A 22-week, multicenter, randomized, double-blind controlled trial of Crocus sativus in the treatment of mild-to-moderate Alzheimer’s disease

Rationale

There is increasing evidence to suggest the possible efficacy of Crocus sativus (saffron) in the management of Alzheimer’s disease (AD).

Objective

The purpose of the present investigation was to assess the efficacy of C. sativus in the treatment of patients with mild-to-moderate AD.

Methods

Fifty-four Persian-speaking adults 55 years of age or older who were living in the community were eligible to participate in a 22-week, double-blind study of parallel groups of patients with AD. The main efficacy measures were the change in the Alzheimer’s Disease Assessment Scale—cognitive subscale and Clinical Dementia Rating Scale—Sums of Boxes scores compared with baseline. Adverse events (AEs) were systematically recorded. Participants were randomly assigned to receive a capsule saffron 30 mg/day (15 mg twice per day) or donepezil 10 mg/day (5 mg twice per day).

Results

Saffron at this dose was found to be effective similar to donepezil in the treatment of mild-to-moderate AD after 22 weeks. The frequency of AEs was similar between saffron extract and donepezil groups with the exception of vomiting, which occurred significantly more frequently in the donepezil group.

Conclusion

This phase II study provides preliminary evidence of a possible therapeutic effect of saffron extract in the treatment of patients with mild-to-moderate Alzheimer’s disease. This trial is registered with the Iranian Clinical Trials Registry (IRCT138711051556N1).     

A comparative double-blind study of loprazolam, 1 mg and 2 mg,versus placebo in anxiety-induced insomnia

Summary

A double-blind trial was carried out in 40 anxious in-patients with insomnia to compare the hypnotic effectiveness and tolerance of loprazolam, 1?mg and 2?mg, versus placebo. Groups of 10 patients received one or other dose of loprazolam or placebo for 7 nights and then placebo for the following 3 nights. Sleep quality and morning residual efiects were assessed each morning during the 10-day trial period by means of a sleep questionnaire. The results showed that I?mg loprazolam was superior to placebo but less effective than 2?mg loprazolam. No side-effects were reported at either dose level.     

A comparative trial of 400 mg cimetidine twice daily and 1000 mg daily in the short-term treatment of duodenal ulceration

Summary

The therapeutic efficacy of cimetidine given as 400?mg twice daily was compared to that of cimetidine given as 1.0?g daily in 4 divided doses (200?mg 3-times daily and 400?mg at night) in two groups of 25 patients (total 50 patients) with active duodenal ulceration. After 4 weeks, healing rates of 72% and 76%, respectively, were observed for the two dosage regimens. Patients who remained unhealed at 4 weeks were treated for a further 4 weeks, after which cumulative healing rates of 84% and 92%, respectively, were obtained. None of the observed differences in healing rates were statistically significant. Symptomatic improvement was similar for the two dosage regimens. No significant adverse reactions were reported.     

Comparison of the adverse event profiles of levofloxacin 500 mg and 750 mg in clinical trials for the treatment of respiratory infections

ABSTRACT

Objective: To compare safety data with levofloxacin 500?mg and 750?mg from clinical trials for the treatment of respiratory infections.

Methods: We compared adverse event data for levofloxacin 500?mg and 750?mg from clinical trials in acute bacterial sinusitis, acute bacterial exacerbation of chronic bronchitis, and community-acquired pneumonia. Adverse events occurring after the initiation of therapy were classified as treatment-emergent adverse events (TEAE); drug-related adverse events (DRAE) were TEAE assessed by the clinical investigator as definitely/very likely or probably related to levofloxacin therapy.

Results: Overall, the safety profile of the two doses was similar but not identical. TEAE occurred in 49.0% (1601/3268) of those treated with 500?mg and in 45.5% (519/1141) of those treated with 750?mg (?p = 0.042); the corresponding rates of DRAE were 7.6% (248/3268) and 8.0% (91/1141) (?p = 0.699). There was no statistically significant difference in terms of overall TEAE and DRAE rates within each of the three infectious conditions, but there were in specific events, all of which are expected with levofloxacin therapy. The limitations of this analysis include that it utilized a subset of available safety data, that it includes data only from clinical trials, and that we report primarily on events occurring in ≥ 2% of patients.

