Effectiveness of nurse-led interventions on medication adherence in adults taking medication for metabolic syndrome: A systematic review and meta-analysis.

AIMS AND OBJECTIVES: To determine the effectiveness of nurse-led interventions on medication adherence, medication knowledge and clinical outcomes in adults taking medication for metabolic syndrome. BACKGROUND: Despite the significance of interventions designed to improve medication adherence, a systematic review of nurse-led intervention studies for metabolic syndrome is lacking. DESIGN: A systematic review and meta-analysis of randomised controlled trials. METHODS: The study was conducted following the PRISMA guidelines checklist. PubMed, EMBASE, PsychINFO, CINAHL, Cochrane CENTRAL and other manual sources were searched in May 2021.The quality assessment was conducted using the Effective Public Health Practice Project Quality Assessment Tool for Quantitative Studies. Comprehensive Meta-Analysis 3.0 was used to calculate the pooled effect sizes with 95% confidence intervals. RESULTS: This review included 20 studies of nurse-led medication adherence interventions in 6017 adults at risk for metabolic syndrome. The pooled effect size using the random effects model indicated that nurse-led interventions had a significantly moderate impact on enhancing medication adherence and medication knowledge and improving selected clinical outcomes of available studies in nurse-led intervention groups compared with control groups. Duration of intervention (median 12 weeks), mode of delivery (group vs. individual) and using multiple strategies influenced outcomes of nurse-led medication adherence interventions. The results revealed that interventions of moderate- to high-quality studies were more likely to show significant improvements in medication adherence than those of low-quality studies. CONCLUSION: The meta-analyses showed that nurse-led interventions may enhance medication adherence and knowledge and improve clinical outcomes of this population. RELEVANCE TO CLINICAL PRACTICE: The findings may contribute to evidence-based information about nurse-led intervention and its selection of appropriate interventions for improving medication adherence in this population. PATIENT OR PUBLIC CONTRIBUTION: Patients or the public were not directly involved in this review.

Psychometric Properties of the Korean Version of the Perceived Therapeutic Efficacy Scale for Physical Activity in Adults With Type 2 Diabetes.

PURPOSE: The purpose of this study is to translate the Perceived Therapeutic Efficacy Scale (PTES) into Korean and investigate its validity and reliability. METHODS: The authors conducted a cross-sectional survey using baseline data from a randomized controlled study to psychometrically validate the PTES-Korean (PTES-K) among 108 adults with type 2 diabetes from an outpatient clinic at a university-affiliated hospital in Korea. The original PTES was forward-translated and back-translated to ensure translation equivalence of the PTES-K. Structured questionnaires were used for psychometric evaluation; exploratory and confirmatory factor analysis assessed validity, and Cronbach's alpha coefficient and intraclass correlation coefficient (ICC) were used for reliability. RESULTS: The interitem correlation analyses revealed that 5 items were redundant; thus, the scale was reduced to 5 items. A 1-factor model explained 76.85% of the variance; confirmatory factor analysis showed that this model adequately fit the data. The ICC for test-retest reliability was .78; Cronbach's alpha was .92. The PTES-K showed significant associations with the scores of diabetes self-care activities for physical activity, quality of life, and depressive symptoms. Participants with good glycemic control and regular physical activity tended to have a higher score on the PTES-K than their counterparts, demonstrating known-groups validity. CONCLUSIONS: The cross-cultural applicability, reliability, and validity of the PTES-K were confirmed. The PTES-K may be used in clinical settings to examine the potential role of perceived therapeutic efficacy for physical activity in enhanced glycemic control among patients with diabetes.

Under Our Nose: The Use of GIS Technology and Case Notes to Focus Search Efforts.

