Number Of Adverse Effects Research Articles

Use of Liposomal Drugs in the Treatment of Rheumatoid Arthritis

Rheumatoid arthritis is an autoimmune disease that results in joint deformity and disability. Conventional nonsteroidal anti-inflammatory drugs (NSAIDs), steroids and disease modifying antirheumatic drugs (DMARDs) are used for its treatment. Unconventional therapies, like enzyme oligodeoxy nucleotides, boron neutron capture therapy & radioisotopes are also being tried. The use of all these drugs is limited by a number of adverse effects. These side effects have been overcome to a large extent by the use of liposomes as delivery systems. This review presents rationale for the use of liposomes for the treatment of arthritis. Systemic as well as intra-articular delivery of liposome encapsulated anti-arthritic drugs is discussed. Success and limitations of this approach are also discussed by taking examples of different drug classes. Keywords: Arthritis, liposomes, DMARDs, NSAIDs, corticosteroids, intra-articular

Understanding the Adverse Effects of Cosmetics

Currently, cosmetics and toiletries are very popular and their use continues to increase because consumers consider physical appearance important and, at the same time, these products are considered to be safe. However, in spite of their safety and tolerability, during recent decades, we have become aware that adverse effects can occur. The number of adverse effects known so far is very low indeed. This is partly because such adverse effects are underestimated as a result of self-diagnosis and self-medication, which are common behaviours in the presence of mild-to-moderate reactions, as in the case of cosmetics. Moreover, such effects are underestimated because of the absence of formal and reliable monitoring systems ('cosmetovigilance'). This requires the creation of a standard reporting form, as well as resolution concerning professional categories authorized to report and the subsequent validation/evaluation of the collected forms. All these items are of great importance, not only to investigate but also to prevent risks caused by cosmetic use. A pilot project was undertaken to test the effectiveness of a notification system by the validation of either a reporting form or the role of dermatologists and community pharmacists as reporting categories. Collection of reporting forms began in July 2006 and it is still in progress; the preliminary data reported here refer to the period July 2006-June 2007 and mainly concern the recording and validation of the collected reporting forms. During this period, we have received 40 reporting forms (32 by dermatologists and 8 by pharmacists). The validation process of the recorded forms revealed several drawbacks, such as incompleteness (19 forms), inadequacy of the description of the suspected undesirable effect and its location (2), illegible handwriting (6) and mistaken statements (3). Six forms reported a misuse of a cosmetic product: four of these were related to the site of application while two were related to time. In one case, instructions for use were not followed. In conclusion, our experience regarding the notification of adverse effects of cosmetics, although limited to a restricted geographical area, suggests that for an efficient and reliable monitoring system to be in place, which includes all the necessary measures to protect public health, an education and training programme for all stakeholders (health professionals, consumers and appropriate authorities) is required.

Hyperglycemia and insulin therapy in preterms

Very low birth weight infants are born with numerous problems that can interfere with insulin/glucose homeostasis. They have essentially no fat stores and minimal glycogen stores, and the maternal source of glucose is acutely cut off at delivery. They inevitably are stressed and rapidly become catabolic, often with glucose intolerance. Consistent administration of adequate calories soon after birth is complicated by the glucose intolerance, variable fluid needs, and other disease specific therapies (e.g. caffeine for apnea of prematurity, hydrocortisone for low blood pressure). Previous studies have demonstrated that the amount of glucose administered to these infants can be increased by concurrent insulin treatment. However, insulin therapy is not easy because frequent measurements of blood glucose are necessary to avoid hypoglycemia. But, hyperglycemia may have a number of adverse effects on short-term and long-term outcomes. Beardsall et al report that an early intervention to deliver glucose and insulin resulted in better glucose control and increased IGF-1. The normalization of counter-regulating and growth related hormones such as IGF-1 may be important benefits of such therapy. However, a compelling case needs to be made that the intensive management of blood glucose will be of significant long-term benefit before clinicians should routinely attempt such management.

