The impact of pegylated interferon and ribavirin combination treatment on lipid metabolism and insulin resistance in chronic hepatitis C patients

Background/Aims

Lipid profile and insulin resistance (IR) are associated with hepatitis C virus (HCV) and may predict the chronic hepatitis C (CHC) treatment response. The aim of this study was to determine the association between CHC treatment response and lipid profile and IR change during treatment.

Methods

In total, 203 CHC patients were reviewed retrospectively between January 2005 and December 2011 at Soon Chun Hyang University Hospital. The lipid profile, homeostasis model for assessment (HOMA) of IR (HOMA-IR), and HOMA of β cells (HOMA-β) were evaluated before interferon plus ribavirin therapy (BTx), at the end of treatment (DTx), and 24 weeks after the end of treatment (ATx).

Results

A sustained virologic response (SVR) was achieved by 81% of all patients (49/60), 60% (n=36) of whom possessed genotype 1, with the remainder being non-genotype-1 (40%, n=24). Apart from age, which was significantly higher in the non-SVR group (SVR, 48.0±11.2 years, mean±SD; non-SVR, 56.6±9.9 years; P<0.01), there were no significant differences in the baseline characteristics between the SVR and non-SVR groups. In the SVR group, low density lipoprotein-cholesterol (LDL-C) had significantly changed at DTx and ATx compared to BTx. In addition, HOMA-IR and HOMA-β were significantly changed at DTx in the SVR group. Among those with a high baseline insulin resistance (HOMA-IR >2.5), HOMA-IR was significantly changed at DTx in the SVR group.

Conclusions

LDL-C appears to be associated with HCV treatment in SVR patients. Furthermore, eradication of HCV may improve whole-body IR and insulin hypersecretion, as well as high baseline insulin resistance (HOMA-IR >2.5).     

Alcohol Abuse and Cardiac Disease

Background

Understanding the relationship between alcohol abuse, a common and theoretically modifiable condition, and the most common cause of death in the world, cardiovascular disease, may inform potential prevention strategies.

Implementing national standards for cancer pain management: Program model and evaluation

The purpose of this quasi-experimental (pre- and posttest) study was to test a model pain management program (PMP) to implement the American Pain Society (APS) quality assurance standards for the management of acute and chronic cancer pain using a continuous quality improvement (CQJ) approach to improve professionals' knowledge and skills, patient satisfaction, and to identify areas needing improvement. The sample consisted of 1210 nurse responses and 698 interviews of patients with pain during hospitalization at a major urban cancer center. The PMP provided a structure (standards), educational opportunities, and training in CQI methods. Outcome measures included a patient evaluation questionnaire and concerns checklist: nurse knowledge, attitude and barriers questionnaire; and focus groups to identify areas needing improvement. Significant improvements were found in patients' satisfaction, nurses' knowledge and attitude scores, and reductions in nurses' perceptions of barriers. Focus groups revealed the need for improved communication among disciplines about pain and better assessment of patients unable to self-report. The program met its goal of implementing the APS standards, educating nurses, and identifying “system” problems, and improving overall patient satisfaction.     

Integration of IEEE 1451 and HL7 Exchanging Information for Patients’ Sensor Data

HL7 (Health Level 7) is a standard developed for exchanging incompatible healthcare information generated from programs or devices among heterogenous medical information systems. At present, HL7 is growing as a global standard. However, the HL7 standard does not support effective methods for treating data from various medical sensors, especially from mobile sensors. As ubiquitous systems are growing, HL7 must communicate with various medical transducers. In the area of sensor fields, IEEE 1451 is a group of standards for controlling transducers and for communicating data from/to various transducers. In this paper, we present the possibility of interoperability between the two standards, i.e., HL7 and IEEE 1451. After we present a method to integrate them and show the preliminary results of this approach.     

Ginseng and ginsenoside Rg3, a newly identified active ingredient of ginseng, modulate Ca2+ channel currents in rat sensory neurons

There is increasing evidence that ginseng influences pain modulation. In spite of extensive behavior studies, the detailed mechanism of ginseng actions at the cellular level and the identity of the active substance have not been elucidated yet. Whole-cell patch-clamp recordings were used to examine the modulation of high-voltage-activated Ca2+ channel currents by ginseng total saponins and its various individual ginsenosides in rat dorsal root ganglion neurons. Application of ginseng total saponins suppressed Ca2+ channel currents in a dose-dependent manner. Occlusion experiments using selective blockers revealed that ginseng total saponins could modulate L-, N-, and P-type currents. The co-application of ginseng total saponins and the gamma-opioid receptor agonist, D-Ala(2), N-MePhe(4), Gly(5)-ol-enkephalin (DAMGO), produced non-additive effects in most cells tested and each effect was significantly relieved by a depolarizing prepulse. Overnight treatment of cells with pertussis toxin profoundly reduced the inhibition. Furthermore, we now report that ginsenoside Rg3, among the major fractions of ginseng saponins, is a newly identified active component for the inhibition. These results suggest that the modulation of Ca2+ channels by ginseng total saponins, in particular by ginsenoside Rg3, could be part of the pharmacological basis of ginseng-mediated antinociception.     

