A cross-sectional assessment of oxidative DNA damage and muscle strength among elderly people living in the community

Objectives

The mechanism by which muscle weakness leads to an increased risk of death remains a subject of interest. In this context, the aim of this study is to assess the relationship between urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) and muscle strength, and other risk factors contributing to poor muscle strength in older persons.

Methods

This was a cross-sectional study in which a total of 86 participants, both men and women, aged 65 years or above were screened for urinary 8-OHdG, and muscle strength as measured by handgrip strength.

Results

Handgrip strength was lower in participants who had history of acute or chronic disease. Urinary 8-OHdG level was negatively associated with muscle strength, and the association remained after adjusting for confounding factors.

Conclusions

Urinary 8-OHdG is associated with muscle strength. These findings may be clinically relevant as there is a possibility of controlling oxidative DNA damage by healthy behaviors related to lifestyle.     

Lactobacillus GG-fermented milk prevents DSS-induced colitis and regulates intestinal epithelial homeostasis through activation of epidermal growth factor receptor

Background

Fermented milk is considered one of the best sources for efficient consumption of probiotic strains by hosts to promote good health. The purpose of this study was to investigate the effects of orally administering LGG-fermented milk (LGG milk) on intestinal inflammation and injury and to study the mechanisms of LGG milk’s action.

Methods

LGG milk and non-LGG-fermented milk (non-LGG milk) were administered through gavage to mice before and during dextran sodium sulfate (DSS)-induced intestinal injury and colitis. Inflammatory/injury score and colon length were assessed. Intestinal epithelial cells were treated with the soluble fraction of LGG milk to detect its effects on the epidermal growth factor receptor (EGFR) and its downstream target, Akt activation, cytokine-induced apoptosis, and hydrogen peroxide (H₂O₂)-induced disruption of tight junctions.

Results

LGG milk treatment significantly reduced DSS-induced colonic inflammation and injury, and colon shortening in mice, compared to that in non-LGG milk-treated and -untreated mice. The soluble fraction of LGG milk, but not non-LGG milk, stimulated the activation of EGFR and Akt in a concentration-dependent manner, suppressed cytokine-induced apoptosis, and attenuated H₂O₂-induced disruption of tight junction complex in the intestinal epithelial cells. These effects of LGG milk were blocked by the EGFR kinase inhibitor. LGG milk, but not non-LGG milk, contained two soluble proteins, p40 and p75, that have been reported to promote survival and growth of intestinal epithelial cells through the activation of EGFR. Depletion of p40 and p75 from LGG milk abolished the effects of LGG milk on prevention of cytokine-induced apoptosis and H₂O₂-induced disruption of tight junctions.

Conclusions

These results suggest that LGG milk may regulate intestinal epithelial homeostasis and potentially prevent intestinal inflammatory diseases through activation of EGFR by LGG-derived proteins.     

Preoperative assessment of hemifacial spasm by the coronal heavily T2-weighted MR cisternography

Background

Microvascular decompression (MVD) has become a well-established surgical procedure for hemifacial spasm (HFS). Before surgery, it is essential to evaluate any possible deformity of the brainstem and establish the precise location of the offending vessels. In the present study of HFS patients we examined coronal sections taken by heavily T2-weighted MR cisternography in addition to routine axial sections, and assessed the usefulness of these images through comparison with intraoperative findings.

Methods

Eighty patients with HFS underwent preoperative coronal heavily T2-weighted MR cisternography before microvascular decompression surgery. Three neurosurgeons examined the preoperative axial and coronal MR images and evaluated vessel invagination into the brainstem. The usefulness of coronal sections was assessed statistically by the Mann-Whitney U test.

Results

Invagination of the offending vessel into the brainstem was observed in 24 cases (30.0%). In 19 patients, it was predicted preoperatively that compression of the flocculus and brainstem would be required in order to approach the offending vessels. Coronal MR cisternography was significantly more useful in cases with vessel invagination into the brainstem than in cases without invagination.

Conclusions

Coronal sections obtained by MR cisternography are able to demonstrate the severity of vessel invagination into the brainstem as well as revealing the presence of the offending vessel. This information is helpful for planning a suitable approach to the root exit zone.     

