text:
Zonegran 25, 50, 100 mg Hard Capsules
Last Updated on eMC 08-Jul-2016 View changes | Eisai Ltd Contact details
- 1. Name of the medicinal product
- 2. Qualitative and quantitative composition
- 3. Pharmaceutical form
- 4. Clinical particulars
- 4.1 Therapeutic indications
- 4.2 Posology and method of administration
- 4.3 Contraindications
- 4.4 Special warnings and precautions for use
- 4.5 Interaction with other medicinal products and other forms of interaction
- 4.6 Fertility, pregnancy and lactation
- 4.7 Effects on ability to drive and use machines
- 4.8 Undesirable effects
- 4.9 Overdose
- 5. Pharmacological properties
- 5.1 Pharmacodynamic properties
- 5.2 Pharmacokinetic properties
- 5.3 Preclinical safety data
- 6. Pharmaceutical particulars
- 6.1 List of excipients
- 6.2 Incompatibilities
- 6.3 Shelf life
- 6.4 Special precautions for storage
- 6.5 Nature and contents of container
- 6.6 Special precautions for disposal and other handling
- 7. Marketing authorisation holder
- 8. Marketing authorisation number(s)
- 9. Date of first authorisation/renewal of the authorisation
- 10. Date of revision of the text
Posology - Adults
Dosage escalation and maintenanceZonegran may be taken as monotherapy or added to existing therapy in adults. The dose should be titrated on the basis of clinical effect. Recommended escalation and maintenance doses are given in Table 1. Some patients, especially those not taking CYP3A4-inducing agents, may respond to lower doses.
WithdrawalWhen Zonegran treatment is to be discontinued, it should be withdrawn gradually (see section 4.4). In clinical studies of adult patients, dose reductions of 100 mg at weekly intervals have been used with concurrent adjustment of other antiepileptic medicine doses (where necessary). Table 1. Adults recommended dosage escalation and maintenance regimen
|Treatment Regimen
|Titration Phase
|Usual Maintenance Dose
|Monotherapy - Newly diagnosed adult patients
|Week 1 + 2
|Week 3 + 4
|Week 5 + 6
300 mg per day (once a day). If a higher dose is required: increase at two-weekly intervals in increments of 100 mg up to a maximum of 500 mg.
| 100 mg/day
(once a day)
| 200 mg /day
(once a day)
| 300 mg / day
(once a day)
Adjunctive therapy
- with CYP3A4-inducing agents (see section 4.5)
|Week 1
|Week 2
|Week 3 to 5
300 to 500 mg per day (once a day or two divided doses).
|50 mg/day (in two divided doses)
|100 mg /day (in two divided doses)
|Increase at weekly intervals in increments of 100 mg
|- without CYP3A4-inducing agents; or with renal or hepatic impairment
|Week 1 + 2
|Week 3 + 4
|Week 5 to 10
300 to 500 mg per day (once a day or two divided doses). Some patients may respond to lower doses.
50 mg/day (in two divided doses)
100 mg / day (in two divided doses)
Increase at two-weekly intervals in increments of up to 100 mg
General dosing recommendations for Zonegran in special patient populations
Paediatric population (aged 6 years and above)
Dosage escalation and maintenanceZonegran must be added to existing therapy for paediatric patients aged 6 years and above. The dose should be titrated on the basis of clinical effect. Recommended escalation and maintenance doses are given in Table 2. Some patients, especially those not taking CYP3A4-inducing agents, may respond to lower doses.Physicians should draw the attention of paediatric patients and their parents/carers to the Patient Alert Box (in the package leaflet) on preventing heatstroke (see section 4.4: Paediatric population). Table 2. Paediatric population (aged 6 years and above) recommended dosage escalation and maintenance regimen
|Treatment Regimen
|Titration Phase
|Usual Maintenance Dose
|Adjunctive therapy - with CYP3A4-inducing agents (see section 4.5)
|Week 1
|Weeks 2 to 8
|Patients of weight 20 to 55 kga
|Patients of weight > 55 kg
|1 mg/kg/day (once a day)
|Increase at weekly intervals in increments of 1 mg/kg
|6 to 8 mg/kg/day (once a day)
|300 - 500 mg/day (once a day)
|- without CYP3A4-inducing agents
|Week 1 + 2
|Weeks ≥ 3
6 to 8 mg/kg/day
(once a day)
300 - 500 mg/day
(once a day)
1 mg/kg/day
(once a day)
Increase at two-weekly intervals in increments of 1 mg/kg
Note:a. To ensure a therapeutic dose is maintained the weight of a child should be monitored and the dose reviewed as weight changes occur up to a weight of 55kg. The dose regime is 6-8 mg/kg/day up to a maximum dose of 500 mg/day. The safety and efficacy of Zonegran in children aged below 6 years or those below 20 kg have not yet been established. There are limited data from clinical studies in patients with a body weight of less than 20 kg. Therefore children aged 6 years and above and with a body weight less than 20 kg should be treated with caution. It is not always possible to precisely achieve the calculated dose with the commercially available capsule strengths of Zonegran. In these cases it is therefore recommended that the Zonegran total dose should be rounded up or down to the nearest available dose that can be achieved with commercially available capsule strengths of Zonegran (25 mg, 50 mg and 100 mg).
WithdrawalWhen Zonegran treatment is to be discontinued, it should be withdrawn gradually (see section 4.4). In clinical studies of paediatric patients, down-titration was completed by dose reductions at weekly intervals in increments of about 2 mg/kg (i.e. in accordance with the schedule in Table 3). Table 3. Paediatric population (aged 6 years and above) recommended down-titration schedule
|Decrease at weekly intervals in increments of:
|20 28 kg
|25 to 50 mg / day*
|29 41 kg
|50 to 75 mg / day*
|42 55 kg
|100 mg / day*
|>55 kg
|100 mg / day*
ElderlyCaution should be exercised at initiation of treatment in elderly patients as there is limited information on the use of Zonegran in these patients. Prescribers should also take account of the safety profile of Zonegran (see section 4.8).
Patients with renal impairmentCaution must be exercised in treating patients with renal impairment, as there is limited information on use in such patients and a slower titration of Zonegran might be required. Since zonisamide and its metabolites are excreted renally, it should be discontinued in patients who develop acute renal failure or where a clinically significant sustained increase in serum creatinine is observed.In subjects with renal impairment, renal clearance of single doses of zonisamide was positively correlated with creatinine clearance. The plasma AUC of zonisamide was increased by 35% in subjects with creatinine clearance < 20 ml/min.
Patients with hepatic impairmentUse in patients with hepatic impairment has not been studied. Therefore use in patients with severe hepatic impairment is not recommended. Caution must be exercised in treating patients with mild to moderate hepatic impairment, and a slower titration of Zonegran may be required.
Method of administrationZonegran hard capsules are for oral use.
Effect of foodZonegran may be taken with or without food (see section 5.2).
Unexplained rash
|Serious rashes occur in association with Zonegran therapy, including cases of Stevens-Johnson syndrome.
Withdrawal seizuresIn accordance with current clinical practice, discontinuation of Zonegran in patients with epilepsy must be accomplished by gradual dose reduction, to reduce the possibility of seizures on withdrawal. There are insufficient data for the withdrawal of concomitant antiepileptic medicines once seizure control with Zonegran has been achieved in the add-on situation, in order to reach monotherapy with Zonegran. Therefore, withdrawal of concomitant anti-epileptic medicinal products must be undertaken with caution.
Sulphonamide reactionsZonegran is a benzisoxazole derivative, which contains a sulphonamide group. Serious immune based adverse reactions that are associated with medicinal products containing a sulphonamide group include rash, allergic reaction and major haematological disturbances, including aplastic anaemia, which very rarely can be fatal.Cases of agranulocytosis, thrombocytopenia, leukopenia, aplastic anaemia, pancytopenia and leucocytosis have been reported. There is inadequate information to assess the relationship, if any, between dose and duration of treatment and these events.
