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PubMed2006

Linezolid and serotonergic drug interactions: a retrospective survey.

BACKGROUND: Linezolid is a reversible, nonselective monoamine oxidase inhibitor. There are currently 11 published case reports of serotonin syndrome being associated with linezolid and selective serotonin reuptake inhibitors (SSRIs). Controversy exists regarding whether linezolid and SSRIs can be given concomitantly. The purpose of this study was to report the incidence of serotonin syndrome in patients receiving linezolid and SSRIs. METHODS: This study was a retrospective chart review of inpatients at the Mayo Clinic (Rochester, MN) with concomitant orders or therapy within 14 days for linezolid and an SSRI from 2000 to 2004. The Sternbach criteria and Boyer criteria for diagnosis of serotonin syndrome were used to identify clinical features of serotonin syndrome. RESULTS: Seventy-two patients received linezolid and an SSRI or venlafaxine within 14 days of each other. Fifty-two patients (72%) received concomitant therapy with linezolid and an SSRI or venlafaxine, and 20 patients (28%) did not receive concomitant therapy but received linezolid and an SSRI within a 14-day period. Overall, only 2 patients (3%) had a high probability of serotonin syndrome. In both patients with high probability, symptoms reversed rapidly on discontinuation of serotonergic therapy. The Boyer criteria were much more specific than the Sternbach criteria for identification of serotonin syndrome. CONCLUSIONS: On the basis of our experience, we suggest that, if the clinical situation warrants use of linezolid in a patient receiving an SSRI, linezolid may be used concomitantly with SSRIs, without a 14-day washout period and with careful monitoring for signs and symptoms of serotonin syndrome. Serotonergic agents should be promptly discontinued if serotonin syndrome is suspected.

Acetamides↗
PubMed2003

Differential effects of immunophilin-ligands (FK506 and V-10,367) on survival and regeneration of rat retinal ganglion cells in vitro and after optic nerve crush in vivo.

Immunophilins belong to the large family of peptidyl-prolyl-cis-trans-isomerases known to be involved in many cellular processes (e.g., protein trafficking and transcriptional regulation). Beside the widespread therapeutic use of ligands of immunophilins as immunosuppressants, it has been shown that some of these compounds such as FK506 and V-10,367 may mediate neuroprotection and improve axonal regeneration following damage to peripheral nerve fibers. Here, we have analyzed the effects of these two compounds on neurite outgrowth of retinal explants in vitro and on axonal regeneration of retinal ganglion cells, a population of central intrinsic neurons, ten days following optic nerve crush in vivo. FK506 enhanced neurite outgrowth/regrowth in vitro in a dose dependent manner up to 135% (control = 100%), while V-10,367 was more effective (up to 168%). In vivo, intravitreal V-10,367 and FK506 significantly reduced the number of dying retinal ganglion cells as demonstrated by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling. Local application of FK506 into the vitreous body, but not V-10,367, immediately provided after the optic nerve crush induced the elongation of regenerating fibers across the lesion site for around 1.2 mm. Our data provide evidence that the ligands of the FK506-binding proteins FK506 and V-10,367 protect (otherwise dying) retinal ganglion cells from optic nerve crush-induced cell death, promote neurite outgrowth in vitro and that locally applied FK506 enhances the sprouting of axotomized central intrinsic neurons such as retinal ganglion cells in vivo after optic nerve crush.

Animals↗
PubMed2003

Effect of aromatics on lung mucociliary clearance in patients with chronic airways obstruction.

