Real-world results of immune checkpoint inhibitors from the Taiwan National Health Insurance Registration System.

OBJECTIVE: Immune checkpoint inhibitors (ICIs) are a major advance in cancer treatment, but their payment benefits are unclear, resulting in financial risk. In Taiwan, the National Health Insurance Administration (NHIA) has adapted risk-sharing mechanisms to cover ICIs by collecting and assessing real-world evidence, such as case registration data, to adjust benefit packages for each medication, increase payment benefits of ICIs, and enable national health insurance sustainability. PATIENTS AND METHODS: This nationwide, multicenter, retrospective cohort study assessed the real-world use, effectiveness, and safety of ICIs reimbursed by the NHIA for treating multiple advanced cancers in Taiwan. We obtained data mainly from the NHIA Immune Checkpoint Inhibitor Registry Database. RESULTS: Between April 1, 2019, and March 31, 2020, 1644 patients received at least one dose of ICIs. The overall response rate (RR) was 29.1%. The metastatic urothelial carcinoma of patients ineligible for chemotherapy showed the highest RR. The estimated median progression-free survival (PFS) was 2.8 months (95% confidence interval [CI]=2.7-3 months), and renal cell carcinoma showed the longest PFS. The median PFS was reached in patients with most cancers except classic Hodgkin's lymphoma, which had a small sample size. The estimated survival probability was 50%. CONCLUSIONS: Under the national registration tracking system, Taiwan's high-cost drug policy has enabled access to new medicines and maximized patient benefits.

The effect of viscous soluble fiber on blood pressure: A systematic review and meta-analysis of randomized controlled trials.

AIMS: Dietary fiber intake, especially viscous soluble fiber, has been established as a means to reduce cardiometabolic risk factors. Whether this is true for blood pressure remains controversial. A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to investigate the effects of viscous soluble fiber supplementation on blood pressure and quantify the effect of individual fibers. DATA SYNTHESIS: MEDLINE, Embase, and Cochrane databases were searched. We included RCTs of ≥4-weeks in duration assessing viscous fiber supplementation from five types: ß-glucan from oats and barley, guar gum, konjac, pectin and psyllium, on systolic blood pressure (SBP) and diastolic blood pressure (DBP). Study data were pooled using the generic inverse variance method with random effects models and expressed as mean differences (MD) with 95% confidence intervals (CIs). Twenty-two (N = 1430) and twenty-one RCTs (N = 1343) were included in the final analysis for SBP and DBP, respectively. Viscous fiber reduced SBP (MD = -1.59 mmHg [95% CI: -2.72,-0.46]) and DBP (MD = -0.39 mmHg [95% CI: -0.76,-0.01]) at a median dose of 8.7 g/day (1.45-30 g/day) over a median follow-up of 7-weeks. Substantial heterogeneity in SBP (I2 = 72%, P < 0.01) and DBP (I2 = 67%, P < 0.01) analysis occurred. Within the five fiber types, SBP reductions were observed only for supplementation using psyllium fiber (MD = -2.39 mmHg [95% CI: -4.62,-0.17]). CONCLUSION: Viscous soluble fiber has an overall lowering effect on SBP and DBP. Inclusion of viscous fiber to habitual diets may have additional value in reducing CVD risk via improvement in blood pressure. PROTOCOL REGISTRATION: ClinicalTrials.gov identifier-NCT02670967.

Salba-chia (Salvia hispanica L.) in the treatment of overweight and obese patients with type 2 diabetes: A double-blind randomized controlled trial.