Suicide ideation and behaviourSuicidal ideation and behaviour have been reported in patients treated with anti-epileptic agents in several indications. A meta-analysis of randomised placebo-controlled trials of anti-epileptic medicinal products has also shown a small increased risk of suicidal ideation and behaviour. The mechanism of this risk is not known and the available data do not exclude the possibility of an increased risk for Zonegran. Therefore patients should be monitored for signs of suicidal ideation and behaviours and appropriate treatment should be considered. Patients (and caregivers of patients) should be advised to seek medical advice should signs of suicidal ideation or behaviour emerge.
Kidney stonesSome patients, especially those with a predisposition to nephrolithiasis, may be at increased risk for renal stone formation and associated signs and symptoms such as renal colic, renal pain or flank pain. Nephrolithiasis may lead to chronic kidney damage. Risk factors for nephrolithiasis include prior stone formation, a family history of nephrolithiasis and hypercalciuria. None of these risk factors can reliably predict stone formation during zonisamide treatment. In addition, patients taking other medications associated with nephrolithiasis may be at increased risk. Increasing fluid intake and urine output may help reduce the risk of stone formation, particularly in those with predisposing risk factors.
Metabolic acidosisHyperchloraemic, non-anion gap, metabolic acidosis (i.e. decreased serum bicarbonate below the normal reference range in the absence of chronic respiratory alkalosis) is associated with Zonegran treatment. This metabolic acidosis is caused by renal bicarbonate loss due to the inhibitory effect of zonisamide on carbonic anhydrase. Such electrolyte imbalance has been observed with the use of Zonegran in placebo-controlled clinical trials and in the post-marketing period. Generally, zonisamide-induced metabolic acidosis occurs early in treatment although cases can occur at any time during treatment. The amounts by which bicarbonate is decreased are usually small moderate (average decrease of approximately 3.5 mEq/l at daily doses of 300 mg in adults); rarely patients can experience more severe decreases. Conditions or therapies that predispose to acidosis (such as renal disease, severe respiratory disorders, status epilepticus, diarrhoea, surgery, ketogenic diet, or medicinal products) may be additive to the bicarbonate lowering effects of zonisamide. The risk of zonisamide induced metabolic acidosis appears to be more frequent and severe in younger patients. Appropriate evaluation and monitoring of serum bicarbonate levels should be carried out in patients taking zonisamide who have underlying conditions which might increase the risk of acidosis, in patients who are at an increased risk of adverse consequences of metabolic acidosis and in patients with symptoms suggestive of metabolic acidosis. If metabolic acidosis develops and persists, consideration should be given to reducing the dose or discontinuing Zonegran (by gradual discontinuation or reduction of a therapeutic dose) as osteopenia may develop.If the decision is made to continue patients on Zonegran in the face of persistent acidosis, alkali treatment should be considered.Zonegran should be used with caution in adult patients being treated concomitantly with carbonic anhydrase inhibitors such as topiramate or acetazolamide, as there are insufficient data to rule out a pharmacodynamic interaction (see also section 4.4 Paediatric population and section 4.5).
Heat strokeCases of decreased sweating and elevated body temperature have been reported mainly in paediatric patients (see section 4.4 Paediatric population for full warning). Caution should be used in adults when Zonegran is prescribed with other medicinal products that predispose patients to heat related disorders; these include carbonic anhydrase inhibitors and medicinal products with anticholinergic activity (see also section 4.4 Paediatric population).
PancreatitisIn patients taking Zonegran who develop the clinical signs and symptoms of pancreatitis, it is recommended that pancreatic lipase and amylase levels are monitored. If pancreatitis is evident, in the absence of another obvious cause, it is recommended that discontinuation of Zonegran be considered and appropriate treatment initiated.
RhabdomyolysisIn patients taking Zonegran, in whom severe muscle pain and/or weakness develop either in the presence or absence of a fever, it is recommended that markers of muscle damage be assessed, including serum creatine phosphokinase and aldolase levels. If elevated, in the absence of another obvious cause such as trauma or grand mal seizures, it is recommended that Zonegran discontinuation be considered and appropriate treatment initiated.
Women of childbearing potentialWomen of childbearing potential have to use effective contraception during treatment with Zonegran and for one month after discontinuation (see section 4.6). Physicians treating patients with Zonegran should try to ensure that appropriate contraception is used, and should use clinical judgement when assessing whether oral contraceptives (OCs), or the doses of the OC components, are adequate based on the individual patient's clinical situation.
Body weightZonegran may cause weight loss. A dietary supplement or increased food intake may be considered if the patient is losing weight or is underweight whilst on this medication. If substantial undesirable weight loss occurs, discontinuation of Zonegran should be considered. Weight loss is potentially more serious in children (see section 4.4. Paediatric population).
Paediatric populationThe warnings and precautions mentioned above are also applicable to adolescent and paediatric patients. The warnings and precautions mentioned below are more relevant to paediatric and adolescent patients.
Heat stroke and dehydration
|Preventing overheating and dehydration in children Zonegran can cause children to sweat less and overheat and if the child is not treated this can lead to brain damage and death. Children are most at risk especially in hot weather. When a child is taking Zonegran: The child should stay cool especially in hot weather The child must avoid heavy exercise especially when the weather is hot The child must drink plenty of cold water The child must not take any of these medicines: carbonic anhydrase inhibitors (like topiramate and acetazolamide), and anticholinergic agents (like clomipramine, hydroxyzine, diphenhydramine, haloperidol, imipramine and oxybutynin). IF ANY OF THE FOLLOWING OCCUR, THE CHILD NEEDS URGENT MEDICAL ATTENTION: The skin feels very hot with little or no sweating, or the child becomes confused or has muscle cramps, or the child's heartbeat or breathing become rapid. • Take the child to a cool, shaded place • Keep the child's skin cool with water • Give the child cold water to drink
Body weightWeight loss leading to deterioration of general condition and failure to take anti-epilepsy medication has been related to a fatal outcome (see section 4.8). Zonegran is not recommended for paediatric patients who are underweight (definition in accordance with the WHO age adjusted BMI categories) or have a decreased appetite.The incidence of decreased body weight is consistent across age groups (see section 4.8); however, given the potential seriousness of weight loss in children, weight should be monitored in this population. A dietary supplement or increased food intake should be considered if the patient is failing to gain weight in accordance with growth charts, otherwise Zonegran should be discontinued. There are limited data from clinical studies in patients with a body weight of less than 20 kg. Therefore children aged 6 years and above with a body weight of less than 20 kg should be treated with caution. The long term effect of weight loss in the paediatric population on growth and development is unknown.
Metabolic acidosisThe risk of zonisamide induced metabolic acidosis appears to be more frequent and severe in paediatric and adolescent patients. Appropriate evaluation and monitoring of serum bicarbonate levels should be carried out in this population (see section 4.4 - Metabolic acidosis for full warning; see section 4.8 for incidence of low bicarbonate). The long term effect of low bicarbonate levels on growth and development is unknown. Zonegran should not be used as co-medication in paediatric patients with other carbonic anhydrase inhibitors such as topiramate and acetazolamide (see section 4.5).
Kidney stonesKidney stones have occurred in paediatric patients (see section 4.4 Kidney stones for full warning). Some patients, especially those with a predisposition to nephrolithiasis, may be at increased risk for renal stone formation and associated signs and symptoms such as renal colic, renal pain or flank pain. Nephrolithiasis may lead to chronic kidney damage. Risk factors for nephrolithiasis include prior stone formation, a family history of nephrolithiasis and hypercalciuria. None of these risk factors can reliably predict stone formation during zonisamide treatment.Increasing fluid intake and urine output may help reduce the risk of stone formation, particularly in those with predisposing risk factors. Renal ultrasound should be performed at the discretion of the physician. In the event kidney stones are detected, Zonegran should be discontinued.
Hepatic dysfunctionIncreased levels of hepatobiliary parameters such as alanine aminotransferase (ALT), aspartate aminotransferease (AST), gamma-glutamyltransferase (GGT) and bilirubin have occurred in paediatric and adolescent patients, without any consistent pattern in the observations of values above the upper limit of normal. Nevertheless, if a hepatic event is suspected, liver function should be evaluated and discontinuation of Zonegran should be considered.