Conclusions: Given similar adverse event profiles and the advantages of higher dose therapy, including shorter courses of therapy and potential impact on preventing resistance, clinicians should consider utilizing the 750?mg dose of levofloxacin when choosing between dosage strengths for treatment of indicated infections.     

A trial of levofloxacin 750 mg once daily for 5 days versus ciprofloxacin 400 mg and/or 500 mg twice daily for 10 days in the treatment of acute pyelonephritis

ABSTRACT

Objective: A double-blind, noninferiority trial was conducted to establish the safety and efficacy of a once-daily, 5-day course of levofloxacin 750?mg compared to a twice-daily, 10-day course of ciprofloxacin in complicated urinary tract infections (cUTI) and acute pyelonephritis (AP). This report focuses on subjects with AP.

Research design and methods: Adult male and female subjects with clinical signs and symptoms of AP and laboratory confirmation of their diagnosis were randomized to receive one dose of levofloxacin 750?mg once daily intravenously (IV) or orally and one dose of placebo for 5 days, followed by placebo; or ciprofloxacin 400?mg IV and/or 500?mg orally twice daily for 10 days.

Main outcome measures: The primary, prospectively defined end point was microbiologic eradication at post-therapy (study days 15–22). Secondary outcomes included clinical response and safety and tolerability.

Results: In the modified intent-to-treat (mITT) population (levofloxacin 94, ciprofloxacin 98), 83% of levofloxacin-treated and 79.6% of ciprofloxacin-treated subjects achieved microbiological eradication (difference –3.4, 95% CI –14.4%, 7.6%). In the microbiologically evaluable (ME) population (levofloxacin 80, ciprofloxacin 76), 92.5% of levofloxacin-treated vs. 93.4% of ciprofloxacin-treated subjects (difference –0.9, 95% CI –7.1%, 8.9%) achieved microbiologic eradication. Clinical success was achieved in 86.2% vs. 80.6% (mITT) and in 92.5% vs. 89.5% (ME) of levofloxacin-treated and ciprofloxacin-treated subjects, respectively. Escherichia coli was the most commonly isolated uropathogen. Few (2.1%) of the pathogens were fluoroquinolone-resistant. Adverse events (AEs) were similar to those seen previously with both agents. Potential limitations are that this analysis is based on a subset of subjects from a larger study and, because of different durations of therapy, the results may be biased against levofloxacin.

Conclusions: High-dose, short-course therapy with levofloxacin in subjects with AP is at least as effective as standard 10-day therapy with ciprofloxacin.     

Rofecoxib 12.5 mg,rofecoxib 25 mg,and celecoxib 200 mg in the treatment of symptomatic osteoarthritis: results of two similarly designed studies

ABSTRACT

Objective: To compare the efficacy of rofecoxib and celecoxib for the treatment of knee or hip OA over 6 weeks.

Methods: Two similarly designed, multicenter, randomized, double-blind, placebo-controlled studies. Patients were randomly assigned 3:3:3:1 in Study 1 to once daily (QD) rofecoxib 12.5?mg (N = 456), rofecoxib 25?mg (N = 459), celecoxib 200?mg (N = 456), or placebo (N = 150) and 3:3:1 in Study 2 to QD rofecoxib 25?mg (N = 471), celecoxib 200?mg (N = 460), or placebo (N = 151). There was no rofecoxib 12.5?mg arm in Study 2. The primary outcome measure of both studies was pain at night over 6 weeks for rofecoxib 25?mg vs. celecoxib 200?mg. Efficacy comparisons with rofecoxib 12.5?mg in Study 1 were included as pre-specified study objectives but not as pre-specified study hypotheses. Secondary endpoints included Patient Global Assessment of Response to Therapy (PGART) over 6 weeks and over 1 week. Safety was evaluated through the assessment of spontaneously reported adverse experiences (AEs), evaluation of vital signs, and laboratory data reported by investigators and patients.

Results: For the primary endpoint, reduction in pain at night over 6 weeks in Study 1 was not significantly different between active treatments; in Study 2 rofecoxib 25?mg significantly (?p = 0.023) reduced pain at night compared with celecoxib 200?mg over 6 weeks. For the secondary endpoints, in both studies, significantly (?p < 0.05) more patients treated with rofecoxib 25?mg than celecoxib 200?mg had a good or excellent PGART over 6 weeks, and over the first week (?p < 0.01). In both studies, there were no significant differences between active medications in the incidence of reported overall, serious, or drug-related AEs. The reported AE rates with the active treatments were generally similar to those with placebo in the two studies.