BACKGROUND AND AIM: Preliminary findings indicate that consumption of Salba-chia (Salvia hispanica L.), an ancient seed, improves management of type 2 diabetes and suppresses appetite. The aim of this study was to assesse the effect of Salba-chia on body weight, visceral obesity and obesity-related risk factors in overweight and obese adults with type 2 diabetes. METHODS: A double-blind, randomized, controlled trial with two parallel groups involved 77 overweight or obese patients with type 2 diabetes (HbA1c: 6.5-8.0%; BMI: 25-40 kg/m2). Both groups followed a 6-month calorie-restricted diet; one group received 30 g/1000 kcal/day of Salba-chia, the other 36 g/1000 kcal/day of an oat bran-based control. Primary endpoint was change in body weight over 6-months. Secondary endpoints included changes in waist circumference, body composition, glycemic control, C-reactive protein, and obesity-related satiety hormones. RESULTS: At 6-months, participants on Salba-chia had lost more weight than those on control (1.9 ± 0.5 kg and 0.3 ± 0.4 kg, respectively; P = 0.020), accompanied by a greater reduction in waist circumference (3.5 ± 0.7 cm and 1.1 ± 0.7 cm, respectively; P = 0.027). C-reactive protein was reduced by 1.1 ± 0.5 mg/L (39 ± 17%) on Salba-chia, compared to 0.2 ± 0.4 mg/L (7 ± 20%) on control (P = 0.045). Plasma adiponectin on the test intervention increased by 6.5 ± 0.7%, with no change observed on control (P = 0.022). CONCLUSIONS: The results of this study, support the beneficial role of Salba-chia seeds in promoting weight loss and improvements of obesity related risk factors, while maintaining good glycemic control. Supplementation of Salba-chia may be a useful dietary addition to conventional therapy in the management of obesity in diabetes. REGISTRATION: clinicaltrials.gov identifier: NCT01403571.

A systematic review and meta-analysis of randomized controlled trials of the effect of barley ß-glucan on LDL-C, non-HDL-C and apoB for cardiovascular disease risk reductioni-iv.

BACKGROUND/OBJECTIVES: There has been recent interest in barley as a therapeutic food owing to its high content of beta-glucan (ß-glucan), a viscous soluble fiber recognized for its cholesterol-lowering properties. The objective of this study was to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) investigating the cholesterol-lowering potential of barley ß-glucan on low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C) and apolipoprotein B (apoB) for cardiovascular disease (CVD) risk reduction. METHODS: MEDLINE, Embase, CINAHL and the Cochrane CENTRAL were searched. We included RCTs of ⩾3-week duration assessing the effect of diets enriched with barley ß-glucan compared with controlled diets on LDL-C, non-HDL-C or apoB. Two independent reviewers extracted relevant data and assessed study quality and risk of bias. Data were pooled using the generic inverse-variance method with random effects models and expressed as mean differences (MDs) with 95% confidence intervals (CIs). Heterogeneity was assessed by the Cochran Q-statistic and quantified by the I2 statistic. RESULTS: Fourteen trials (N=615) were included in the final analysis. A median dose of 6.5 and 6.9 g/day of barley ß-glucan for a median duration of 4 weeks significantly reduced LDL-C (MD=-0.25 mmol/l (95% CI: -0.30, -0.20)) and non-HDL-C (MD=-0.31 mmol/l (95% CI: -0.39, -0.23)), respectively, with no significant changes to apoB levels, compared with control diets. There was evidence of considerable unexplained heterogeneity in the analysis of non-HDL-C (I2=98%). CONCLUSIONS: Pooled analyses show that barley ß-glucan has a lowering effect on LDL-C and non-HDL-C. Inclusion of barley-containing foods may be a strategy for achieving targets in CVD risk reduction.

The effect of ginseng (genus Panax) on blood pressure: a systematic review and meta-analysis of randomized controlled clinical trials.