Diabetes mellitus as a prothrombotic condition

Diabetes mellitus (DM) is characterized by fasting hyperglycaemia and a high risk of atherothrombotic disorders affecting the coronary, cerebral and peripheral arterial trees. The risk of myocardial infarction (MI) is 3-5 fold higher in Type 2 DM and a DM subject with no history of MI has the same risk as a non-DM subject with a past history of MI. In total around 70% of deaths are vascular with poorer outcomes to both acute events and cardiological interventions. It was proposed that clustering of vascular risk factors (hyperinsulinaemia, dysglycaemia, dyslipidaemia and hypertension) around insulin resistance (IR) accounted for the increase in risk with Type 2 DM. The importance of this became apparent with the recognition that risk clustering occurs in normoglycaemic and impaired glucose tolerance (IGT) subjects with IR, in total around 25% of the population in addition to long-standing Type 1 subjects with renal disease. Evidence indicates that thrombotic risk clustering also occurs in association with IR, suppression of fibrinolysis due to elevated concentrations of the fibrinolytic inhibitor, plasminogen activator inhibitor-1 (PAI-1) is invariable with IR and there is evidence that this is regulated by the effects of triglyceride on the PAI-1 gene promoter. Other studies indicated that prothrombotic risk (coagulation factors VII, XII and fibrinogen) also associates with the IR syndrome. The development of endothelial cell dysfunction with suppression of nitric oxide and prostacyclin synthesis, combined with platelet resistance to the anti-aggregatory effects of these hormones leads to loss of control over platelet activation. In addition, hyperglycaemia and glycation have marked effects on fibrin structure function, generating a clot which has a denser structure, resistant to fibrinolysis. The combination of increased circulating coagulation zymogens, inhibition of fibrinolysis, changes in fibrin structure/function and alterations in platelet reactivity creates a thrombotic risk clustering which underpins the development of cardiovascular disease.

Therapy Insight: the risks and benefits of bisphosphonates for the treatment of tumor-induced bone disease

Bisphosphonates are a valuable class of drugs with potent anti-resorptive actions that make them ideal for skeletal protection in osteoporosis, cancer bone metastasis, multiple myeloma, and Paget's disease of bone. It has become apparent, however, that these drugs also have the potential to cause a number of adverse effects. While these do not limit bisphosphonate use, the incidence of these adverse events can be minimized if appropriate care is taken with their administration, and by maintaining appropriate surveillance and patient care. We review the range of adverse reactions to bisphosphonate therapy with a particular emphasis on the recently identified association between long-term bisphosphonate treatment and osteonecrosis of the jaw. This is a potentially serious side effect seen mostly in patients with multiple myeloma or breast cancer bone metastases who receive intravenous bisphosphonate treatment. While the etiology is uncertain, a strong association with dental pathology and interventions highlights the need for close attention to dental health in this patient group.

Immunosuppressive Therapy in Older Cardiac Transplant Patients

Cardiac transplantation has become an established intervention for end-stage heart disease. Clinical outcomes in older cardiac transplant patients have improved over the last decade and are almost similar to those in younger patients. Nevertheless, morbidity and mortality due to infections, cancer and chronic allograft vasculopathy remain problematic. On the other hand, older transplant patients seem to have lower incidences of acute rejection episodes than younger patients. Conventional immunosuppression with calcineurin-inhibiting drugs, azathioprine and corticosteroids is responsible for a number of adverse effects. Although these adverse effects can also be seen in younger patients, tolerance to these agents seems to decrease with increasing age. In particular, diabetes mellitus, osteoporosis and chronic renal insufficiency are associated with higher morbidity and mortality in older cardiac transplant patients. As the elderly become an ever-increasing segment of the cardiac transplant population, new and innovative immunosuppressive strategies will have to be developed and applied.Currently, the availability of new immunosuppressive drugs means more individualised immunosuppressive protocols can be used. New antibodies for induction therapy, a choice between ciclosporin and tacrolimus, and the advent of mycophenolate mofetil as well as proliferation signal inhibitors (everolimus, sirolimus) have changed immunosuppressive protocols dramatically. Therefore, a generalised protocol for all patients has been replaced by individualised immunosuppression depending on the patient group. Moreover, protocols can be modified during follow-up depending on the individual patient's requirements and problems. Hypertension and hyperlipidaemia could be influenced by the selection of tacrolimus over ciclosporin, and weaning of corticosteroids might have a positive impact on osteoporosis or diabetes. There is also no clear evidence that tacrolimus is associated with a higher risk for new onset of diabetes. Chronic renal insufficiency can be managed with calcineurin inhibitor-free immunosuppression consisting of mycophenolate mofetil and proliferation signal inhibitors. Both everolimus and sirolimus also seem to have a protective effect against the onset of graft vasculopathy and some sorts of cancer after cardiac transplantation. As a general rule, however, older cardiac transplant patients should be treated with lower doses and fewer immunosuppressive drugs to avoid over-immunosuppression.

