Protective effect of microorganism biotransformation-produced resveratrol on the high fat diet-induced hyperlipidemia, hepatic steatosis and synaptic impairment in hamsters.

Background: Resveratrol, a natural antioxidant polyphenol, has the functions of anti-inflammation, anti-cancer, liver protection and cardioprotection. Microorganism biotransformation-produced resveratrol (MBR) product shows higher purity than the natural source of resveratrol and costs less than the chemically synthesized resveratrol. The aim of the present study was to investigate the protective effects of MBR in hamsters treated with a high-fat diet (HFD). Methods: MBR was obtained by the fermentative process of piceid. Hamsters were randomly divided into four groups: HFD plus oral administration of MBR 0 (C), 5 (L), 20 (M) or 50 mg/kg (H), respectively. After six-week of treatment, hamsters were sacrificed, and tissues were collected for further analysis. Results: MBR at these three dosages did not influence the appetite or growth of the hamsters. Liver enzymes, blood glucose, total cholesterol, triglyceride, and liver weight were significantly reduced in the MBR groups than in the control group. Additionally, high-density lipoprotein-cholesterol (HDL-C) was also elevated in all MBR groups. On the other hand, serum low-density lipoprotein-cholesterol (LDL-C) was decreased in the MBR groups. Triglyceride (TG) in liver tissue and fatty liver level were lower in group H. Memory-associated proteins, phosphorylation of calmodulin-dependent protein kinase II (p-CaMK II) and synaptophysin (SYP), were increased in the brains of MBR groups. Conclusion: The high yield- and short procedure-produced MBR has the potential to protect animals fed with HFD from hyperlipidemia, hepatic steatosis, hyperglycemia, and synaptic impairment, which might be beneficial for patients with these types of diseases.

Effects of everolimus on tuberous sclerosis complex-associated renal angiomyolipoma: A preliminary report.

AIM: Tuberous sclerosis complex (TSC) presents with multisystem benign neoplasm induced by dysregulation of the mammalian target of rapamycin pathway. This study aimed to examine the effects of oral everolimus at either 2.5 or 5.0 mg daily on the treatment of TSC-associated renal angiomyolipoma (AML). METHODS: Between July 2012 and August 2015, patients with TSC-associated renal AML were selected for everolimus therapy protocol. An oral everolimus starting dose at 2.5 mg was administered daily, and was gradually increased to 5.0 mg daily. All patients were evaluated using magnetic resonance imaging or computed tomography scanning at baseline, 12, 24, and 36 months after the start of treatment for measuring the changes of renal AML mass volume. RESULTS: Eight patients were finally enrolled for analysis in this study. Everolimus treatment had a statistically significant effect on the renal AML volume reduction during follow-up (P < 0.05). Renal AML mass volume reduction rates were 10.5-45.3% in four patients with everolimus 2.5 mg and 40.7-73.1% in four patients with everolimus 5.0 mg daily; the difference was statistically significant between the two groups (P < 0.05). Longitudinal follow-up for response to everolimus showed volume reduction rates to be around 10.5-73.1% in the initial 6-24 months after everolimus treatment, which remained stable during follow-up up to 36 months. CONCLUSION: The results suggest that an oral everolimus is effective and provides a non-invasive way to treat TSC-associated renal AML, and patients are likely to require maintenance therapy to continue to derive benefit.

Association between the growth rate of subependymal giant cell astrocytoma and age in patients with tuberous sclerosis complex.

PURPOSE: The most common neurological complications associated with tuberous sclerosis complex (TSC) include intractable seizures that begin in infancy and subependymal giant cell astrocytoma (SEGA) complicated by hydrocephalus with increasing age. Information on SEGA growth of TSC patients is limited. This study aimed to examine the TSC-SEGA growth rates by periodic neuroimaging. METHODS: This study evaluated the TSC-SEGA growth rates by serial neuroimaging. Fifty-eight patients with TSC underwent systematic evaluation, including a review of medical history and serial brain neuroimaging. RESULTS: While magnetic resonance imaging was more sensitive in detecting cortical tubers than computed tomography (73.1 vs. 0 %, p < 0.001), its efficacy in identifying intracranial lesions was comparable to that of computed tomography (96.2 vs. 100 %, p = 0.658). Significant tumor growth was observed in children (p = 0.012) and adults (p = 0.028) during follow-up periods, respectively (median for children 23.5 months, interquartile range 18-40 months and median for adults 23 months, interquartile range 12-34 months). Further, the SEGA growth rate in children was significantly higher than that in adults (75.6 vs. 16.5 %, p = 0.03). CONCLUSIONS: The results of the study show that SEGA has a significantly higher growth rate in children using serial follow-up brain imaging, suggesting the importance of performing follow-up neuroimaging at yearly intervals in childhood to identify and prevent potential comorbidities.

Environmentally relevant concentration of arsenic trioxide and humic acid promoted tumor progression of human cervical cancer cells: In vivo and in vitro studies.

