Enhanced efficacy of TD53, a novel algicidal agent, against the harmful algae via the liposomal delivery system

The present study aimed to design the liposomal delivery system for TD53, a novel algicial drug in order to improve the delivery properties of TD53 and evaluate its algicidal effects as well as selectivity against harmful and non-harmful algae. Liposomes of TD53 were prepared with 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) by a lyophilization, resulting in relatively small size vesicles (234±38nm) and narrow size distribution (PI=0.130±0.027). The drug leakage from the liposome was negligible in the F/2 media (<2% during 96h incubation). Subsequently algicidal activity of liposomal TD53 against harmful and nonharmful algae was evaluated at various concentrations. The IC(50) values of TD53 in liposome against harmful algae such as Chattonella marina, Heterosigma akashiwo and Cocholodinium polykrikoides were 2.675, 2.029, and 0.480μM, respectively, and were reduced by approximately 50% compared to those obtained from non-liposomal TD53. In contrast, the algicidal effect of liposomal TD53 was insignificant against non-harmful algae including Navicula pelliculosa, Nannochloropsis oculata and Phaeodactylum EPV. Those results suggested that liposomal delivery systems might be effective to enhance the efficacy of TD53 while maintaining the selectivity to harmful algal species.     

Do young hepatocellular carcinoma patients with relatively good liver function have poorer outcomes than elderly patients?

BACKGROUND AND AIM: The risk of hepatocellular carcinoma (HCC) is known to be age dependent; the influence of age on prognosis is, however, controversial. The aim of this study was to compare the tumor characteristics and survival rates of young and old HCC patients, with respect to tumor stage. METHODS: We reviewed the clinical data and survival times of 71 young HCC patients from 1987 to 2003 and compared these with those of their older counterparts (n = 239). Patients were categorized into three age groups: group A, age <30 years (n = 71); group B, age >/=30 to <61 years (n = 168); and group C, age >/=61 years (n = 81). Kaplan-Meier methods and Cox proportional hazards regression were used to analyze survival. RESULTS: The overall survival time of group A was shorter than groups B or C (P = 0.0071). Survival was not different in the three groups in subgroup analysis according to several tumor staging systems (e.g. Japan Integrated Staging score, Cancer of the Liver Italian Program scoring system and Barcelona Clinic Liver Cancer staging classification). The multivariate hazard ratio of group B was 0.840 (95% confidence interval [CI] 0.490-1.440) and that of group C was 0.770 (95% CI 0.410-1.446) in reference to group A. CONCLUSIONS: Young HCC patients showed a poorer prognosis than older HCC patients because they have a more advanced tumor stage at diagnosis. However, age was not an independent prognostic factor when stages were matched. Therefore, we suggest that periodic surveillance in young chronic hepatitis B virus carriers would improve outcomes.     

Metabolic inhibition and kinetics of raloxifene by pharmaceutical excipients in human liver microsomes

This study was originally undertaken to establish the in vitro metabolic conditions and then evaluate the effect of pharmaceutical excipients (PEs) on drug metabolism in uridine diphosphoglucuronic acid-supplemented human liver microsomes. Poorly bioavailable raloxifene was chosen as a model drug. Intact drug and its two glucuronide metabolites were successfully isolated using gradient HPLC analysis and LC/MS analysis. Formation of raloxifene metabolites was affected by buffer compositions, incubation time and initial raloxifene concentrations. Under optimized metabolic conditions, 41.0% of raloxifene was converted to its metabolites after 2h incubation. This metabolic inhibition of raloxifene by the PEs occurred in a dose-dependent manner and accordingly formed two glucuronide metabolites. In the metabolic kinetics using Lineweaver-Burk analyses, Cremophor EL competitively inhibited formation of metabolites while sodium lauryl sulfate (SLS), polyvinylpyrrolidone K30 (PVP) and Tween 80 significantly inhibited in a mixed competition. Although some PEs showed inhibition on glucuronidation of raloxifene in vitro, their effects on in vivo bioavailability of raloxifene need to be confirmed directly due to the dilution factors and other complicated situations influencing the bioavailability.     

