A double-blind, randomized, and active-controlled phase III study of Herbiron drink in the treatment of iron-deficiency anemia in premenopausal females in Taiwan.

BACKGROUND: About 468 million non-pregnant women are estimated to suffer from iron-deficiency anemia (IDA) worldwide. The highest prevalence of IDA occurs in the Taiwanese population. OBJECTIVE: To evaluate the effectiveness of Herbiron to increase iron absorption in women with IDA. DESIGN: Phase III double-blind, randomized, active-controlled, and parallel comparative study enrolled 124 patients with IDA and consisted of a 2-week run-in period, randomization, 12 weeks of supplementation, and 4 weeks of follow-up. The treatment group received Herbiron drink 50 mL p.o., b.i.d., before meals (daily iron intake: 21 mg/day) plus placebo tablets. The control group received a ferrous sulfate tablet, t.i.d., plus placebo 50-mL drink before meals (daily iron intake: 195 mg/day). RESULTS: Both treatments significantly improved hemoglobin and all secondary efficacy endpoints. Most IDA patients treated with Herbiron or ferrous sulfate finished the study in the normal range. Ferrous sulfate treatment induced a rapid rate of hemoglobin synthesis, which plateaued by week 8, whereas Herbiron treatment increased the rate of hemoglobin synthesis more slowly, likely due to its nine-fold lower iron content. Gastrointestinal adverse events (diarrhea, abdominal pain, dyspepsia, and nausea) but not infectious adverse events were significantly more common in the ferrous sulfate group (n=11, 18.3%) than those in the Herbiron group (n=1, 1.6%) (p=0.004). CONCLUSION: Twelve weeks of Herbiron treatment delivering 21mg of iron or ferrous sulfate treatment delivering 195 mg of iron induced normal hemoglobin levels in 62 or 91% of non-pregnant women with IDA in Taiwan, respectively, suggesting dose-dependent and bioavailability effects.

Health-related quality of life and healthcare resource utilization in Taiwanese women with menopausal symptoms: a nation-wide survey.

BACKGROUND: Menopausal experience differs among women with different cultural and ethnic backgrounds and may impact quality of life. Some women with severe menopausal symptoms seek medical help to alleviate menopause-related symptoms. PURPOSE: This study examined the demographic characteristics and health-related quality of life (HRQOL) of Taiwanese women experiencing menopausal symptoms and examined associations between menopausal symptoms and, respectively, poor HRQOL and healthcare resource utilization. METHODS: This cross-sectional study used data from the 2005 National Health Interview Survey in Taiwan, which used a multistaged stratified systematic sampling scheme. A total of 4,437 women aged 35-64 years were analyzed. We used multivariable logistic regression models to identify variables significantly and independently associated with the presence of menopausal symptoms. We also used the model to assess the odds of poor HRQOL and healthcare resource utilization in women with menopausal symptoms compared with those without. RESULTS: Eight hundred and forty-six women (19.1%) reported experiencing menopausal symptoms. Age, religion, smoking, exercise, and comorbidity were independently associated with the presence of such symptoms. The propensity score-adjusted odds ratio of poor physical HRQOL, poor mental HRQOL, use of outpatient, traditional Chinese medicine and emergency room services, and hospitalization for women with menopausal symptoms were 1.85 (95% CI [1.54, 2.21]), 1.66 (95% CI [1.40, 1.97]), 1.39 (95% CI [1.18, 1.63]), 1.73 (95% CI [1.37, 2.18]), 1.44 (95% CI [1.15, 1.81]), and 1.36 (95% CI [1.02, 1.81]), respectively, compared with those without symptoms. CONCLUSIONS: Nearly one fifth of women aged 35-64 years in Taiwan experience menopausal symptoms. The presence of menopausal symptoms increases the likelihood of poor HRQOL and healthcare resource utilization even after controlling for possible confounders.

In vitro study of the tocolytic effect of oroxylin A from Scutellaria baicalensis root.

