated with cognitive decline (F = 2.449, p = 0.045). Simple main effect analysis showed that compared with highest HC, lowest HC was associated with a cognitive decline. Nutritional risk was associated with cognitive function decline only in individuals with small HC. Therefore, the prevention for cognitive impairment and dementia should involve nutritional strategies throughout life.     

Portal Hypertensive Gastropathy: Correlation with Portal Hypertension and Prognosis in Cirrhosis

Background

Portal hypertensive gastropathy (PHG) is a common endoscopic finding in patients with cirrhosis. However, the relationship between PHG and portal hypertension is controversial. Furthermore, nothing is known regarding the correlation between PHG and prognosis in patients with cirrhosis.

Methods

The hepatic venous pressure gradient (HVPG), endoscopic PHG grade, Child–Pugh score, and model for end-stage liver disease (MELD) score were assessed at baseline and were followed prospectively in 331 cirrhotic patients (284 males, 85.8%; mean age, 52.16 ± 9.05 years) from January 2001 to April 2009. The relationship between PHG with HVPG and survival was investigated.

Results

The HVPG was significantly higher in patients with severe PHG than in those with mild or no PHG (absent, 4.9 ± 1.7 mmHg; mild, 10.7 ± 4.1 mmHg; severe, 15.6 ± 4.6 mmHg; P < 0.001). During follow-up, 28 patients (8.5%) died from liver-related disease. In the Cox regression analysis, severe PHG (none and mild vs. severe) (hazard ratio 1.153, 95% confidence interval: 1.048–1.269) showed a significantly high relative risk of mortality, and in the Kaplan–Meier analysis, severe PHG showed a significantly shorter expected survival time than none or mild PHG (median survival time, 77.6 ± 9.6 months in severe PHG; log-rank test, P = 0.030).

Conclusions

PHG was associated with portal hypertension severity and prognosis in patients with cirrhosis.     

TNF superfamily gene polymorphism as prognostic factor in early breast cancer

Purpose

Since apoptosis may play a role in the prognosis of breast cancer, the present study analyzed the polymorphisms of apoptosis-related genes and their impact on the survival of 240 patients with early invasive ductal breast cancer.

Methods

The genomic DNA was extracted from paraffin-embedded tumor-free tissue or blood, and 12 single nucleotide polymorphisms (SNPs) of 11 apoptosis-related genes in the apoptosis pathway determined using a Sequenom MassARRAY system.

Results

During the median follow-up of 53.4 (range 2.9–205.9) months, 37 relapses and 22 deaths occurred. Among the target polymorphisms, the tumor necrosis factor superfamily member 10 gene polymorphism (TNFSF10 rs1131532) in a recessive model of the T allele and prostaglandin-endoperoxide synthase 2 gene polymorphism (PTGS2 rs5275) in a dominant model of the C allele were associated with survival in a log-rank test. The TT genotype of TNFSF10 (rs1131532) was also significantly correlated with a lower disease-free, distant disease-free, and overall survival in a multivariate analysis (HR = 3.304, 4.757, and 6.459; P = 0.002, 0.001, and 0.009, respectively), while PTGS2 rs5275 was only associated with a higher distant disease-free survival (HR = 0.302; P = 0.041). No clinicopathologic difference was observed according to the genotypes of these two polymorphisms.

Conclusion

The TNFSF10 (rs1131532) polymorphism was identified as a possible prognostic factor of survival in patients with operated invasive breast cancer.     

Chronological changes in the systemic manifestations of intestinal Behcet’s disease and their significance in diagnosis

Purpose

Intestinal Behçet's disease (BD) is challenging to diagnose, especially if the patient presents with typical colonoscopic findings of intestinal BD without systemic manifestations of BD. We performed this study to evaluate the systemic manifestations of BD in patients with typical colonoscopic findings of intestinal BD at the time of initial presentation and to identity the chronologic changes of these features during an extended follow-up period.

Methods

One hundred twenty-six consecutive patients who showed typical colonoscopic findings of intestinal BD at a single institution in Korea were enrolled. Clinical and endoscopic data were collected from a medical database and using a written questionnaire. Parameters including demographic characteristics and the subset type of BD at the initial and endpoints of the follow-up were analyzed.

Results

The mean follow-up period was 63.9?±?50.9 months. The number of cases that satisfied the International Study Group for Behçet’s Disease criteria at initial diagnosis, 19.0%, increased to 53.2% by the end of follow-up. When the Japanese criteria were used for classification, the proportion of complete and incomplete type BD increased (2.4% and 26.2% to 18.3% and 49.2%, respectively), while that of suspected and not-satisfied subtype BD decreased (22.2% and 49.2% to 19.0% and 13.5%, respectively) during the follow-up period.

Conclusions

Our data suggest that patients who lack the systemic manifestations of BD could be included in the category of intestinal BD when typical intestinal lesion is identified, indicating that close examination and early treatment should be considered in such patients.     

