Rebound acid hypersecretion after withdrawal of gastric acid suppressing drugs: new evidence of similitude

Background: Homeopathy is based on the principle of similitude (similia similibus curentur) using medicines that cause effects similar to the symptoms of disease in order to stimulate the reaction of the organism. Such vital, homeostatic or paradoxical reaction of the organism is closely related to rebound effect of drugs. Method: Review of the literature concerning the rebound effects of drugs used to suppress gastric acidity, particularly proton pump inhibitors (PPIs). Results: The mechanism of action of these effects is discussed. Rebound in terms of clinical symptoms and physiological effects occur in about 40% of people taking PPIs, their timing depends on the half-life of the drug and the adaptation period of the physiological mechanisms involved. The wide use of PPIs may be linked to the rising incidence of carcinoid tumours. Conclusions: These findings support Hahnemann`s concept of secondary action of drugs. We are developing a homeopathic materia medica and repertory of modern drugs on the basis of reported rebound effects. Homeopathy (2011) 100, 148-156.

Pentoxyphylline in association with vitamin E reduces cutaneous fibrosis in systemic sclerosis

Systemic sclerosis (SSc) is a disorder characterized by skin thickness and vasculopathy. The objective of the study was to evaluate the therapeutic effect and safety of the association of pentoxyphylline and vitamin E in SSc patients. Twelve SSc patients (American College of Rheumatology criteria) enrolled this 24-week open-label study. Patients received daily 800 mg of pentoxyphylline and 800 UI of vitamin E and were evaluated at 4-week interval. The primary efficacy endpoint was the change in Modified Rodnan Skin Score (MRSS) at week 24. Nine diffuse SSc patients treated 6 months with cyclophosphamide were used as a historical control group. The mean age of the treated group was 43.6 years, and ten of 12 (84%) patients were women. Their mean MRSS reduced from 25.7 to 18.7 (p = 0.03) at 16th week and remained significantly reduced throughout the study. In contrast, only a trend of MRSS reduction was observed in the historical control group (p = 0.06). Two patients started the study with active ischemic ulcers and ended with a complete healing of them. No serious side effects were reported. Pentoxyphylline and vitamin E might be an alternative therapeutic approach in SSc patients.

THE EFFECTS OF BROMAZEPAM ON THE PERFORMANCE OF A SENSORY-MOTOR ACTIVITY: AN ELECTROENCEPHALOGRAPHIC STUDY

Aims. To investigate the effects of using bromazepam on the relative power in alpha while performing a typing task. Bearing in mind the particularities of each brain hemisphere, our hypothesis was that measuring the relative power would allow its to investigate the effects of bromazepam oil specific areas of the cortex. More, specifically, we expected to observe different patterns of powers in sensory-motor integration, attention and activation processes. Subjects and methods. The sample was made up of 39 subjects (15 males and 24 females) with a mean age of 30 +/- 10 years. The control (placebo) and experimental (3 mg and 6 mg of bromazepam) groups were trained ill the typing task with a randomised double-blind model. Results. A three-way ANOVA and Scheffe test were used to analyse interactions between the factors condition and moment, and between condition and sector Conclusions. The doses used ill this study facilitated motor performance of the typing task. Ill this study, the use of the drug did not prevent learning of the task, but it did appear to concentrate mental effort on more restricted and specific aspects of typing. It also seemed to influence the rhythm and effectiveness of the operations performed during mechanisms related to the encoding and storage often, information. Likewise, a predominance of activity was observed in the left (dominant) frontal area in the 3 mg bromazepam group, which indicates that this close of the drug affords the subject a greater degree of directionality of cortical activity for planning and performing the task. [REV NEUROL 2009; 49: 295-9]

A randomized, comparative study of formoterol and terbutaline dry powder inhalers in the treatment of mild to moderate asthma exacerbations in the pediatric acute care setting