In a previous study, treatment at higher concentrations of arsenic trioxide or co-exposure to arsenic trioxide and humic acid was found to be inhibited cell growth of cervical cancer cells (SiHa cells) by reactive oxygen species generation. However, treatment at lower concentrations slightly increased cell viability. Here, we investigate the enhancement of progression effects of environmentally relevant concentration of humic acid and arsenic trioxide in SiHa cell lines in vitro and in vivo by measuring cell proliferation, migration, invasion, and the carcinogenesis-related protein (MMP-2, MMP-9, and VEGF-A) expressions. SiHa cells treated with low concentrations of humic acid and arsenic trioxide alone or in co-exposure significantly increased reactive oxygen species, glutathione levels, cell proliferation, scratch wound-healing activities, migration abilities, and MMP-2 expression as compared to the untreated control. In vivo the tumor volume of either single drug (humic acid or arsenic trioxide) or combined drug-treated group was significantly larger than that of the control for an additional 45 days after tumor cell injection on the back of NOD/SCID mice. Levels of MMP-2, MMP-9, and VEGF-A, also significantly increased compared to the control. Histopathologic effects of all tumor cells appeared round in cell shape with high mitosis, focal hyperkeratosis and epidermal hyperplasia in the skin, and some tumor growth in the muscle were observed. Our results may indicate that exposure to low concentrations of arsenic trioxide and humic acid is associated with the progression of cervical cancer. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1121-1132, 2016.

The effect of benzodiazepine and nonbenzodiazepine prescriptions for diabetes mellitus type 2 in elderly Taiwanese with depressive symptoms.

BACKGROUND: This study examined the relationship between depression, benzodiazepine (BZD)/nonbenzodiazepine hypnotics (non-BZD), and other risk factors in a national sample of Taiwan's elderly diabetic patients. METHODS: Data were drawn from the 2005 Taiwan National Health Interview Survey and adults aged 65 years and older. A total of 1331 subjects were included in this study. The Chinese version of Center for Epidemiologic Studies Depression Scale was used to evaluate patients' depression symptoms. RESULTS: The rates of depression in the diabetes mellitus (DM) and non-DM groups were 13.5% (39/288) and 9.8% (102/1043) and the average ages were 73.7 and 73.4 years, respectively. In multivariate regression, the odds ratio of depression was 1.66-fold higher among BZD/non-BZD users (95% confidence interval: 1.10-2.51, model 2) than among those without BZD/non-BZD use. In addition, hyperlipidaemia, poor physical function, and antidepressant use were associated with a higher risk of depressive symptoms. Meanwhile, a monthly household income of NT$30 000-NT$49 999, exercise, and betel chewing were associated with a lower risk of depression. We performed an additional logistic analysis for which the odds ratio of depression significantly increased to 1.52 in non-DM elderly patients (95% confidence interval: 1.06-2.19) who were prescribed BZD/non-BZD. In contrast, there was no significant difference in the odds ratio of depression in the DM elderly regardless of BZD/non-BZD use, although there was a slight tendency for depression among those who used BZD/non-BZD. CONCLUSION: Depression in non-DM Taiwanese elderly patients was found to be associated with BZD/non-BZD use, whereas depression in DM Taiwanese elderly patients was not found to be associated with BZD/non-BZD use.

Benzodiazepine & nonbenzodiazepine prescriptions for Taiwanese elderly with type 2 diabetes contributes to cognitive dysfunction.

BACKGROUND: This study examined the relationship of cognitive function and benzodiazepine/nonbenzodiazepine hypnotics (BZD/nonBZD) and other risk factors in a national sample of Taiwan's elderly diabetic patients. METHODS: Data were drawn from the "2005 Taiwan National Health Interview Survey (NHIS)", a population-based study of a national sample of adults aged 65 years and older. A total of 653 participants were included in this study. The Mini-Mental State Examination (MMSE) was used to evaluate patient's cognitive function for which the cut-off score is education-adjusted. RESULTS: There were 130 participants left in the diabetic group and 523 participants in the control group. The average age was 74.2 and 73.3 respectively. The rate of cognitive dysfunction in DM and non DM participants was 11.5% (15/130) and 8.4% (44/523). Compared with those without diabetes in multivariate logistic regression, the odds ratio of cognitive impairment was 1.87-fold higher for diabetic patients (95% CI 1.04-3.61) after adjusting for sociodemographic characteristics, comorbidities, and BZD/nonBZD. Other factors were not significant. We performed an additional logistic analysis for which the odds ratio of cognitive impairment in diabetic patients with BZD/nonBZD was significantly increased to 2.41 (95% CI 1.08-5.40) than for patients without diabetes and BZD/nonBZD. CONCLUSION: In our research, cognitive dysfunction was associated with diabetes. BZD/nonBZD may have conferred additional risk of cognitive impairment in our elderly diabetic patients. We should consider examining the mental function of DM patients regularly and try our best to avoid potentially inappropriate medications (PIMs).

Topical N-acetylcysteine accelerates wound healing in vitro and in vivo via the PKC/Stat3 pathway.