Missing person searches can entail much time, effort, and resources. With scientific data and techniques increasingly available to law enforcement and investigations units, can these tools be used to predict likely areas where persons or remains may be discovered, especially in cases where little to no information about the disappearance is available? A retrospective study of seventy-three (73) cases was conducted in Onondaga County, New York, U.S.A., in order to explore this question. Quantitative (geospatial) and qualitative (investigator notes) data were utilized to determine whether patterns exist that may assist in investigations of recent and "cold" missing person cases. Results showed a majority of cases with relative proximity (<5 miles) between victim last seen (VLS) and body recovered (BR) locations. Furthermore, investigators' notes demonstrated repeated descriptors reflecting natural or cultural features associated with hidden, clandestine provenance (e.g., near bodies of water, wooded areas). With future external validation of this study, consistent priority areas may be identified as foci of searches; these priority areas ideally should be thoroughly checked/cleared before the search zone is expanded.

Evaluation of the Measurement Properties of Self-reported Medication Adherence Instruments Among People at Risk for Metabolic Syndrome: A Systematic Review.

PURPOSE: The purpose of this study was to present a systematic review of available published studies that evaluated the measurement properties of self-reported instruments assessing global medication adherence in adults at risk for metabolic syndrome. METHODS: The authors searched PubMed, EMBASE, PsycINFO, and CINAHL in January 2015 for appropriate studies. The methodological quality (based on reliability, validity, responsiveness, and interpretability) of selected studies was assessed with the COSMIN checklist (Consensus-Based Standards for the Selection of Health Measurement Instruments). RESULTS: Of the 44 studies reviewed, 32 used classical test theory, and 14 used self-reported medication adherence instruments. More than half the studies included patients with hypertension, followed by diabetes, dyslipidemia, and increased body mass index. Among the measurement properties, internal consistency, hypothesis testing, and structural validity were frequently assessed items, whereas only 1 study evaluated responsiveness, and none evaluated measurement error. The MMAS-8 (Morisky Medication Adherence Scale-8 items) and the Hill-Bone scale were the most frequently used instruments. They were found to be well validated, with strong evidence for internal consistency and strong positive evidence for reliability, structural validity, hypothesis testing, and criterion validity. CONCLUSIONS: The MMAS-8 and Hill-Bone scale seem to be well-validated instruments for assessing medication adherence in adults at risk for metabolic syndrome. These findings may assist clinicians with selecting the appropriate instruments for assessing medication adherence in this population. However, further studies might be needed to define concepts to better understand the dimensions of each medication adherence instrument.

Psychometric Evaluation of a Korean Version of the Adherence to Refills and Medications Scale (ARMS) in Adults With Type 2 Diabetes.

PURPOSE: The purpose of the study was to examine the reliability and validity of the Adherence to Refills and Medications Scale-Korean (ARMS-K) among Korean adults with type 2 diabetes. METHODS: The Korean translated ARMS-K was back-translated to ensure translation equivalency. A cross-sectional survey was used to evaluate the psychometric properties with exploratory factor analysis for validity and Cronbach's alpha coefficients for reliability. RESULTS: The factor analysis of construct validity identified 3 dimensions of the ARMS-K, explaining 54.7% of the total variance. The internal consistency reliability for the total instrument was acceptable with a Cronbach's alpha of .801. There was good correlation between the ARMS-K and 8-item Morisky Medication Adherence Scale-Korean version (r = -0.698), indicating that these scales measure theoretically related constructs as evidence of convergent validity. As evidence of known groups validity, there was a significant association between the ARMS-K score and glycemic control (P = .048), indicating that the good glycemic controlled group was more likely to have a higher rate of adherence to refills and medications than the poor glycemic controlled group. CONCLUSIONS: These results support the cross-cultural applicability of the concepts underlying the ARMS-K. The ARMS-K can be used not only to assess adherence to refills and medications in Koreans with diabetes but also to examine the potential role of adherence to refills and medications in enhanced glycemic control of people with diabetes in a variety of clinical settings.

Optimal management for alcoholic liver disease: Conventional medications, natural therapy or combination?