BACKGROUND: Complementary and alternative medicine have become an increasingly topical theme in respiratory medicine. Aromatics are a commonly used ingredient in a number of proprietary medicines. It is well established that lung mucus clearance is impaired in patients with chronic airways obstruction. This study investigated whether aromatics delivered by inunction could be objectively shown to enhance lung clearance. METHODS: We studied 12 patients with chronic bronchitic with a mean standard error (SE) age of 67 (2) years (mean [SE] tobacco consumption history of 64 [12] pack-years). We used a randomized, single-blinded, placebo-controlled crossover trial within patient design assessing the effect of 7.5 g of aromatics inunction (compared to a "no-treatment baseline" and to a petrolatum "placebo") on lung mucus clearance measured by a standard radioaerosol technique. RESULTS: Aromatic treatment significantly enhanced clearance at two time points 30 (p < 0.05) and 60 (p < 0.02) minutes postradioaerosol inhalation but had no demonstrable further effect over the following 5 hours despite further application of the inunction. The clearance improvement (relative to a baseline) observed during the first hour of testing was significantly correlated (p < 0.01) with the concentration level of aromatics. CONCLUSION: Our data, thus, provide objective evidence of a positive effect of aromatics inunction on mucus clearance in chronic airways obstruction.

Aged↗
PubMed1996

An open trial of venlafaxine in the treatment of attention-deficit/hyperactivity disorder in children and adolescents.

A 5-week open trial of venlafaxine was conducted in 16 children and adolescents (mean age 11.6 years) with attention-deficit/hyperactivity disorder (ADHD) in order to estimate the appropriate dosage range and to determine the extent of side effects. Subjects were evaluated using a structured clinical interview and a computerized diagnostic assessment, and subjects diagnosed with ADHD and without comorbid depression were asked to enter the study. Conners Parent Rating Scale (CPRS) and Conners Continuous Performance Test (CPT) were performed at baseline and at the end of the 5-week trial. Two subjects were lost to follow-up. Of the remaining 14 patients, 7 subjects displayed a decrease of at least one standard deviation from their baseline on one of the CPRS subscale scores and had subjective reports from parents of improved behavior. There were no statistically significant effects of venlafaxine on reaction times or on the number of commission and omission errors on CPT. Three ADHD subjects displayed a worsening of their hyperactivity and required discontinuation of venlafaxine, and nausea led to drug discontinuation in 1 patient. The mean daily dose of venlafaxine was 60 mg (1.4 mg/kg), administered 2-3 divided doses, there were no effects on blood pressure or heart rate. In this sample, low doses of venlafaxine appeared to be effective in reducing behavioral but not cognitive symptoms of ADHD in 7 of 16 children and adolescents (44%), and adverse effects were not tolerable in 4 of 16 patients (25%). These preliminary results suggest that venlafaxine may aggravate symptoms of hyperactivity, consistent with the behavioral activation reported with fluoxetine and sertraline in children.

Adolescent↗
PubMed2005

Effect of different locations on the chemical composition of essential oils of laurel (Laurus nobilis L.) leaves growing wild in Turkey.

The essential oil components of Laurus nobilis gathered from seven different locations of Turkey were identified by gas chromatography/mass spectrometry. The oil yields on a dry weight basis ranged between 1.4% to 2.6%. The major component was 1,8-cineole (51.73-68.48%); other predominant components were alpha-terpinyl acetate (4.04-9.87%), sabinene (4.44-7.75%), alpha-pinene (2.93-4.89%), beta-pinene (2.58-3.91%), terpinene-4-ol (1.33-3.24%), and alpha-terpineol (0.95-3.05%). Minor qualitative and major quantitative variations of some compounds were determined with respect to localities of collection. As a result, the 1,8-cineole content of these oils was significantly higher than those of other constituents of L. nobilis. Laurel is usually considered as the natural source of this compound, used in the flavor and fragrance industry.

Bicyclic Monoterpenes↗
PubMed2005

Pilot evaluation of citalopram for the treatment of hot flashes in women with inadequate benefit from venlafaxine.