Functional expression of a novel ginsenoside Rf binding protein from rat brain mRNA in Xenopus laevis oocytes

We have shown that ginsenoside Rf (Rf) regulates voltage-dependent Ca(2+) channels through pertussis toxin (PTX)-sensitive G proteins in rat sensory neurons. These results suggest that Rf can act through a novel G protein-linked receptor in the nervous system. In the present study, we further examined the effect of Rf on G protein-coupled inwardly rectifying K(+) (GIRK) channels after coexpression with size-fractionated rat brain mRNA and GIRK1 and GIRK4 (GIRK1/4) channel cRNAs in Xenopus laevis oocytes using two-electrode voltage-clamp techniques. We found that Rf activated GIRK channel in a dose-dependent and reversible manner after coexpression with subfractions of rat brain mRNA and GIRK1/4 channel cRNAs. This Rf-evoked current was blocked by Ba(2+), a potassium channel blocker. The size of rat brain mRNA responding to Rf was about 6 to 7 kilobases. However, Rf did not evoke GIRK current after injection with this subfraction of rat brain mRNA or GIRK1/4 channel cRNAs alone. Other ginsenosides, such as Rb(1) and Rg(1), evoked only slight induction of GIRK currents after coexpression with the subfraction of rat brain mRNA and GIRK1/4 channel cRNAs. Acetylcholine and serotonin almost did not induce GIRK currents after coexpression with the subfraction of rat brain mRNA and GIRK1/4 channel cRNAs. Rf-evoked GIRK currents were not altered by PTX pretreatment but were suppressed by intracellularly injected guanosine-5'-(2-O-thio) diphosphate, a nonhydrolyzable GDP analog. These results indicate that Rf activates GIRK channel through an unidentified G protein-coupled receptor in rat brain and that this receptor can be cloned by the expression method demonstrated here.     

Stress, coping, and depression in non-ulcer dyspepsia patients

Thirty adults with upper gastrointestinal symptoms in the absence of structural organic disease diagnosed with non-ulcer dyspepsia (NUD) were compared to 30 healthy adults who had visited the hepatobiliary clinic for medical evaluation of non-organic complaints without NUD. Medical investigation in both groups were negative. Before independent gastrointestinal physicians conducted diagnostic evaluations, all subjects were evaluated for anxiety and depressive symptoms, stressful life events, coping style, and social support. The measures included Symptom Checklist 90-Revised (SCL-90-R), Beck Depression Inventory (BDI), Spielberger State-Trait Anxiety Inventory (STAI), Ways of Coping Checklist, and Interpersonal Support Evaluation List, and a self-report questionnaire, which measured the quantity of perceived stressful life events. The NUD patients reported significantly more symptoms of depression, more perceived stressful life events, less problem-focused coping, and less social support than the control subjects. Depressive symptoms were negatively correlated with interpersonal support, whereas, problem-focused coping was positively correlated with interpersonal support in the NUD patients. The two groups did not differ significantly in terms of anxiety and emotion-focused coping. The implications of these findings for the diagnosis and treatment of NUD are discussed.     

Modulation of thymidine incorporation by κ-opioid ligands in rat spinal cord-dorsal root ganglion co-cultures

β-Endorphin, met-enkephalin and several μ-selective opioid agonists were shown to decrease thymidine incorporation into DNA in various neural cell cultures. We now report that the κ-selective opioid agonists U50488, U69593 and MR2034 modulate [³H]thymidine incorporation into DNA in rat spinal cord-dorsal root ganglion co-cultures. U50488 at 10 μM increased by 60% thymidine incorporation in 6-day-old cultures. The thymidine incorporation induced by U50488 was blocked by the κ-selective antagonist nor-binaltorphimine, as well as by pertussis toxin and LiCl U50488 treatment stimulated phosphatidylinositol turnover by three-fold compared with untreated controls. These findings suggest that κ-opioid agonists modulate DNA synthesis in spinal cord-dorsal root ganglion co-cultures through a mechanism which involves pertussis toxin-sensitive GTP-binding proteins, as well as activation of phosphatidylinositol turnover.     

Flow calorimetry--a useful tool for determination of immobilized cis-epoxysuccinate hydrolase activity from Nocardia tartaricans

Bacterial cells Nocardia tartaricans with cis-epoxysuccinate hydrolase activity were entrapped in hardened calcium pectate gel by a commercial high performance encapsulator. This enzyme (in a single step reaction with no formation of side products) was used to hydrolyze disodium cis-epoxysuccinate to a pure enantiomer--disodium L-(+)-tartrate. Activities of this enzyme were determined using flow calorimetry. The validity of this method was corroborated by HPLC and isotachophoresis. The immobilized biocatalyst has activity (75.8 U/mgdry) able to convert disodium cis-epoxysuccinate to disodium tartrate at 94% yield in 5.5h. Immobilization of N. tartaricans in hardened calcium pectate gel beads had a positive effect on the activity of cis-epoxysuccinate hydrolase, storage stability, yield, and time of bioconversion.