Alcohol consumption is the principal factor in the pathogenesis of chronic liver diseases. Alcoholic liver disease (ALD) is defined by histological lesions on the liver that can range from simple hepatic steatosis to more advanced stages such as alcoholic steatohepatitis, cirrhosis, hepatocellular carcinoma and liver failure. As one of the oldest forms of liver injury known to humans, ALD is still a leading cause of liver-related morbidity and mortality and the burden is exerting on medical systems with hospitalization and management costs rising constantly worldwide. Although the biological mechanisms, including increasing of acetaldehyde, oxidative stress with induction of cytochrome p450 2E1, inflammatory cytokine release, abnormal lipid metabolism and induction of hepatocyte apoptosis, by which chronic alcohol consumption triggers serious complex progression of ALD is well established, there is no universally accepted therapy to prevent or reverse. In this article, we have briefly reviewed the pathogenesis of ALD and the molecular targets for development of novel therapies. This review is focused on current therapeutic strategies for ALD, including lifestyle modification with nutrition supplements, available pharmacological drugs and new agents that are under development, liver transplantation, application of complementary medicines, and their combination. The relevant molecular mechanisms of each conventional medication and natural agent have been reviewed according to current available knowledge in the literature. We also summarized efficacy vs safety on conventional and herbal medicines which are specifically used for the prevention and treatment of ALD. Through a system review, this article highlighted that the combination of pharmaceutical drugs with naturally occurring agents may offer an optimal management for ALD and its complications. It is worthwhile to conduct large-scale, multiple centre clinical trials to further prove the safety and benefits for the integrative therapy on ALD.

Tetracyclic triterpenoids in herbal medicines and their activities in diabetes and its complications.

Tetracyclic triterpenoids, including the dammarane, cucurbitane, cycloartane, lanostane and protostane groups, is a class of triterpenoids widely distributed in various medicinal plants, particularly those commonly used for the treatment of diabetes and its complications, such as Panax ginseng, Panax quinquefolium, Panax notoginseng, Gynostemma pentaphyllum, Astragalus membranaceus, Momordica charantia, and Ganoderma lucidum. This review highlights recent findings on the chemistry and bioactivities of tetracyclic triterpenoids from these plants and other popular herbal medicines.

The role of social support on the relationship of depressive symptoms to medication adherence and self-care activities in adults with type 2 diabetes.

AIM: To examine the mediating role of social support on the relationship of depressive symptoms to medication adherence and self-care activities in Korean adults. BACKGROUND: Recent evidence suggests that higher levels of social support are associated with improved medication adherence and self-care activities; however, the role of social support on the relationship of depressive symptoms to medication adherence and self-care activities is less well understood. DESIGN: A cross-sectional survey. METHODS: The data were collected from 311 Korean adults with type 2 diabetes who were taking hypoglycaemic agents in the period 2012-2013. Depressive symptoms, social support, medication adherence and self-care activities were assessed using structured questionnaires. Multiple regression analysis with adjustment for covariates and the Sobel test were used to examine the mediating effect of social support on the relationship of depressive symptoms to medication adherence and self-care activities. RESULTS: There were statistically significant differences by subgroups with and without depressive symptoms in social support, medication adherence and self-care activities of diet, physical activity and stress management. The Sobel test confirmed that social support mediated the effect of depressive symptoms on medication adherence and self-care activities of diet, physical activity and stress management. CONCLUSION: The evidence from this study suggests that social support-enhancing interventions that also manage depressive symptoms may be more timely and effective than interventions that target depressive symptoms alone in promoting adherence to medication adherence and self-care activities in this population.

Suppressor of cytokine signaling (SOCS) genes are silenced by DNA hypermethylation and histone deacetylation and regulate response to radiotherapy in cervical cancer cells.