BACKGROUND: While newer antidepressants, such as venlafaxine and paroxetine, substantially decrease hot flashes, there is no published information with regards to whether a different antidepressant will be effective when one antidepressant does not adequately relieve hot flashes. OBJECTIVE: The objective of this trial was to provide pilot information with regards to whether citalopram would effectively reduce hot flashes in patients who did not receive adequate enough hot flash reduction with venlafaxine. DESIGN: This was a prospective pilot trial. MEASUREMENTS: Validated patient-completed hot flash diary questionnaires were utilized for measuring hot flashes. SUBJECTS: Thirty patients were recruited to this trial, 22 of whom were fully evaluable. RESULTS: Compared to a baseline week, hot flash scores were reduced by 53% 4 weeks later. The citalopram appeared to be well tolerated with many quality-of-life and potential toxicity symptoms much improved compared to the baseline week. At the end of the 4-week treatment, 19 patients (63% of patients entering the study and 86% of the patient completing the study treatment) chose to continue to use citalopram. CONCLUSION: This pilot information supports the hypothesis that citalopram will reduce hot flashes in patients with inadequate hot flash relief while taking venlafaxine.

Adult↗
PubMed2006

Duloxetine versus routine care in the long-term management of diabetic peripheral neuropathic pain.

INTRODUCTION: Duloxetine hydrochloride is a dual reuptake inhibitor of both serotonin and norepinephrine. In the present open-label study, the safety of duloxetine at a fixed-dose of 60 mg twice daily (BID) for up to 52 weeks was evaluated and compared to routine care in the therapy of patients diagnosed with diabetic peripheral neuropathic pain (DPNP). METHODS: Patients who completed a 13-week, double-blind, duloxetine and placebo acute therapy period were rerandomly assigned in a 2:1 ratio to therapy with duloxetine 60 mg BID (N=161) or routine care (N=76) for an additional 52 weeks. Routine care consisted primarily of gabapentin, amitriptyline, and venlafaxine. The study included male or female outpatients 18 years of age or older with a diagnosis of DPNP caused by type 1 or type 2 diabetes. RESULTS: A higher percentage of routine care-treated patients experienced 1 or more serious adverse events. No statistically significant therapy-group difference was observed in the overall incidence of treatment-emergent adverse events (TEAEs). The TEAEs reported by 10% or more of duloxetine 60 mg BID-treated patients were nausea, and by the routine care-treated patients were peripheral edema, pain in the extremity, somnolence, and dizziness. Duloxetine did not appear to adversely affect glycemic control, lipid profiles, nerve function, or the course of DPNP. There were no statistically significant therapy-group differences observed in the 36-item Short-Form Health Survey subscales or in the EuroQol 5-Dimension Questionnaire. CONCLUSIONS: In this study, duloxetine was safe and well tolerated compared to routine care in the long-term management of patients with DPNP.

Amines↗
PubMed2005

Relative antidepressant efficacy of venlafaxine and SSRIs: sex-age interactions.

OBJECTIVE: To investigate whether differences in antidepressant efficacy are moderated by an interaction of age and gender. METHODS: A pooled dataset from eight randomized, controlled trials of patients with major depressive disorder (MDD) was reanalyzed to compare remission rates following therapy with venlafaxine (n = 851), one of several selective serotonin reuptake inhibitors (SSRIs) (n = 748), or placebo (n = 446). Remission was defined as a final Hamilton Rating Scale for Depression (HAM-D) score < or =7. Pairwise comparisons were conducted using stepwise multiple logistic regression models with main effect and interaction terms for treatment, sex, and age (younger: <50; older: > or =50). Among older women, the impact of hormone replacement therapy (HRT) on remission rates also was examined. RESULTS: Remission rates on venlafaxine therapy were not affected by age, sex, or HRT use. Among women, but not men, there was a significant interaction reflecting poorer SSRI response in the older age group (Wald chi-square = 4.21, df = 1, p = 0.04); HRT appeared to eliminate this difference. Whereas the advantage in remission rates favoring venlafaxine was modest for men and younger women (6%-9%), the difference among older women not taking HRT was 23%. CONCLUSIONS: These findings provide further evidence that age, gender, and HRT moderate response to antidepressant medications.