Pre-clinical evidence indicates the potential for ginseng to reduce cardiovascular disease risk and acutely aid in blood pressure (BP) control. Clinical evidence evaluating repeated ginseng exposure, however, is controversial, triggering consumer and clinician concern. A systematic review and meta-analysis were conducted to assess whether ginseng has an effect on BP. MEDLINE, EMBASE, Cochrane and CINAHL were searched for relevant randomized controlled trials ⩾4 weeks that compared the effect of ginseng on systolic (SBP), diastolic (DBP) and/or mean arterial (MAP) BPs to control. Two independent reviewers extracted data and assessed methodological quality and risk of bias. Data were pooled using random-effects models and expressed as mean differences (MD) with 95% confidence intervals (CIs). Heterogeneity was assessed and quantified. Seventeen studies satisfied eligibility criteria (n=1381). No significant effect of ginseng on SBP, DBP and MAP was found. Stratified analysis, although not significant, appears to favour systolic BP improvement in diabetes, metabolic syndrome and obesity (MD=-2.76 mm Hg (95% CI=-6.40, 0.87); P=0.14). A priori subgroup analyses revealed significant association between body mass index and treatment differences (ß=-0.95 mm Hg (95% CI=-1.56, -0.34); P=0.007). Ginseng appears to have neutral vascular affects; therefore, should not be discouraged for concern of increased BP. More high-quality, randomized, controlled trials assessing BP as a primary end point, and use of standardized ginseng root or extracts are warranted to limit evidence of heterogeneity in ginseng research and to better understand its cardiovascular health potential.

Prenatal fat-rich diet exposure alters responses of embryonic neurons to the chemokine, CCL2, in the hypothalamus.

Maternal consumption of a high-fat diet (HFD) during pregnancy is found to stimulate the genesis of hypothalamic orexigenic peptide neurons in the offspring, while HFD intake in adult animals produces a systemic low-grade inflammation which increases neuroimmune factors that may affect neurogenesis and neuronal migration. Building on this evidence and our recent study showing that the inflammatory chemokine, CCL2, stimulates the migration of hypothalamic neurons and expression of orexigenic neuropeptides, we tested here the possibility that prenatal exposure to a HFD in rats affects this chemokine system, both CCL2 and its receptors, CCR2 and CCR4, and alters its actions on hypothalamic neurons, specifically those expressing the neuropeptides, enkephalin (ENK) and galanin (GAL). Using primary dissociated hypothalamic neurons extracted from embryos on embryonic day 19, we found that prenatal HFD exposure compared to chow control actually reduces the expression of CCL2 in these hypothalamic neurons, while increasing CCR2 and CCR4 expression, and also reduces the sensitivity of hypothalamic neurons to CCL2. The HFD abolished the dose-dependent, stimulatory effect of CCL2 on the number of migrated neurons and even shifted its normal stimulatory effect on migrational velocity and distance traveled by control neurons to an inhibition of migration. Further, it abolished the dose-dependent, stimulatory effect of CCL2 on neuronal expression of ENK and GAL. These results demonstrate that prenatal HFD exposure greatly disturbs the functioning of the CCL2 chemokine system in embryonic hypothalamic neurons, reducing its endogenous levels and ability to promote the migration of neurons and their expression of orexigenic peptides.

Effect of whole and ground Salba seeds (Salvia Hispanica L.) on postprandial glycemia in healthy volunteers: a randomized controlled, dose-response trial.

OBJECTIVE: Incorporation of seeds into food products may attenuate postprandial glycemia. Whether these should be consumed as whole or in ground form is not known. SUBJECTS/METHODS: Using an acute, randomized controlled crossover design, the glycemic response of 13 healthy participants (6M:7F; 25.4±2.6 kg/m(2)) was studied on nine separate occasions. Test meals consisted of 7, 15 or 24 g of whole or ground Salba baked into white bread, and three control breads matched for energy, and macronutrient profile. Capillary blood samples were collected at fasting and over 2 h post consumption. RESULTS: A significant effect of dose (P=0.04), but no effect of form (P=0.74) or dose-form interaction (P=0.98) was found. No adverse events were reported. CONCLUSION: This study demonstrates that both ground and whole Salba are equally effective in attenuating blood glucose levels in a dose-dependent manner when incorporated into bread. Flexibility in the use of either the ground or whole seed may increase the ease of incorporation and acceptability as a dietary supplement.

Increased stroke risk in Bell's palsy patients without steroid treatment.