Role of JNK activation in pancreatic β-cell death by streptozotocin

c-Jun N-terminal kinase (JNK) is activated by cellular stress and plays critical roles in diverse types of cell death. However, role of JNK in β-cell injury is obscure. We investigated the role for JNK in streptozotocin (STZ)-induced β-cell death. STZ induced JNK activation in insulinoma or islet cells. JNK inhibitors attenuated insulinoma or islet cell death by STZ. STZ-induced JNK activation was decreased by PARP inhibitors, suggesting that JNK activation is downstream of PARP-1. Phosphatase inhibitors induced activation of JNK and abrogated the suppression of STZ-induced JNK activation by PARP inhibitors, suggesting that the inhibition of phosphatases is involved in the activation of JNK by STZ. STZ induced production of reactive oxygen species (ROS) as potential inhibitors of phosphatases, which was suppressed by PARP inhibitors. PARP-1 siRNA attenuated insulinoma cell death and JNK activation after STZ treatment, which was reversed by MKP (MAP kinase phosphatase)-1 siRNA. These results suggest that JNK is activated by STZ downstream of PARP-1 through inactivation of phosphatases such as MKP, which plays important roles in STZ-induced β-cell death.     

Arsenic trioxide-induced apoptosis in TM4 Sertoli cells: the potential involvement of p21 expression and p53 phosphorylation

Arsenic is a toxic metalloid that exists ubiquitously in the environment, and exhibits carcinogenicity. Conversely, arsenic trioxide (AsTO) has successfully been employed in the treatment of acute promyelocytic leukemia (APL). It has been shown that AsTO efficiently induces apoptosis in the malignant cells of APL in vitro. Although the mechanisms underlying AsTO-induced apoptosis in certain types of cancer cells, such as APL cells, have been delineated, the mechanism underlying AsTO-induced cell death in non-cancer cells remains unknown. In the present study, we examined AsTO-provoked cytotoxicity and cell death mechanism(s) in TM4 Sertoli cells. Exposure of these cells to AsTO generates reactive oxygen species and alters mitochondrial apoptosis, inducing cell death via both caspase-dependent and caspase-independent pathways. AsTO-induced apoptosis was concomitant with the downregulation of p53, phosphorylation of p53 at serine residues, and G2/M cell cycle arrest. Particularly, the interaction of p21 with caspase-3 proteins during AsTO treatment suggested an antiapoptotic role of p21 against genotoxic stresses in TM4 Sertoli cells. However, clinically relevant concentrations of AsTO failed to induce cell death in TM4 Sertoli cells, indicating that these cells could be resistant to cancer treatment. The results presented herein may not represent the actual effect of AsTO on Sertoli cells in vivo. Thus, further studies on the exposure effects of AsTO on the morphology and function of Sertoli cells in animal experiments will provide a more precise knowledge of AsTO cytotoxicity on male reproduction.     

Comparing the toxic mechanism of synthesized zinc oxide nanomaterials by physicochemical characterization and reactive oxygen species properties

We studied the toxicity of ZnO nanomaterials in terms of physicochemical characteristics and reactive oxygen species (ROS) properties. ZnO nanorods [synthesized at room temperature (ZnO-RT, length; 18.0 ± 4.2 nm) and at 60 °C (ZnO-60, length; 80.5 ± 6.8 nm)] were used to evaluate the potential toxicity upon growth velocity-related particle size. The cytotoxicity of ZnO-60 was higher than that of ZnO-RT. We observed that the toxicity of ZnO-RT and ZnO-60 was related with ROS formation by using antioxidant N-acetylcysteine and electron spin resonance. Also, we found that the source of toxicity was not related to Zn²⁺ ions released from ZnO in 24 h treatment. Our results indicate that toxicity of ZnO nanorods is caused by the amounts of ROS. Our study strongly suggests that size of nanomaterial is not the sole factor to be considered, thus, the development of appropriate criteria based on morphological/physicochemical characteristics as well as synthesis procedures is needed to evaluate the precise toxicity.     

Inhibition of aldose reductase by phenylethanoid glycoside isolated from the seeds of Paulownia coreana

Aldose reductase (AR) inhibitors have considerable therapeutic potential against diabetic complications and do not increase the risk of hypoglycemia. Through bioassay-guided fractionation of the 70% acetone extract obtained from Paulownia coreana seeds, phenylpropanoid glycosides (compounds 1-4) and 5 phenolic compounds were isolated (compounds 5-9). Their structures were determined on the basis of spectroscopic analysis and comparison with reported data. All the isolates were subjected to in vitro bioassays to evaluate their inhibitory activities against recombinant human aldose reductase (rhAR) and sorbitol formation in human erythrocytes. Phenylethanoid glycosides showed more effective than the phenolic compounds in inhibiting rhAR. Among the compounds, isocampneoside II (3) was found to significantly inhibit rhAR with an IC(50) value of 9.72 μM. In kinetic analyses performed using Lineweaver-Burk plots of 1/velocity and 1/concentration of substrate, isocampneoside II (3) showed uncompetitive inhibition against rhAR. Furthermore, it inhibited sorbitol formation in a rat lens incubated with a high concentration of glucose; this finding indicated that isocampneoside II (3) may effectively prevent osmotic stress in hyperglycemia. Thus, the P. coreana-derived phenylethanoid glycoside isocampneoside II (3) may have a potential therapeutics against diabetic complications.