CognitionCognitive impairment in patients affected by epilepsy has been associated with the underlying pathology and/ or the administration of anti-epileptic treatment. In a zonisamide placebo-controlled study conducted in paediatric and adolescent patients, the proportion of patients with impaired cognition was numerically greater in the zonisamide group compared with the placebo group. Excipients Zonegran 100 mg hard capsules contain a yellow colour called sunset yellow FCF (E110), and a red colour called allura red AC (E129), which may cause allergic reactions.
Effect of Zonegran on cytochrome P450 enzymesIn vitro studies using human liver microsomes show no or little (<25%) inhibition of cytochrome P450 isozymes 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1 or 3A4 at zonisamide levels approximately two-fold or greater than clinically relevant unbound serum concentrations. Therefore, Zonegran is not expected to affect the pharmacokinetics of other medicinal products via cytochrome P450-mediated mechanisms, as demonstrated for carbamazepine, phenytoin, ethinylestradiol and desipramine in vivo.
Potential for Zonegran to affect other medicinal products
Anti-epileptic medicinal productsIn epileptic patients, steady-state dosing with Zonegran resulted in no clinically relevant pharmacokinetic effects on carbamazepine, lamotrigine, phenytoin, or sodium valproate.
Oral contraceptivesIn clinical studies in healthy subjects, steady-state dosing with Zonegran did not affect serum concentrations of ethinylestradiol or norethisterone in a combined oral contraceptive.
Carbonic anhydrase inhibitorsZonegran should be used with caution in adult patients treated concomitantly with carbonic anhydrase inhibitors such as topiramate and acetazolamide, as there are insufficient data to rule out a possible pharmacodynamic interaction (see section 4.4).Zonegran should not be used as co-medication in paediatric patients with other carbonic anhydrase inhibitors such as topiramate and acetazolamide (see section 4.4 Paediatric population).
P-gp substrateAn in vitro study shows that zonisamide is a weak inhibitor of P-gp (MDR1) with an IC50 of 267 µmol/l and there is the theoretical potential for zonisamide to affect the pharmacokinetics of substances which are P-gp substrates. Caution is advised when starting or stopping zonisamide treatment or changing the zonisamide dose in patients who are also receiving medicinal products which are P-gp substrates (e.g. digoxin, quinidine).
Potential medicinal product interactions affecting ZonegranIn clinical studies co-administration of lamotrigine had no apparent effect on zonisamide pharmacokinetics. The combination of Zonegran with other medicinal products that may lead to urolithiasis may enhance the risk of developing kidney stones; therefore the concomitant administration of such medicinal products should be avoided.Zonisamide is metabolised partly by CYP3A4 (reductive cleavage), and also by N-acetyl-transferases and conjugation with glucuronic acid; therefore, substances that can induce or inhibit these enzymes may affect the pharmacokinetics of zonisamide:- Enzyme induction: Exposure to zonisamide is lower in epileptic patients receiving CYP3A4-inducing agents such as phenytoin, carbamazepine, and phenobarbitone. These effects are unlikely to be of clinical significance when Zonegran is added to existing therapy; however, changes in zonisamide concentrations may occur if concomitant CYP3A4-inducing anti-epileptic or other medicinal products are withdrawn, dose adjusted or introduced, an adjustment of the Zonegran dose may be required. Rifampicin is a potent CYP3A4 inducer. If co-administration is necessary, the patient should be closely monitored and the dose of Zonegran and other CYP3A4 substrates adjusted as needed.- CYP3A4 inhibition: Based upon clinical data, known specific and non-specific CYP3A4 inhibitors appear to have no clinically relevant effect on zonisamide pharmacokinetic exposure parameters. Steady-state dosing of either ketoconazole (400 mg/day) or cimetidine (1200 mg/day) had no clinically relevant effects on the single-dose pharmacokinetics of zonisamide given to healthy subjects. Therefore, modification of Zonegran dosing should not be necessary when co-administered with known CYP3A4 inhibitors.
Paediatric populationInteraction studies have only been performed in adults.
Women of childbearing potentialWomen of childbearing potential have to use effective contraception during treatment with Zonegran, and for one month after discontinuation.
PregnancyThere are limited data from the use of Zonegran in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown.Zonegran must not be used during pregnancy unless clearly necessary, in the opinion of the physician, and only if the potential benefit is considered to justify the risk to the foetus. The need for anti-epileptic treatment should be reviewed in patients planning to become pregnant. If Zonegran is prescribed, careful monitoring is recommended.Specialist advice should be given to women who are likely to become pregnant in order to consider the optimal treatment during pregnancy. Women of childbearing potential should be given specialist advice regarding possible effects of Zonegran on the foetus and the risk should be discussed with the patient in relation to the benefits before starting treatment. The risk of birth defect is increased by factor 2 to 3 in the offspring of mothers treated with an antiepileptic medicinal product. The most frequently reported are cleft lip, cardiovascular malformations and neural tube defect. Multiple antiepileptic medicinal product therapy may be associated with a higher risk of congenital malformations than monotherapy. No sudden discontinuation of anti-epileptic therapy should be undertaken as this may lead to breakthrough seizures, which could have serious consequences for both mother and child.
Breast-feedingZonisamide is excreted in human milk; the concentration in breast milk is similar to maternal plasma. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Zonegran therapy. Due to the long retention time of zonisamide in the body, breast-feeding must not be resumed until one month after Zonegran therapy is completed.
FertilityThere are no clinical data available on the effects of zonisamide on human fertility. Studies in animals have shown changes in fertility parameters (see section 5.3).
Summary of the safety profileZonegran has been administered to over 1,200 patients in clinical studies, more than 400 of whom received Zonegran for at least 1 year. In addition there has been extensive post-marketing experience with zonisamide in Japan since 1989 and in the USA since 2000.It should be noted that Zonegran is a benzisoxazole derivative, which contains a sulphonamide group. Serious immune based adverse reactions that are associated with medicinal products containing a sulphonamide group include rash, allergic reaction and major haematological disturbances including aplastic anaemia, which very rarely can be fatal (see section 4.4).The most common adverse reactions in controlled adjunctive-therapy studies were somnolence, dizziness and anorexia. The most common adverse reactions in a randomised, controlled monotherapy trial comparing zonisamide with carbamazepine prolonged release were decreased bicarbonate, decreased appetite, and decreased weight. The incidence of markedly abnormally low serum bicarbonate (a decrease to less than 17 mEq/l and by more than 5 mEq/l) was 3.8%. The incidence of marked decreases in weight of 20% or more was 0.7%.