Scutellariae Radix is one of the well-known tocolytic Chinese herbs. Oroxylin A is isolated from the root of Scutellaria baicalensis. The main syndrome of preterm birth is caused by uterus contractions from excitatory factors. Administration of tocolytic agents is a strategy to prevent the occurrence of preterm births. The aim of this study was to investigate the effects of oroxylin A on contractions of uterine strips isolated from non-pregnant female Wistar rats (250-350 g). Contractions of the uterus were induced with acetylcholine (Ach) (1 microM), PGF2alpha (0.1 microM), oxytocin (10-3 U/ml), KCl (56.3 mM), tetraethylammonium (TEA; 1 and 10 mM), 4-aminopyridine (4-AP; 5 mM), glipizide (30 microM), a nitric oxide synthase (NOS) inhibitor (LNNA; 10-3M), a beta-receptor blocker (propranolol; 10 microM), and a cyclooxygenase inhibitor (indomethacin; 60 microM). The inhibitory effects of the amplitude and frequency of spontaneous contractions by oroxylin A were antagonized with Ach (IC50 22.85 microM), PGF2alpha (IC5027.28 microM), oxytocin (IC50 12.34 microM), TEA; 1 and 10 mM (IC50 52.73 and 76.43 microM), 4-AP (IC50 67.16 microM), and glipizide (IC5027.53 microM), but oroxylin A was not influenced by Ca2+-free medium, LNNA, propranolol, or indomethacin. Otherwise, oroxylin A-mediated relaxation of the rat uterus might occur through opening of uterine calcium-dependent potassium channels or adenosine triphosphate potassium channel activation. This suggests that oroxylin A is the tocolytic principle constituent of Scutellariae Radix, and oroxylin A may provide a lead compound for new tocolytic drug development in the future.

Treatment of interstitial cystitis with hydrodistention and bladder training.

This study aimed to evaluate the efficacy of hydrodistention (HD) and bladder training for interstitial cystitis (IC). From 1997 to 2006, 361 consecutive IC patients were treated by HD, followed by bladder training. Each patient was followed up using a diary for 8 weeks after HD weekly and monthly thereafter. The efficacy of the treatment was evaluated using the average of the voided volumes and the voiding frequency. The mean +/- standard deviation of the pre-HD daytime voided volumes and voiding frequency were 110.0 +/- 47.0 ml and 14.7 +/- 11.0, respectively. Furthermore, the nocturnal values were 173.1 +/- 91.8 ml and 2.8 +/- 1.7, respectively. After 72 weeks post-HD, the 185 patients who completed the follow-up had volumes/frequency of daytime, 306.5 +/- 80 ml and 6.9 +/- 2.1, respectively, and nocturnal, 325.8 +/- 122.4 ml and 1.3 +/- 0.6, respectively. The implementation of HD and bladder training is crucially important for long-term remission among IC patients.

Effects of omega-3 fatty acids on leukocyte Th1/Th2 cytokine and integrin expression in rats with gut-derived sepsis.

OBJECTIVES: This study examined the effect of fish oil (FO)-enriched diets before and/or omega-3 fatty acid-containing total parenteral nutrition (TPN) after sepsis on the distribution of the T-lymphocyte subpopulation, intracellular cytokine, and intestinal immunity in rats with gut-derived sepsis. METHODS: Rats were assigned to a control or one of four experimental groups. The control group and groups 1 and 2 were fed a semipurified diet, and groups 3 and 4 received FO instead of 20% soybean oil. After feeding the diets for 10 d, sepsis was induced by cecal ligation and puncture (CLP) in the experimental groups, whereas a sham operation was performed in the control group. TPN was maintained for 3 d after the CLP or sham operation. The control group and groups 1 and 3 were infused with conventional TPN, whereas the TPN solution used for groups 2 and 4 were supplemented with FO. All rats were sacrificed 3 d after the operation to examine their immune responses. RESULTS: Plasma and intestinal immunoglobin A levels were higher in the FO-supplemented groups than in the control group and group 1. Lymphocyte interferon-gamma expression in groups 3 and 4 was significantly lower, whereas interleukin-4 expression was higher than those of the control group and groups 1 and 2. The splenocyte CD4 percentage in groups 3 and 4 and the CD4/CD8 ratio in group 4 were significantly higher than those in group 1. CONCLUSION: These findings suggest that FO administration before and/or after CLP are not immunosuppressive. FO-enriched diets before or before and after CLP resulted in a T-helper type 2 response and enhanced immunoglobulin A secretion. In addition, the splenocyte CD4 levels and CD4/CD8 ratio were maintained in rats with gut-derived sepsis.