Conclusions: Rofecoxib 25?mg was significantly better than celecoxib 200?mg in relieving night pain at 6 weeks in one study; this was not confirmed in the accompanying study.     

Ranitidine versus ranitidine and prazepam in the short-term treatment of duodenal ulcer — a double-blind controlled trial

Summary Fifty out-patients with an active, endoscopically proven duodenal ulcer were entered a double-blind trial of ranitidine + prazepam or ranitidine + placebo. Two drop-outs occurred in the prazepam group and 1 in the placebo group. After 28 days of treatment, the ulcer had healed in 95.6% of the patients on ranitidine + prazepam and 75% of the patients on ranitidine + placebo (p=0.03). Sleepiness was the most frequent side effect, reported by 8 subjects in the prazepam group and by 1 subject in the placebo group. It is concluded that prazepam can be usefully combined with ranitidine in the short-term treatment of duodenal ulcer.     

Evaluation of the efficacy and safety of β-d-mannuronic acid in patients with ankylosing spondylitis: A 12-week randomized,placebo-controlled,phase I/II clinical trial

ObjectiveTo evaluate the efficacy, safety and tolerability of β-d-mannuronic acid (M2000) in the treatment of ankylosing spondylitis (AS).MethodsThe study was a 12-week randomized, double-blind, placebo-controlled, phase I/II clinical trial with 3 treatment arms: placebo, β-d-mannuronic acid and naproxen. Patients who had AS according to the modified New York criteria, with active disease at baseline were eligible for study. Primary outcome measure was the Assessment of SpondyloArthritis international Society (ASAS) 20 response rate at week 12.ResultsOf the 85 randomized patients, 27 were allocated to receive placebo, 28 naproxen, and 30 β-d-mannuronic acid. There were no statistically significant differences between treatment groups at baseline. Of the patients receiving β-d-mannuronic acid, 57.7% achieved an ASAS20 response at week 12, compared with 59% of the patients in the naproxen group (P > 0.05) and 19% of the patients in the placebo group (P = 0.007). In comparison with patients receiving placebo over the 12-week treatment period, those receiving β-d-mannuronic acid and naproxen demonstrated statistically significantly greater improvement in all secondary endpoints. Interestingly, β-d-mannuronic acid reduced some parameters associated with inflammation more effectively than naproxen and placebo. The incidence of gastrointestinal and other adverse events were higher on naproxen than on β-d-mannuronic acid and placebo.ConclusionThe present study demonstrated similar efficacy, but with a more favorable safety profile for β-d-mannuronic acid than naproxen and, therefore, suggest that β-d-mannuronic acid is suitable for the management of AS.Trial registrationIranian registry of clinical trials; www.irct.ir; IRCT2013062213739N1.     

Efficacy of single-dose,extended-release naproxen sodium 660 mg in postsurgical dental pain: two double-blind,randomized, placebo-controlled trials

Objective:

To evaluate the efficacy of a novel formulation of extended-release/immediate-release (ER) naproxen sodium over 24?h in a dental pain model.

Research design and methods:

Two randomized, double-blind, placebo-controlled trials in moderate to severe pain after extraction of one or two impacted third molars (at least one partial mandibular bony impaction). Treatment comprised oral ER naproxen sodium 660?mg (single dose), placebo (both studies) or immediate-release (IR) naproxen sodium 220?mg tid (study 2).

Main outcome measures:

Primary efficacy endpoint: 24-h summed pain intensity difference (SPID). Secondary variables included total pain relief (TOTPAR), use of rescue medication. All treatment-emergent adverse events were recorded.

Clinical trial registration:

NCT00720057 (study 1), NCT01389284 (study 2).

Results:

Primary efficacy analyses: pain intensity was significantly lower over 24?h with ER naproxen sodium vs. placebo (p?<?0.001), with significant relief from 15?min (study 2). In study 2, ER naproxen sodium was non-inferior to IR naproxen sodium, reducing pain intensity to a comparable extent over 24?h. TOTPAR was significantly greater with ER and IR naproxen sodium vs. placebo at all time points, with generally comparable differences between active treatments. Significantly more placebo patients required rescue medication vs. ER and IR naproxen sodium from 2–24?h post-dose. Once daily ER naproxen sodium was generally safe and well tolerated, with a similar safety profile to IR naproxen sodium tid.