Background: Formoterol is a fast-acting, long-acting beta-agonist. Its on-demand use by outpatients has been beneficial in controlling asthma. Objective: To evaluate the efficacy of formoterol as rescue medication for pediatric asthma exacerbation. Methods: A randomized, double-blind study was conducted on parallel groups involving 79 pediatric patients (mean [SD] age, 9.92 [2.5] years) with mild to moderate asthma exacerbations. They were treated with up to 3 doses of formoterol aerolizer, 12 mu g, or terbutaline Turbuhaler, 0.5 mg (dry powder inhalers). Respiratory rate, clinical score, pulse oximetry, and spirometry were analyzed at baseline and 15 minutes after administration of each bronchodilator dose. All the patients received oral prednisolone, 1 mg/kg, at study entry, followed by a single daily dose for 4 days. Forty-one patients were treated with formoterol and 38 with terbutaline. The groups were comparable in age and in severity of asthma exacerbation. Results: Both treatments resulted in similar clinical and functional improvement; 37 patients (47%) required 1 bronchodilator dose. Increases of 19.5% and 1.5.3% occurred in forced expiratory volume in 1 second in the formoterol and terbutaline groups, respectively. Therapeutic failures occurred in 2 patients. No adverse effects were observed. At 1-week follow-up, patients were stable, with pulmonary function close to normal. Conclusion: Formoterol therapy was at least as effective as terbutaline therapy in children and adolescents with mild and moderate asthma exacerbations. Ann Allergy Asthma Immunol. 2009; 103:248-253.

Phototherapy Promotes Healing of Chronic Diabetic Leg Ulcers That Failed to Respond to Other Therapies

Objective: We tested the hypothesis that combined 660 and 890 nm LED phototherapy will promote healing of diabetic ulcers that failed to respond to other forms of treatment. Research Design and Methods: A double-blind randomized placebo controlled design was used to study 23 diabetic leg ulcers in two groups of 14 patients. Group one ulcers were cleaned, dressed with 1% silver sulfadiazine cream and treated with ""placebo"" phototherapy (<1.0 J cm(-2)) twice per week, using a Dynatron Solaris 705 (R) device. Group two ulcers were treated similarly but received 3 J cm(-2) dose. Results: At each of 15,30,45,60,75, and 90 days of healing, mean ulcer granulation and healing rates were significantly higher for group two than the ""placebo"" group (P < 0.02). While ""placebo"" treated ulcers worsened during the initial 30 days, group two ulcers healed rapidly; achieving 56% more granulation and 79.2% faster healing by day 30, and maintaining similarly higher rates of granulation and healing over the ""placebo"" group all through. By day 90, 58.3% of group two ulcers had healed fully and 75% had achieved 90-100% healing. In contrast, only one ""placebo"" treated ulcer healed fully by day 90; no other ulcer attained >90% healing. Conclusion: Combined 660 and 890 nm light promotes rapid granulation and healing of diabetic ulcers that failed to respond to other forms of treatment. Lasers Surg. Med. 41:433-441, 2009. (C) 2009 Wiley-Liss, Inc.

Performance of Brazilian long and short IQCODE on the screening of dementia in elderly people with low education

Background: Dementia screening in elderly people with low education can be difficult to implement. For these subjects, informant reports using the long (L) (26 items) and short (C) (16 items) versions of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) can be useful. The objective of the present study was to investigate the performance of Brazilian versions of the IQCODE L, S and a new short version (SBr) (15 items) in comparison with the Mini-mental State Examination (MMSE) for dementia screening in elderly people with low education. Methods: Thirty-four patients with mild to moderate dementia, diagnosed according to ICD-10 criteria, and 57 controls were evaluated and divided into three groups based on their socioeconomic status and level of education. Patients were evaluated using the MMSE and the informants were interviewed using the IQCODE by interviewers blind to the clinical diagnosis. Results: Education was correlated with MMSE results (r = 0.280, p = 0.031), but not with the versions of the IQCODE. The performance of the instruments, evaluated by the ROC curves, was very similar, with good internal consistency (Cronbach`s alpha = 0.97). MMSE correctly classified 85.7% of the subjects while the three IQCODE versions (L, S and SBr) correctly classified 91.2% of the subjects. Conclusions: The long, short and the new short Brazilian IQCODE versions can be useful as a screening tool for mild and moderate patients with dementia in Brazil. The IQCODE is not biased by schooling, and it seems to be an adequate instrument for samples with low levels of education.