Antitumor effects of Osthol from Cnidium monnieri: an in vitro and in vivo study.

Cnidium monnieri (L.) Cusson is a Chinese medicine which is used widely by traditional medicine doctors. Osthol is a major bio-activity compound of the herb. In this study, osthol was isolated from C. monnieri and its in vitro and in vivo antitumor effects studied. The results of the in vitro study showed: that osthol inhibited the growth of HeLa, in a time- and concentration-dependent manner, with IC(50) values of 77.96 and 64.94 microm for 24 and 48 h, respectively; that osthol had lower cytotoxic effects in primary cultured normal cervical fibroblasts; and that increased DNA fragmentation and activated PARP in HeLa after treatment with osthol which could induce apoptosis. The results of the in vivo model showed that the survival days of the P-388 D1 tumor-bearing CDF(1) mice were prolonged (ILS% = 37) after osthol (30 mg/kg) was given once a day for 9 days. Based on these results, it is suggested that osthol could inhibit P-388 D1 cells in vivo and induce apoptosis in HeLa cells in vitro, and that osthol is good lead compound for developing antitumor drugs. However, C. formosanum Yabe of Taiwan's endemic plants contained little osthol, with no imperatorin, and its major components were different from that of C. monnieri. Therefore, it is suggested that C. formosanum also may possess economic worth.

Dietary arginine enhances adhesion molecule and T helper 2 cytokine expression in mice with gut-derived sepsis.

This study investigated the effects of arginine (Arg) on cellular adhesion molecules and intracellular Th1/Th2 cytokine expressions in mice with polymicrobial sepsis. Myeloperoxidase activity in organs was also analyzed to identify the extent of tissue injury resulting from neutrophil infiltration. Mice were randomly assigned to a normal group (NC), a control group, or an Arg group. The NC group was fed a standard chow diet. The control group was fed a common semipurified diet, and in the Arg group, part of the casein was replaced by Arg, which provided 2% of the total calories. After 3 weeks, sepsis was induced by cecal ligation and puncture (CLP) in the control and Arg groups. Mice in the experimental groups were sacrificed at 0, 6, 12, and 24 h after CLP, whereas mice in the NC group were sacrificed when the CLP was performed. Blood and organ samples were immediately collected for further analysis. Results showed that compared with the control group, plasma intracellular adhesion molecule-1 levels were significantly higher in the Arg group 12 and 24 h after CLP. Lymphocyte interferon-gamma expression in the Arg groups was significantly lower, whereas interleukin (IL)-4 expression was higher than the control group at various time points after CLP. The expression of lymphocyte CD11a/CD18 was significantly higher in the Arg group 6, 12, and 24 h after CLP than those of the corresponding control group and the NC group. PMN expressions of CD11b/CD18 in the Arg groups were higher than those in the control group at 12 and 24 h after CLP. The Arg group had higher IL-6 levels at 6 and 12 h in the kidney and intestine and 12 h in the lung after CLP. Higher myeloperoxidase activities were observed in the Arg groups at 24 h after CLP than those in the control group in various organs. These findings suggest that pretreatment with an Arg-supplemented diet enhances adhesion molecule and inflammatory cytokine expression during sepsis, which may aggravate the inflammatory reaction and increase neutrophil infiltration into tissues. In addition, Arg supplementation reduced intracellular interferon-gamma and enhanced IL-4 expression. This change may promote the Th2-type response and suppress the cellular immune response in gut-derived sepsis.

Dietary glutamine supplementation reduces cellular adhesion molecule expression and tissue myeloperoxidase activity in mice with gut-derived sepsis.

