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Zonisamide

 

Definition

Zonisamide is an anti-convulsant used to control seizures in the treatment of epilepsy, a neurological dysfunction in which excessive surges of electrical energy are emitted in the brain.

Purpose

Zonisamide decreases abnormal activity and excitement within the brain that may trigger seizures. While zonisamide controls the partial seizures (focal seizures) associated with epilepsy, there is no known cure for the disease.

Some physicians have also used zonisamide in the treatment of mood disorders. As of 2004, zonisamide is additionally under study for the treatment of migraine headaches and neuropathic (nerve) pain.

Description

In the United States, zonisamide is sold under the brand name Zonegran. Zonisamide is classified as a sulfonamide anticonvulsant. The precise mechanisms by which it works are unknown.

Recommended dosage

Zonisamide is taken by mouth in tablet form. It is prescribed by physicians in varying dosages, usually from 100 mg to 400 mg daily.

Beginning a course of treatment which includes zonisamide requires a gradual dose-increasing regimen. Adults and teenagers 16 years or older typical take 100 mg per day for the first two weeks. Daily dosages of zonisamide may then be increased 100 mg once every two weeks until reaching the full daily dose (usually not more than 400 mg.) It may take several weeks to realize the full benefits of zonisamide.

Persons should not take a double dose of anticonvulsant medications. If a daily dose is missed, it should be taken as soon as possible. However, if it is almost time for the next dose, the missed dose should be skipped.

When discontinuing treatment with zonisamide, physicians typically direct patients to gradually reduce their daily dosages. Stopping the medicine suddenly may cause seizures to occur or become more frequent.

Precautions

Persons taking zonisamide should avoid alcohol and central nervous system depressants (medications including antihistimines, sleep medications, and some pain medications). Combining these substances with zonisamide can exacerbate (heighten) the side effects of alcohol and other medications.

A physician should be consulted before taking zonisamide with certain non-perscription medications, such as medicines for asthma, appetite control, coughs, colds, sinus problems, allergies, and hay fever.

Zonisamide may inhibit perspiration, causing body temperature to increase during physical activity. Persons taking zonisamide are at a greater risk for heat stroke. Caution should be used during strenuous exercise, prolongued exposure during hot weather, and while using saunas or hot tubs.

Zonisamide may not be suitable for persons with a history of liver or kidney disease, mental illness, high blood presure, angina (chest pain), irregular heartbeats, or other heart problems.

Before beginning treatment with zonisamide, patients should notify their physician if they consume a large amount of alcohol, have a history of drug use, are pregnant, or plan to become pregnant. Most physicians recommend using effective birth control while taking zonisamide, as it may cause defects to a developing fetus. Patients who become pregnant while taking zonisamide should contact their physician.

Side effects

Research indicates that zonisamide is generally well tolerated. However, it may case a variety of usually mild side effects. Headache, nausea and fatigue, and weakness are the most frequently reported side effects of zonisamide. Other possible side effects include:

  • difficulty sleeping
  • nervousness
  • anxiety
  • abdominal pain
  • difficulty with memory
  • double vision
  • loss of appetite
  • restlessness
  • drowsiness
  • diarrhea or constipation
  • indigestion
  • aching joints and muscles
  • unpleasant taste in mouth or dry mouth
  • tingling or prickly feeling on the skin

Many of these side effects disappear or occur less frequently during treatment as the body adjusts to the medication. However, if any symptoms persist or become too uncomfortable, the prescribing physician should be consulted.

Other, uncommon side effects of zonisamide can be serious. A patient taking zonisamide who experiences any of the following symptoms should contact their physician:

  • rash or bluish patches on the skin
  • discouragement, feeling sad or empty
  • mood or mental changes
  • shakiness or unsteady walking
  • lack of appetite
  • kidney stones
  • difficulty breathing
  • chest pain
  • slow or irregular heartbeat
  • faintness
  • confusion or loss of consciousness
  • persistent, severe headaches
  • persistent fever or pain

Interactions

Zonisamide may have negative interactions with some antifungal medications, antihistimines, antidepressants, antibiotics, and monoamine oxidase inhibitors (MAOIs). Other medications such as diazepam (Valium), fluoxetine (Prozac, Sarafem), fluvoxamine (Luvox), HIV protease inhibitors (indinavir), ritonavir (Norvir), ipratropium (Atrovent), isoniazid, phenobarbital (Luminal, Solfoton), nefazodone, metronidazole, acetazolamide (Diamox), phenytoin (Dilantin), primidone, propranolol (Inderal); and rifampin (Rifadin, Rimactane) may also adversely react with zonisamide.

