Red American ginseng: ginsenoside constituents and antiproliferative activities of heat-processed Panax quinquefolius roots

Red Asian ginseng ( Panax ginseng C. A. Meyer, Araliaceae) is used in many Oriental countries. In this study, the saponin constituents and anticancer activities of steamed American ginseng ( Panax quinquefolius L.) roots were evaluated. The contents of 12 ginsenosides in the roots were determined using high performance liquid chromatography (HPLC). After the steaming treatment (100 - 120 degrees C for 1 h and 120 degrees C for 0.5 - 4 h), the quantity of 7 ginsenosides decreased and that of 5 others increased. The content of ginsenoside Rg3, a previously recognized anticancer compound, increased significantly when the root was steamed at 120 degrees C for 0.5 - 3 h. The antiproliferative effects of unsteamed and steamed (120 degrees C for 1 h and 2 h) American ginseng root extracts were assayed by the modified trichrome stain (MTS) method using three cancer cell lines (SW-480, HT-29, NSCLC). Heat-processing increased the antiproliferative effect of American ginseng significantly, and the activity of the extract from roots steamed for 2 h was greater than that of roots steamed for 1 h. Chemical constituents and antiproliferative activities of white and red Asian ginseng have also been evaluated. Five representative ginsenosides, Rb1, Rd, Re, Rg2 and Rg3, were studied. Ginsenoside Rg3 had the most potent effect. The antiproliferative activities of red American ginseng are augmented when ginsenoside Rg3 is increased.     

The effect of glucose dose and fasting interval on cognitive function: a double-blind,placebo-controlled,six-way crossover study

Rationale  

Previous research has identified a number of factors that appear to moderate the behavioural response to glucose administration. These include physiological state, dose, types of cognitive tasks used and level of cognitive demand. Another potential moderating factor is the length of the fasting interval prior to a glucose load.     

Estradiol in premenstrual asthma: a double-blind,randomized, placebo-controlled,crossover study

STUDY OBJECTIVES: To characterize asthma symptoms and pulmonary function throughout two menstrual cycles, with and without exogenous estradiol administration, in women with premenstrual asthma, and to determine the effect of estradiol administration on asthma symptoms, pulmonary function, quality of life, and biomarkers of airway inflammation. DESIGN: Double-blind, randomized, placebo-controlled, crossover study. SETTING: Respiratory clinic and clinical research center. SUBJECTS: Twelve women with documented premenstrual asthma (> or = 20% premenstrual worsening of asthma symptoms and/or of peak expiratory flow [PEF] during a 1-month screening phase). INTERVENTION: Each woman received either estradiol 2 mg or placebo orally between cycle days 23 and 28 (i.e., premenstrually, or before the onset of menses) in the first cycle and then crossed over to the other arm in the second cycle. Throughout both cycles, the women recorded daily morning and evening PEF readings and asthma symptoms. MEASUREMENTS AND MAIN RESULTS: Spirometry testing and measurement of serum estradiol and biomarkers of airway inflammation were performed on days 8 (follicular phase), 22 (luteal phase), and 28 (premenstrually) of both the estradiol and placebo cycles. During the two premenstrual visits, the Asthma Quality of Life Questionnaire was administered. No notable differences were observed between the estradiol and placebo cycles in daily PEF recordings or composite asthma symptoms scores. The area under the curve (AUC) for the composite asthma symptoms versus time profile was numerically, but not statistically, lower (denoting less severe symptoms) during the estradiol cycle than during the placebo cycle. Likewise, no significant difference in AUC values for morning PEF or evening PEF was found between the estradiol cycle and the placebo cycle. Despite differences (p<0.05) in day-28 estradiol concentrations for estradiol and placebo cycles, no significant differences were found in forced expiratory volume in 1 second, serum endothelin-1, serum and urine eosinophil protein X, urine leukotriene E4, or quality-of-life scores. CONCLUSION: Exogenously administered estradiol did not have a significant effect in women with premenstrual asthma whose asthma was classified predominantly as mild and under excellent control. As in the case of premenstrual syndrome, the placebo effect may be prominent in premenstrual asthma. Further trials, involving women with more severe asthma under poorer control, are warranted to discern underlying mechanisms for the worsening of asthma in relation to menstruation.     