OBJECTIVES: This study investigated the effects of glutamine (Gln) on plasma intracellular adhesion molecule-1 levels and leukocyte integrin (CD11a/CD18 and CD11b/CD18) expressions in gut-derived sepsis. Myeloperoxidase (MPO) activities in organs were also analyzed to identify the extent of tissue injury resulting from neutrophil infiltration. METHODS: Mice were randomly assigned to a normal group (NC), a control group, or a Gln group. The NC group was fed standard chow diet; the control group was fed a common semipurified diet; and the Gln group received a diet in which part of the casein was replaced by Gln, which provided 25% of total amino acid nitrogen. After 3 wk, sepsis was induced by cecal ligation and puncture (CLP) in the control and Gln groups. Mice in the experimental groups were killed at 0, 6, 12, and 24 h after CLP. Mice in the NC group were killed when CLP was performed. Blood and organ samples were collected for further analysis. RESULTS: Plasma intracellular adhesion molecule-1 levels were significantly lower in the Gln group than in the control group at 6, 12, and 24 h after CLP. Expressions of lymphocyte CD11a/CD18 were significantly higher, whereas polymorphonuclear lymphocyte expressions of CD11b/CD18 were lower in the Gln group than in the corresponding control group at 6 and 12 h after CLP. In comparisons of MPO activities in various organs, the Gln group had lower MPO activities at 6 and 12 h in the lung, at 6, 12, and 24 h in the liver, at 12 and 24 h in the kidneys, and at 12 h in the intestine than those in the control group. CONCLUSIONS: Results of this study demonstrate that a Gln-supplemented enteral diet increased lymphocyte CD11a/CD18 expressions, whereas neutrophil CD11b/CD18 expressions, circulating intracellular adhesion molecule-1 levels, and MPO activities in various organs decreased with gut-derived sepsis. These findings suggest that, under septic conditions, Gln administration may enhance lymphocyte function, attenuate interactions between polymorphonuclear lymphocytes and endothelium, and thus may decrease neutrophil infiltration into tissues.

Analysis of the health risk of exposure to breast milk mercury in infants in Taiwan.

The aim of this study was to assess the total concentration and health risk to infants of breast milk mercury in urban mothers and mothers married to fishermen in relation to fish intake in Taiwan. A total of sixty-eight healthy mothers were recruited for the study. The breast milk mercury geometric mean concentration was 2.02 microgl(-1) (n=56, range: 0.24-9.45 microgl(-1)) for the city group and 2.04 microgl(-1) (n=12, range: 0.26-8.62 microgl(-1)) for the fishermen's group. Of the three sources of mercury exposure (i.e., ingestion (breast milk), inhalation (ambient air), and dermal exposure (shower)), breast-feeding was found to be the largest (96.3-99.6% of the total). From a Monte Carlo simulation, in which methyl mercury accounted for about 50% of total mercury, the hazard quotient (exposure estimate/oral minimal risk level or target organ toxicity dose) exceeded 1.0 for 12.9% of urban babies and 18.8% of fishermen's babies (chronic oral minimal risk level and target organ toxicity dose: 3 x 10(-4)mgkg(-1)d(-1)). The calculated mercury exposure was 3.02 x 10(-1) microgkg(-1)d(-1) for a 3.49 kg urban baby boy and 3.06 x 10(-1) microgkg(-1)d(-1) for a 3.44 kg urban baby girl. These results suggest the life style of mothers (eating raw fish and shellfish such as used in "Sashimi" and "Sushi," and vitamin supplementation) may influence the mercury concentration in breast milk.

Alcohol levels in Chinese lactating mothers after consumption of alcoholic diet during postpartum "doing-the-month" ritual.

This study examined the effects of exposure to ethanol through cultural practices by lactating mothers. Specifically, the pharmacokinetics of alcohol in Chinese lactating mothers was investigated after they consumed chicken soup flavored with sesame oil and rice wine (CSSR), a typically prescribed diet during the postpartum "doing-the-month" period. Experimental findings were employed to estimate the potential ethanol dose to neonates and determine associated health risks. Twenty-three lactating mothers were examined. Informed consent was obtained from each subject. The target alcohol dosage was 0.3g/kg. Milk and blood samples were collected at fixed time intervals from each subject following exposure to CSSR, and alcohol levels were determined. Acute health risks to infants were estimated by comparing the potential infant dosage to an established criterion dose. Blood alcohol level peaked at 20 min after exposure to CSSR and decreased almost linearly thereafter. Alcohol in milk reached a plateau roughly at 20-40 min after exposure to CSSR and then decreased. Alcohol pharmacokinetics among subjects varied widely. The coefficients of variation in subject alcohol concentrations were 16.5-46.2% (mean, 30.0%) for blood and 32.8-57.6% (mean, 44.4%) for milk. Mean maximal alcohol concentration in blood (30.2+/-5.0 mg/dl) was achieved at 23.5+/-7.6 min and in milk (31.6+/-10.3 mg/dl) at 31.7+/-12.7 min. Potential infant doses were 3.0-58.8 mg (mean, 13.4 mg), and the predicted time required for milk alcohol level to return to zero level was 175 min. The acute health risks for infants exposed to alcohol through their mothers' milk under the current exposure scenario are low (hazard index<0.2). Nursing infants at least 3h after ingesting a diet containing alcohol would further reduce potential health risks.