Limitations:

The studies were single dose, with limited ability to assess efficacy or safety of multiple doses over time. As the imputed pain score meant that estimated treatment differences may have been biased in favor of ER naproxen sodium, a post hoc analysis evaluated the robustness of the results for pain relief.

Conclusions:

A single dose of ER naproxen sodium 660?mg significantly reduced moderate to severe dental pain vs. placebo and was comparable to IR naproxen sodium 220?mg tid. Significant pain relief was experienced from 15?min and sustained over 24?h, resulting in a reduced need for rescue medication. ER naproxen sodium 660?mg once daily is a convenient and effective therapy providing 24?h relief of pain.     

Zaltoprofen,a noninferior alternative to diclofenac for the treatment of primary knee osteoarthritis – a comparative evaluation of efficacy and safety in a 4-week,multicentric, randomized,double-blind,double-dummy trial

Objective: To demonstrate the clinical noninferiority of the analgesic effect of zaltoprofen (80 mg t.i.d.) compared with diclofenac (50 mg t.i.d.) in active knee osteoarthritis patients.

Method: In this multicentric, double-blind, double-dummy, randomized, parallel-group, comparative study, 213 patients of either sex, aged 40 – 65 years having radiological and clinically confirmed primary knee osteoarthritis were randomized either to zaltoprofen (n = 105) or diclofenac (n = 108) and were followed-up at weeks 1, 2, 3 and 4. The treatment period was preceded by a washout period of 1 week.

Results: Patients in both the zaltoprofen and diclofenac groups exhibited significant improvement (p < 0.001) in pain intensity, functional status and pain relief at each visit from baseline with no statistically significant difference between the two treatment groups. There was no statistically significant difference between the treatment groups for global assessment rating done by the patient and investigator at the end of therapy (p > 0.05) and the proportion of patients who consumed ranitidine (p = 0.135) and paracetamol (p = 0.086) tablets during the treatment period on both the treatment arms. Both the study medications were well tolerated with no incidence of serious adverse events.

Conclusions: This study demonstrated that efficacy and safety of zaltoprofen is clinically noninferior to that of diclofenac.     

Efficacy and safety of linagliptin 2.5 mg twice daily versus 5 mg once daily in patients with type 2 diabetes inadequately controlled on metformin: a randomised, double-blind, placebo-controlled trial

Abstract Objective: Glycaemic control in patients with type 2 diabetes (T2DM) is often not achieved or not sustained using monotherapy such as metformin, necessitating the addition of other antihyperglycaemic agents. Linagliptin, a dipeptidyl peptidase-4 inhibitor, is licensed for 5?mg once-daily dosing. As metformin is administered twice daily, a fixed-dose combination of these compounds would require twice-daily administration of linagliptin. This study evaluated whether 2.5?mg twice-daily dosing of linagliptin has comparable efficacy and safety to 5?mg once-daily dosing when given in addition to metformin twice daily in patients with inadequate glycaemic control. Methods: A total of 491 T2DM patients with glycated haemoglobin (HbA1c) 7.0-10.0% were randomised (5:5:1) to double-blind treatment with linagliptin 2.5?mg twice daily, 5?mg once daily or placebo, respectively, in addition to continuing metformin twice daily (≥1500?mg/day or maximally tolerated dose). The primary endpoint was change from baseline in HbA1c after 12 weeks. ClinicalTrials.gov, NCT01012037. Results: Mean baseline HbA1c for all patients was 7.97%. After 12 weeks, linagliptin 2.5?mg twice daily and 5?mg once daily both significantly reduced HbA1c (placebo-adjusted changes from baseline -0.74% (95% CI -0.97, -0.52) and -0.80% (95% CI -1.02, -0.58), respectively, both p?相似文献   

Efficacy and safety of aceclofenac in the treatment of osteoarthritis: a randomized double-blind comparative clinical trial versus diclofenac – an Indian experience

ABSTRACT

Objective: Osteoarthritis is one of the most common forms of arthritis seen in primary care. Non-steroidal anti-inflammatory drugs (NSAIDs) play an important role in the management of osteoarthritis. However, gastrointestinal (GI) side effects limit their use. Cyclooxygenase-2 (COX‐2) selective inhibitors exhibit better GI tolerability than conventional NSAIDs, but their cardiovascular safety is controversial. An NSAID with high efficacy, high GI tolerability and devoid of adverse cardiovascular effects is therefore a profile preferred by physicians. Aceclofenac is an anti-inflammatory and analgesic drug with preferential COX-2 inhibition. The objective of this study was to assess the efficacy and safety of aceclofenac in the treatment of osteoarthritis in an Indian population.