Pantoprazole does not affect performance in traffic-related safety tests: a double-blind, randomised, placebo-controlled, crossover study in healthy volunteers

OBJECTIVE AND STUDY PARTICIPANTS: The effects of pantoprazole, a potent inhibitor of gastric acid production, were evaluated in traffic-related performance tests in 18 healthy male and female volunteers, aged 18 to 60 years, in a randomised, placebo-controlled, double-blind, crossover study. METHODS: Oral pantoprazole (40mg) or a placebo tablet was taken once a day for two periods of 5 days each, with a washout period of 7 to 14 days. Drug tolerability was assessed by vital signs, clinical laboratory parameters and volunteers' own subjective appraisal of their mental condition. The computerised Viennese test system (WTS 90) was used to examine parameters related to traffic safety including visual orientation, concentration span, acoustic reaction time, multiple choice reaction, stress, tolerance, vigilance and motor coordination. The effects were tested one day before and then on the first and fifth days of each medication period. RESULTS: Results showed that in comparison with placebo, neither single nor multiple doses of pantoprazole led to clinically relevant differences in the performance of standardised, traffic-related safety tests. CONCLUSION: Pantoprazole did not appear to impede normal everyday activities, including car driving, and thus can be administered without special precautions in this regard.     

A multi-centre,randomised, double-blind,placebo-controlled clinical trial of methylphenidate in the initial treatment of acute mania (MEMAP study)

Based on many clinical and preclinical findings the ‘vigilance regulation model of mania’ postulates that an unstable regulation of wakefulness is a pathogenetic factor in both mania and Attention Deficit Hyperactivity Disorder (ADHD) and induces hyperactivity and sensation seeking as an autoregulatory attempt to stabilize wakefulness. Accordingly, stimulant medications with their vigilance stabilizing properties could have rapid antimanic effects similar to their beneficial effects in ADHD. The MEMAP study – a multi-center, double-blind, placebo-controlled and randomized clinical trial (RCT) – assessed the antimanic efficacy and safety of a 2.5-day treatment with methylphenidate (20–40 mg/day). Of 157 screened patients with acute mania, 42 were randomly assigned to receive 20–40 mg per day of methylphenidate in one or two applications, or placebo. The primary outcome was the change in Young Mania Rating Scale (YMRS) sum scores from baseline to day 2.5 in the methylphenidate group compared to the placebo group. A group sequential design was chosen to justify early RCT termination based on efficacy or futility at an interim analysis after inclusion of 40 patients. In the interim analysis, the change from baseline in the YMRS total score at day 2.5 was not significantly different between both groups (F(1,37)=0.23; p=0.64). Thus, futility was declared for methylphenidate and the RCT was stopped. In summary, although methylphenidate was well tolerated and safe in the full analysis set, it failed to show efficacy in the treatment of acute mania. Trial registration: clinicaltrials.gov (URL: http://www.clinicaltrials.gov; registration number: NCT01541605).     

Magnetic pulse treatment for knee osteoarthritis: a randomised, double-blind, placebo-controlled study

