Quantification of Epstein-Barr virus DNA load, interleukin-6, interleukin-10, transforming growth factor-β1 and stem cell factor in plasma of patients with nasopharyngeal carcinoma

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a common epithelial neoplasm among the Chinese populations in Southern China and South East Asia. Epstein-Barr virus (EBV) is known to be an important etiologic agent of NPC and the viral gene products are frequently detected in NPC tissues along with elevated antibody titres to the viral proteins (VCA and EA) in a majority of patients. Elevated plasma EBV DNA load is regarded as an important marker for the presence of the disease and for the monitoring of disease progression. However, other serum/plasma parameters such as the levels of certain interleukins and growth factors have also been implicated in NPC. The objectives of the present study are, 1) to investigate the correlations between plasma EBV DNA load and the levels of interleukin (IL)-6, IL-10, TGF-β1 and SCF (steel factor) and 2) to relate these parameters to the stages of NPC and the effect of treatment. METHODS: A total of 78 untreated NPC patients were enrolled in this study. Of these, 51 were followed-up after treatment. The remaining patients had irregular or were lost to follow-up. Plasma EBV DNA was quantified using real-time quantitative PCR. The levels of plasma interleukins and growth factors were quantified using ELISA. RESULTS: A significant decrease in EBV DNA load was detected in plasma of untreated NPC patients (1669 ± 637 copies/mL; n = 51) following treatment (57 ± 37 copies/mL, p < 0.05); n = 51). Plasma EBV DNA load was shown to be a good prognosticator for disease progression and clinical outcome in five of the follow-up patients. A significant difference in IL-6 levels was noted between the untreated patients (164 ± 37 pg/mL; n = 51) and following treatment (58 ± 16 pg/mL, p < 0.05; n = 51). Positive correlations between EBV DNA load and IL-10 (r(49) = 0.535, p < 0.01), between IL6 and IL-10 (r(49) = 0.474, p < 0.01) and between TGF and SCF (r(49) = 0.464, p < 0.01) were observed in patients following treatment. None of the parameters tested including IgA-VCA were associated with tumour stages. CONCLUSION: We conclude that among the parameters investigated, EBV DNA load and IL-6 levels were promising markers for the presence of NPC and for the assessment of treatment outcome

Long-Term Mortality of Patients with Septic Ocular or Central Nervous System Complications from Pyogenic Liver Abscess: A Population-Based Study

Background: Taiwan is endemic for pyogenic liver abscess (PLA). Septic ocular or central nervous system (CNS) complications derived from PLA can result in catastrophic disability. We investigated the epidemiology and long-term prognosis of PLA patients with septic ocular or CNS complications over an 8-year period. Methodology/Principal Findings: We extracted 21,307 patients with newly diagnosed PLA from a nationwide health registry in Taiwan between 2000 and 2007. The frequency of and risk factors for PLA with septic ocular or CNS complications were determined. The 2-year survival of these patients was compared between those with and without septic ocular or CNS complications. Septic ocular or CNS complications accounted for 2.1 % of all PLA patients. Age and the Charlson comorbidity index were significantly lower in PLA patients with ocular or CNS complications than those without. Diabetes and age,65 years were independent predictors of septic ocular or CNS complications. The 2-year mortality of patients with septic ocular or CNS complications was similar to those without complications (24.8 % vs. 27.5%, p = 0.502). However, among patients,65 years old and a Charlson index #1, the 2-year mortality was significantly higher in those with than without complications (18.6 % vs. 11.8%, p = 0.001). Conclusions/Significance: Physicians should recognize that catastrophic disability due to ocular or neurologica

Identification of IGF1, SLC4A4, WWOX, and SFMBT1 as Hypertension Susceptibility Genes in Han Chinese with a Genome-Wide Gene-Based Association Study