Suppressor of cytokine signaling (SOCS) family is an important negative regulator of cytokine signaling and deregulation of SOCS has been involved in many types of cancer. All cervical cancer cell lines tested showed lower expression of SOCS1, SOCS3, and SOCS5 than normal tissue or cell lines. The immunohistochemistry result for SOCS proteins in human cervical tissue also confirmed that normal tissue expressed higher level of SOCS proteins than neighboring tumor. Similar to the regulation of SOCS in other types of cancer, DNA methylation contributed to SOCS1 downregulation in CaSki, ME-180, and HeLa cells. However, the expression of SOCS3 or SOCS5 was not recovered by the inhibition of DNA methylation. Histone deacetylation may be another regulatory mechanism involved in SOCS1 and SOCS3 expression, however, SOCS5 expression was neither affected by DNA methylation nor histone deacetylation. Ectopic expression of SOCS1 or SOCS3 conferred radioresistance to HeLa cells, which implied SOCS signaling regulates the response to radiation in cervical cancer. In this study, we have shown that SOCS expression repressed by, in part, epigenetically and altered SOCS1 and SOCS3 expression could contribute to the radiosensitive phenotype in cervical cancer.

The effect of pH on crystal characteristics and IR absorbance of copper sulfide nanoparticles.

Copper sulfide, CuS, was synthesized by an aqueous sonochemical method and it was investigated the effect of pH on crystal characteristics of CuS and IR absorbance. The formed CuS has main peaks as 27.68 degrees, 29.28 degrees, 31.79 degrees, 32.85 degrees, 47.94 degrees, 52.72 degrees and 59.3 degrees with the hexagonal structure. Average diameter of CuS was about 18 nm and molar ratio of Cu:S was as 1:1. The CuS prepared at pH 11 presents the highest visible light transmittance of 82.6% and that at pH 4 presents the highest IR rejected of 93.8%. The formation of CuS was affected by pH and led to new absorption band in the IR region. The CuS nanoparticles from this study could be used as thermal insulating materials for car- and house-window films with a high IR-cut.

Compound K modulates fatty acid-induced lipid droplet formation and expression of proteins involved in lipid metabolism in hepatocytes.

BACKGROUND & AIMS: A key factor in the development of type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) is hepatic steatosis. Incubation of human hepatic cells with free fatty acids (FFAs) causes accumulation of neutral lipids in lipid droplets (LDs) and serves as a model for hepatic steatosis. Ginsenosides, active constituents of ginsengs, have demonstrated beneficial effects in various pharmacological areas, including diabetes, however their effect on lipid accumulation in hepatocytes remains unclear. Here, we examine the effect of compound K (ComK), an active metabolite of ginsenosides, on the regulation of LD formation and on the expression of proteins involved in lipid homeostasis in hepatocytes. METHODS: HuH7 cells were pretreated with ComK, followed by lipid loading with FFA. LDs were visualized using Oil Red O staining and immunohistochemistry for the LD-related protein PLIN2. Triglyceride levels were determined in isolated LDs. The expression of proteins involved in lipid homeostasis was examined by Western blotting. RESULTS: Treatment with ComK significantly decreased LD formation in FFA-loaded HuH7 cells and increased phosphorylation levels of AMPK, and its substrate ACC. ComK also increased protein expression of peroxisome proliferator-activated receptor-α (PPAR-α) and acyl-CoA oxidase (ACOX1) together with elevated activity of a PPAR-α response element reporter construct. These effects were inhibited by the PPAR-α antagonist MK886. CONCLUSIONS: ComK reduced LD formation and TG accumulation in FFA-loaded hepatocytes, in part by up-regulating AMPK activity and PPAR-α related pathways. These results suggest that ComK may have efficacy for the treatment of hepatic steatosis and associated diseases.

High-mobility group box 2 (HMGB2) modulates radioresponse and is downregulated by p53 in colorectal cancer cell.