Tabulated list of adverse reactionsAdverse reactions associated with Zonegran obtained from clinical studies and post-marketing surveillance are tabulated below. The frequencies are arranged according to the following scheme:
|very common
|≥ 1/10
|≥ 1/100 to < 1/10
|≥ 1/1,000 to < 1/100
|≥ 1/10,000 to < 1/1,000
|very rare
|< 1/10,000
|not known
|cannot be estimated from the available data
Table 4. Adverse reactions associated with Zonegran obtained from adjunctive use clinical studies and post-marketing surveillance
|System Organ Class (MedDRA terminology)
|Very Common
|Very Rare
|Infections and infestation
|Pneumonia Urinary tract infection
|Blood and lymphatic system disorders
|Agranulocytosis Aplastic anaemia Leucocytosis Leucopoenia Lymphadenopathy Pancytopenia, Thrombocytopenia
|Immune system disorders
|Drug-induced hypersensitivity syndrome Drug rash with eosinophilia and systemic symptoms
|Metabolism and nutrition disorders
|Metabolic acidosis Renal tubular acidosis
|Psychiatric Disorders
|Agitation Irritability Confusional state Depression
|Affect lability Anxiety Insomnia Psychotic disorder
|Anger Aggression Suicidal ideation Suicide attempt
|Nervous system disorders
|Ataxia Dizziness Memory impairment Somnolence
|Bradyphrenia Disturbance in attention Nystagmus Paraesthesia Speech disorder Tremor
|Amnesia Coma Grand mal seizure Myasthenic syndrome Neuroleptic malignant syndrome Status epilepticus
|Eye disorders
|Respiratory, thoracic and mediastinal disorders
|Dyspnoea Pneumonia aspiration Respiratory disorder Hypersensitivity-type Pneumonitis
|Gastrointestinal disorders
|Abdominal pain Constipation Diarrhoea Dyspepsia Nausea
|Hepatobiliary disorders
|Cholecystitis Cholelithiasis
|Hepatocellular damage
|Skin and subcutaneous tissue disorders
|Rash Pruritis Alopecia
|Anhidrosis Erythema multiforme Stevens-Johnson syndrome Toxic epidermal necrolysis
|Musculoskeletal and connective tissue disorders
|Renal and urinary disorders
|Calculus urinary
|Hydronephrosis Renal failure Urine abnormality
|General disorders and administration site conditions
|Fatigue Influenza-like illness Pyrexia Oedema peripheral
|Decreased bicarbonate
|Weight decreased
|Blood creatine phosphokinase increased Blood creatinine increased Blood urea increased Liver function tests abnormal
|Injury, poisoning and procedural complications
|Heat stroke
|System Organ Class (MedDRA terminology)
|Very Common
|Infections and infestation
|Urinary tract infection Pneumonia
|Blood and lymphatic disorders
|Leukopenia Thrombocytopenia
|Metabolism and nutrition disorders
|Decreased appetite
|Psychiatric Disorders
|Agitation Depression Insomnia Mood swings Anxiety
|Confusional state Acute psychosis Aggression Suicidal ideation Hallucination
|Nervous system disorders
|Ataxia Dizziness Memory impairment Somnolence Bradyphrenia Disturbance in attention Paraesthesia
|Nystagmus Speech disorder Tremor Convulsion
|Eye disorders
|Respiratory, thoracic and mediastinal disorders
|Respiratory disorder
|Gastrointestinal disorders
|Constipation Diarrhoea Dyspepsia Nausea Vomiting
|Abdominal pain
|Hepatobiliary disorders
|Cholecystitis acute
|Skin and subcutaneous tissue disorders
|Pruritus Ecchymosis
|General disorders and administration site conditions
|Fatigue Pyrexia Irritability
|Decreased bicarbonate
|Weight decreased Blood creatinine phosphokinase increased Alanine aminotransferase increased Aspartate aminotransferase increased
|Urine analysis abnormal
Additional information on special populations:
ElderlyA pooled analysis of safety data on 95 elderly subjects has shown a relatively higher reporting frequency of oedema peripheral and pruritus compared to the adult population.Review of post-marketing data suggests that patients aged 65 years or older report a higher frequency than the general population of the following events: Stevens-Johnson syndrome (SJS) and Drug Induced Hypersensitivity syndrome (DIHS).
Paediatric populationThe adverse event profile of zonisamide in paediatric patients aged 6 to 17 years in placebo-controlled clinical studies was consistent with that of adults. Among 465 subjects in the paediatric safety database (including a further 67 subjects from the extension phase of the controlled clinical trial) there were 7 deaths (1.5%; 14.6/1000 person-years): 2 cases of status epilepticus, of which one was related to severe weight loss (10% within 3 months) in an underweight subject and subsequent failure to take medication; 1 case of head injury/haematoma, and 4 deaths in subjects with pre-existing functional neurological deficits for various causes (2 cases of pneumonia-induced sepsis/organ failure, 1 SUDEP and 1 head injury). A total of 70.4% of paediatric subjects who received ZNS in the controlled study or its open label extension had at least one treatment-emergent bicarbonate measurement below 22 mmol/L. The duration of low bicarbonate measurements was also long (median 188 days). A pooled analysis of safety data on 420 paediatric subjects (183 subjects aged 6 to 11 years, and 237 subjects aged 12 to 16 years with a mean duration of exposure of approximately 12 months) has shown a relatively higher reporting frequency of pneumonia, dehydration, decreased sweating, abnormal liver function tests, otitis media, pharyngitis, sinusitis and upper respiratory tract infection, cough, epistaxis and rhinitis, abdominal pain, vomiting, rash and eczema, and fever compared to the adult population (particularly in subjects aged below 12 years) and, at a low incidence, amnesia, creatinine increased, lymphadenopathy, and thrombocytopenia. The incidence of a decrease in body weight of 10% or more was 10.7% (see section 4.4). In some cases of weight decrease there was a delay in transition to the next Tanner stage and in bone maturation.
Reporting of suspected adverse reactionsReporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard
TreatmentNo specific antidotes for Zonegran overdose are available. Following a suspected recent overdose, emptying the stomach by gastric lavage or by induction of emesis may be indicated with the usual precautions to protect the airway. General supportive care is indicated, including frequent monitoring of vital signs and close observation. Zonisamide has a long elimination half-life so its effects may be persistent. Although not formally studied for the treatment of overdose, haemodialysis reduced plasma concentrations of zonisamide in a patient with reduced renal function, and may be considered as treatment of overdose if clinically indicated.
Mechanism of actionThe mechanism of action of zonisamide is not fully elucidated, but it appears to act on voltage-sensitive sodium and calcium channels, thereby disrupting synchronised neuronal firing, reducing the spread of seizure discharges and disrupting subsequent epileptic activity. Zonisamide also has a modulatory effect on GABA-mediated neuronal inhibition.
Pharmacodynamic effectsThe anticonvulsant activity of zonisamide has been evaluated in a variety of models, in several species with induced or innate seizures, and zonisamide appears to act as a broad-spectrum anti-epileptic in these models. Zonisamide prevents maximal electroshock seizures and restricts seizure spread, including the propagation of seizures from cortex to sub-cortical structures and suppresses epileptogenic focus activity. Unlike phenytoin and carbamazepine however, zonisamide acts preferentially on seizures originating in the cortex.
Clinical efficacy and safety
Monotherapy in partial seizures, with or without secondary generalisationEfficacy of zonisamide as monotherapy was established in a double-blind, parallel group, non-inferiority comparison to carbamazepine prolonged release (PR) in 583 adult subjects with newly diagnosed partial seizures with or without secondary generalised tonic-clonic seizures. Subjects were randomised to carbamazepine and zonisamide received treatment for a duration of up to 24 months depending on response. Subjects were titrated to the initial target dose of 600 mg carbamazepine or 300 mg of zonisamide. Subjects who experienced a seizure were titrated to the next target dose i.e. 800 mg carbamazepine or 400 mg of zonisamide. Subjects who experienced a further seizure were titrated to the maximal target dose of 1200 mg carbamazepine or 500 mg zonisamide. Subjects who were seizure-free for 26 weeks at a target dose level continued on this dose for another 26 weeks.Main outcomes of this study are presented in this table: Table 6. Efficacy results for Monotherapy Study 310
|n (ITT population)
|Six months seizure freedom
|-12.2% ; 3.1%
|-13.6% ; 1.4%
|< 4 seizures during 3 month baseline period
|-11.7% ; 3.7%
|> 4 seizures during 3 month baseline period
|-37.5% ; 5.6%
|Twelve months seizure freedom
|- 17.2% ; 1.5%
|- 16.1% ; 0.7%
|< 4 seizures during 3 month baseline period
|-15.7% ; 1.3%
|> 4 seizures during 3 month baseline period
|-26.9% ; 17.4%
|Seizure Sub-type (6 month seizure freedom-PP population)
|All partial
|-19.2% ; 0.0%
|Simple partial
|-20.0% ; 14.7%
|Complex partial
|-26.3% ; -5.9%
|All generalized Tonic-Clonic
|-11.5% ; 6.0%
|Secondary Tonic-Clonic
|-12.4% ; 7.1%
|Generalized Tonic-Clonic
|-23.1% ; 10.5%
PP = Per Protocol Population; ITT = Intent To Treat Population
*Primary endpoint
Adjunctive therapy in the treatment of partial seizures, with or without secondary generalisation in adultsIn adults, efficacy has been demonstrated with Zonegran in 4 double-blind, placebo-controlled studies of periods of up to 24 weeks with either once or twice daily dosing. These studies show that the median reduction in partial seizure frequency is related to Zonegran dose with sustained efficacy at doses of 300-500 mg per day.