Adult↗
PubMed1992

The effect of the immunophilin ligands rapamycin and FK506 on proliferation of mast cells and other hematopoietic cell lines.

The immunosuppressive drugs FK506 and cyclosporin A have an identical spectrum of activities with respect to IgE receptor (Fc epsilon RI)-mediated exocytosis from mast cells and T cell receptor-mediated transcription of IL-2. These findings suggest a common step in receptor-mediated signal transduction leading to exocytosis and transcription and imply that immunosuppressive drugs target specific signal transduction pathways, rather than specific cell types. This hypothesis is supported by studies on the effect of rapamycin on IL-3 dependent proliferation of the rodent mast cell line PT18. Rapamycin inhibits proliferation of PT18 cells, achieving a plateau of 80% inhibition at 1 nM. This inhibition is prevented in a competitive manner by FK506, a structural analogue of rapamycin. Proliferation of rat basophilic leukemia cells and WEHI-3 cells was also inhibited, at doses comparable to those shown previously to inhibit IL-2-dependent proliferation of cytotoxic T lymphocyte line (CTLL) cells. In contrast, proliferation of A-431 cells, a epidermoid cell line, was not affected by rapamycin. DNA histograms indicate that complexes formed between the rapamycin-FK506-binding protein (FKBP) and rapamycin arrest-proliferating PT18 cells in the G0/G1-phase. It is concluded that FKBP-rapamycin complexes may inhibit proliferative signals emanating from IL-3 receptors, resulting in growth arrest of cytokine-dependent, hematopoietic cells.

Animals↗
PubMed1992

Effect of an intestinal disaccharidase inhibitor (AO-128) on obesity and diabetes.

A new disaccharidase inhibitor, AO-128, showed 190-3900-fold more potent inhibition of purified rat small intestine sucrase-isomaltase (S-1) complex and 23-33-fold more potent inhibition of semipurified porcine small intestine disaccharidases than acarbose. AO-128 suppressed elevation of the blood glucose concentration after oral sucrose, maltose, and starch, but not after oral glucose, fructose, and lactose. The chronic addition of AO-128 to the diet produced antiobesity and antidiabetic actions in obese and/or diabetic animals. Undesirable side effects, such as diarrhea and soft feces, were observed only for the first 5-7 d and suppression of intestinal disaccharidase activities was observed even at the end of the experiment, suggesting that the suppressive or delaying effect of AO-128 on elevation of the postprandial blood glucose concentrations is involved in reduction in body weight gain and prevention and/or amelioration of the diabetic state. Thus, AO-128 is useful as an adjunct to the dietary management of obesity and diabetes.

Acarbose↗
PubMed2005

Pharmacological manipulation of CB1 receptor function alters development of tolerance to alcohol.

AIMS: The current study investigated the efficacy of CB1 receptor-targeted drugs on the development and expression of tolerance to alcohol (EtOH). METHODS: An EtOH-inhalation model was used to induce tolerance, as measured by EtOH-induced sedation and hypothermia after a 24 h withdrawal period. Two drug treatment procedures, (i) co-treatment with EtOH and (ii) acute drug administration following chronic EtOH treatment, were used to test the efficacy of CB1 receptor manipulations on EtOH tolerance. RESULTS: The effects of the CB1 receptor agonist CP-55,940 varied depending on paradigm and behavioural measure. Chronic CP-55,940 co-treatment blocked tolerance to EtOH-induced hypothermia but not to the sedative effect (sleep time) in EtOH-exposed mice. However, chronic CP-55,940 administration alone resulted in tolerance to the sedative effect of a challenge dose of EtOH in control mice. Acute CP-55,940 administration after chronic alcoholization blocked the development of tolerance to EtOH-induced sedation compared to the EtOH alone exposed group, but induced tolerance to the hypothermic effects of EtOH in control mice. Chronic blockade of CB1 receptor function by SR141716A resulted in tolerance to both the sedative and hypothermic effects of EtOH in control mice, but had no effect on EtOH-exposed mice. CONCLUSIONS: The data support a role for the endocannabinoid (EC) system in EtOH tolerance/dependence and suggest that drugs targeted against EC system could be therapeutically useful in treating alcohol-related disorders.