Efficacy and Tolerability of Lodenafil Carbonate for Oral Therapy in Erectile Dysfunction: A Phase II Clinical Trial

Oral treatment with phosphodiesterase type 5 inhibitor (PDE5) is considered the first-line treatment for patients with erectile dysfunction (ED). Lodenafil carbonate (LC) is a novel PDE5. This is a phase II, prospective, randomized, double-blind, and placebo controlled clinical trial of LC. Efficacy end points were International Index of Sexual Function (IIEF) erectile domain, IIEF questions 3 and 4, and Sexual Encounter Profile (SEP) questions 2 and 3, before and after the use of LC or placebo. Seventy-two men older than 18 years, with ED for at least 6 months with stable sexual relationship were enrolled. Patients were randomized to placebo or LC 80 mg, 40 mg, or 20 mg and followed for 4 weeks. IIEF erectile domain scores before and after the use of medications were (mean +/- standard deviation [SD]): placebo: 11.9 +/- 3.4 and 12.6 +/- 5.5; LC 20 mg: 15.8 +/- 4.1 and 18.9 +/- 6.6; LC 40 mg: 11.9 +/- 4.4 and 15.4 +/- 8.1; LC 80 mg: 14.2 +/- 4.7 and 22.8 +/- 6.0 (anova P < 0.01). The SEP-2 scores before and after the use of medications were (Mean +/- SD): placebo: 71.0 +/- 33.1 and 51.2 +/- 43.1; LC 20 mg 70.3 +/- 34.2 and 75.5 +/- 31.5; LC 40 mg: 48.4 +/- 42.1 and 60.8 +/- 42.5; LC 80 mg: 68.6 +/- 33.5 and 89.6 +/- 26.0. The SEP-3 scores were: placebo 23.3 +/- 27.6 and 33.6 +/- 42.3; LC 20 mg: 32.3 +/- 38.9 and 51.2 +/- 41.7; LC 40 mg: 39.7 +/- 44.7 and 46.7 +/- 41.1; LC 80 mg* 17.2 +/- 29.5 and 74.3 +/- 36.4 (*P < 0.05 for difference to placebo). The drug was well tolerated. Adverse reactions were mild and self-limited and included headache, rhinitis, flushing, color visual disorders, and dyspepsia. This study showed that the dosage of 80 mg of LC was significantly more efficacious than placebo and well tolerated. Glina S, Toscano I, Gomatzky C, de Goes PM, Junior AN, de Almeida Claro JF, and Pagani E. Efficacy and tolerability of lodenafil carbonate for oral therapy in erectile dysfunction: A phase II clinical trial. J Sex Med 2009;6:553-557.

The effects of bromazepam over the temporo-parietal areas during the performance of a visuomotor task: A qEEG study

This study investigated the effects of bromazepam on qEEG when 14 healthy subjects were asked to perform a visuomotor task (i.e., motor vehicle driving task). The subjects were exposed to two experimental conditions: the placebo (PL) and 6 mg of bromazepam (Br 6 mg), following a randomized, double-blind design on different days. Specifically, we observe absolute power extracted from qEEG data for theta band. We expected to see a decrease in absolute theta power in the temporal and parietal areas due to the influence of bromazepam for the experimental group when compared with the placebo group. We found a main effect for the condition factor for electrodes T3, T4, P3 and P4. We also observed a main effect for the period factor for electrodes P3 and P4. We observed that the ingestion of 6 mg of bromazepam induces different patterns in theta power at the temporal and parietal sites. We concluded that 6 mg of bromazepam was an important factor in the fluctuation of the activities in the temporal and parietal areas. We then hypothesize about the specific role of this drug during the execution of a visuomotor task and within the sensorimotor integration process. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

Responsiveness of sensorimotor cortex during pharmacological intervention with bromazepam

The aim of this study was to investigate the influence of bromazepam on EEG and the motor learning process when healthy subjects were submitted to a typewriting task. We investigated bromazepam due to its abuse by various populations and its prevalent clinical use among older individuals which are more sensitive to the negative effects of long half-life benzodiazepines. A randomized double-blind design was used with subjects divided into three groups: placebo (n = 13), bromazepam 3 mg (n = 13) and bromazepam 6 mg (n = 13). EEG data comprising theta, alpha and beta bands was recorded before, during and after the motor task. Our results showed a lower relative power value in the theta band in the Br 6 mg group when compared with PL. We also observed a reduction in relative power in the beta band in the Br 3 mg and Br 6 mg when compared with PL group. These findings suggest that Br can contribute to a reduced working memory load in areas related to attention processes. On the other hand, it produces a higher cortical activation in areas associated with sensory integration. Such areas are responsible for accomplishing the motor learning task. The results are an example of the usefulness of integrating electrophysiological data, sensorimotor activity and a pharmacological approach to aid in our understanding of cerebral changes produced by external agents. (c) 2008 Elsevier Ireland Ltd. All rights reserved.