Overexpression of high-mobility group box 2 (HMGB2) is recently reported in several malignant cancers and was correlated with poor response to preoperative chemoradiotherapy of colorectal cancer patients. To enhance the chemoradiotherapy efficacy, the biological function of HMGB2 was investigated with respect to radiation response. HMGB2 gene knockdown cells were constructed by infecting shRNA expressing lentivirus and clonogenic assay was performed to count the radiosensitivity. HMGB2 knockdown sensitized HCT-116 and HT-29 colorectal cancer cells to ionizing radiation. This could be due to an increased DNA damage and an inefficient DNA damage repair in HMGB2 knockdown cells. In addition, an exposure to radiation downregulated HMGB2 expression in colorectal cancer cells with an intact TP53 gene. HMGB2 gene expression of TP53-mutant cell was not affected by irradiation. p53-mediated downregulation of HMGB2 was confirmed by direct activation of p53 using Nutlin-3 or by inducing p53 expression using Tet-On system. Luciferase reporter assay showed that HMGB2 promoter activity was inversely correlated with the amount p53 cotransfected. Our study revealed that HMGB2 is necessary to protect colorectal cancer cells from DNA damage and efficient DNA repair and p53-mediated downregulation is a critical mechanism of modulating HMGB2 expression.

Masticatory function following implants replacing a second molar.

PURPOSE: The aim of this study was to obtain objective and standardized information on masticatory function and patient satisfaction following second molar single implant therapy. METHODS: Twenty adult patients, who had restored second molar single implants more than 1 month before the study, were enrolled in this study. All patients received a chewing test using peanuts before and after insertion of the implant prosthesis, with a questionnaire and visual analogue scale (VAS) to evaluate the effect of second molar single implant therapy. RESULTS: This study obtained standardized information on the masticatory function objectively (e.g., P, R, X(50)) before (Pre-insertion) and after insertion (Post-insertion) of the implant prosthesis. Masticatory performance (P) after insertion of the implant prosthesis significantly increased from 67.8±9.9 to 84.3±8.5% (P<0.0001). With the implant prosthesis, the P value increased by 24%. The masticatory efficiency index (R) of Post-insertion is higher than that of Pre-insertion (P<0.0001). With the implant prosthesis, the R value increased by 29%. The median particle size (X(50)) of Post-insertion is lower than that of Pre-insertion (P<0.0001). More than 90% of the patients were satisfied with the second molar single implant therapy from a functional point of view. CONCLUSIONS: These findings indicate that a second molar single implant can increase masticatory function.

Application of a hybrid system comprising carbon-doped TiO2 film and a ceramic media-packed biofilter for enhanced removal of gaseous styrene.

It is difficult to efficiently remove gaseous styrene using a TiO(2) film-coated photoreactor under UV light. Therefore, we used a hybrid system consisting of a carbon-doped TiO(2) (C-TiO(2)) film and a media-packed biofilter in order to enhance the removal efficiency (RE) of gaseous styrene compared to that of a pure (undoped) TiO(2) photoreactor. The C-TiO(2) was synthesized by a sol-gel combustion method, and its absorption spectrum was stronger that of pure (undoped) TiO(2) in the UV-vis range. The resultant RE of the C-TiO(2) film was 113-200% higher than that of the pure TiO(2) film. The initial RE of the photoreactor for input styrene concentrations of 630 mg m(-3), 420 mg m(-3), and 105 mg m(-3) was 20.6%, 29.8%, and 40.0%, respectively. When the biofilter was added, the RE increased to 93.3%, 97.9%, and 99.0%, respectively. Thus, application of the hybrid system consisting of both a photoreactor coated with a C-TiO(2) film and a biofilter is advantageous in terms of the removal efficiency of gaseous styrene.

Benign paroxysmal positional vertigo as a complication of sinus floor elevation.