Cerebral lateralization index based on intensity of bold signal of FMRI

This study proposes a new cerebral lateralization index (LI) on the basis of neural activation intensity. Eight right-handed male college students (mean age 23.5 years) and 10 right-handed male college students (the mean age 25.1 years) participated in this study of visuospatial and verbal tasks, respectively. Functional brain images were taken from 3T MRI using the single-shot EPI method. A cerebral LI based on neural activation area (i.e., number of activated voxels) and another based on neural activation intensity (i.e., intensity of BOLD (blood oxygen level dependent)) were calculated for both cognition tasks. The result of calculating a cerebral LI based on neural activation area suggested that the right hemisphere is dominant during visuospatial tasks and the left hemisphere is dominant during verbal tasks. When a cerebral LI was computed on the basis of the neural activation intensity, it was shown that the area of cerebral lateralization closely related to visuospatial tasks is the superior parietal lobe, and the area of cerebral lateralization closely related to verbal tasks is the inferior and middle frontal lobe. Since the proposed method can determine the dominance of the cerebrum by each area, it can be helpful to determine cerebral lateralization accurately and easily.     

Biopsy site for detecting Helicobacter pylori infection in patients with gastric cancer

Background:  Helicobacter pylori eradication is recommended in post-gastric cancer resection, but premalignant changes may prevent the detection of H. pylori . The aim of this study was to determine appropriate biopsy site for detecting H. pylori in gastric cancer patients.
Materials and Methods:  Consecutive patients (194) with gastric adenocarcinoma were prospectively enrolled. Helicobacter pylori was evaluated by serology, histology and rapid urease test. Biopsy sites included antrum lesser curvature, upper body lesser curvature (UBLC) and upper body greater curvature (UBGC). Two biopsy specimens were obtained from each site for histological examination. One additional specimen was obtained from UBGC for the rapid urease test.
Results:  The overall infection rate of H. pylori was 84.0% (95% CI 78.9–89.2). The sensitivity of histology for detecting H. pylori at various sites was: antrum (54.9%; 95% CI 45.7–63.9), UBLC (80.3%; 95% CI 72.2–87.0) and UBGC (95.1%; 95% CI 89.6–98.2). Specificities of all three biopsy sites were more than 95%. Sensitivity and specificity of the rapid urease test performed at UBGC were 96% and 100%, respectively. Sensitivities of histology decreased in correlation with increasing severity of atrophy and intestinal metaplasia (both P  < 0.001 using the chi-square test for trend). The proportions of moderate to marked atrophy/intestinal metaplasia at UBGC (12.8%/14.7%) were significantly lower than those at antrum (50.0%/57.8%, P  < 0.001 respectively) or UBLC (40.0%/48.9%, P  < 0.001 respectively).
Conclusions:  The UBGC side is the most sensitive and specific biopsy site to detect H. pylori in gastric cancer patients due to less frequent atrophy and intestinal metaplasia than at the antrum or UBLC side.     

Alcoholism and diabetes mellitus

Chronic use of alcohol is considered to be a potential risk factor for the incidence of type 2 diabetes mellitus (T2DM), which causes insulin resistance and pancreatic β-cell dysfunction that is a prerequisite for the development of diabetes. However, alcohol consumption in diabetes has been controversial and more detailed information on the diabetogenic impact of alcohol seems warranted. Diabetes, especially T2DM, causes dysregulation of various metabolic processes, which includes a defect in the insulin-mediated glucose function of adipocytes, and an impaired insulin action in the liver. In addition, neurobiological profiles of alcoholism are linked to the effects of a disruption of glucose homeostasis and of insulin resistance, which are affected by altered appetite that regulates the peptides and neurotrophic factors. Since conditions, which precede the onset of diabetes that are associated with alcoholism is one of the crucial public problems, researches in efforts to prevent and treat diabetes with alcohol dependence, receives special clinical interest. Therefore, the purpose of this mini-review is to provide the recent progress and current theories in the interplay between alcoholism and diabetes. Further, the purpose of this study also includes summarizing the pathophysiological mechanisms in the neurobiology of alcoholism.     