Research design and methods: The trial was controlled, comparative, randomized, and double-blind. The study included 247 patients (82 males and 165 females, 40–82 years), suffering from osteoarthritis. Patients were randomized to receive either aceclofenac (100?mg twice daily) or diclofenac (75?mg twice daily).

Main outcome measures: Clinical assessment was done at screening, randomization, and at 2 weeks, 4 weeks and 8 weeks of treatment by calculating Western Ontario MacMaster (WOMAC) scores, time taken to walk 100 feet, visual analogue scores for pain, investigator's assessment on a Likert scale and joint tenderness. Tolerability assessment was based on adverse events. Patient compliance was also assessed.

Results: Aceclofenac was found to be statistically superior to diclofenac in efficacy parameters of WOMAC scores, investigator's assessment and joint tenderness. Aceclofenac was found to be statistically superior to diclofenac in terms of epigastric discomfort, dyspepsia and abdominal pain. Compliance was also better with aceclofenac. The overall response of patients’ osteoarthritis to aceclofenac was found to be statistically superior to diclofenac by both physician and patient.

Conclusions: Aceclofenac is an effective and well-tolerated drug in osteoarthritis in the Indian setting.     

Pharmacokinetics,pharmacodynamics, and clinical efficacy of albuterol RespiClick™ dry-powder inhaler in the treatment of asthma

Introduction: Incorrect use of inhaler devices by patients with asthma is common and can adversely affect clinical outcomes. Devices that are straightforward to use are less likely to result in dosing errors and can improve patients’ satisfaction with therapy and adherence. A novel dry-powder formulation of the rescue bronchodilator albuterol (salbutamol) administered using a multidose dry-powder inhaler (mDPI; RespiClick?) has recently been approved in the USA.

Areas covered: Studies on the albuterol mDPI were identified in searches of PubMed and www.clinicaltrials.gov. Pharmacokinetic, pharmacodynamic, efficacy, and safety data, and patients’ experiences with the albuterol mDPI are presented.

Expert opinion: The albuterol mDPI has an efficacy/tolerability profile consistent with other inhaled forms of albuterol, and is reliable, easy to use, and associated with a high level of patient satisfaction. This is the first albuterol dry-powder inhaler (DPI) to become available in the USA, with most other formulations being delivered using a pressurized metered-dose inhaler (pMDI). The availability of a breath-actuated device avoids the challenge of coordinating actuation and breathing when using pMDIs, and could simplify treatment for patients also using a DPI for controller medication. Additional features of RespiClick, such as an integrated dose counter and minimal pre-inhalation preparation, facilitate its use.     

Comparison of buprenorphine and methadone in the treatment of opiate withdrawal: possible advantages of buprenorphine for the treatment of opiate-benzodiazepine codependent patients?

The study is a preliminary investigation to compare the effectiveness of buprenorphine and methadone as opiate detoxification treatments. The sample comprised 123 drug misusers who were dependent upon opiates only or who were codependent upon opiates and benzodiazepines. Drug misusers dependent upon methadone doses up to 70 mg were eligible for the study. Detoxification took place within a specialist inpatient drug-dependence unit. Withdrawal symptom severity was assessed on a daily basis by means of the Short Opiate Withdrawal Scale. Outcome was assessed for reductions in severity of withdrawal symptoms, treatment retention, and treatment completion. Buprenorphine detoxification was associated with less severe opiate withdrawal symptoms than methadone. Opiate/Benzodiazepine codependent patients reported less severe withdrawal symptoms during treatment with buprenorphine than with methadone and were also more likely to complete detoxification when treated with buprenorphine.     

Two 6-week, randomized, double-blind, placebo-controlled studies of ziprasidone in outpatients with bipolar I depression: did baseline characteristics impact trial outcome?