Abuse liability of intra-nasal midazolam in inhaled-cocaine abusers

Intra-nasally instilled benzodiazepines have been proposed for acute anxiety episodes. However, routes with faster absorption may increase abuse liability. This study compared abuse liability of intra-nasal midazolam between subjects with a history of intra-nasal drug abuse and non-psychiatric subjects on a single-blind randomized controlled trial. Thirty-one inhaled-cocaine abusers and 34 normal volunteers received either 1 mg intra-nasal midazolam or active placebo. Visual analogue scales assessing desire to repeat the experience (ER) and Experience Liking (EL) assessed abuse liability. Profile analysis for repeated measures showed a significant effect of time over ER (F-[5,F-57]=3.311, p=0.011) and EL (F-[5,F-57]=3.947, p=0.004), diagnostic group (cocaine abusers scoring higher on both - F-[5,F-57]=5.229, p=0.026; F-[5,F-57]=4.946, p=0.030), regardless of the administered substance. It is concluded that the intra-nasal route does not seem to pose risks for non-psychiatric individuals, but it may represent a risk in itself for subjects with a history of drug abuse through this path. (C) 2008 Elsevier B.V. and ECNP. All rights reserved.

Impaired interhemispheric interactions in patients with major depression

Previous studies have shown that patients with major depression have an interhemispheric imbalance between right and left prefrontal and motor cortex. We aimed to investigate the interhemispheric interactions in patients with major depression using repetitive transcranial magnetic stimulation (rTMS). Thirteen patients with major depression and 14 age-matched healthy subjects participated in this study. Corticospinal excitability before and after 1 Hz rTMS (applied to the left primary motor cortex) was assessed in the left and right motor cortex and these results were compared with those in healthy subjects. There was a significant difference in the interhemispheric effects between patients with depression and healthy subjects. In healthy subjects, 1 Hz rTMS significantly decreased corticospinal excitability in the stimulated, left hemisphere and increased it in the contralateral, right hemisphere. In depressed subjects, 1 Hz rTMS also decreased corticospinal excitability in the left hemisphere; however, it induced no significant changes in corticospinal excitability in the contralateral, right hemisphere. In addition, there was a significant correlation between the degree of interhemispheric modulation and the severity of the depression as indexed by the Beck Depression Inventory scores. Our findings showing a decreased interhemispheric modulation in patients with major depression are consistent with the notion that mood disorders are associated with slow interhemispheric switching mechanisms.

A randomized, placebo-controlled trial of the effects of physical exercises and estrogen therapy on health-related quality of life in postmenopausal women

Objective: The purpose of this study was to evaluate the isolated and associated effects of estrogen therapy (estradiol valerate 1 mg/d orally) and physical exercise (moderate aerobic exercise, 3 h/wk) on health-related quality of life (HRQOL) and menopausal symptoms among women who had undergone hysterectomy. Design: A 6-month, randomized, double-blind, placebo-controlled clinical trial with 44 postmenopausal women who had undergone hysterectomy. The interventions were physical exercise and hormone therapy (n = 9), being sedentary and hormone therapy (n = 14), physical exercise and placebo (n = 11), and being sedentary and placebo (n = 10). HRQOL was assessed by a Brazilian standard version of the Medical Outcome Study Short-Forrn Health Survey and symptoms by Kupperman Index at baseline and after 6 months. Results: There was a decrease in symptoms in all groups, but only groups who performed physical exercise showed an increase in quality of life. Analysis of variance showed that changes in physical functioning (P = 0.001) and bodily pain (P = 0.012) scores over the 6-month period differed significantly between women who exercised and women who were sedentary, regardless of hormone therapy. Hormone therapy had no effect, and there was also no significant association between physical exercise and hormone therapy in HRQOL. Conclusions: Physical exercises can reduce menopausal symptoms and enhance HRQOL, independent of whether hormone therapy is taken.

