Oral gene therapy for hypoparathyroidism: a rat model.

The use of nonionic polymeric micelles orally to protect and deliver plasmid DNA in vivo was investigated. Parathyroid hormone (PTH)(1-34) gene (179 bp) was inserted into a human cytomegalovirus promoter (PCMV) and E. coli competent cells were used to amplify the cDNA. Polymeric micelle formations (100 microl) formed from PCMV-PTH(1-34) cDNA (7.2 microg/microl) and 6% (w/v) polyethylene oxide-polypropylene oxide-polyethylene oxide (PEO-PPO-PEO) was administered at 8-hr intervals for 48 hr and then at 8-hr intervals for 24 hr weekly for 3 weeks. Parathyroidectomized rats receiving 150 microl of EDTA (10 mM) before each dose of formation served as the study group; rats receiving drinking water, EDTA (10 mM), PCMV-PTH(1-34) cDNA and PCMV-PTH(1-34) cDNA plus EDTA at the same amount and time intervals served as the control groups. Serum levels of calcium and PTH(1-34) were measured weekly for 4 weeks. Immunohistochemical stain for PTH(1-34), reverse transcriptase polymerase chain reaction for PTH(1-34) mRNA and the relative density of PTH(1-34) mRNA were performed at 2 and 4 weeks after oral gene therapy in different organs. One third to three of five rats in the control groups died after parathyroidectomy. Serum levels of calcium and PTH(1-34) were higher in the study than in the control groups. In the study group, positive stain of PTH(1-34) and PTH(1-34) mRNA could be found in those organs. Relative densities of PTH(1-34) mRNA were higher in the study than in the drinking water group in different organs. Oral gene therapy can maintain calcium and PTH(1-34) levels in parathyroidectomized rats.

Validity, reliability and application of the taiwan version of the migraine disability assessment questionnaire.

BACKGROUND/PURPOSE: The seven-item Migraine Disability Assessment (MIDAS) questionnaire is a simple and useful tool for evaluating migraine-related disability. The goals of this study were: (1) to test the reliability and validity of the Taiwan version of the MIDAS (MIDAS-T) questionnaire, and (2) to measure the impact of migraine among Taiwanese patients in a headache clinic. METHODS: Consecutive migraine patients, aged 20-50 years, visiting the headache clinic at the Taipei Veterans General Hospital were invited to participate in the study. They completed the MIDAS-T and a form, which collected headache-related information including characteristics and impact on their lives. Of them, about 30 patients were randomly invited to repeat the MIDAS-T 3 weeks later. RESULTS: A total of 281 migraine patients (M/F, 63/218; mean age, 35.27 +/- 8.21 years) participated in the study. Of them, 31 completed the MIDAS-T again 3 weeks later. MIDAS-T showed acceptable internal consistency (Cronbach alpha = 0.79), test-retest reliability (r = 0.67) and criterion validity (r = 0.37 for question A [headache frequency] and r = 0.34 for question B [headache intensity], p < 0.001). The mean score of migraine patients on MIDAS-T was 34.21 +/- 45.90, ranging from 0 to 265. MIDAS grade I (score 0-5) was found in 22% of patients, grade II (6-10) in 15%, grade III (11-20) in 17%, and grade IV (>or=21) in 46%. CONCLUSION: This study supports the reliability and validity of MIDAS-T for use in Taiwanese patients. Almost half of the migraine patients were classified as having severe disability (grade IV).

[The application of migraine disability assessment questionnaire (MIDAS)].

Migraine is a recurring and disabling pain disorder. The prevalence is estimated as 9.1% in Taiwan. Patients suffer from significant loss of work, time at school or ability to perform household chores, as well as other family or leisure activities. Treatment strategies during migraine attacks should be tailored based on the severity of disability. Stewart and Lipton (1999) developed the Migraine Disability Assessment Questionnaire (MIDAS) to assess the severity of disability related to migraine. This simple, self-administered, 7-item questionnaire focuses on disability in three domains (school or paid work, household chores, and family, social, or leisure activities) in the first 5 items of the questionnaire. The internal consistency, test-retest reliability, validity, ease of use, and clinical utility were all tested with good results. The questionnaire offers a simple tool to improve physician-patient communication. As for treatment strategies, a recent large-scale study done in the USA showed that it is more efficacious to treat migraine patients by adopting a strategy of stratified care based on different disability status than a stepped-care strategy. The simple questionnaire, MIDAS, has received world-wide popularity and has been translated into Japanese, Italian and Turkish. All of these versions showed good reliability and validity. Recently, one of our studies demonstrated that the Taiwan version also yielded comparable internal consistency, reliability, and validity. We hope that the MIDAS questionnaire can be widely adopted in Taiwan to help physicians assess their patients' disability related to migraine and provide clues for clinical management.

Single intravenous injection of naked plasmid DNA encoding erythropoietin provides neuroprotection in hypoxia-ischemia rats.

Hypoxic-ischemic (H-I) encephalopathy is a major contributor to morbidity and mortality in infants and children. To delineate the nature and mechanism(s) of neuroprotection via erythropoietin (EPO) gene therapy, we evaluated the effects of single intravenous injection of naked plasmid DNA encoding EPO in H-I infant rats. Single administration of naked plasmid containing EPO cDNA driven under cytomegalovirus promoter (pCMV-EPO) by rapid injection via the tail vein produced a remarkable level of human EPO protein in the circulation, peaking at one day and lasting for 14 days after injection. There were significant improvements of water maze task in H-I rats after EPO gene therapy. Our data showed that the mechanisms of EPO gene therapy were rescue of CA1 neurons from lethal H-I injury, prevention of neuronal apoptosis in CA1 region, and decrease of glial activation in corpus callosum. This could be the first report of successful treatment of H-I injury by a single intravenous infusion of EPO gene.