Two randomized, double-blind, placebo-controlled, 6-week studies comparing ziprasidone versus placebo for treatment of bipolar depression (BPD) failed to meet their primary study objectives, indicating that either ziprasidone is ineffective in the treatment of BPD or the study failed. Adult outpatients with bipolar I depression with 17-item Hamilton Rating Scale for Depression total score more than 20 at screening and baseline received either ziprasidone 40 to 80 mg/d, 120 to 160 mg/d, or placebo (study 1), or ziprasidone 40 to 160 mg/d or placebo (study 2). Primary efficacy measure in both studies was change from baseline in Montgomery-?sberg Depression Rating Scale total scores at week 6 (end of the study). Mixed-model repeated-measures methodology was used to analyze the primary efficacy measure in both studies. Secondary efficacy measures in both studies included Hamilton Rating Scale for Depression total score and Clinical Global Impression-Improvement score. Post hoc analyses were conducted for both studies to examine potential reasons for study failure. In both, ziprasidone treatment groups failed to separate statistically from placebo for change from baseline Montgomery-?sberg Depression Rating Scale score at week 6. Response rates were 49%, 53%, and 46% for placebo, ziprasidone 40 to 80 mg/d, and ziprasidone 120 to 160 mg/d, respectively (study 1), and 51% and 53% for placebo and ziprasidone 40 to 160 mg/d, respectively (study 2). Ziprasidone 40 to 160 mg/d did not show superiority over placebo at week 6 in the treatment of BPD. Post hoc analyses revealed serious inconsistencies in subject rating that may have limited the ability to detect a difference between drug and placebo response. Rating reliability warrants further investigation to improve clinical trial methodology in psychiatry.     

Efficacy and safety of losartan 100 mg or losartan 100 mg plus hydrochlorothiazide 25 mg in the treatment of patients with essential arterial hypertension and CV risk factors: obser-vational,prospective study in primary care

ABSTRACT

Background: Patients with high cardiovascular risk are prevalent in ambulatory care. To achieve adequate blood pressure control, such patients require higher drug doses and/or combination therapy. We aimed to assess the efficacy and safety of losartan 100?mg as monotherapy or in fixed-dose combination with hydrochlorothiazide 25?mg.

Design and methods: Multicentre, prospective, open observational study over 13 weeks in patients with essential hypertension, whose blood pressure was not adequately controlled despite pretreatment. Main outcome parameters were the systolic (SBP) and diastolic (DBP) blood pressure reduction, the rate of normalized patients at study end compared to baseline, and the number and type of adverse events (AEs).

Results: Of the 7702 documented patients, 53.1% (N?=?4088) were men, with a mean age of 63.5?±?10.7 years. Comorbidities were frequent (diabetes mellitus in 57.4% [N?=?4418], coronary heart disease in 30.3% [N?=?2330], left ventricular hypertrophy in 28.2% [N?=?2172], heart failure in 14.0% [N?=?1079], and peripheral arterial disease in 9.0% [N?=?690]). Patients received losartan 100?mg in 45.7% (N?=?3521), losartan/HCTZ in 53.8% (N?=?4143); additional antihypertensive drugs were given in 45.5% (N?=?3505). Physicians reported somewhat lower target values than those stipulated by the guidelines (irrespective of age, gender, and concomitant diseases except for diabetes). Mean SBP/DBP decreased from a baseline value of 158/93?mmHg by 24/12?mmHg at study end. The BP lowering effect was similar in subgroups by treatment or comorbidity, respectively, however target attainment rates were substantially higher in non-diabetic patients. Metabolic and renal parameters (fasting glucose, HbA_1c, serum creatinine and albumin in urine) showed trends for improvement. Tolerability was very good, as only 0.43% (N?=?33) experienced an AE (in 0.31% [N?=?24] serious AEs), and 0.08% (N?=?6) discontinued therapy due to reasons related to study drug.

Conclusion: In high-risk patients, treatment with losartan 100?mg or losartan/HCTZ 100/25?mg was effective and well tolerated, irrespective of comorbidity. These findings from a real-life setting are in line with those from randomized controlled trials.     

The role of selenium, zinc and antioxidant vitamin supplementation in the treatment of bronchial asthma: adjuvant therapy or not?