Alcoholism↗
PubMed2007

Venlafaxine is superior to clonidine as treatment of hot flashes in breast cancer patients--a double-blind, randomized study.

BACKGROUND: Classical hormone replacement therapy for hot flashes is contraindicated in breast cancer especially in endocrine responsive disease. PATIENTS AND METHODS: In a double-blind, randomized phase III study, breast cancer patients suffering from hot flashes at least twice a day, who were not taking any medication against hypertension and depression received either clonidine 0.075 mg twice a day or venlafaxine 37.5 mg twice a day for 4 weeks. The primary end point was defined as the frequency of hot flashes after 4 weeks of treatment. A self-reported 1-week hot flash and other symptom questionnaire were kept before the start of treatment until the end of treatment course. RESULTS: From April 2002 to October 2004, 80 patients were recruited of whom 64 were assessable for efficacy analyses. Thirty-three received clonidine and 31 venlafaxine, nine patients stopped early because of side-effects and seven withdrew consent. At the end of treatment week 4, the median hot flash frequency dropped by 7.6 hot flashes per day for patients receiving venlafaxine and 4.85 hot flashes per day for those receiving clonidine (P = 0.025). CONCLUSION: Venlafaxine is significantly more effective in reducing the frequency of hot flashes in breast cancer patients than clonidine.

Adult↗
PubMed2003

Cannabinoids inhibit neurodegeneration in models of multiple sclerosis.

Multiple sclerosis is increasingly being recognized as a neurodegenerative disease that is triggered by inflammatory attack of the CNS. As yet there is no satisfactory treatment. Using experimental allergic encephalo myelitis (EAE), an animal model of multiple sclerosis, we demonstrate that the cannabinoid system is neuroprotective during EAE. Mice deficient in the cannabinoid receptor CB1 tolerate inflammatory and excitotoxic insults poorly and develop substantial neurodegeneration following immune attack in EAE. In addition, exogenous CB1 agonists can provide significant neuroprotection from the consequences of inflammatory CNS disease in an experimental allergic uveitis model. Therefore, in addition to symptom management, cannabis may also slow the neurodegenerative processes that ultimately lead to chronic disability in multiple sclerosis and probably other diseases.

Animals↗
PubMed1994

Functional imaging of effects of fragrances on the human brain after prolonged inhalation.

Beside olfactory or trigeminal stimulation of chemosensory receptor-cells some results in published literature suggest that fragrances show a direct affect on the brain. The effect of the fragrance 1,8-cineol, which was described in literature as 'stimulating', on regional and global cerebral blood flow (rCBF and gCBF) in the human brain after prolonged inhalation was investigated. The results show an increase of global-CBF without preference to primary or secondary olfactory centres after an inhalation-time of 20 min.

Adult↗
PubMed1995

Variation in odor thresholds for l-carvone and cineole and correlations with suprathreshold intensity ratings.

Specific anosmias have been reported for l-carvone and cineole, two compounds of importance in food flavor perception. Detection thresholds were assessed in groups of 50+ individuals by ascending forced-choice tests conducted in quadruplicate. Wide individual differences in thresholds were observed. Within the same session, threshold correlations were in the range of +0.8 to +0.9, showing good short-term reliability. Correlations with suprathreshold ratings were moderate (in the range of r = -0.5) after subtraction of false positive ratings for blank samples. However, a cineole mixture experiment failed to show any differences between subgroups that were previously classified as high or low sensitivity on the basis of threshold measurements. Re-testing selected groups after a period of months showed considerable within-individual variation in the thresholds, especially for l-carvone. These results call into question the stability and utility of threshold classification for these two compounds.

Adult↗