Effects of arginine supplementation on splenocyte cytokine mRNA expression in rats with gut-derived sepsis.

AIM: To investigate the effects of arginine (Arg)-enriched diets before sepsis and/or Arg-containing total parenteral nutrition (TPN) after sepsis or both on cytokine mRNA expression levels in splenocytes of rats with gut-derived sepsis. METHODS: Rats were assigned to four experimental groups. Groups 1 and 2 were fed with a semipurified diet, while groups 3 and 4 had part of the casein replaced by Arg which provided 2% of the total calories. After the rats were fed with these diets for 10 d, sepsis was induced by cecal ligation and puncture (CLP), at the same time an internal jugular vein was cannulated. All rats were maintained on TPN for 3 d. Groups 1 and 3 were infused with conventional TPN, while groups 2 and 4 were supplemented with Arg which provided 2% of the total calories in the TPN solution. All rats were killed 3 d after CLP to examine their splenocyte subpopulation distribution and cytokine expression levels. RESULTS: Plasma interleukin (IL)-2, IL-4, tumor necrosis factor-alpha (TNF-alpha) and interferon (IFN-gamma) were not detectable 3 d after CLP. There were no differences in the distributions of CD45Ra(+), CD3(+), CD4(+), and CD8(+) cells in whole blood and splenocytes among the four groups. The splenocyte IL-2 mRNA expression in the Arg-supplemented groups was significantly higher than that in group 1. IL-4 mRNA expression in groups 3 and 4 was significantly higher than that in groups 1 and 2. The mRNA expression of IL-10 and IFN-gamma was significantly higher in group 4 than in the other three groups. There was no difference in TNF-alpha mRNA expression among the four groups. CONCLUSION: The influence of Arg on the whole blood and splenic lymphocyte subpopulation distribution is not obvious. However, Arg administration, especially before and after CLP, significantly enhances the mRNA expression levels of Th1 and Th2 cytokines in the spleen of rats with gut-derived sepsis.

Effect of a dysmenorrhea Chinese medicinal prescription on uterus contractility in vitro.

Dysmenorrhea is a common gynecologic complaint. After their first menstrual period, 30%-60% of American women suffer from some level of discomfort. It is estimated that 6 billion work hours are lost in this manner every year in the United States which equals an economic loss of nearly US$200 million. Dysmenorrhea is not only a problem for women but also one which affects quality of life and even reduces productivity in general. Dysmenorrhea is directly related to elevated levels of PGF2alpha (prostaglandins F2alpha) and is treated using nonsteroid anti-inflammatory drugs in Western medicine. Though efficacy of the latter is rapid, there are many side effects to the liver, kidney, and digestive system. The anti-inflammatory effect is temporary, and such drugs are unable to provide a long-term cure. Because of this, Chinese medicinal therapy is being considered as a feasible alternative medicine. In this study, Wen-Jing Tang (one of the dysmenorrhea Chinese medicinal prescriptions) was selected. A 50% alcoholic solution was used to extract active ingredients and create a freeze-dried product. At first, Wen-Jing Tang was used to suppress spontaneous contractions and prostaglandins F2alpha-induced contractions of rat uterine smooth muscle in vitro. Then, an assessment was performed to determine the mechanism of the prescription. Acetylcholine, ergonovine, propranolol, oxytocin, and KCl were used to analyze the physiological mechanisms of WJT. The results show that antagonism of both PGF2alpha and ACh are the major mechanisms for treating dysmenorrhea by Wen-Jing Tang. Furthermore, the antagonistic effect of KCl-depolarization contractions may be an auxiliary mechanism of the curative effect.