BACKGROUND AND PURPOSE: To investigate the risk of stroke development following a diagnosis of Bell's palsy in a nationwide follow-up study. METHODS AND MATERIALS: Information on Bell's palsy and other factors relevant for stroke was obtained for 433218 eligible subjects without previous stroke who had ambulatory visit in 2004. Of those, 897 patients with Bell's palsy were identified. Over a median 2.9 years of follow-up, 4581 incident strokes were identified. We estimated hazard ratios (HR) and 95% confidence intervals [CI] with Cox proportional hazard models adjusting for age, sex, co-morbidities, and important risk factors. Standardized incidence ratio of stroke amongst patients with Bell's palsy was analyzed. RESULTS: Compared with non-Bell's palsy patients, patients with Bell's palsy had a 2.02-times (95% CI, 1.42-2.86) higher risk of stroke. The adjusted HR of developing stroke for patients with Bell's palsy treated with and without systemic steroid were 1.67 (95% CI, 0.69-4) and 2.10 (95%, 1.40-3.07), respectively. CONCLUSIONS: Patients with Bell's palsy carry a higher risk of stroke than the general population. Our data suggest that these patients might benefit from a more intensive stroke prevention therapy and regular follow-up after initial diagnosis.

Necrotizing soft tissue infections in the intensive care unit.

Necrotizing soft tissue infection is a severe illness that is associated with significant morbidity and mortality. It is often caused by a wide spectrum of pathogens and is most frequently polymicrobial. Care for patients with necrotizing soft tissue infection requires a team approach with expertise from critical care, surgery, reconstructive surgery, and rehabilitation specialists. The early diagnosis of necrotizing soft tissue infection is challenging, but the keys to successful management of patients with necrotizing soft tissue infection are early recognition and complete surgical debridement. Early initiation of appropriate broad-spectrum antibiotic therapy must take into consideration the potential pathogens. Critical care management components such as the initial fluid resuscitation, end-organ support, pain management, nutrition support, and wound care are all important aspects of the care of patients with necrotizing soft tissue infection. Soft tissue reconstruction should take into account both functional and cosmetic outcome.

Polyphyllin D induces mitochondrial fragmentation and acts directly on the mitochondria to induce apoptosis in drug-resistant HepG2 cells.

We previously showed that polyphyllin D (PD) produced a stronger apoptotic effect in R-HepG2 with multi-drug resistance (MDR) than that in its parent HepG2 cells without MDR. In this study, PD was found to elicit mitochondrial fragmentation in live cells by using total internal reflection fluorescence microscopy (TIRFM). When mitochondria were isolated and treated directly with PD, a stronger swelling, deeper transmembrane depolarization, and more apoptosis-inducing factor (AIF) release were observed from the mitochondria of R-HepG2 than that of HepG2. These observations suggest that PD is a potent anti-cancer agent that bypasses MDR and elicits apoptosis via mitochondrial injury.

Evaluation of a new transcutaneous bilirubinometer in Chinese newborns.

OBJECTIVE: To evaluate the use of a new transcutaneous bilirubinometer (JM-103 Minolta Airshields) for detection of hyperbilirubinaemia in term or near-term healthy Chinese newborns. METHODS: Transcutaneous bilirubin (TcB) was used to screen for severe hyperbilirubinaemia in newborn infants. Blood was taken for total serum bilirubin (TSB) measurement if the initial TcB level was higher than the 40th centile in Bhutani's nomogram. Paired TcB and TSB results were then reviewed over 6 months. The correlation as well as the mean difference between the two methods were calculated. The clinical application of TcB with Bhutani's nomogram in the prediction of severe hyperbilirubinaemia in low-risk, medium-risk and high-risk thresholds for phototherapy was also analysed. RESULTS: 997 paired TcB and TSB measurements were evaluated in term or near-term newborns. TcB was significantly correlated with TSB, with a correlation coefficient of 0.83 (p<0.001). Their mean difference was 21.7 micromol/l (SD 21.2, p<0.001), with the 95% limits of agreement between -19.9 and 63.3 micromol/l. In both low-risk and medium-risk thresholds for phototherapy, using the 75th centile of Bhutani's nomogram as threshold, TcB could identify all cases and had a sensitivity and negative predictive value of 100% each, a specificity of 56% and positive predictive value of 23%. For high-risk cases, using the 75th centile as cut-off, the sensitivity and negative predictive value were reduced to 86.7% and 97.0%, respectively. CONCLUSION: An accurate point-of-care bilirubin analyser facilitates bilirubin screening and avoids unnecessary blood tests. Although using the transcutaneous bilirubinometer JM-103 might result in a significant difference between TcB and TSB measured in Chinese newborns, combining the use of TcB and the 75th centile in Bhutani's nomogram as the cut-off level can identify all cases of significant hyperbilirubinaemia.