N-Acetylcysteine (Nac) is an antioxidant administered in both oral and injectable forms. In this study, we used Nac topically to treat burn wounds in vitro and in vivo to investigate mechanisms of action. In vitro, we monitored glutathione levels, cell proliferation, migration, scratch-wound healing activities and the epithelialization-related proteins, matrixmetalloproteinase-1 (MMP-1) and proteins involved in regulating the expression of MMP-1 in CCD-966SK cells treated with Nac. Various Nac concentrations (0.1, 0.5, and 1.0 mM) increased glutathione levels, cell viability, scratch-wound healing activities and migration abilities of CCD-966SK cells in a dose-dependent manner. The MMP-1 expression of CCD-966SK cells treated with 1.0 mM Nac for 24 h was significantly increased. Levels of phosphatidylinositol 3-kinase (PI3K), protein kinase C (PKC), janus kinase 1 (Jak1), signal transducer and activator of transcription 3 (Stat3), c-Fos and Jun, but not extracellular signal-regulated protein kinases 1 and 2 (Erk1/2), were also significantly increased in a dose-dependent manner compared to the controls. In addition, Nac induced collagenous expression of MMP-1 via the PKC/Stat3 signaling pathway. In vivo, a burn wound healing rat model was applied to assess the stimulation activity and histopathological effects of Nac, with 3.0% Nac-treated wounds being found to show better characteristics on re-epithelialization. Our results demonstrated that Nac can potentially promote wound healing activity, and may be a promising drug to accelerate burn wound healing.

Impact of potentially inappropriate medication and continuity of care in a sample of Taiwan elderly patients with diabetes mellitus who have also experienced heart failure.

AIMS: Continuity of care (COC) and potentially inappropriate medication (PIM) can affect the elderly healthcare outcome. We evaluated the COC and PIM effects in older diabetes mellitus (DM) patients with heart failure (HF). METHODS: The Longitudinal Health Insurance Database of 2005 was multiple-year claim data collected from 2005 to 2010 in Taiwan. There were both 823 DM and non-DM subjects aged 65 years and older in this observational study. The COC index and 2012 Beers criteria were applied to evaluate the COC and HF-PIM in older DM patients with heart failure. The dependent variables were either hospital admissions or emergency department visits. Generalized estimating equation was used to adjust all covariates. RESULTS: During 2005-2010, the rate of HF-PIM in the elderly DM group was 86.1%, the mean COC index was 0.28 ± 0.19, the admission rate was 31.9% and the emergency department rate was 38.8 %. Lower COC index was associated with HF-PIM and HF-PIM duration in older DM patients with HF. Lower COC index was associated with hospitalizations (OR 0.07, 95% CI 0.05-0.11) and ED visits (OR 0.10, 95% CI 0.07-0.13), but HF-PIM was not significant. The duration of HF-PIM was related with poor health outcomes over 90 and 180 days for hospitalization and emergency department visit, respectively. CONCLUSION: Among elderly DM patients with HF, COC had positive effects on healthcare outcomes. Improving COC and reducing PIM duration for elderly DM patients with HF seems warranted. Geriatr Gerontol Int 2016; 16: 1117-1126.

Antimicrobial Resistance and Diagnostic Imaging in Infants Younger Than 2 Months Old Hospitalized With a First Febrile Urinary Tract Infection: A Population-based Comparative Study.

BACKGROUND: Data on urinary tract infection (UTI) in infants ≤2 months of age are limited. We examined clinical characteristics, antimicrobial resistance, imaging findings and clinical outcomes in infants ≤2 months of age and children 2-24 months of age hospitalized with the first febrile UTI. METHODS: Children ≤24 months of age hospitalized with their first-diagnosed febrile UTI were prospectively studied. Renal ultrasonography, Tc-dimercaptosuccinic acid scanning and voiding cystourethrography were performed in all children. RESULTS: Of the 388 children analyzed (255 boys and 133 girls), 61 patients were ≤2 months of age, representing 15.7% of the whole population, whereas 327 patients were 2-24 months of age. Escherichia coli was the predominant bacterium, with similar antimicrobial resistance in the 2 groups, and associated E. coli bacteremia occurred in 9 patients (2.3%). Renal ultrasonography showed abnormal findings in 130 patients (33.5%), but there was no difference in the rate of abnormal findings between the groups. Vesicoureteral reflux (VUR) was present in 130 children (33.5%), including 93 (24%) with grades III-V VUR. VUR was more prevalent in the infants ≤2 months of age (P = 0.007), but there was no difference in the prevalence of grades III-V VUR between the groups. The incidence of renal scarring was 28.6% (111/388), and it did not differ between the groups. CONCLUSIONS: There are similarities in clinical characteristics, antimicrobial resistance, imaging findings and clinical outcomes after a first UTI between the young infants ≤2 months and children 2-24 months of age. The same guidelines for the diagnosis and management after the first febrile UTI can be applied to children who are ≤24 months of age.