We assessed the efficacy and tolerability of low-frequency pulsed electromagnetic fields (PEMF) therapy in patients with clinically symptomatic knee osteoarthritis (OA) in a randomised, placebo-controlled, double-blind study of six weeks' duration. Patients with radiographic evidence and symptoms of OA (incompletely relieved by conventional treatments), according to the criteria of the American College of Rheumatology, were recruited from a single tertiary referral centre. 75 patients fulfilling the above criteria were randomised to receive active PEMF treatment by unipolar magnetic devices (Medicur) manufactured by Snowden Healthcare (Nottingham, UK) or placebo. Six patients failed to attend after the screening and were excluded from analysis. The primary outcome measure was reduction in overall pain assessed on a four-point Likert scale ranging from nil to severe. Secondary outcome measures included the WOMAC Osteoarthritis Index (Likert scale) and the EuroQol (Euro-Quality of Life, EQ-5D). Baseline assessments showed that the treatment groups were equally matched. Although there were no significant differences between active and sham treatment groups in respect of any outcome measure after treatment, paired analysis of the follow-up observations on each patient showed significant improvements in the actively treated group in the WOMAC global score (p = 0.018), WOMAC pain score (p = 0.065), WOMAC disability score (p = 0.019) and EuroQol score (p = 0.001) at study end compared to baseline. In contrast, there were no improvements in any variable in the placebo-treated group. There were no clinically relevant adverse effects attributable to active treatment. These results suggest that the Medicur unipolar magnetic devices are beneficial in reducing pain and disability in patients with knee OA resistant to conventional treatment in the absence of significant side-effects. Further studies using different types of magnetic devices, treatment protocols and patient populations are warranted to confirm the general efficacy of PEMF therapy in OA and other conditions.     

Treatment of acute bronchitis with a liquid herbal drug preparation from Pelargonium sidoides (EPs 7630): a randomised,double-blind,placebo-controlled,multicentre study

ABSTRACT

Objective: The objective of this study was to examine the efficacy and safety of a herbal drug preparation from the roots of Pelargonium sidoides (EPs^* 7630) in the treatment of acute bronchitis in adults outside the very restricted indication for an antibiotic therapy.

Research design and methods: This was a randomised, double-blind, placebo-controlled, multicentre study with 217 patients aged between 18 and 66 years with acute bronchitis. One hundred and eight patients were given 30 drops of EPs 7630-solution three times daily and 109 patients 30 drops of placebo three times daily for a period of 7 days.

Main outcome measures: Individual change in bronchitis symptom score (BSS) over 7 days, individual symptoms, patient satisfaction and adverse events.

Results: After 7 days of treatment, the BSS decreased by 7.6 ± 2.2 points in the EPs 7630 group and by 5.3 ± 3.2 points in the placebo group. The 95% confidence interval for the difference between the effects was calculated as 1.6–3.1, showing highly significant superiority for the EPs 7630 treatment (?p < 0.0001).

There were also marked improvements in the individual symptoms, which are the components of BSS – cough, chest pain on coughing, sputum, rales/rhonchi and dyspnoea – in the treatment group, relative to placebo. Patient satisfaction was very good. Only minor and transitory adverse events were recorded. No serious adverse events occurred during the trial.

Conclusion: EPs 7630-solution is a well tolerated and effective treatment for acute bronchitis in adults outside the very restricted indication for an antibiotic therapy.     

Vitamin B12 in low back pain: a randomised, double-blind, placebo-controlled study

OBJECTIVES: The objective of this double-blind randomised, placebo-controlled study was to examine the efficacy and safety intramuscular vitamin B12 (Tricortin 1000) in the treatment of low back pain in patients with mechanical or irritative lumbago. METHODS: 60 patients aged between 18 and 65 years with lumbago or sciatic neuritis of mechanical origin without need for surgical procedures were enrolled. Patients had to present with a proven medical history for back pain (lasting from 6 months to 5 years) and a pain intensity [as evaluated with a Visual Analogic Scale (VAS)] equal or greater than 60 mm. Efficacy primary end-point was evaluated by means of a visual analogic scale (VAS) and a Disability Questionnaire (DQ). Consumption of paracetamol during the study period was the secondary efficacy end-point. RESULTS: Both treatment groups experienced a sharp decrease in pain and disability. However, comparison between groups at the end of the treatment period showed a statistically significant difference in favour of the active treatment both for VAS and DQ (p < 0.0001 and p < 0.0002, respectively). Consumption of paracetamol proved significantly higher in the placebo group than in the active treatment (p < 0.0001). CONCLUSIONS: The efficacy and safety of parenteral Vitamin B12 in alleviating low back pain and related disability and in decreasing the consumption of paracetamol was confirmed in patients with no signs of nutritional deficiency.     