Paediatric populationAdjunctive therapy in the treatment of partial seizures, with or without secondary generalisation, in adolescent and paediatric patients (aged 6 years and above) In paediatric patients (aged 6 years and above), efficacy has been demonstrated with zonisamide in a double-blind, placebo-controlled study, which included 207 subjects and had a treatment duration of up to 24 weeks. A 50% or greater reduction from baseline in seizure frequency during the 12-week stable dose period was seen in 50% of the zonisamide-treated subjects and 31% of the patients on placebo. Specific safety issues that were encountered in the paediatric studies were: decreased appetite and weight loss, decreased bicarbonate levels, increased risk of kidney stones and dehydration. All these effects and specifically weight loss may have deleterious implications for growth and development, and may lead to general deterioration of health. Altogether, data on effects on long-term growth and development are limited.
AbsorptionZonisamide is almost completely absorbed after oral administration, generally reaching peak serum or plasma concentrations within 2 to 5 hours of dosing. The first-pass metabolism is believed to be negligible. Absolute bioavailability is estimated to be approximately 100%. Oral bioavailability is not affected by food, although peak plasma and serum concentrations may be delayed.Zonisamide AUC and Cmax values increased almost linearly after single dose over the dose range of 100-800 mg and after multiple doses over the dose range of 100-400 mg once daily. The increase at steady state was slightly more than expected on the basis of dose, probably due to the saturable binding of zonisamide to erythrocytes. Steady state was achieved within 13 days. Slightly greater than expected accumulation occurs relative to single dosing.
DistributionZonisamide is 40 - 50 % bound to human plasma proteins, with in vitro studies showing that this is unaffected by the presence of various antiepileptic medicinal products (i.e., phenytoin, phenobarbitone, carbamazepine, and sodium valproate). The apparent volume of distribution is about 1.1 1.7 l/kg in adults indicating that zonisamide is extensively distributed to tissues. Erythrocyte/plasma ratios are about 15 at low concentrations and about 3 at higher concentrations.
BiotransformationZonisamide is metabolised primarily through reductive cleavage of the benzisoxazole ring of the parent drug by CYP3A4 to form 2-sulphamoylacetylphenol (SMAP) and also by N-acetylation. Parent drug and SMAP can additionally be glucuronidated. The metabolites, which could not be detected in plasma, are devoid of anticonvulsant activity. There is no evidence that zonisamide induces its own metabolism.
EliminationApparent clearance of zonisamide at steady-state after oral administration is about 0.70 l/h and the terminal elimination half-life is about 60 hours in the absence of CYP3A4 inducers. The elimination half-life was independent of dose and not affected by repeat administration. Fluctuation in serum or plasma concentrations over a dosing interval is low (< 30 %). The main route of excretion of zonisamide metabolites and unchanged drug is via the urine. Renal clearance of unchanged zonisamide is relatively low (approximately 3.5 ml/min); about 15 30 % of the dose is eliminated unchanged.
Linearity/non-linearityZonisamide exposure increases with time until steady state is achieved by approximately 8 weeks. When comparing the same dose level, subjects of higher total body weight appear to have lower steady-state serum concentrations, but this effect appears to be relatively modest. Age (≥ 12 years) and gender, after adjustment for body weight effects, have no apparent effect on zonisamide exposure in epileptic patients during steady-state dosing. There is no need for dose adjustment with any of the AEDs including CYP3A4 inducers.
Pharmacokinetic/pharmacodynamic relationshipZonisamide lowers the 28-day average seizure frequency and the decrease is proportional (log-linear) to zonisamide average concentration.
Special patient groupsIn subjects with renal impairment, renal clearance of single doses of zonisamide was positively correlated with creatinine clearance. The plasma AUC of zonisamide was increased by 35% in subjects with creatinine clearance <20 ml/min (see also section 4.2.).Patients with an impaired liver function: The pharmacokinetics of zonisamide in patients with impaired liver function have not been adequately studied. Elderly: No clinically significant differences were observed in the pharmacokinetics between young (aged 21-40 years) and elderly (65-75 years).Children and adolescents (5-18 years): Limited data indicate that pharmacokinetics in children and adolescents dosed to steady state at 1, 7 or 12 mg/kg daily, in divided doses, are similar to those observed in adults, after adjustment for bodyweight.
Capsule contentsMicrocrystalline cellulose Hydrogenated vegetable oil Sodium laurilsulfateCapsule shells (25 mg and 50 mg hard capsules)Gelatin Titanium dioxide (E171) Shellac Propylene glycol Potassium hydroxide Black iron oxide (E172)Capsule shells (100 mg hard capsules)Gelatin Titanium dioxide (E171) Allura red AC (E129) Sunset yellow FCF (E110) Shellac Propylene glycol Potassium hydroxide Black iron oxide (E172)
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|by Ruth Contreras
|Date Added: Monday 22 December, 2014
This is very cute and sexy, but it runs small. I suggest going 2 sizes bigger than your normal size. Its not what I would consider top quality but Its Totally worth the price.
|by Yvette Moses "Yvette"
|Date Added: Wednesday 01 January, 2014
My waist line is a little fuller so I asked for a larger size, customer service was rude and the size I received was for a person about the size of 0-3.... it fit my thigh perfectly; but not wrapped fully around me....it was pretty, that's it.
|by alaina
|Date Added: Friday 06 September, 2013
I ordered this corset for Halloween because I was a vampire. Pretty cute but I wouldn't say its worth the price because after I wore it for Halloween the lace started to fall off. Also the sizing was weird, I am usually a size medium I dont have large breasts so it fit me fine there but the rest was too tight almost couldn't breathe, I should have got a size large. Still very cute though.
|by Matthew Brown
|Date Added: Wednesday 24 April, 2013
She will not wear it... Ordered the right size but it must be in metric versus SAE. Took it out of the package, washed it, placed it on the bed, she came home, went into the bathroom to change into it, called me in, I had a smile, Huston we have a problem... Off to good will it goes...
|by Mike H.
|Date Added: Sunday 24 February, 2013
Description stated one size fits all. My wife is not a large person and this came no where near to fitting her.
|by Brittany
|Date Added: Sunday 24 February, 2013
The product is of great quality, it was a perfect fit and all I expected out. However, I wish it had more push-up for the chest.

subset: commoncrawl


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Telephone 01253 594211
Rowlands & Hames Insurance Brokers provides General Insurance and Independent Financial Planning solutions to Commercial/Corporate business in all sectors and to connected Private Clients.
Our team of qualified and experienced professionals strive to fully understand our clients' needs and the risks they are exposed to, allowing us to tailor our advice and policies accordingly. Service is paramount as is breadth of cover and competitive premiums. Read more »
We encourage clients to report any claims to us in the first instance – allowing us to report the claim to the appropriate insurer's contacts, encouraging its progression, whilst ensuring we keep your records up to date for future renewals. Read more »
The industry's gold standard for firms of insurance brokers, it confirms that we have satisfied rigorous qualification criteria in terms of retaining highly-qualified staff who subscribe to the membership conditions of the CII. We work in an ethical manner that places clients' interests at the heart of the advice we give. Read more »
Our Financial Planning division provides independent financial planning advice for both private clients and business organisations. As independent financial planners, we can guide you through the financial maze whether for your business or in your personal capacity. Read more »
From the one-man band to public limited companies, Rowlands & Hames will arrange a bespoke programme to suit your demands and needs, recognising your particular exposures in the sector you operate. Read more »
Many professional businesses run the risk of suffering a financial and professional disaster without the invaluable protection that Professional Indemnity (PI) insurance provides. Read more »
Historically many businesses considered trade credit insurance as a luxury. Today companies are recognising how trade credit insurance can offer invaluable protection against invoiced clients – particularly in the current economic environment. Read more »
The protection of landlords' assets, revenues and liabilities is key. Failure to insure properly may have a devastating financial effect in the event of a loss. Our experienced team will offer guidance on various insurances available; seeking quotations from a number of insurers. Read more »
With the increasing numbers of commercial and residential properties available, the arrangement of bespoke insurance is vital for any landlord to protect both their asset and liability position. Read more »
Insurance for gradual pollution liability or to cover the costs of cleaning-up contamination is no longer expensive or difficult to obtain. Cover is now readily available and premiums now start as low as £650 for a £1m Limit of Indemnity. Read more »
We cater for the construction firm's assets and revenue risks, contract works, latent defects risks, performance bonds, credit insurance, fleet insurances, employment and management exposures, not forgetting personal accident, engineering and of course design and construct professional indemnity. Read more »
Latent Defects Insurance provides a long-term warranty against a building's defect in design, workmanship or materials - damage can range from the banal to the spectacular! This is an effective alternative to collateral warranties and allows property owners to reduce their risk exposure. Read more »
From single company vehicles to major fleets, we have access to the full range of general and specialist vehicle insurers including Lloyd's. Read more »


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Results tagged "celebrity autobiography" from Drama Queen
My new favorite blog is Mark Blankenship's The Critical Condition, and not just because he sparked up my Lazy Sunday by posting his distressingly catchy Silence of the Lambs hip-hop track right after a post about Eminem's imminent return. I love it because even though he's often critiquing theater for the New York Times, he's not afraid to simultaneously feed his pop culture jones. And why not? If someone has to check out Celebrity Autobiography or Perez Hilton Saves the Universe, then all the better if they own a copy of Suzanne Somers' "Touch Me," (everyone should) or check in on the pink poseur several times a day anyway.