In the last few years, nutrition has represented an important conditioning factor of many cardiovascular, gastrointestinal and pulmonary chronic diseases. Many published works have documented specific inflammatory abnormalities in the airways of subjects with mild-to-moderate persistent bronchial asthma in which the inflammation state is often associated with an increased generation of reactive oxygen species and free radical-mediated reactions. This evidence has stimulated many researchers to suppose that the oxidative stress could be an important pathogenetic determining factor in the progression of chronic diseases, and the decrease of oxidant insults to the lung can be modified with antioxidant supplementary therapy. There are many studies regarding dietary interventions that confirm the relationship to oxidative stress, bronchial inflammation, the development of asthmatic symptoms and the lowered cellular reducing capacity. Simple dietary and environmental supplementations significantly reduce the oxidant stress, minimise the development of asthmatic symptoms, and should prove to be an effective new approach to asthma management in addition to current pharmacological strategies. Many randomised controlled trials with antioxidant vitamins and trace element supplements have not confirmed the results shown in other clinical trials. The aim of this review is to focus the attention on published works discussing the relationship between asthma and nutritional supplements (some trace elements and vitamins) and the effectiveness of these supplements in the treatment of bronchial asthma.     

The role of selenium,zinc and antioxidant vitamin supplementation in the treatment of bronchial asthma: adjuvant therapy or not?

In the last few years, nutrition has represented an important conditioning factor of many cardiovascular, gastrointestinal and pulmonary chronic diseases. Many published works have documented specific inflammatory abnormalities in the airways of subjects with mild-to-moderate persistent bronchial asthma in which the inflammation state is often associated with an increased generation of reactive oxygen species and free radical-mediated reactions. This evidence has stimulated many researchers to suppose that the oxidative stress could be an important pathogenetic determining factor in the progression of chronic diseases, and the decrease of oxidant insults to the lung can be modified with antioxidant supplementary therapy. There are many studies regarding dietary interventions that confirm the relationship to oxidative stress, bronchial inflammation, the development of asthmatic symptoms and the lowered cellular reducing capacity. Simple dietary and environmental supplementations significantly reduce the oxidant stress, minimise the development of asthmatic symptoms, and should prove to be an effective new approach to asthma management in addition to current pharmacological strategies. Many randomised controlled trials with antioxidant vitamins and trace element supplements have not confirmed the results shown in other clinical trials. The aim of this review is to focus the attention on published works discussing the relationship between asthma and nutritional supplements (some trace elements and vitamins) and the effectiveness of these supplements in the treatment of bronchial asthma.     

Acute psychological and physiological effects of psilocybin in healthy humans: a double-blind, placebo-controlled dose–effect study

Rationale Serotonin (5-Hydroxytryptamine, 5-HT) receptors play an important role in perception, affect regulation and attention. Pharmacological challenge with the 5-HT_2A agonist psilocybin (PY) is useful in studying the neurobiological basis of cognition and consciousness.Objective Investigation of dose-dependent effects of PY on psycho(patho)logical and physiological parameters.Methods Eight subjects received placebo (PL), and 45 (very low dose, VLD), 115 (low dose, LD), 215 (medium dose, MD), and 315 (high dose, HD) g/kg body weight PY. The Altered States of Consciousness Rating Scale (5D-ASC), the Frankfurt Attention Inventory (FAIR), and the Adjective Mood Rating Scale (AMRS) were used to assess the effects of PY on psycho(patho)logical core dimensions, attention, and mood. A 24-h electrocardiogram (EKG) was recorded and blood pressure was measured. Plasma concentrations of thyroid-stimulating hormone (TSH), prolactin (PRL), cortisol (CORT), adrenocorticotropic hormone (ACTH), and standard clinical chemical parameters were determined.Results PY dose dependently increased scores of all 5D-ASC core dimensions. Only one subject reacted with transient anxiety to HD PY. Compared with PL, MD and HD PY led to a 50% reduction of performance in the FAIR test. General inactivation, emotional excitability, and dreaminess were the only domains of the AMRS showing increased scores following MD and HD PY. The mean arterial blood pressure (MAP) was moderately elevated only 60 min following administration of HD PY. Neither EKG nor body temperature was affected by any dose of PY. TSH, ACTH, and CORT plasma levels were elevated during peak effects of HD PY, whereas PRL plasma levels were increased following MD and HD PY.Conclusion PY affects core dimensions of altered states of consciousness and physiological parameters in a dose-dependent manner. Our study provided no cause for concern that PY is hazardous with respect to somatic health.