Combination regimen in the treatment of chronic prostatitis.

The aim of the study was to report our experiences in the treatment of chronic prostatitis using combination regimen including ciprofloxacin, doxazosin, allopurinol and biofeedback perineal massage. From May 2003 to April 2004, 7 patients with NIH Category II-chronic bacterial prostatitis and 7 patients with NIH Category IIIA-inflammatory chronic pelvic pain syndrome were treated. The NIH-Chronic Prostatitis Symptom Index (NIH-CPSI) was scored by the patient before and after the treatment, 6 months later. In Category II patients, the bacterial eradication rate was 71% after ciprofloxacin treatment during a follow-up of 6 months. The beneficial response rate to allopurinol, doxazosin and biofeedback perineal massage was 50%, 42% and 85%, respectively. In NIH Category IIIA patients, the individual beneficial response rate to ciprofloxacin, allopurinol, doxazosin and biofeedback perineal massage was 57%, 100%, 71% and 100%, respectively. Comparing pre-treatment and post-treatment results of the combination regimen, there was a statistically significant improvement in the 3 domains of pain score, urinary symptoms and quality of life impact of the NIH-CPSI. Combination regimen including ciprofloxacin, doxazosin allopurinol and biofeedback perineal massage in the treatment of chronic prostatitis is a safe and effective modality in our limited experience.

Intractable livedoid vasculopathy successfully treated with hyperbaric oxygen.

We describe a new method for treating livedoid vasculopathy. The typical presentation of livedoid vasculopathy includes chronic, recurrent painful ulcers, satellite scar-like atrophy and telangiectasia involving the lower extremities. Histologically, these lesions show areas of ulceration and dermal vessel occlusion without frank inflammatory cell infiltration. There is currently no satisfactory therapy available for this disease. Hyperbaric oxygen (HBO) has recently established itself as one of the most effective methods of treating ischaemic wounds, including diabetic ulcers. We used this therapy in two patients whose lesions were resistant to multiple therapeutic modalities. Not only did their ulcers respond rapidly to the HBO therapy, but the disturbing wound pain also resolved at the same time. To our knowledge, this is the first successful trial of HBO therapy in livedoid vasculopathy. We believe this to be a very promising new therapy for livedoid vasculopathy and to be worth further investigation.

Quercetin glucuronides inhibited 2-aminofluorene acetylation in human acute myeloid HL-60 leukemia cells.

Our earlier study has demonstrated that following the exposure of rat to the arylamine carcinogen 2-aminofluorene, DNA-2-aminofluorene adducts were found in the target tissues liver, bladder, colon, lung and also in circulating leukocytes (lymphocytes and monocytes). The result also demonstrated that orally treated antioxidants decreased N-acetylation of 2-aminofluorene in target tissues and leukocytes. Therefore, this study investigated whether quercetin glucuronides could affect N-acetylation of 2-aminofluorene in human acute myeloid leukemia HL-60 cells. Evidence is presented here that human leukemia cells are capable of acetylating 2-aminofluorene. Quercetin glucuronides did inhibit 2-aminofluorene acetylation in intact cells. The results also indicated that quercetin glucuronides induced cytotoxicity in dose-dependent manner in the examined human acute myeloid leukemia HL-60 cells.

Intracavernosal injection of vascular endothelial growth factor induces nitric oxide synthase isoforms.