Caregiver Acceptance of Adverse Effects and Use of Cholinesterase Inhibitors in Alzheimer's Disease

Caregivers play a determining role in choosing treatments for persons with Alzheimer's disease. The objective of this study was to examine caregivers' willingness to have persons with Alzheimer's disease continue taking cholinesterase inhibitors in the event that any 1 of 11 adverse effects was to occur. Data were gathered via postal questionnaire from 375 caregivers in Montreal. Sixty-four per cent of caregivers responded ( n = 201), and most (> or =59%) were willing to continue treatment if persons with Alzheimer's disease suffered from weight loss or loss of appetite. However, most (> or =53%) were not willing to continue treatment in the event of headache, dizziness, nausea, diarrhea, vomiting, drop in blood pressure, insomnia, muscle cramps, or stomach bleeding. The use of cholinesterase inhibitors by persons with Alzheimer's disease was positively associated with caregivers' willingness to accept greater numbers of adverse effects (adjusted relative risk = 1.97; 95% CI = 1.11 to 3.61). Caregivers appear to make a risk-benefit assessment when they decide whether or not care-recipients should continue pharmacotherapy in the event of adverse effects.

Intra-individual propofol dosage variability in children undergoing repetitive procedural sedations

Objectives: Propofol sedation/anesthesia has been used successfully in children undergoing procedural sedation. We prospectively assessed intra- and inter-individual variability in propofol dosage for sedation in repetitive procedures in children with malignancies. Patients and methods: A total of 80 procedures including lumbar puncture, radiation therapy, magnetic resonance imaging, bone marrow biopsiy, endoscopy, drainage of ascites (range: 2–19 procedures/patient) were performed in 24 children (mean age: 9,6±5,4 years). The mean propofol induction dose was 2,61±0,74mg.kg-1 to achieve deep sedation. Primary outcome measure was the inter- and intra-individual propofol dosage required to achieve adequate sedation; secondary outcome measures were the number of adverse effects, the need for therapeutic interventions, and cardiovascular parameters. Results: All 80 procedures were completed with satisfactory sedation levels. There was a remarkable inter- and intra-individual variability in propofol dosage required to achieve adequate sedation (interindividual range 1.1–4.1mg.kg-1; intraindividual difference concerning the needed propofol induction 0.0–2.2mg.kg-1, 25% of the patients had a dose range of 0.0–0.5mg.kg-1, 37,5% >0.5–1.0mg.kg-1, 37,5% >1.0–2.2mg.kg-1. In 10% (n=8) of the procedures side effects were seen, mainly short episodes of desaturation which required no or only minor interventions. Conclusions: Due to great inter- and intra-individual differences, propofol dosage should be titrated towards the desired level of sedation. Thus propofol can be adjusted to the individual's need while achieving adequate sedation. Considering the substancial rate of adverse effects procedural sedation with propofol should be performed only by physicians experienced in advanced pediatric cardiorespiratory support.

Cerebral oxygen saturation changes during modified ultrafiltration

A number of adverse effects are associated with the use of cardiopulmonary bypass (CPB) in pediatric patients undergoing cardiac surgery. Pulmonary compliance and gas exchange are decreased, and myocardial edema may result in diastolic dysfunction. Modified ultrafiltration (MUF) after CPB in children decreases body water, removes inflammatory mediators, improves hemodynamics, and decreases transfusion requirements. To determine the factors that influence cerebral tissue oxygenation during MUF. Pediatric patients received the usual treatment, with MUF times from 10 to 19 min, as determined by circuit volume and patient hemodynamic stability. Preliminary results in five patients with arterial saturation > 95% during MUF demonstrates four predictors of cerebral oxygenation, using stepwise multiple linear regression with cerebral oxygen saturation as the dependant variable. In order of significance, they are pCO2, ultrafiltration flow rate, mean arterial pressure, and hematocrit. The results of this study will be used to determine the optimal performance of MUF. Maximizing cerebral oxygen delivery during this early post-bypass period is extremely important, and identifying the factors responsible for increased cerebral oxygen delivery during MUF allows the clinician to make the appropriate changes necessary to achieve this.