Zonisamide is sometimes prescribed as part of a combination of drugs to prevent seizures. The physician will carefully monitor the combination drug therapy, as sometimes zonisamide will potentite (enhance) the effects of other anticonvulsant medications.

Zonisamide may decrease the effectiveness of some forms of oral contraceptives (birth control pills).

Zonisamide should not be taken by those allergic to sulfa drugs.

Resources

BOOKS

Weaver, Donald F. Epilepsy and Seizures: Everything You Need to Know. Richmond Hill, Ontario: Firefly Books, 2001.

OTHER

"Zonisamide." Medline Plus. National Library of Medicine. (March 20, 2004). http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500137.html.

ORGANIZATIONS

Epilepsy Foundation. 4351 Garden City Drive, Landover, MD 20785-7223. (800) 332-1000. http://www.epilepsyfoundation.org.

American Epilepsy Society. 342 North Main Street, West Hartford, CT 06117-2507. (860)586-7505. http://www.aesnet.org.


Adrienne Wilmoth Lerner


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Drug Info: Zonisamide
Top

Brand names: Zonegran®

Chemical formula:



Zonisamide Oral capsule

What is this medicine?

ZONISAMIDE is used to control partial seizures in adults with epilepsy.

This medicine may be used for other purposes; ask your health care provider or pharmacist if you have questions.

What should I tell my health care provider before I take this medicine?

They need to know if you have any of these conditions:
•dehydrated
•diarrhea
•ketogenic diet
•kidney disease
•liver disease
•lung disease
•suicidal thoughts, plans, or attempt; a previous suicide attempt by you or a family member
•an unusual or allergic reaction to zonisamide, sulfa drugs, other medicines, foods, dyes, or preservatives
•pregnant or trying to get pregnant
•breast-feeding

How should I use this medicine?

Take this medicine by mouth with a glass of water. Follow the directions on the prescription label. Swallow whole. Do not break open the capsule. This medicine may be taken with or without food. Take your doses at regular intervals. Do not take your medicine more often than directed. Do not stop taking this medicine unless instructed by your doctor or health care professional. Stopping your medicine suddenly can increase your seizures or their severity.

Contact your pediatrician or health care professional regarding the use of this medication in children. Special care may be needed.

Overdosage: If you think you have taken too much of this medicine contact a poison control center or emergency room at once.
NOTE: This medicine is only for you. Do not share this medicine with others.

What if I miss a dose?

If you miss a dose, skip that dose and continue with your regular schedule. Do not use extra doses, or use for a longer period of time than directed by your prescriber or health care professional. Too much or too frequent mequinol-tretinoin will not lead to more rapid or better results, and skin side effects may occur (marked redness, peeling, discomfort, or light spots on the skin).

What may interact with this medicine?

•barbiturates like phenobarbital
•carbamazepine
•phenytoin

This list may not describe all possible interactions. Give your health care provider a list of all the medicines, herbs, non-prescription drugs, or dietary supplements you use. Also tell them if you smoke, drink alcohol, or use illegal drugs. Some items may interact with your medicine.

What should I watch for while using this medicine?

Visit your doctor or health care professional for regular checks on your progress. Wear a medical identification bracelet or chain to say you have epilepsy, and carry a card that lists all your medications.
 
It is important to take this medicine exactly as directed. When first starting treatment, your dose will need to be adjusted slowly. It may take weeks or months before your dose is stable. You should contact your doctor or health care professional if your seizures get worse or if you have any new types of seizures.
 