Hypertension is a complex disorder with high prevalence rates all over the world. We conducted the first genome-wide gene-based association scan for hypertension in a Han Chinese population. By analyzing genome-wide single-nucleotide-polymorphism data of 400 matched pairs of young-onset hypertensive patients and normotensive controls genotyped with the Illumina HumanHap550-Duo BeadChip, 100 susceptibility genes for hypertension were identified and also validated with permutation tests. Seventeen of the 100 genes exhibited differential allelic and expression distributions between patient and control groups. These genes provided a good molecular signature for classifying hypertensive patients and normotensive controls. Among the 17 genes, IGF1, SLC4A4, WWOX, and SFMBT1 were not only identified by our gene-based association scan and gene expression analysis but were also replicated by a gene-based association analysis of the Hong Kong Hypertension Study. Moreover, cis-acting expression quantitative trait loci associated with the differentially expressed genes were found and linked to hypertension. IGF1, which encodes insulin-like growth factor 1, is associated with cardiovascular disorders, metabolic syndrome, decreased body weight/size, and changes of insulin levels in mice. SLC4A4, which encodes the electrogenic sodium bicarbonate cotransporter 1, is associated with decreased body weight/size and abnormal ion homeostasis in mice. WWOX, which encodes the WW domain-containing protein, is related to hypoglycemia and hyperphosphatemia. SFMBT1, which encodes the scm-like with four MBT domains protein 1, is a novel hypertension gene. GRB14, TMEM56 and KIAA1797 exhibited highly significant differential allelic and expressed distributions between hypertensive patients and normotensive controls. GRB14 was also found relevant to blood pressure in a previous genetic association study in East Asian populations. TMEM56 and KIAA1797 may be specific to Taiwanese populations, because they were not validated by the two replication studies. Identification of these genes enriches the collection of hypertension susceptibility genes, thereby shedding light on the etiology of hypertension in Han Chinese populations

Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to 300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m 2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

A Novel Approach to Link Process Parameters to BSIM Model Parameters

In this paper, we demonstrate a methodology to link process parameters to BSIM model parameters. Here, we have combined well-known statistical methods like principal component analysis (PCA), design of experiments (DOE), and response surface methodology (RSM) to bridge the missing link between process parameters and model parameters. The proposed methodology uses the concept of a correlation matrix, which transforms the process level information to the device and circuit level information through the BSIM model parameters. The proposed methodology has been successfully implemented on an advanced CMOS process. Our results show a strong linear correlation for the data obtained from two techniques namely TCAD technique and the standard HSPICE simulation technique. In both cases the process conditions were kept identical for comparison

In situ formation of nanocrystals from a self-microemulsifying drug delivery system to enhance oral bioavailability of fenofibrate

You-Meei Lin1, Jui-Yu Wu2, Ying-Chen Chen3, Yu-Der Su3, Wen-Tin Ke3, Hsiu-O Ho31Department of Pharmacy, Shuang Ho Hospital, 2Department of Biochemistry, School of Medicine, 3School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan, ROCObjectives: In situ formation of nanocrystals and dissolution profiles of fenofibrate (FFB) from a self-microemulsifying drug delivery system (SMEDDS) were characterized.Methods: SMEDDS formulated with Myritol&amp;reg; and surfactant mixture (Smix) of D-&amp;alpha;-Tocopheryl polyethylene glycol 1000 succinate (TPGS) and either Tween&amp;reg; 20 (A, C, E, G, M, S, N, T, O) or Tween&amp;reg; 80 (B, D, F, H, P, U, Q, V, R) at various oil/Smix ratios (Group I: A and B of 0.42, C and D of 0.25, E and F of 0.11; Group II: G and H of 1.38, M and P of 1.11, S and U of 0.9, N and Q of 0.73, T and V of 0.58, and O and R of 0.46) and water contents (1: 9.5%, 2: 5.0%, 3: 0.0%, G-V: 4.5%). Their dissolutions were conducted at different rotation speeds. Two optimal SMEDDSs containing Tween 80(B2) or a higher oil/Smix ratio(Q) and B2(solution) were selected for pharmacokinetic study.Results: FFB particles formed within the nanosize range from Group I gradually increased with time but decreased with increasing stirring rates. However, the mean size of FFB formed by B series was as low as 200 nm, which was smaller than that of A series at three stirring rates. The release rate from both groups obviously increased with increasing stirring rate. However, incomplete release was observed for S and N in Tween 20 series, whereas a faster release rate and complete release were observed for Tween 80 series with an insignificant difference among them. Results of pharmacokinetic study demonstrated that the highest-ranked area under the curve and Cmax values were for Q(SMEDDS) and B2(solution), respectively. The relative bioavailability of Q(SMEDDS) with respect to Tricor&amp;reg; was enhanced by about 1.14-1.22-fold.Conclusion: SMEDDS, consisting of Myritol 318 and TPGS combined with Tween 80 at 4:1, was able to enhance the oral bioavailability of FFB.Keywords: SMEDDS, fenofibrate, microemulsion, dissolution, TPG