Delay of ovulation by meloxicam in healthy cycling volunteers: A placebo-controlled, double-blind, crossover study

This study aimed to assess the effect of meloxicam on female ovulation. Twenty consented fertile females were monitored for 4 menstrual cycles: a baseline cycle, 2 treatment cycles, and a washout cycle between treatment cycles. In the first cycle visit, transvaginal ultrasound was performed, a blood sample for progesterone and meloxicam analysis was withdrawn, and volunteers were given a luteinizing hormone (LH) urine test kit and meloxicam or placebo. Volunteers started the treatment on the following day and asked to return the day the LH kit was positive to detect the dominant follicle. At subsequent visits, transvaginal ultrasound and progesterone and meloxicam levels were investigated. Compared to placebo, a 5-day delay in follicle rupture, a 55.7% increase in the mean maximum follicle diameter, and 33.5% decrease of plasma progesterone level were observed in the meloxicam-treated group. Such demonstrated meloxicam effects were reversed in participants who were randomized to meloxicam first and then placebo. Only minor side effects were reported by volunteers during the course of treatment. It is concluded that meloxicam resulted in a reversible delay of ovulation, an increase in follicular diameter, and a decrease in plasma progesterone level.     

Clomipramine versus haloperidol in the treatment of autistic disorder: a double-blind, placebo-controlled, crossover study

Clomipramine, haloperidol, and placebo were compared with baseline in the treatment of autism, and overall outcome, specific symptoms, and side effects were examined. It was hypothesized that clomipramine would be better tolerated than haloperidol and prove superior on a measure of stereotypy. Individuals with a DSM-IV diagnosis of autistic disorder (mean age, 16.3 years; range, 10-36 years) were randomly assigned, by using a Latin square design, to the following 7-week trials: placebo, clomipramine (mean daily dose, 128.4 mg; range, 100-150 mg), or haloperidol (mean daily dose, 1.3 mg; range, 1-1.5 mg). Data on 36 subjects were analyzed and taken together; the results favored haloperidol. In those patients who were able to complete a full therapeutic trial, clomipramine proved comparable to haloperidol in terms of improvement compared with baseline. However, significantly fewer individuals receiving clomipramine versus haloperidol were able to complete the trial (37.5% vs. 69.7%, respectively) for reasons related to both side effects and efficacy or behavior problems. In the intent-to-treat sample, which is perhaps more clinically relevant, only haloperidol proved superior to baseline on a global measure of autistic symptom severity, as well as specific measures for irritability and hyperactivity. Clomipramine did not seem more effective on a measure of stereotypy, nor was it better tolerated.     

Effects of oral isradipine on left ventricular function at rest and during exercise in patients with stable chronic angina: a double-blind, placebo-controlled crossover study.

We evaluated the effects of a single oral dose of 5 mg of isradipine compared to placebo in a randomized, double-blind, crossover study using gated radionuclide angiography at rest and during exercise in 20 patients with stable chronic angina. Isradipine improved both anginal symptomatology and ST-segment depression during exercise, with a concomitant favorable effect on the isotopic parameters exploring systolic and diastolic left ventricular function. There was a marked increase of the ejection fraction during exercise with isradipine compared to placebo (61 +/- 14% vs. 55 +/- 15%, respectively, p less than 0.001) as well as a significant improvement in the peak ejection rate and the peak filling rate at rest [2.56 +/- 0.62 vs. 2.16 +/- 0.54 end diastolic volume (EDV) per second and 2.14 +/- 0.59 vs. 1.87 +/- 0.37 EDV/s, respectively] and during exercise (3.49 +/- 0.97 vs. 3.10 +/- 1.07 EDV/s and 4.05 +/- 1.34 vs. 3.65 +/- 1.25 EDV/s, respectively). We conclude that isradipine has a beneficial effect on the clinical and electrocardiographic signs of exercise-induced ischemia, leading to a significant improvement of the systolic and diastolic parameters of left ventricular function. Therefore, isradipine is potentially a useful treatment for patients with exertional angina and hypertension, alone or associated with beta blocker medication.