You may get drowsy, dizzy, or have blurred vision. Do not drive, use machinery, or do anything that needs mental alertness until you know how this medicine affects you. To reduce dizzy or fainting spells, do not sit or stand up quickly, especially if you are an older patient. Alcohol can increase drowsiness and dizziness. Avoid alcoholic drinks.
 
This medicine may increase the chance of developing metabolic acidosis. If left untreated, this can cause kidney stones, bone disease, or slowed growth in children. Symptoms include breathing fast, fatigue, loss of appetite, irregular heartbeat, or loss of consciousness. Call your doctor immediately if you experience any of these side effects. Also, tell your doctor about any surgery you plan on having while taking this medicine since this may increase your risk for metabolic acidosis.
 
This medicines may increase the risk of kidney stones. Drinking 6 to 8 glasses of water a day may help prevent the formation of kidney stones.
 
The use of this medicine may increase the chance of suicidal thoughts or actions. Pay special attention to how you are responding while on this medicine. Any worsening of mood, or thoughts of suicide or dying should be reported to your health care professional right away.
 
Women who become pregnant while using this medicine may enroll in the North American Antiepileptic Drug Pregnancy Registry by calling 1-888-233-2334. This registry collects information about the safety of antiepileptic drug use during pregnancy.

What side effects may I notice from receiving this medicine?

Side effects that you should report to your doctor or health care professional immediately:
•allergic reactions like skin rash, itching or hives, swelling of the face, lips, or tongue
•decreased sweating or a rise in body temperature, especially in patients under 17 years old
•depression
•difficulty breathing or tightening of the throat
•feeling faint or lightheaded, falls
•fever, sore throat, sores in your mouth, or bruising easily
•hallucination, loss of contact with reality
•irregular heartbeat
•loss of appetite
•redness, blistering, peeling or loosening of the skin, including inside the mouth
•severe drowsiness, difficulty concentrating, or coordination problems
•speech or language problems
•sudden back pain, abdominal pain, pain when urinating, bloody or dark urine
•unusually tired
•vomiting
•worsening of mood, thoughts or actions of suicide or dying
 
Side effects that usually do not require medical attention (report to your doctor or health care professional if they continue or are bothersome):
•headache
•nausea
 
This list may not describe all possible side effects. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Where should I keep my medicine?

Keep out of reach of children.

Store at room temperature between 15 and 30 degrees C (59 and 86 degrees F). Keep in a dry place protected from light. Throw away any unused medicine after the expiration date.

Last updated: 7/1/2002

Important Disclaimer: The drug information provided here is for educational purposes only. It is intended to supplement, not substitute for, the diagnosis, treatment and advice of a medical professional. This drug information does not cover all possible uses, precautions, side effects and interactions. It should not be construed to indicate that this or any drug is safe for you. Consult your medical professional for guidance before using any prescription or over the counter drugs.

Wikipedia: Zonisamide
Top
Zonisamide
Systematic (IUPAC) name
1,2-benzisoxazole-3-methanesulfonamide
Identifiers
CAS number 68291-97-4
ATC code N03AX15
PubChem 5734
DrugBank APRD00004
Chemical data
Formula C8H8N2O3S 
Mol. mass 212.227 g/mol
Physical data
Melt. point 162 °C (324 °F)
Pharmacokinetic data
Bioavailability  ?
Protein binding 40%
Metabolism Hepatic
Half life 105 hours in red blood cells, 63 hours in plasma
Excretion Renal
Therapeutic considerations
Pregnancy cat.

C(US)

Legal status

Prescription only

Routes Oral

Zonisamide is a sulfonamide anticonvulsant approved for use as an adjunctive therapy in adults with partial-onset seizures for adults; infantile spasm, mixed seizure types of Lennox-Gastaut syndrome, myoclonic, and generalized tonic clonic seizure[1].