Effect of COMT Val108/158Met Genotype on Risk for Polydipsia in Chronic Patients with Schizophrenia

Polydipsia is a serious condition often seen among patients with schizophrenia (SCZ). The cause of polydipsia is unknown; hence, it is hard to treat or manage. Animal studies showed that the drinking behavior is regulated by central dopaminergic neurotransmission at the hypothalamus. Meanwhile, the existence of a genetic predisposition to polydipsia in patients with SCZ has been suggested. The purpose of this study was to assess whether a functional polymorphism, Val^108/158Met in the gene for catechol-O-methyltransferase (COMT), is associated with susceptibility to polydipsia using a Japanese sample of SCZ. Our sample includes 330 chronic patients with SCZ (83 polydipsic patients and 247 non-polydipsic controls). The common COMT Val^108/158Met polymorphism was genotyped, and the differences in genotype distribution and allele frequency between cases and controls were evaluated using the χ ² test. A significant association between the COMT Val^108/158Met polymorphism and polydipsia was found (genotype distribution: χ ² = 13.0, df = 2, p = 0.001; allele frequency: χ ² = 7.50, df = 1, p = 0.006). The high-COMT activity group (Val/Val) was more frequent among patients with polydipsia compared with the low-COMT activity group (Val/Met + Met/Met) [odds ratio (OR) = 2.46]. The association survived after controlling for other possible confounding factors, including gender, age, age of onset, current antipsychotic dose, and smoking status. Our results suggest that the COMT Val^108/158Met genotype may confer susceptibility to polydipsia in SCZ. To our knowledge, this is the first association study between the COMT gene and polydipsia in SCZ. Further studies with larger sample sizes are warranted to confirm present findings.     

Low fasting plasma glucose level predicts morbidity and mortality in symptomatic adults with congenital heart disease

Background

Adults with complex congenital heart disease (ACHD) have a high prevalence of abnormal glucose regulation (AGR: impaired glucose tolerance and diabetes mellitus). However, the impact of AGR on the prognosis remains unclear.

Purpose

Our purpose was to clarify the prognostic value of AGR in ACHD.

Methods and results

We performed a 75 g oral glucose tolerance test in 438 consecutive patients with ACHD (age 26 ± 8 years), including 38 unrepaired, 148 Fontan, 252 biventricular, and 27 healthy subjects and investigated associations between AGR and clinical events that required hospitalization or caused deaths from all-causes. When compared with the healthy group, fasting blood glucose level (FPG, mg/dl) was lower in the unrepaired and Fontan subjects (p < 0.05–0.01) and the prevalence of low FPG (≤ 80 mg/dl) was also higher in the unrepaired (58%), Fontan (47%), and biventricular group (33%) than in the healthy control (11%) (p < 0.0001). Postprandial hyperglycemia (area under the curve of glucose: PG-AUC) was higher in all ACHD groups (p < 0.0001 for all). New York Heart Association class and lower FPG independently predicted the hospitalization (FPG ≤ 84 mg/dl) and mortality (FPG ≤ 80 mg/dl) (p < 0.05–0.0001), while the PG-AUC was not an independent predictor. When compared with the asymptomatic ACHD, symptomatic ACHD with lower FPG had high hazard ratios of 2.2 (95% confidence interval [CI]: 1.3–3.8, p < 0.002) and 3.3 (95% CI: 1.2–11.9, p < 0.03) for the hospitalizations and all-cause mortality, respectively.

Conclusions

Low FPG is not uncommon in ACHD and the low FPG predicts the morbidity and all-cause mortality in symptomatic ACHD.     

Comparative analysis of different enzyme immunoassays for assessment of phosphatidylserine-dependent antiprothrombin antibodies

Phosphatidylserine-dependent antiprothrombin antibodies (aPS/PT) were strongly correlated with the presence of lupus anticoagulant showing a high specificity for the diagnosis of antiphospholipid syndrome. However, the main criticism for the clinical applicability of aPS/PT testing is the lack of reproducibility of the results among laboratories. In this study, we measured IgG and IgM aPS/PT using our original in-house enzyme-linked immunosorbent assays (ELISA) and commercial ELISA kits to assess the assay performance and to evaluate the accuracy of aPS/PT results. The study included 111 plasma samples collected from patients and stored at our laboratory for aPS/PT assessment. Sixty-one samples were tested for IgG aPS/PT using two assays: (1) aPS/PT in-house ELISA and (2) QUANTA Lite? aPS/PT IgG ELISA kit (INOVA Diagnostics, Inc., USA). Fifty samples were evaluated for IgM aPS/PT using two assays: (1) aPS/PT in-house ELISA and (2) QUANTA Lite? aPS/PT IgM ELISA kit (INOVA Diagnostics). Ninety-eight percent of samples yielded concordant results for IgG aPS/PT and 82 % for IgM aPS/PT. There was an excellent agreement between the IgG aPS/PT assays (Cohen κ = 0.962) and moderate agreement between the IgM aPS/PT assays (κ = 0.597). Statistically significant correlations in the aPS/PT results were obtained from both IgG and IgM aPS/PT assays (r = 0.749, r = 0.622, p < 0.001, respectively). In conclusion, IgG and IgM detection by ELISA is accurate. The performance of aPS/PT is reliable, and concordant results can be obtained using different ELISA methods.