Rituximab alone or in association with corticosteroids in the treatment of acquired factor VIII inhibitors: report of two cases

Acquired haemophilia is a factor VIII (FVIII) deficiency due to autoantibodies directed against FVIII that can be responsible for severe haemorrhage. The therapeutic approach, in addition to the treatment of bleeding episodes with clotting factor infusion, relies on corticosteroids (CS), cyclophosphamide (CYC), and/or high-dose intravenous immunoglobulins (IVIg). However, the efficacy of IVIg is limited, and CS and CYC may cause a number of adverse effects. Recently, rituximab has been proposed, alone or in combination with CS and immunosuppressants in a small number of patients with acquired anti-FVIII antibodies with a good efficacy. We report here on two patients, aged 74 and 81, respectively, who developed acquired haemophilia, with high titre FVIII inhibitors and severe haemorrhage, in the absence of a detectable cause. Both of them received rituximab as a first line therapy with a marked and prolonged efficacy.

The Can-SAD Study: A Randomized Controlled Trial of the Effectiveness of Light Therapy and Fluoxetine in Patients With Winter Seasonal Affective Disorder

Objective: Light therapy and antidepressants have shown comparable efficacy in separate studies of seasonal affective disorder treatment, but few studies have directly compared the two treatments. This study compared the effectiveness of light therapy and an antidepressant within a single trial. Method: This double-blind, randomized, controlled trial was conducted in four Canadian centers over three winter seasons. Patients met DSM–IV criteria for major depressive disorder with a seasonal (winter) pattern and had scores ≥23 on the 24-item Hamilton Depression Rating Scale. After a baseline observation week, eligible patients were randomly assigned to 8 weeks of double-blind treatment with either 1) 10,000-lux light treatment and a placebo capsule, or 2) 100-lux light treatment (placebo light) and fluoxetine, 20 mg/day. Light treatment was applied for 30 minutes/day in the morning with a fluorescent white-light box; placebo light boxes used neutral density filters. Results: A total of 96 patients were randomly assigned to a treatment condition. Intent-to-treat analysis showed overall improvement with time, with no differences between treatments. There were also no differences between the light and fluoxetine treatment groups in clinical response rates (67% for each group) or remission rates (50% and 54%, respectively). Post hoc testing found that light-treated patients had greater improvement at 1 week but not at other time points. Fluoxetine was associated with greater treatment-emergent adverse events (agitation, sleep disturbance, palpitations), but both treatments were generally well-tolerated with no differences in overall number of adverse effects. Conclusions: Light treatment showed earlier response onset and lower rate of some adverse events relative to fluoxetine, but there were no other significant differences in outcome between light therapy and antidepressant medication. Although limited by lack of a double-placebo condition, this study supports the effectiveness and tolerability of both treatments for seasonal affective disorder and suggests that other clinical factors, including patient preference, should guide selection of first-line treatment.

The Can-SAD Study: A Randomized Controlled Trial of the Effectiveness of Light Therapy and Fluoxetine in Patients With Winter Seasonal Affective Disorder

Light therapy and antidepressants have shown comparable efficacy in separate studies of seasonal affective disorder treatment, but few studies have directly compared the two treatments. This study compared the effectiveness of light therapy and an antidepressant within a single trial. This double-blind, randomized, controlled trial was conducted in four Canadian centers over three winter seasons. Patients met DSM-IV criteria for major depressive disorder with a seasonal (winter) pattern and had scores > or = 23 on the 24-item Hamilton Depression Rating Scale. After a baseline observation week, eligible patients were randomly assigned to 8 weeks of double-blind treatment with either 1) 10,000-lux light treatment and a placebo capsule, or 2) 100-lux light treatment (placebo light) and fluoxetine, 20 mg/day. Light treatment was applied for 30 minutes/day in the morning with a fluorescent white-light box; placebo light boxes used neutral density filters. A total of 96 patients were randomly assigned to a treatment condition. Intent-to-treat analysis showed overall improvement with time, with no differences between treatments. There were also no differences between the light and fluoxetine treatment groups in clinical response rates (67% for each group) or remission rates (50% and 54%, respectively). Post hoc testing found that light-treated patients had greater improvement at 1 week but not at other time points. Fluoxetine was associated with greater treatment-emergent adverse events (agitation, sleep disturbance, palpitations), but both treatments were generally well-tolerated with no differences in overall number of adverse effects. Light treatment showed earlier response onset and lower rate of some adverse events relative to fluoxetine, but there were no other significant differences in outcome between light therapy and antidepressant medication. Although limited by lack of a double-placebo condition, this study supports the effectiveness and tolerability of both treatments for seasonal affective disorder and suggests that other clinical factors, including patient preference, should guide selection of first-line treatment.