Contents

History

Zonisamide was discovered by Uno and colleagues in 1972[2] and launched by Dainippon Sumitomo Pharma (大日本住友製薬 Dainippon Sumitomo Seiyaku?) (formerly Dainippon Pharmaceutical (大日本製薬 Dainippon Seiyaku?)) in 1989 as Excegran in Japan.[3] It was marketed by Élan in the United States starting in 2000 as Zonegran, before Élan transferred their interests in zonisamide to Eisai (エーザイ?) in 2004.[4] Eisai also markets Zonegran in Asia (China, Taiwan, and fourteen others)[5] and Europe (starting in Germany and the United Kingdom).[6]

Indications

Epilepsy

Zonisamide is approved in the United States,[7] United Kingdom,[8] for adjunctive treatment of partial seizures in adults and in Japan for both adjunctive and monotherapy for partial seizures (simple, complex, secondarily generalized), generalized (tonic, tonic-clonic (grand mal), and atypical absence) and combined seizures.[9]

Parkinson's

An open trial on zonisamide in seven Parkinson's disease patients had positive results, according to this 2001 report.[10] Since then, it has been reported to treat the resting tremor that other therapies may leave behind.[11] By early November 2005, Dainippon Sumitomo had filed a NDA for the use of zonisamide in Parkinson's disease; it is to be marketed as Tremode.[12]

Obesity

It has also been studied for obesity[13] with significant positive effects on body weight and there are three ongoing clinical trials for this indication.[14][15][16]

Migraines

Zonisamide has been studied for and used as a migraine preventative medication, and has also been shown to be effective in some cases of neuropathic pain.

Bipolar Depression

It has also been used off-label by psychiatrists as a mood stabilizer to treat bipolar depression.[17][18]

Metabolism

Zonisamide is metabolized mostly by the CYP3A4 isoenzyme, but also CYP3A7 and CYP3A5,[19] to 2-(sulphamoylacetyl)-phenol via reductive cleavage of the 1,2-benzisoxazole ring.[20]

Mechanism of action

The exact mechanism of action is not known for zonisamide. According to Leppik, while zonisamide may be a carbonic anhydrase inhibitor like acetazolamide, this is not one of the primary mechanisms of action, which might be blocking repetitive firing of voltage-gated sodium channels and reduction of T-type calcium channel currents,[21] or by binding allosterically to GABA receptors like the benzodiazepines and muscimol,[22],[23] or increasing the levels of the glutamate transport protein in the brain while decreasing the amount of GABA transport protein, in other words, inhibiting the uptake of the inhibitory neurotransmitter GABA while enhancing the uptake of the excitatory neurotransmitter glutamate.[24]

Side effects

The most common side effects include drowsiness, loss of appetite, dizziness, headache, nausea, and agitation/irritability. Zonisamide has also been associated with hypohidrosis.[25]

On February 23, 2009 the U.S. Food and Drug Administration (FDA) issued a warning that zonisamide can cause metabolic acidosis in some patients. It is now recommended that serum bicarbonate levels are assessed before starting treatment and periodically during treatment with zonisamide, even in the absence of symptoms.[26]

Interactions

Zonisamide and other carbonic anhydrase inhibitors such as topiramate, furosemide, and hydrochlorothiazide have been known to interfere with amobarbital, which has led to inadequate anesthetization during the Wada test.[27]

Additionally, the metabolism of zonisamide is inhibited by ketoconazole, ciclosporin, miconazole, fluconazole and carbamazepine in descending order.[28]