Effects of exercise on leukocyte death: prevention by hydrolyzed whey protein enriched with glutamine dipeptide

Lymphocyte and neutrophil death induced by exercise and the role of hydrolyzed whey protein enriched with glutamine dipeptide (Gln) supplementation was investigated. Nine triathletes performed two exhaustive exercise trials with a 1-week interval in a randomized, double blind, crossover protocol. Thirty minutes before treadmill exhaustive exercise at variable speeds in an inclination of 1% the subjects ingested 50 g of maltodextrin (placebo) or 50 g of maltodextrin plus 4 tablets of 700 mg of hydrolyzed whey protein enriched with 175 mg of glutamine dipeptide dissolved in 250 mL water. Cell viability, DNA fragmentation, mitochondrial transmembrane potential and production of reactive oxygen species (ROS) were determined in lymphocytes and neutrophils. Exhaustive exercise decreased viable lymphocytes but had no effect on neutrophils. A 2.2-fold increase in the proportion of lymphocytes and neutrophils with depolarized mitochondria was observed after exhaustive exercise. Supplementation of maltodextrin plus Gln (MGln) prevented the loss of lymphocyte membrane integrity and the mitochondrial membrane depolarization induced by exercise. Exercise caused an increase in ROS production by neutrophils, whereas supplementation of MGln had no additional effect. MGln supplementation partially prevented lymphocyte apoptosis induced by exhaustive exercise possibly by a protective effect on mitochondrial function.

The effect of early virological response in health-related quality of life in HCV-infected patients

Twenty-nine HCV-infected patients were treated with pegylated interferon alpha. Diagnosis was based on serum HCV RNA-PCR positive results and liver biopsy. All patients had elevated serum levels of alanine aminotransferase at the time of the study, but liver disease was compensated. Patients were evaluated at baseline treatment and after 4 and 12 weeks of antiviral treatment with the Medical Outcomes Study 36-item Short-Form Health Survey. The Mini-International Neuropsychiatric Interview was used to exclude previous or current psychiatric diagnoses. Both patients and psychiatrists were blind to the HCV RNA status, and serum HCV RNA test results only became available after the visit at week 12. After antiviral treatment, 16 patients (55.2%) were classified as nonresponders and 13 (44.8%) were classified as responders. When compared to nonresponders, responders had a greater improvement in the HRQOL scores for the mental health domain (P<.019). Differences in other domains were not significant. The present study confirms that active viral infection is one possible reason for the poor Health-Related Quality of Life in this population.

Intranasal Corticosteroid Administration Reduces Nonspecific Bronchial Hyperresponsiveness and Improves Asthma Symptoms

Introduction. Rhinitis and asthma are currently recognized as manifestations of a single syndrome, the chronic allergic respiratory syndrome. Nearly all individuals with asthma have rhinitis, and severe rhinitis has been associated with worse outcomes in asthma patients. Intranasal treatment has been reported to be beneficial for the lower airways. Methods. This was a randomized, double-blind, placebo-controlled study. The objective was to evaluate the effects that treatment with intranasal beclomethasone dipropionate (BDP; 400 g/d) has on nasal and bronchial symptoms, as well as on lung function test results and bronchial responsiveness to histamine in patients with allergic rhinitis and asthma. We evaluated 33 patients, divided into two groups: treatment (n = 17); and placebo (n = 16). Over the course of the 125-day study period, each patient reported daily rhinitis and asthma symptoms, as well as the need for additional medication. All patients were submitted to spirometry and histamine challenge at baseline and at each subsequent evaluation (on days 50 and 75). Results. In comparison with the patients in the placebo group, those in the BDP treatment group presented significantly fewer nasal symptoms on day 50 and fewer asthma symptoms on day 75 (p 0.01 for both); required rescue medications less often; and presented a significantly lower degree of bronchial responsiveness to histamine on day 75 (p 0.01). Conclusion. In this study, intranasal BDP was effective in treating rhinitis as well as asthma. The benefits for the lower airways were observed only after prolonged treatment and might be better evaluated through nonspecific bronchial challenge.