Leucocyte depletion of blood components -- guidelines of the Blood Transfusion Services of South Africa.

Extracted from text ... Leucocyte depletion of blood components - guidelines of the Blood Transfusion Services of South Africa Arthur Bird, Robert Crookes Leucocytes in blood components are responsible for a number of adverse effects associated with blood transfusion. In many instances the pathogenesis has not been elucidated precisely, but it is likely that it is immunologically mediated. Potential mechanisms include clonal deletion or anergy, induction of suppressor cells, production of anti-idiotypic antibody, suppression of natural killer (NK) cell activity and several others.1 As a consequence a number of clinicians prefer to use leucocyte-depleted components. The clinical indications advanced for depleting blood components of leucocytes (leucodepletion) are as follows: (i) avoidance of febrile non-haemolytic transfusion reactions (FNHTRs); (ii) reduction ..

Alteraciones electrolíticas inducidas por la preparación para los estudios de imagen del colon

An adequate bowel cleansing is needed prior to radiologic and endoscopic procedures. However, it may have a number of adverse effects, including abnormalities of calcium-phosphorus homeostasis. This was an observational prospective study in a hospital practice setting. We included consecutive inpatients (n = 47) subjected to a barium enema or colon endoscopy. Prior cleansing was done as indicated by the attending physician by using a low-salt oral poliethylenglicol (PEG) solution, oral sodium phosphate or a phosphate-containing enema. PEG solution frequently caused mild increases in serum sodium, and decreases in serum potassium. Oral phosphate caused a significant increase in serum phosphorus and parathormone concentrations, whereas it decreased serum calcium. Mild hyperphosphatemia was found in 57% of cases, and hypocalcemia in 36%. Phosphate enema also increased serum phosphate, causing mild hyperphosphatemia (33% cases). Although in the whole subgroup of enema-treated patients there were no significant changes in serum calcium, mild hypocalcemia was found in 27% cases. Bowel cleansing procedures, particularly those using oral phosphate salts, frequently induce hyperphosphatemia and other abnormalities in serum electrolytes. Although usually transitory and without overt clinical consequences, clinicians should be aware of this potential risk, especially in elderly patients and those with impaired renal function.

Self-lubricating coatings containing fullerene-like WS2 nanoparticles for orthodontic wires and other possible medical applications

Uneven malaligned teeth are a problem afflicting large numbers of people, having significant economic and societal repercussions. Sliding a tooth along an archwire during orthodontic treatment involves a frictional type of force which resists this movement, causing a number of adverse effects. First, using excessive orthodontic force, leads to unwanted movements of the anchor teeth and increasing the risk of damage to the roots of the teeth. Furthermore, the frictional force is distributed unevenly between the archwire and the brackets interface, leading to strong adhesion between the wire and the bracket’s corner. This force-asymmetry causes lengthening of treatment and frequent visits for fine-tuning of the orthodontic appliances. Despite numerous efforts to lower the friction, no satisfactory solution to this issue has been obtained. In the present work a self-lubricating metal coating containing fullerene-like WS2 (IF) nanoparticles is demonstrated. Such coatings significantly reduce archwire friction, and may alleviate the adverse complications. Moreover, a number of other medical applications of the self-lubricating coatings are foreseen.

Intra-individual propofol dosage variability in children undergoing repetitive procedural sedations