PURPOSE: Osteotome sinus floor elevation (OSFE) is an often-used technique of great utility in certain implant patients with resorbed posterior maxilla. Recently benign paroxysmal positional vertigo (BPPV) has been reported as an early postoperative complication following OSFE. Although OSFE-induced BPPV commonly resolves itself within a month without treatment, this complication can be a cause of trouble between the implant surgeon and patient. This report presents a case of BPPV following OSFE. METHODS: A 27-year-old man without any significant medical problems and missing his maxillary right first molar, was scheduled for OSFE and simultaneous implant placement. RESULTS: The patient suffered dizziness accompanied by nausea immediately after implant placement using OSFE. Following referral to the ear nose throat clinic, "right posterior canal BPPV" was diagnosed. Despite anti vertigo medication and a single episode of the Epley maneuver, the condition did not improve completely. The Epley maneuver was then applied 7 and 8 days later and the symptoms of BPPV disappeared. One year later, the patient remained symptom-free. CONCLUSIONS: Before sinus elevation with an osteotome, implant surgeons should screen out patients with a history of vertigo, to diminish the possibility of BPPV. Operators should be aware of BPPV symptoms. As the symptoms may be very incapacitating, immediate referral to an otorhinolaryngologist is recommended.

Effect of myristyl nicotinate on retinoic acid therapy for facial photodamage.

Based on the hypothesis that skin barrier impairment is a contributor to side-effects associated with retinoic acid therapy, a double-blind, placebo-controlled pilot study examined the combined use of retinoic acid with myristyl nicotinate (MN), a lipophilic derivative of niacin that enhances skin barrier function, in female subjects with mild to moderate facial photodamage. The study involved a 1-month run-in period with placebo or MN prior to initiation of retinoic acid therapy for 3 months. Analysis of skin biopsies revealed that retinoic acid therapy resulted in stratum corneum thinning of approximately 25% (P = 0.006 versus baseline) that was ameliorated by MN use (P < 0.005). Therapy resulted in an increased rate of transepidermal water loss (TEWL) of approximately 45% (P = 0.001 versus baseline) and use of MN protected against the increase in TEWL with the strongest protection provided by prior use of MN (P = 0.056 versus placebo). MN use reduced the incidence of side-effects of the therapy and again prior use provided the greatest reduction of side-effects. Subjects showed statistically significant clinical improvement (P < 0.05 versus baseline) during the study. MN use did not interfere with any clinical improvement parameters and improved effects on temple laxity (P = 0.01 versus placebo). Analysis of changes in epidermal thickness, Ki67-positive cells and intensity of loricrin staining demonstrated that MN either improved or did not interfere with retinoic acid efficacy. These results show that prior and concurrent use of MN can mitigate barrier impairment and improve the tolerability of retinoic acid therapy for facial photodamage without interfering with efficacy.

A topical lipophilic niacin derivative increases NAD, epidermal differentiation and barrier function in photodamaged skin.

The effects of myristyl nicotinate (MN), a nicotinic acid derivative designed to deliver nicotinic acid to skin without vasodilatation, on subjects with photodamaged skin have been studied. MN increased skin cell nicotinamide adenine dinucleotide (NAD) by 25% (P = 0.001) demonstrating effective delivery of nicotinic acid to skin. Relative to placebo, MN treatment of photodamaged facial skin increased stratum corneum thickness by approximately 70% (P = 0.0001) and increased epidermal thickness by approximately 20% (P = 0.001). In two separate studies, MN treatment increased rates of epidermal renewal by 6% (P = 0.003) to 11% (P = 0.001) and increased the minimal erythemal dose by 8.9 (P = 0.07) and 10% (P = 0.05) relative to placebo. MN treatment resulted in reductions in the rates of transepidermal water loss (TEWL) of approximately 20% relative to placebo on cheeks (P = 0.012) and arms (P = 0.017) of study subjects. Results of a tape stripping challenge before and after MN treatment demonstrated a significant correlation (P = 0.03) between increased skin NAD content and resistance to changes in TEWL for MN treated but not placebo subjects. Rates of TEWL changed more rapidly and to a greater extent in atopic subjects compared with normal subjects. The results indicate that MN enhances epidermal differentiation and barrier function in skin, suggesting that this method of nicotinic acid delivery may prove useful in limiting progression of actinic skin damage and possibly in treating other conditions involving skin barrier impairment.

