Delivery of Factor VIII Gene into Skeletal Muscle Cells Using Lentiviral Vector

PURPOSE: This study was designed to investigate whether transduction of lentiviral vectors (LV) carrying human coagulation factor VIII (hFVIII) cDNA into skeletal muscle could increase circulating hFVIII concentrations. MATERIALS AND METHODS: A LV containing bacterial LacZ gene as a control or human FVIII gene was intramuscularly administered into the thigh muscle of 5 weeks old Sparague-Dawley rats. The plasma human FVIII concentration and neutralizing anti-FVIII antibodies were measured for up to 12 weeks in these experimental animals. RESULTS: The plasma human FVIII levels in the rats injected with LV carrying FVIII cDNA peaked at post-injection 1st week (5.19 +/- 0.14 ng/mL vs. 0.21 +/- 0.05 ng/mL in control rats , p < 0.05). Elevated hFVIII concentrations were maintained for 4 weeks (2.52 +/- 0.83 ng/mL vs. 0.17 +/- 0.08 ng/mL in control rats, p < 0.05) after a single intramuscular injection. In the Bethesda assay, neutralizing antibodies for FVIII protein were detected only in FVIII-LV injected rats by the 10th week, but not in control rats. CONCLUSION: This study suggested that a single administration of an advanced generation LV carrying the human FVIII cDNA resulted in elevation of FVIII level in immune competent rats, and that this gene transfer approach to the skeletal muscle could be an effective tool in treatment of hemophilia A.

The association of chemokine receptor 5 gene 59029A/G polymorphisms with diabetic nephropathy in type 2 diabetic patients / 대한내과학회지

BACKGROUND/AIMS: Chemokine receptor 5 (CCR5) is a receptor for several chemokines, including regulated upon activation, normal T-cell-expressed and -secreted (RANTES; also known as CCL5) and macrophage inflammatory protein 1 (MIP-1), and mediates the recruitment of monocytes and their differentiation to macrophages during the inflammatory process. As such, CCR5 plays an important role in the development and progression of atherosclerosis, which has an underlying inflammation component and contributes to the development or progression of diabetic complications. Several studies have reported that a genetic variation of the CCR5 gene with A/G at basepair 59029 (59029 A/G) was associated with diabetic complications, although conflicting data exist. We evaluated the association of the CCR5 59029 A/G polymorphism with diabetic complications in type 2 diabetes patients. METHODS: We conducted a case-control study, enrolling 325 patients with type 2 diabetes. We examined the association of CCR5 genotypic variations with diabetic nephropathy, retinopathy, and macrovascular complications such as coronary heart disease and stroke. Genotyping was performed using the polymerase chain reaction and restriction fragment length polymorphism technology with Bsp1286I restriction enzyme. RESULTS: We determined no allelic association of CCR5 59029 A/G with diabetic nephropathy (p=0.500) in the male or female patients. Diabetic retinopathy and macrovascular complications such as coronary heart disease and stroke were not associated with the 59029 A/G polymorphism. Among those patients with diabetic nephropathies, those with the GG genotype showed a tendency toward higher serum levels of LDL-cholesterol. CONCLUSIONS: These results suggest that that the 59029 A/G polymorphism of the CCR5 gene is not associated with diabetic complications in type 2 diabetes patients. Further studies are required to understand the role of CCR5 polymorphisms in the development of diabetic complications.

Systolic Time Interval on Hypertension

The duration of the phases of left ventricular systole was measured from simultaneous recordings of the electrocardiogram, phonocardiogram and carotid arterial pulse tracing using a multichannel photographic system with paper speed at 100 mm per second. Observations were made in 81 male and 66 female patients with hypertension and 41 healthy males and 38 healthy females who served as controls. All hypertension patients were classified by change in funduscopic finding, EKG and grade of diastolic pressure. STI were measured in each group and analysed. The resutls were as follows: 1. The normal PEP/LVET was 0.293 in male and 0.303 in female. 2. In male & female hypertensive patients, all STI were significantly difference to that of normal control except QA2. 3. In male hypertensive patients, the degree of EKG, funduscopic change and diastolic pressure were positive relation to the increase of PEP/LVET.