At this point, Pop culture is so pop that VH1 is already loving up the naughty aughties while we're still waist deep in their muck, and FakeSarahPalin has 4,263 followers on Twitter (Yes, I'm one of them). With troupes like Les Freres Corbusier eliding easily between Schoolhouse Rock and Ibsen, it ain't enough anymore to brush up your Shakespeare. You've gotta watch New York brush up on hers as well. Or not. But still, you never know.
So hallelujah that playwrights like Tom Stoppard are there to worry about the big stuff, to school us on Havel and Housman, and that theater critics are, for the most part, thrilled to have such a deep well from which to draw. But considering the heaping helping of Pink Floyd in his latest work, it seems even Stoppard's been dipping into the shallow end of the waterhole lately.
Though Blankenship--kicking back and mixing up his arts coverage with "Clay is gay" stories--may not save the world, he just might help save informed, professional criticism from extinction by expanding its reach outside the realm of a handful of subscribers and niche enthusiasts. And by "save it," I mean, "make a video for his Silence of the Lambs rap." Hey, whatever works.
Below: the meta-moment of the pop culture year. So far.
September 24, 2008 3:59 PM | Permalink | Comments (4)
Everything I Know I Learned from Musicals
Theater Alliance of Greater Philadelphia
What's Good/What Blows in NY Theatre


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SLE212 - Biochemistry
Unit details
|2017 unit information
|Enrolment modes:
|Trimester 1: Burwood (Melbourne), Waurn Ponds (Geelong)
|Credit point(s):
|EFTSL value:
|Previously coded as:
|Unit chair:
Bernhard Dichtl
SLE152 or SLE155
SLE010 and recommended study of SBB111 or SLE111
|Incompatible with:
|Contact hours:
3 x 1 hour class per week, 5 x 3 hour practicals per trimester.
Biochemistry is the study of biological molecules that are related to living organisms. In SLE212 students will apply their fundamental knowledge of chemistry, biology and mathematics to describe the structure, chemistry and biology of various classes of biomolecules (amino acids, proteins, enzymes, carbohydrates, fatty acids and nucleic acids). Students will learn about the structure function relationship of proteins and the principles of enzymatic catalysis. They will explore the influence of thermodynamic principles on biochemical processes that sustain life. In practical sessions, students will learn essential skills in biochemical experimentation. They will be required to apply knowledge of chemical and physical principles to investigate how biochemical reactions are dependent upon the chemistry of water, buffers and pH. Classes will complement student learning of the structure-function-interaction of biomolecules.
Examination 40%, 4 x practical reports 40%, in-class test 20%. To be eligible to obtain a pass in the unit, students must achieve a minimum of 25 marks of the possible 60 for the examination and mid-trimester test components (combined).
Unit Fee Information
Click on the fee link below which describes you:


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There are many different types of feline cancer, but detecting this cat illness can be tricky as there may be no noticeable or only very subtle signs of illness. Taking your feline friend to the veterinary hospital for regular checkups can be the best way to catch health issues early. The North Carolina Veterinary Medical Association reports that vets are able to run blood tests and check for abnormalities which may indicate the early stages of cancer.
Cat cancer comes in many forms and may be caused by either genetic predisposition or environmental factors. The most common type, lymphosarcoma, is sometimes caused by the feline leukemia virus (FeLV), according to the ASPCA. Regular screening tests for FeLV should be conducted to ensure your cat is healthy.
While there are several signs that may indicate your cat has cancer, it is important to have your pet evaluated by a professional as the signs of many cat health problems overlap. Lumps are perhaps the most commonly thought of clinical sign of cancer, but not all lumps or masses are malignant. If you find a lump on your furry companion, a vet may need to perform a biopsy to determine if the tumor is cancerous. Persistent infections, bad breath, weight loss, diarrhea, vomiting, difficulty breathing, changes in behavior may all be indicative of cancer or other health issues, according to the ASPCA.


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South Dayton Valentine Heart Fundraiser Is Saturday
SOUTH DAYTON – At 10 a.m. on Saturday, the village of South Dayton will be adorned with Valentines and anxiously awaiting the arrival of the New York & Lake Erie Railroad's "Valentine Express."
Each February, the village library sponsors a $1 Valentine heart fundraiser. This year the heart fundraiser proceeds will benefit the updating project for the village playground.
Attendees can check out the project design on display at the village library by the South Dayton Community Organization. This group is working to secure funding for the update that includes grills, tables, trees and an exercise path that will compliment the existing ball fields. With this update, the playground will become a community park for family and friends outings to be fun and memorable.
From 10 a.m. to 2 p.m., children will enjoy making crafts at the library. Face painting will be at 10:30 a.m.
The Dayton Historical Society will have a display at the library, and Becky Dudley, of the Cornell Cooperative Extension, will present "East Smart New York." The Dye family will speak on making maple syrup.
The $2 tickets for the New York & Lake Erie Railroad's "Valentine Express" will be sold at 10:30 in the depot; there will be no pre-sale tickets. The first mini-ride will begin at 11 a.m. and on the top of the hour through 4 p.m. The Valentine Express rides, in a heated car, will start at the depot and travel to the east and west ends of the village and back to the depot. The street in front of the depot will be closed to traffic.
Coffee and hot chocolate, prepared by the Mustardseed, will be sold in the gazebo to benefit the village playground update.
Also, attendees can view the areas where the Robert Redford movie, "The Natural," was filmed and take their Valentine's picture near the movie's filming site by the depot.
The businesses will have the $1 fundraiser hearts. On the heart, attendees can write a special message to their Valentine and hang it on the "Tree of Love" in the gazebo. The Cattaraugus County Bank will have hot chocolate.
Linda Frederickson, of The Mane Event, is chairperson for Pine Valley students expressing their art talent on the Village Square making snow hearts and other sculptures. No snow? There will still be hearts to enjoy.
Herbal Expressions has jewelry along with complimentary refreshments. The Mustardseed will offer a free beverage with a meal. The Super Market will be selling pizza. Capozzi's Too will serve a "Valentine Lunch for Two."
The historical Zollinger's Restaurant, on the square, will offer beef on weck and potato salad. In Kim's Cafe, with tables for two, there will be old-fashioned cotton candy along with Valentine specials. A grilled hot dog, served with a cup of soup, special in Debbie & Charlie's, will be warming before the Valentine Express rides.
Also, while dining, attendees can enjoy the model railroad display set up by members of the Gowanda and Buffalo Model Railroad Club. In the rustic atmosphere of Roughkutt's, there will be heart specials. Austin Milling will host a Valentine special on bird seed, dog and cat food.
Valentine hearts will also be sold during the week in Valley Hardware, Sunrise Cargo Corporation, The Mane Event, Astry's hardware, Amerigas, Bob G's Garage, Deb's Korner Kutters, Howard Lime Service and Affordable Chiropractic.


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Ladies, it's time to ditch the elliptical and make friends with the weight rack.