OBJECTIVE: To identify genes that are affected by vascular endothelial growth factor (VEGF), as an intracavernosal injection with VEGF improved the recovery of erectile function in a rat model of arteriogenic impotence, specifically examining the three nitric oxide synthase (NOS) genes, nNOS, eNOS, and iNOS. MATERIALS AND METHODS: Male rats had their pudendal arteries ligated or underwent a sham operation. They were then treated by an intracavernosal injection with 4 microg of VEGF in phosphate-buffered saline (PBS) or PBS alone. At 6 and 24 h after treatment electrostimulation was applied to the cavernosal nerve and the intracorporal pressure measured. The erectile tissue was then harvested for RNA isolation and cryo-sectioning. The isolated RNA was used for microarray and reverse transcription-polymerase chain reaction (RT-PCR) analyses, and the tissue sections for immunohistochemical analysis. RESULTS: Microarray analysis detected nNOS, eNOS and iNOS at very low expression levels in PBS-treated rats; expression levels were higher for eNOS and iNOS in all VEGF-treated rats. These results were further confirmed by RT-PCR analysis. Immunohistochemical analysis identified the cavernosal endothelium and smooth muscle as the tissue types where eNOS and iNOS were up-regulated, respectively. CONCLUSIONS: This is the first report of the induction of both eNOS and iNOS in the penis after intracavernosal VEGF. These events may help support a significant recovery of erectile function after interrupting the blood supply to the penis.

Gene expression profiling of an arteriogenic impotence model.

Penile arterial insufficiency is one of the most common causes of ED. We have established a traumatic arteriogenic insufficiency rat model by the ligation of the pudendal arteries. To simulate both acute and chronic traumatic injuries, five ligation periods (6 h, 3 days, 7 days, 3 weeks, and 6 weeks) were chosen. By electrostimulation of the cavernous nerve, the intracavernous pressure was determined to be between 20 and 40-cm H(2)O for the ligated rats compared to around 100-cm H(2)O for the control rats. The erectile tissue in the corpus cavernosum of these rats was then subjected to microarray analysis, in which an array that contains cDNA fragments representing 1176 rat genes was used. The results demonstrated that normal rat corpus cavernosum expressed approximately 200 genes at detectable levels and that ligation produced differential expression of approximately 25 genes, depending on the duration of ligation. The most highly ligation-induced gene was apolipoprotein D (ApoD), with peak expression in the 3- and 7-day ligated rats. Three of the insulin-like growth factor binding proteins (IGFBP-1, 3, and 5) were upregulated in all ligated rats. IGFBP-6, which was one of the most highly expressed genes in the normal corpus cavernosum, was down-regulated in all ligated rats. Cysteine proteases of the cathepsin family were also differentially expressed between control and ligated rats, with cathepsin K being down-regulated most. A few genes were upregulated only in the 6-week ligated rats, including angiotensin-converting enzyme. Finally, VEGF, whose induction has been identified in many other ischemic tissues, was not induced in corpus cavernous tissue of ligated rats.

Lead chelation therapy and urate excretion in patients with chronic renal diseases and gout.

BACKGROUND: It is known that chronic renal insufficiency (CRI) patients with gout may have subtle lead poisoning. In addition, gout episodes frequently aggravate progressive renal insufficiency because of the use of nephrotoxic drugs and urate deposition. Our study was arranged to evaluate the causal effect of environmental lead exposure on urate excretion in CRI patients. METHODS: A cross-section study and a randomized, controlled trial were performed. Initially, 101 patients with CRI and without a history of previous lead exposure received ethylenediaminetetraacetic acid mobilization tests to assess body lead stores (BLS). Then, a clinical trial was performed; 30 CRI patients with gout and high-normal BLS and the changes of urate excretion in these patients were compared before and after lead chelating therapy. The treated group received four-week chelating therapy, and the control group received a placebo therapy. RESULTS: The BLS of patients with CRI and gout was higher than that of patients with CRI only, and none had subtle lead poisoning. The BLS, not the blood lead level (BLL), significantly correlated to indices of urate excretion in all CRI patients after related factors were adjusted. In addition, after lead chelating therapy, urate clearance markedly improved after a reduction of the BLS of patients with CRI and gout (study group 67.9 +/- 80.0% vs. control group 1.2 +/- 34.0%, P = 0.0056). CONCLUSION: Our findings suggest that the chronic low-level environmental lead exposure may interfere with urate excretion of CRI patients. Importantly, the inhibition of urate excretion can be markedly improved by lead chelating therapies. These data shed light on additional treatment of CRI patients with gout; however, more studies are needed to confirm our findings.