Pregnancy and delivery outcomes in the women who have received adenomyomectomy: Performed by a single surgeon by a uniform surgical technique

ObjectiveAlthough adenomyomectomy for fertility-sparing is an expanding procedure worldwide, there is no guideline or consensus about how to manage the pregnant women who have previously received conservative surgery for adenomyosis. The aim of this study is to evaluate antenatal care and delivery outcomes in pregnant women after adenomyomectomy.Materials and methodsBetween May 2011 and May 2019, the medical record was reviewed in all delivery of pregnant women received adenomyomectomy performed by a single surgeon by a uniform surgical technique. The evaluating parameters consisted of antenatal care outcomes, delivery outcomes, intrapartum outcome, and neonatal outcomes.ResultsTwenty-two patients were evaluated to monitor pregnancy and delivery outcomes after the adenomyomectomy. Mean age of delivery was 37.0 years old (SD = 3.1, range 32–45, median 37). All were delivered by cesarean section. Mean gestational age was 36.2 weeks (SD = 3.6, range 27.4–39.4, median 37.3). The mean birth weight was 2560.9 g (SD = 771.8, range 1100–3920, median 2550) and the number of preterm births admitted for prematurity care was seven (31.8%, 7/22). Placental abnormality was found in the four cases, which included two placenta accreta and two previa. However, there were no cases of hysterectomy or intervention. We identified one case of uterine rupture during pregnancy (4.5%, 1/22) at 27 weeks of gestation. Except for preterm birth, adverse neonatal outcomes were not found in this study.ConclusionDelivery of pregnant women who received adenomyomectomy can obtain safe perinatal outcomes under close monitoring of preterm labor and surveillance of catastrophic pregnancy related complications.     

The association of increased lung resistance protein expression with acquired etoposide resistance in human H460 lung cancer cell lines

Chemoresistance remains the major obstacle to successful therapy of cancer. In order to understand the mechanism of multidrug resistance (MDR) that is frequently observed in lung cancer patients, here we studied the contribution of MDR-related proteins by establishing lung cancer cell lines with acquired resistance against etoposide. We found that human H460 lung cancer cells responded to etoposide more sensitively than A549 cells. Among MDR-related proteins, the expression of p-glycoprotein (Pgp) and lung resistance protein (LRP) were much higher in A549 cells compared with that in H460 cells. When we established H460-R1 and -R2 cell lines by progressive exposure of H460 cells to increasing doses of etoposide, the response against etoposide as well as doxorubicin was greatly reduced in R1 and R2 cells, suggesting MDR induction. Induction of MDR was not accompanied by a decrease in the intracellular accumulation of etoposide and the expression of MDR-related proteins that function as drug efflux pumps such as Pgp and MRP1 was not changed. We found that the acquired resistance paralleled an increased expression of LRP in H460 cells. Taken together, our data suggest the implicative role of LRP in mediating MDR in lung cancer.     

Self-expandable metallic stent placement for malignant obstruction in patients with locally recurrent gastric cancer

Background  

Self-expandable metallic stents (SEMSs) provide effective palliation for inoperable malignant gastric outlet obstruction (GOO). The objective of this study was to evaluate the effectiveness of SEMSs in patients with recurrent gastric cancer after radical gastrectomy.     

Assessment of fluid shifts of body compartments using both bioimpedance analysis and blood volume monitoring

Fluid shifts are commonplace in chronic hemodialysis patients during the intra- and interdialytic periods. In this study, we evaluated fluid shifts of body compartments using both bioimpedance spectroscopy and blood volume monitoring from the start to the end of hemodialysis. 24 stable hemodialysis patients were included on the study. Relative change of blood volume was progressively reduced from the start to the end of hemodialysis (1 hr, -7.22+/-3.23%; 2 hr, -9.78+/-4.69%; 3 hr, -12.88+/-5.65%; 4 hr, -15.41+/-6.54%, respectively). Mean % reduction of intracellular fluid was not significantly different to that of extracellular fluid at the end of hemodialysis (delta ICF, -6.58+/-5.34% vs. delta ECF, -7.07+/-5.12%). Mean % fluid reduction of arms, legs and trunk was -11.98+/-6.76%, -6.43+/-4.37% and -7.47+/-4.56%, respectively at the end of hemodialysis. There were 3 characteristic patterns in blood-volume change. Similar amounts of fluid were removed from the extracellular and intracellular compartments during hemodialysis, with the arms showing the greatest loss in terms of body segments. The pattern of blood volume change measured by blood volume monitoring may be useful for more accurate determination of dry-weight and for correcting volume status in hemodialysis patients.