References

  1. ^ Comprehensive Pharmacy Review, Leon Shargel, 6th edition, p988
  2. ^ Shah, Jaymin; Kent Shellenberger, Daniel M. Canafax (2002-06-15) [1972]. "Zonisamide". in René H. Levy, Richard H. Mattson, Brian S. Meldrum, and Emilio Perrucca (ed.). Antiepileptic Drugs (Fifth ed.). Philadelphia: Lippincott Williams & Wilkins. p. 873. ISBN 0-7817-2321-3. 
  3. ^ Dainippon Sumitomo Pharma Co., Ltd. (2005). "Company History". Company Information. Dainippon Sumitomo Co., Ltd.. http://www.ds-pharma.co.jp/english/profile/history.html. Retrieved 12 November 2005. 
  4. ^ Dainippon Pharmaceutical Co., Ltd. (2004). "Transfer of Rights Agreement for North America and Europe Reached on Zonegran". News Releases for Dainippon Pharmaceutical in 2004. Dainippon Sumitomo Pharma Co., Ltd. http://www.ds-pharma.co.jp/english/news/dainippon_2004.html. Retrieved 12 November 2005. 
  5. ^ Dainippon Pharmaceutical Co., Ltd. (2005). "Dainippon Pharmaceutical and Eisai Conclude Agreement for the Development, Manufacture and Marketing of the Anti-Epileptic Agent Zonisamide in Asia". Dainippon Pharmaceutical News Releases for 2005. Dainippon Sumitomo Pharma Co., Ltd.. http://www.ds-pharma.co.jp/english/news/dainippon_2005/no_002.html. Retrieved 12 November 2005. 
  6. ^ Eisai Co., Ltd. (2005). "Eisai Announces Launch of Zonegran (zonisamide), Treatment For Epilepsy In the UK and Germany". Eisai 2005 News Releases. Eisai Co., Ltd.. http://www.eisai.co.jp/enews/index.html. Retrieved 12 November 2005. 
  7. ^ Élan Pharmaceuticals Inc (August 22, 2003). "NDA 20-789/S-001; Zonegran (zonisamide) Capsules 25, 50, 100 mg FDA Approvable Labeling Text" (PDF). Zonisamide Approval History. Food and Drug Administration. http://www.accessdata.fda.gov/drugsatfda_docs/label/2003/20789scm001_zonegran_lbl.pdf. Retrieved August 24, 2009. 
  8. ^ Eisai Ltd. (2005). "Zonegran Summary of Product Characteristics". electronic Medicines Compendium. Medicines.org.uk. http://emc.medicines.org.uk/. Retrieved November 13, 2005. 
  9. ^ Dainippon Pharmaceutical Co., Ltd. (2004). "EXCEGRAN Tablets 100 mg & EXCEGRAN Powder 20%" (PDF). http://www.e-search.ne.jp/~jpr/PDF/DAINIP03.PDF. Retrieved March 13, 2006. 
  10. ^ Murata, Miho; Horiuchi Emiko and Kanazawa Ichiro (December 2001). "Zonisamide has beneficial effects on Parkinson's disease patients". Neuroscience Research 41 (4): 397–9. doi:10.1016/S0168-0102(01)00298-X. PMID 11755227. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&list_uids=11755227&dopt=ExternalLink. 
  11. ^ Nakanishi, I; Kohmoto J, Miwa H, Kondo T (August 2003). "[Effect of zonisamide on resting tremor resistant to antiparkinsonian medication]". No To Shinkei 55 (8): 685–9. PMID 13677302. 
  12. ^ Dainippon Sumitomo Pharma Co., Ltd. (2005). "New Drugs in the R&D Pipeline (under development by DSP)" (PDF). List of Product Development Project. http://www.ds-pharma.co.jp/english/rd/item.html. Retrieved 2005-11-21. 
  13. ^ Gadde, Kishore M.; Deborah M. Franciscy, H. Ryan Wagner, II; K. Ranga R. Krishnan (April 2003). "Zonisamide for Weight Loss in Obese Adults: A Randomized Controlled Trial". Journal of the American Medical Association 289 (14): 1820–1825. doi:10.1001/jama.289.14.1820. PMID 12684361. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&list_uids=12684361&dopt=ExternalLink. 
  14. ^ University of Cincinnati (2005). "Zonegran in the Treatment of Binge Eating Disorder Associated With Obesity". ClinicalTrials.gov. http://clinicaltrials.gov/show/NCT00221442. Retrieved 2006-05-04. 
  15. ^ Tuscaloosa Research & Education Advancement Corporation (2005). "Zonegran for the Treatment of Weight Gain Associated With Psychotropic Medication Use: A Placebo-Controlled Trial". ClinicalTrials.gov. http://clinicaltrials.gov/show/NCT00203450. Retrieved 2006-05-04. 