Sustained-release effect of codried excipients of microcrystalline cellulose and Ganoderma fiber.

The sustained-release effects of codried excipient of modified Ganoderma (treated with alkaline solution) and microcrystalline cellulose at different ratios were examined using acetaminophen (ACT) as a model drug. Results demonstrate that the crushing strength of most ACT tablets made with codried powder at all ratios increased as compaction force increased; but a rapid decline was observed when compression force exceeded 2 tons. Drug release from tablets compressed at 0.5 ton increased as modified Ganoderma fiber content increased. But when the compression force exceeded 1 ton, the release rate was not influenced by the compaction force or the increasing content of Ganoderma fiber. However, the dissolution of ACT from these tablets could be sustained for longer than 24 h. The extent of drug release was shown to increase with increasing amounts of modified Ganoderma in the codried excipient. The addition of disintegrants could further accelerate the drug release from the tablet. Drug release was also dependent upon the amount and kind of disintegrant used. The influence was in the following order: primojel>crospovidone>starch 1500.

High-performance liquid chromatographic analysis for the characterization of triterpenoids from Ganoderma.

A high-performance liquid chromatographic (HPLC) analysis of triterpenoids from Ganoderma is developed and validated in an attempt to explore a way to differentiate a number of species of the genus Ganoderma. Results show that 64 samples examined in this study could be divided into 18 groups based on characteristics of the HPLC pattern of triterpenoids. This result also conforms with those of the morphological examination and the interfertility test by di-monokaryotic mating. The HPLC analysis of triterpenoids further reveals that differentiation among samples from three different regions each of the two species G. lucidum and G. tsugae is workable. Even then, an incorrect designation is found for two of the groups of samples that were originally classified as G. resinaceum but showed different morphological characteristics and mating incompatibility. In conclusion, an HPLC analysis of triterpenoids is a simple and easy way to differentiate among different species of the genus Ganoderma.

L-arginine enhances aerobic exercise capacity in association with augmented nitric oxide production.

We tested whether supplementation with L-arginine can augment aerobic capacity, particularly in conditions where endothelium-derived nitric oxide (EDNO) activity is reduced. Eight-week-old wild-type (E(+)) and apolipoprotein E-deficient mice (E(-)) were divided into six groups; two groups (LE(+) and LE(-)) were given L-arginine (6% in drinking water), two were given D-arginine (DE(+) and DE(-)), and two control groups (NE(+) and NE(-)) received no arginine supplementation. At 12-16 wk of age, the mice were treadmill tested, and urine was collected after exercise for determination of EDNO production. NE(-) mice demonstrated a reduced aerobic capacity compared with NE(+) controls [maximal oxygen uptake (VO(2 max)) of NE(-) = 110 +/- 2 (SE) vs. NE(+) = 122 +/- 3 ml O(2). min(-1). kg(-1), P < 0.001]. This decline in aerobic capacity was associated with a diminished postexercise urinary nitrate excretion. Mice given L-arginine demonstrated an increase in postexercise urinary nitrate excretion and aerobic capacity in both groups (VO(2 max) of LE(-) = 120 +/- 1 ml O(2). min(-1). kg(-1), P < 0.05 vs. NE(-); VO(2 max) of LE(+) = 133 +/- 4 ml O(2). min(-1). kg(-1), P < 0.01 vs. NE(+)). Mice administered D-arginine demonstrated an intermediate increase in aerobic capacity in both groups. We conclude that administration of L-arginine restores exercise-induced EDNO synthesis and normalizes aerobic capacity in hypercholesterolemic mice. In normal mice, L-arginine enhances exercise-induced EDNO synthesis and aerobic capacity.