Cyclooxygenase-2 inhibitory phenylbutenoids from the rhizomes of Zingiber cassumunar.

Phenylbutenoids isolated previously from the CHCl3 extracts of the rhizomes of Zingiber cassumunar, were evaluated for their cyclooxygenase-2 (COX-2) inhibitory activity along with a new isolate, from the n-BuOH extracts of this plant. The COX-2 inhibitory assay was performed by measuring prostaglandin E2 production in lipopolysaccharide-stimulated mouse macrophage RAW 264.7 cells. Two phenylbutenoid dimers, and, exhibited considerable activity with IC50 values of 2.71 and 3.64 microM. Two phenylbutenoid monomers, and, showed moderate activity (IC50 14.97, 20.68 microM, respectively). The other three phenylbutenoids, were found to be inactive. Compound was elucidated as a new phenylbutenoid glycoside, namely, (E)-4-(3,4-dimethoxyphenyl)but-3-en-1-O-beta-D-glucopyranoside by spectral analysis including various 1D- and 2D-NMR experiments.

Simultaneous determination of myristyl nicotinate, nicotinic acid, and nicotinamide in rabbit plasma by liquid chromatography-tandem mass spectrometry using methyl ethyl ketone as a deproteinization solvent.

Myristyl nicotinate (Nia-114) is an ester prodrug being developed for delivery of nicotinic acid (NIC) into the skin for prevention of actinic keratosis and its progression to skin cancer. To facilitate dermal studies of Nia-114, a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method using methyl ethyl ketone (MEK) as a deproteinization solvent was developed and validated for the simultaneous determination of Nia-114, NIC, and nicotinamide (NAM) in rabbit plasma. NAM is the principal metabolite of NIC, which is also expected to have chemopreventive properties. The analytes were chromatographically separated using a Spherisorb Cyano column under isocratic conditions, and detected by multiple reaction monitoring (MRM) in positive-ion electrospray ionization mode with a run time of 9 min. The method utilized a plasma sample volume of 0.2 ml and isotope-labeled D4 forms of each analyte as internal standards. The method was linear over the concentration range of 2-1000, 8-1000, and 75-1000 ng/ml, for Nia-114, NIC, and NAM, respectively. The intra- and inter-day assay accuracy and precision were within +/-15% for all analytes at low, medium, and high quality control standard levels. The relatively high value for the lower limit of quantitation (LLOQ) of NAM was demonstrated to be due to the high level of endogenous NAM in the rabbit plasma (about 350 ng/ml). Endogenous levels of NIC and NAM in human, dog, rat, and mouse plasma were also determined, and mean values ranged from <2 ng/ml NIC and 38.3 ng/ml NAM in human, to 233 ng/ml NIC and 622 ng/ml NAM in mouse. Nia-114 was generally unstable in rabbit plasma, as evidenced by loss of 44-50% at room temperature by 2 h, and loss of 64-70% upon storage at -20 degrees C for 1 week, whereas it was stable (<7% loss) upon storage at -80 degrees C for 1 month.

Humulene derivatives from Zingiber zerumbet with the inhibitory effects on lipopolysaccharide-induced nitric oxide production.

A new humulene sesquiterpene, 5-hydroxyzerumbone (5-hydroxy-2E,6E,9E-humulatrien-8-one) (1) and a known compound, zerumboneoxide (2) were isolated from the rhizomes of Zingiber zerumbet (Zingiberaceae), and found to inhibit lipopolysaccharide-induced nitric oxide production in murine macrophage RAW 264.7 cells with IC50 values of 14.1 and 23.5 microM, respectively, by bioassay-guided fractionation (positive control: N(omega)-monomethyl-L-arginine, IC50=21.3 microM). The structure of 1 was determined by spectroscopic methods including 1D and 2D-NMR.