�I don�t lift weights because it�ll make me bulky.� �I want to try Cross Fit, but I'm afraid I'll get too big.� Do these statements sound familiar? Yes? We thought so. Among the general female population, there exists a prevalent myth that lifting dumbbells heavier than 5 lbs will transform a normal-sized woman into the female version of the Incredible Hulk. But we�re here to clear something up, once and for all: Lifting weights will not make you �bulky� or �big� or �manly.� Toned and lean and sexy, yes. But manly? No. The truth is, weight training�when combined with a sensible diet and cardio�will help you lose fat, shape up and have the body you�ve always dreamed of. First, let�s address the �manly� myth. Nix the worry that weight training will give you big, veiny, Schwarzenegger-like muscles. In order to appear super-duper shredded, the body requires a lot of testosterone, which the female body simply doesn�t have. So, physiologically speaking, it�s pretty much impossible for a woman to look like a linebacker, unless she�s a bodybuilder on a serious training regimen or is shooting up steroids. As far as getting �bulky,� the appearance of bulk most likely stems from a poor diet, not weight training. The true culprit that gives women a bulky look is excess body fat. Period. Despite study after study documenting the benefits of strength training,�most women are still shying away from the weight rack. According to the National Center for Health Statistics, less than a quarter of women regularly strength train. Whether this is due to fear of bulking or sheer intimidation, who knows, but if you step into any gym, the gender divide becomes immediately apparent: Men tend to congregate around the weights, while women tend to consign themselves to the cardio machines. Ladies, it�s time to ditch the elliptical and make friends with the weight rack. Don�t believe us? Below are some scientifically-proven reasons to stop shying away from the weight rack: You�ll look better in a swimsuit. Covet arms like Jennifer Aniston? Want a booty like Rihanna? Pick up some weights. Weight lifting will help you sculpt a leaner, more defined look, reducing overall flab and tightening up problem areas (saddlebags, anyone?). Not to mention, just two strength training sessions a week can reduce overall body fat by about three percentage points in just 10 weeks, even if you don't cut a single calorie. You�ll fit into your jeans. Once you start strength training, you might notice a slight increase in your weight, but the number on the scale doesn�t tell the whole story. Because muscle is denser than fat, it squeezes the same amount of weight into less space. By contrast, the more fat you have, the more space you'll take up. So, in other words, the more muscle you build, the tighter and leaner you�ll look. A smaller pants size? We�ll take it! You�ll burn calories 24/7. Here�s the thing with cardio: You scorch mega calories while you�re doing it, but the calorie burn stops as soon as you hop off the treadmill. When you pump iron, on the other hand, you continue to expend calories for hours afterward. A study published in The Journal of Strength and Conditioning Research found that women who completed an hour-long strength-training workout burned an average of 100 more calories in the 24 hours afterward than those who skipped the weights. Plus, muscle burns more calories than fat, so the more muscular you are, the faster your metabolic rate will be. This means that even when you�re sitting on the couch, you�re still burning calories. Pretty cool, huh? You�ll look younger. If you feel like your arms keep getting more jiggle-y with each passing decade, blame Mother Nature. As we age, we steadily lose muscle mass, making us look flabbier over time. Luckily, regular resistance training can counteract this fate, helping older adults turn the clock back on time and regain lost muscle mass. Research published in the journal Medicine & Science In Sports & Exercise finds older adults who begin lifting weights after 50 may win the battle against age-related muscle loss. Here are the best moves for getting rid of pesky "batwings." You�ll reduce your risk of injury.�Find yourself constantly getting knee tendonitis or suffering from low back pain? Take this as a warning sign that your muscles are weak and that it's time to hit the weight room. Strength training has been shown to reduce the risk of muscle injuries in athletes, studies show. According to the American College of Sports Medicine, adhering to a resistance training program strengthens the connective tissue surrounding the joints and corrects muscle imbalances, making yourself less prone to pesky knee injuries and similar ailments. You�ll strengthen your bones. Regular weight training strengthens your bones and wards off osteoporosis-related fractures. A study in the Journal of Applied Physiology found that 16 weeks of resistance training increased subjects' hip bone density, and elevated their blood levels of osteocalcin�a marker of bone growth�by 19 percent. By boosting your balance, weight training also slashes your odds of winding up with a fall-related fracture. You�ll gain some serious confidence.�When you strictly do cardio time and time again, progress eventually stalls out. With strength training, you'll see results much more quickly. What's more, you'll feel like a total boss when you master the perfect deadlift or kill it at the squat rack. Seeing yourself get stronger�and witnessing the results of your physical progress (ahem, a rounder booty!)�cultivates self-confidence like none other. This article originally appeared as on Spry Living


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More information: 2010 Earthquake in Haiti
One year ago, on January 12, a 7.0 magnitude earthquake rocked the nation of Haiti and took the lives of more than 200,000 people. Hundreds of thousands more were injured and more than a million were left homeless.
As we mark one year since the earthquake, President Barack Obama said, "...We honor the memory of the quarter of a million Haitians who were lost, along with more than one hundred Americans, many United Nations personnel and citizens from dozens of nations. We recall how Americans, civilian and military, joined with people from around the world in one of the largest humanitarian efforts ever attempted. And we continue to be inspired by the Haitian people, and our vibrant Haitian American community, who have faced unimaginable loss with extraordinary courage and faith."
The President continued, "Since the first moments of the disaster, the United States has helped to rally international support for Haiti's recovery and reconstruction and respond to new challenges, such as the outbreak of cholera and Hurricane Tomas. This global effort, led by the Haitian government, continues today and has been matched by the tremendous compassion of the American people, who in difficult economic times have given generously to help.
"Over the past year, countless lives have been saved and many Haitians affected by the earthquake now have better access to food, water and health care than they did before the disaster. Still, too much rubble continues to clog the streets, too many people are still living in tents, and for so many Haitians progress has not come fast enough. As we have said all along, helping the poorest nation in the Western Hemisphere recover from one of the worst natural disasters ever to strike our hemisphere will take years, if not decades.
"So on this day when our thoughts and prayers are with the Haitian people, my message is the same as it was last year. Haiti can and must lead the way, with a strong vision for its future. The international community must now fulfill the pledges it has made to ensure a strong and sustained long-term effort. And as they forge ahead with the hard work of rebuilding their proud country, the people of Haiti will continue to have an enduring partner in the United States."
Secretary of State Hillary Rodham Clinton said, "As we mark this day, let us pause to remember all those who lost their lives or loved ones in this tragedy. Here at the State Department and USAID, we also honor the service and sacrifice of our friends and colleagues who were lost and those who have tenaciously persevered, selflessly dedicating themselves to rebuilding Haiti.""In the past year more than 140 nations came together to support Haiti in its time of need. That spirit of cooperation must continue if we are to help Haiti overcome this tragedy. The resilience of the people of Haiti continues to inspire us. Their determination has set an example for all of us to follow and serves as a beacon of hope for the country's future. The United States continues to work with the Haitian people along with our international partners and non-governmental organizations to help catalyze Haiti's renewal. Let us all rededicate ourselves to partnering with the people of Haiti in their pursuit to build back anew."
You can learn more about the international response to the Haiti earthquake and find out ways you can help here on state.gov. In the slideshow above, you can view photographs from USAID's Kendra Helmer, who captured images of U.S. assistance in Haiti after the earthquake.


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The Dog Days of Summer at Sunriver Resort
As I drive into work at Sunriver Resort at 4:30 each morning (my commute is not like most), I carpool with my 90 pound dog, Zoe. A Bernese Mountain Dog-Golden Retriever mix, she is quite a sight as we roll along; her large head out the window, wind in her face, eyes wide open and ears flapping.
I pull into Sunriver Resort's Meadows Golf Course Maintenance shop and load her up next to me in my golf cart. She sits on the seat next to me- ready to go to work. We head down the fairways with the Central Oregon High Desert morning frost and dew and pass a herd of deer grassing and Zoe perks up- like coffee does for me that early!
We come over the hill and there they are….any golf course maintenances nemesis- geese. Zoe looks at me and we both know what comes next, she jumps down and runs 100 yards and forces the geese to fly off or they head back into the water. I believe she is actually scared of geese but knows her job is to keep them from making a mess of the fairways and greens.
Zoe has since been promoted at Sunriver Resort as our Director of Geese Control! Honestly all joking aside, she has assisted with making sure the golf experience and course standards at the Meadows are better than ever.
No comments yet!