Objectives: Propofol sedation/anesthesia has been used successfully in children undergoing procedural sedation. We prospectively assessed intra- and inter-individual variability in propofol dosage for sedation in repetitive procedures in children with malignancies. Patients and methods: A total of 80 procedures including lumbar puncture, radiation therapy, magnetic resonance imaging, bone marrow biopsiy, endoscopy, drainage of ascites (range: 2–19 procedures/patient) were performed in 24 children (mean age: 9,6±5,4 years). The mean propofol induction dose was 2,61±0,74mg.kg-1 to achieve deep sedation. Primary outcome measure was the inter- and intra-individual propofol dosage required to achieve adequate sedation; secondary outcome measures were the number of adverse effects, the need for therapeutic interventions, and cardiovascular parameters. Results: All 80 procedures were completed with satisfactory sedation levels. There was a remarkable inter- and intra-individual variability in propofol dosage required to achieve adequate sedation (interindividual range 1.1–4.1mg.kg-1; intraindividual difference concerning the needed propofol induction 0.0–2.2mg.kg-1, 25% of the patients had a dose range of 0.0–0.5mg.kg-1, 37,5% >0.5–1.0mg.kg-1, 37,5% >1.0–2.2mg.kg-1. In 10% (n=8) of the procedures side effects were seen, mainly short episodes of desaturation which required no or only minor interventions. Conclusions: Due to great inter- and intra-individual differences, propofol dosage should be titrated towards the desired level of sedation. Thus propofol can be adjusted to the individual's need while achieving adequate sedation. Considering the substancial rate of adverse effects procedural sedation with propofol should be performed only by physicians experienced in advanced pediatric cardiorespiratory support.

Adverse Effects of Atypical Antipsychotics in the Elderly

Use of antipsychotic medication is very common in the elderly and often an essential therapy. However, successful treatment in the elderly requires appropriate multidimensional assessment of the patient, knowledge of possible multiple co-morbidities, and awareness of the complexities of polypharmacy, age-dependent changes in pharmacokinetics and pharmacodynamics, and drug-drug interactions in this age group. Antipsychotics are known to have a number of adverse effects. New antipsychotics, such as amisulpride, clozapine, olanzapine, risperidone, quetiapine, ziprasidone, zotepine and aripiprazole, may interact with both dopamine and serotonin receptors. However, compared with conventional antipsychotics, they are less likely to cause extrapyramidal symptoms and are better tolerated in the elderly. At the same time, consistent differences between atypical antipsychotics have been demonstrated. Use of clozapine, for example, is limited by the risk of agranulocytosis, whereas this is not a disadvantage of olanzapine, risperidone, quetiapine and, more recently, ziprasidone, which are being widely used with good results in schizophrenia. However, use of the latter agents to treat the behavioural and psychological symptoms of dementia has been restricted because of recent observations of increased cardiovascular events in patients taking risperidone and olanzapine treatment. Nonetheless, careful review of the literature suggests that the available evidence does not support any causal relationship between use of risperidone or olanzapine and cardiovascular events. This article focuses on some of the main adverse effects commonly reported during administration of atypical antipsychotics to elderly patients. Such effects may be partly explained by age-related changes in pharmacokinetics and pharmacodynamics, and partly by the characteristics of the drugs themselves and their different receptor binding profiles.

Galanin Receptor Antagonists

The pathophysiology of mood disorders involves several genetic and social predisposing factors, as well as a dysregulated response to chronic stress. Accumulated evidence during the last two decades has implicated disturbances in brain serotonin and/or noradrenaline (norepinephrine) neurotransmission in the aetiology of depression. In fact, current pharmacological treatment for mood disorders is based on the use of drugs that act mainly by enhancing brain serotonin and noradrenaline neurotransmission by blockade of the active reuptake mechanism for these neurotransmitters. However, current antidepressant drugs have a delayed onset of therapeutic action, and a substantial number of patients do not respond adequately to them. In addition, these drugs have a number of adverse effects that limit patient compliance. In view of this, there is an intense search to identify novel (receptor) targets for antidepressant therapy. Recent studies have indicated that several neuropeptides and their receptors are potential candidates for the development of novel antidepressant treatment. In this context, galanin is of particular interest, since it is co-localised with serotonin in the dorsal raphe nucleus and with noradrenaline in the locus coeruleus, nuclei known to play a major role in affective disorders and in the action of antidepressant drugs. The actions of galanin are mediated by three receptor subtypes (GAL1, GAL2 and GAL3), which are coupled to different intracellular effector systems. Studies in rats have shown that galanin administered intracerebroventricularly is a potent inhibitor of mesencephalic serotonergic neurotransmission, as indicated by a long-lasting reduction in the release of serotonin in the hippocampus. This inhibitory effect is related to activation of the galanin receptors located on the dorsal raphe neurons. Moreover, intracerebroventricular galanin alters the gene expression of serotonin 5-HT1A autoreceptors in the dorsal raphe and also changes their functional activity. In addition, galanin produces a functional blockade of postsynaptic 5-HT1A receptor-mediated responses. Both pharmacological and genetic studies suggest a role for galanin in depression-like behaviour in rodent models. Transgenic mice overexpressing galanin under the control of the platelet-derived growth factor-beta promoter display increased immobility in the forced swim test. Intracerebroventricular administration of galanin in the rat increases depression-like behaviour, and this is fully blocked by the nonselective peptide galanin receptor antagonist M35. Importantly, M35 alone administered intracerebroventricularly produces an antidepressant-like effect. Recently, newly developed receptor-specific nonpeptidergic galanin GAL3 receptor antagonists (SNAP-37889 and SNAP-398299), which cross the blood-brain barrier after systemic administration, have shown antidepressant-like activity in several animal models. On the other hand, stimulation of the GAL2 receptor at the raphe level by local application of the GAL2 receptor agonist galanin (2-11) has been shown to increase serotonin levels in the hippocampus and dorsal raphe. These results indicate an important (mainly inhibitory) role of galanin as a regulator of brain serotonin and 5-HT1A receptor-mediated transmission, which may be of potential importance for understanding mood disorders and for the development of antidepressant drugs. Taken together, the present evidence suggests that antidepressant efficacy may be associated with compounds acting as antagonists at the GAL3 and/or possibly GAL1 receptors, and/or agonists at the GAL2 receptor.