  16. ^ National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (2006). "Zonisamide for Weight Reduction in Obese Adults". ClinicalTrials.gov. http://clinicaltrials.gov/show/NCT00275834. Retrieved 2006-05-04. 
  17. ^ Dr. Brian D. Loftus (2004). "Zonegran". http://www.loftusmd.com/Articles/AED/zonegran.html. Retrieved 2006-11-29. 
  18. ^ Hasegawa, Hisanori (May 2004). "Utilization of zonisamide in patients with chronic pain or epilepsy refractory to other treatments: a retrospective, open label, uncontrolled study in a VA hospital". Curr Med Research Opinion 20 (5): 577–580. doi:10.1185/030079904125003313. PMID 15140322. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&list_uids=15140322&dopt=ExternalLink. 
  19. ^ Ohmori, S.; Nakasa H, Asanome K, Kurose Y, Ishii I, Hosokawa M, Kitada M (1998 May 8). "Differential catalytic properties in metabolism of endogenous and exogenous substrates among CYP3A enzymes expressed in COS-7 cells". Biochimica et Biophysica Acta 1380 (3): 297–304. PMID 9555064. 
  20. ^ Stiff, D. D.; Robicheau JT, Zemaitis MA. (January 1992). "Reductive metabolism of the anticonvulsant agent zonisamide, a 1,2-benzisoxazole derivative". Xenobiotica 22 (1): 1–11. PMID 1615700. 
  21. ^ Leppik, Ilo E. (December 2004). "Zonisamide: chemistry, mechanism of action, and pharmacokinetics". Seizure 13 (Suppl 1): S5–9; discussion S10. doi:10.1016/j.seizure.2004.04.016. PMID 15511691. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&list_uids=15511691&dopt=ExternalLink. 
  22. ^ Mimaki, T.; Suzuki Y, Tagawa T, Karasawa T, Yabuuchi H (March 1990). "Interaction of zonisamide with benzodiazepine and GABA receptors in rat brain". Medical Journal of Osaka University 39 (1-4): 13–7. PMID 1369646. 
  23. ^ Mimaki, T.; Suzuki Y, Tagawa T, Karasawa T, Yabuuchi H (March 1990). "[3H]zonisamide binding in rat brain". Medical Journal of Osaka University 39 (1-4): 19–22. PMID 1369647. 
  24. ^ Ueda, Yuto; Doi Taku, Tokumaru Jun, and L. James Willmore (2003 August 19). "Effect of zonisamide on molecular regulation of glutamate and GABA transporter proteins during epileptogenesis in rats with hippocampal seizures". Molecular Brain Research 116 (1-2): 1–6. doi:10.1016/S0169-328X(03)00183-9. PMID 12941455. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&list_uids=12941455&dopt=ExternalLink. 
  25. ^ Miller JL, Hurley HJ (2007). "Diseases of the Eccrine and Apocrine Sweat Glands". in Bolognia, Jean L.. Dermatology. St. Louis: Mosby. pp. 539. ISBN 1-4160-2999-0. 
  26. ^ "FDA alert-Zonisamide". February 23, 2009. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm095251.htm. Retrieved February 24, 2009. 
  27. ^ Bookheimer, Susan; Schrader, Lara M.; Rausch, Rebecca; Sankar, Raman; Engel, Jerome Jr. (February 2005). "Reduced anesthetization during the intracarotid amobarbital (Wada) test in patients taking carbonic anhydrase-inhibiting medications". Epilepsia 46 (2): 236. doi:10.1111/j.0013-9580.2005.23904.x. http://www.blackwell-synergy.com/doi/full/10.1111/j.0013-9580.2005.23904.x. 
  28. ^ Nakasa, H.; Nakamura H, Ono S, Tsutsui M, Kiuchi M, Ohmori S, Kitada M. (April 1998). "Prediction of drug-drug interactions of zonisamide metabolism in humans from in vitro data". European Journal of Clinical Pharmacology 54 (2): 177–83. doi:10.1007/s002280050442. PMID 9626925. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&list_uids=9626925&dopt=ExternalLink. 

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Neurological Disorder. Gale Encyclopedia of Neurological Disorders. Copyright © 2005 by The Gale Group, Inc. All rights reserved.  Read more
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