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{update 1/24/11} this template is no longer available. And I gave these mug rugs away. I no longer have the measurements for the tree. SO sorry... guessing and looking at photos on the tutorial, I would say the bottom of the tree is approx. 4" across and approx. 5- 5.5" tall }
My background is a White on White Snowflake. Sew the strip to one side of the tree, leaving about 1" between trees.
Then you can sew the bottom piece of the background.
I grabbed another scrap for the backing;
(This tree fabric is from Riley Blake I think the line is called "Be Merry")


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"The president of the company and I often fly together because we have such a hard time finding enough time in the office. We'll say 'save that for the trip.' "
Cabin Tech 2012
When it comes to outfitting a new airplane or refurbishing an old one, technology almost invariably tops the list of customer concerns. And no wonder: Innovation is happening at a faster clip than ever before, and buyers now face a dazzling array of choices. Interestingly, moreover, technology is no longer customer driven, according to Hawker Beechcraft vice president of business development Brian Howell. Instead, technology is driving the customers. Here's a look at where it's driving them right now.
Faster Connections
On the connectivity front, ViaSat now offers its Yonder service, with speeds as high as 2 mbps up and 256 kbps down, using its leased Ku-band satellite array. ViaSat service is available everywhere but Russia and China, and the company expects to add those countries by the end of this year. The cost is $5,995 a month with a two-year contract, $6,495 a month with a one-year contract and $7,995 a month with no contract. Installation generally costs $400,000 to $500,000.
Switzerland-based OnAir, meanwhile, has announced its intent to expand its telephony, message and Internet service to business jets. With a GSM network chip and Wi-Fi cabin hotspot, its product allows passengers to use mobile devices to make and receive telephone calls, exchange text or multimedia messages or access the Internet. At this point, OnAir offers its package only as a retrofit item but a spokesman said the company is in discussions with "certain OEMs." The price of the hardware starts at about $250,000 and varies with the size of the airplane.
Idair, a joint venture of Lufthansa Technik and Panasonic Avionics, has introduced its Eclipsair wireless "infotainment" system. It delivers news, video, audio, data and flight information wirelessly through a single-box access point and Web-based media server to the user's mobile device.
Roku has unveiled the Roku Streaming Stick. The wireless device, about the size of a USB drive, will plug into MHL-enabled HDMI television ports. According to the Saratoga, Calif. company, the streaming stick features built-in Wi-Fi, processor, memory and software and allows interface with onboard devices from laptop computers to iPads to smartphones. It should be available in the second half of 2012.
Apps and More Apps
Two years ago, Gulfstream introduced an app designed to turn everyone's iPod or iPhone into a device to control everything in the cabin, from window shades to entertainment. Today, such apps are commonplace.
Nextant Aerospace, meanwhile, now offers a free iPhone app guide to its 400XT airplane, giving prospective buyers immediate access to features, enhancements and performance.
If you've ever wondered about the noise level in the cabin of an aircraft you're thinking about buying, you'll be glad to know there's an app for that, too. Just 10 years ago, an analyzer to measure cabin noise would have cost $60,000 and required special training to operate, according to Jeff Weisbeck, director of product development at ITT Enidine. Now the Analyzer by DSP Mobile sells for $9.99 in Apple's App Store and anybody can use it.
Think that's cool? A year ago, apps were available with an entertainment system that would allow you to wirelessly access any movie stored in the AVOD (audiovisual on demand) system and view it on an iPad or iPhone. Now, there are apps that will let you wirelessly view anything on that iPad or iPhone anywhere on the aircraft's entertainment system. Rockwell Collins, meanwhile, recently unveiled CabinRemote, an app that lets you control a wide variety of functions and makes it possible for you to watch the company's Airshow Moving Map on your iPad.
Blu-ray Is So Yesterday
Just a couple of years ago, the Blu-ray player, with its ability to process high-definition video, was the future of onboard entertainment. Now, it seems likely to become obsolete, overtaken by the AVOD server, which can store hundreds of videos and allow any passenger access from any seat.
Meanwhile, monitors continue to improve. Today's choices are LCD (liquid crystal display) and LED (light-emitting diode), and to a lesser degree, gas plasma. LCD has a slight edge over LED, thanks to brighter whites and deeper blacks. LCD is also less expensive and the overall package is thinner, making it easier to hide in a bulkhead or credenza. But if big is your thing, note that Custom Control Concepts in Kent, Wash., now offers a 70-inch LED monitor.
Still to come in the business jet cabin is OLED (organic light-emitting diode) television. This past winter, LG introduced a 55-inch OLED consumer model and the advantages were immediately obvious. Not only are images sharper but the screen is only four millimeters thick and the package weighs just 22 pounds. Shipments of OLED monitors have begun and you can be sure that some entertainment-system supplier is already looking at how to certify them for flight.
How about a handset that "speaks" your language? TrueNorth Avionics has announced its Stylus, described as "business aviation's first handset with a multilingual text option." The Canadian company, based in Ottawa, claims it can be programmed to operate in any language, including those with dedicated character sets, such as Arabic and Chinese.
The Hi-Tech Lav
When it comes to toilet seats, up or down is often the subject of acrimonious conversation. EcoDomo has another choice–leather. The Rockville, Md. company is offering leather toilet seats it describes as not only luxurious and stylish but antimicrobial. They can be cleaned with a mild mixture of bleach and water, followed by a leather-wipe similar to those used to treat automobile leather. The cost? About $500.
Gulfstream offers a somewhat related innovation for the same end of the cabin–an aft lavatory exhaust system that is standard on the G450, the G550 and the new G650. The main component is a semi-circular vented aluminum tube mounted just under the toilet-bowl cover. It is automatically activated when the padded seat is raised. Odors are exhausted overboard via the drain mast. Overboard venting can also be activated by a switch in the lavatory.
Dassault has designed an installed a shower in the aft cabin section of a Falcon 7X. The stand-up (or sit-down) stall features a "rain sky" ceiling and an outside window that can be electrochemically dimmed for privacy. The shower was built at the request of a customer and is not yet being offered as a standard option.
Bombardier has made a shower optional equipment on its Global 5000 and Global 6000 for about three years, and Gulfstream will offer one as an option on its new G650, beginning next year.
The Latest in Galley Tech
As business and private aircraft fly farther and farther on global routes, the need for a better-equipped galley is becoming apparent, and manufacturers are doing something about it. Among the latest products to catch our eye:
• The galley in Gulfstream's G650 includes a 40-pound refrigerator/freezer that the Savannah, Ga. company designed in its own laboratory. It incorporates an insulated and ducted enclosure with cooling unit. Electronic controls on the outside and dual direct-current fans are designed to be ultra quiet.
• Italian cabin-components supplier Iacobucci has introduced an espresso maker that eschews the usual boiler in favor of patented heat exchangers to ensure instant and continuous operation. What's more, the unit accommodates all brands of espresso pods.
• Flying Colours, a completion and refurbishment center in Peterborough, Ontario, has created a proprietary smoke-extraction system to remove galley odors.
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Topic: creating an edit form that saves info to multiple tables...
I am working on making a todo list application as a way to learn rails. I already have set up two tables (todos and details) that are linked by a foreign key todo_id in the details table.
Currently the user can create a new todo item on the main page that creates the title(description in the db) for the item.
There is an edit button associated with each todo item. The detail for each item is stored in the details table (I only retrieve it if/when it is asked for and display it in a div using ajax - I already coded this).
I am using belongs_to :todo in the detail model and had_one :detail in the todo model.
I am at a loss as to how to use these to show any detail that already exists for the todo item in the edit form or how to update that detail when the edit form is submitted.
Basically it comes down to not completely comprehending has_one, belongs_to. So if you can help here or point me to a good resource that would be greatly appreciated!


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Hello Tea Lovers,
Just a quick question. I am a tea drinker, but i currently only drink from the standard earl grey teabag, i drink about 7 cups a day with milk. I was just wondering if it is unhealthy to drink this much tea in one day?
I also buy from a compant called Graze, a little healthy shop online where you can order a box of healthy snacks per week, and one of their items is a tea infusion of Assam, Kenyan and Earl Grey tea leaves that dont require milk. Would this option be healthier?
Thank you!