Successful Conversion of Equine Atrial Fibrillation Using Oral Flecainide

Atrial fibrillation is the most common arrhythmia affecting performance in horses. Conversion to sinus rhythm carries a good prognosis if no significant underlying cardiac disease is present and horses commonly return to performance at the previous level or above. The drug most commonly used to convert equine atrial fibrillation is quinidine. However, quinidine has the potential for a number of adverse effects including colic, nasal mucosal edema, dyspnea and laminitis. Quinidine also requires administration through a nasogastric tube, as the drug is very bitter and acidic and may cause oral ulcerations if administered PO. Flecainide is an antiarrhythmic agent of Singh-Vaughan Williams class Ic, whereas quinidine belongs to class Ia. Intravenously administered flecainide has been reported to be a safe and effective drug for treatment of induced atrial fibrillation in the horse, with fewer adverse effects compared to quinidine, but has been less effective when administered to horses with naturally occurring atrial fibrillation. The pharmacokinetics of oral flecainide and the oral dosage required to treat equine atrial fibrillation have been determined. To the authors' knowledge, there are no reports describing treatment of equine atrial fibrillation with oral flecainide. This report describes the successful conversion of naturally occurring atrial fibrillation, by means of oral flecainide, in a horse.

Psychiatric Symptoms Induced by??Antiviral Therapy in Chronic??Hepatitis C

Interferon-alpha treatment is associated with a large number of adverse effects. Depressive symptoms are not unexpected, and potentially dangerous psychiatric adverse effects can induce life-threatening conditions. We compared the incidence of depressive symptoms in patients with chronic hepatitis C during treatment with pegylated interferon-alpha-2a (IFNalpha-2a) and pegylated interferon-alpha-2b (IFNalpha-2b). We randomly divided 186 subjects with chronic hepatitis C into two treatment groups: group A, treated with IFNalpha-2a, and group B, treated with IFNalpha-2b. Treatment was continued for up to 48 weeks. Liver biopsy and hepatitis C virus RNA assay were carried out in all patients. Depressive symptoms and the prevalence of psychiatric adverse effects during treatment with IFN were evaluated using the Hamilton Depression Rating Scale, the Zung Self-Rating Depression Scale, and the Structured Clinical Interview for Diagnostic and Statistic Manual-IV axis disorders. At baseline 53% of subjects in group A and 57% of subjects in group B presented with depressive symptoms; at 12 weeks we found a high incidence of depressive symptoms in both groups (group A 61% and group B 65%) and three cases of life-threatening psychiatric symptoms (i.e. psychosis and delirium requiring discontinuation of antiviral therapy and admission to a psychiatric unit) in group A. Long-term administration of IFN can be associated with serious psychiatric adverse effects. It is very important that psychiatric symptoms are diagnosed early in IFN treatment so to improve treatment compliance and prevent fatal and/or life-threatening adverse events, as were documented in some subjects treated with IFNalpha-2a in our study.