Change of Selection to Antihypertensive Drugs in Hypertensive Patients with Diabetes Mellitus: In Pohang . Gyeongju Primary Care Research Network / 가정의학회지

BACKGROUND: Angiotensin converting enzyme inhibitors (ACEIs) or Angiotensin II type 1 receptor blockers (ARBs) are compelling indication drugs for hypertensive patients with diabetes mellitus. But prescription rate in 2005 year study of Pohang . Gyeongju area was only 30.8%. Therefore, a study on the change of prescription rate in the same area after 3 years was done. METHODS: During three months from January 2008, 152 hypertensive patients with diabetes mellitus on their prescribed antihypertensive medications by 9 family physicians in visiting order were analyzed. After the analysis, the infl uencing factors for such prescriptions were ascertained by directly visiting each physicians who prescribed them. RESULTS: A regimen of 16 antihypertensive agents were prescribed by these family physicians. Prescription count of ACEIs or ARBs was 101 cases (66.4%). ACEIs single therapy was 19 cases (12.5%), ACEIs combination therapy was 7 cases (4.6%), ARBs single therapy was 31 cases (20.4%) and ARBs combination therapy was 44 cases (28.9%). The ACEIs or ARBs which were selected by physicians that followed "compelling indication" was 5 (55.6%), "excellent reduce pressure effect" was 3 (33.3%) and "public relations of new medicine" was 1 (11.1%). CONCLUSION: In prescribing antihypertensive agents for patients with diabetes mellitus, selection of ACEIs or ARBs was increased from 30.8% to 66.4%. Education of recommended standard by participating in such study and developing of excellent new medicines may increase such change.

Adenovirus-Mediated Antisense Vector-Induced Inhibition of Human Telomerase RNA May Induce Differentiation of CD34+ Cells

BACKGROUND: Background Telomerase activation and human telomerase RNA (hTR) expression are known to be related to the preservation of the "stemness" of stem cells. In this study, we have inhibited the expression of hTR to find the relationship between the telomerase activity and differentiation of normal hematopoietic stem cells. METHODS: We used cord blood collected from 10 full term pregnant women. We classified the CD34+ hematopoietic stem cells from the same donor into three groups: the Ad-OA group was treated with the recombinant adenoviral (Ad) vector Ad-OA using telomerase antisense, the Ad-M6 group was treated with a mutant version of the Ad-OA without telomerase antisense, and a control group without any treatment. RESULTS: The mean number of colony-forming cells (CFCs) were 110+/-38 for the Ad-OA groups, 540+/-56 for the Ad-M6 groups, and 650+/-72 for the control groups. Thus, CFCs in the Ad-OA group were lower than in the Ad-M6 group (P<0.01). The myeloid portion of the CFCs in the Ad-OA group was higher than the Ad-M6 and control groups (P<0.01). The Ad-OA group showed a higher percentage of granulocytes suggesting more of a tendency for myeloid differentiation than the Ad-M6 and control groups (P<0.01). We found that the suppression of telomerase activity by the antisense telomerase adenovirus induced the differentiation of hematopoietic stem cells confirmed by differential cell count and cytochemical staining. CONCLUSION: These findings suggest that the activity of the telomerase may play a role in the differentiation of normal CD34+ hematopoietic stem cells into mature cells.

Manipulation of Human Telomerase Activity in Cancer and Stem Cells: Application of siRNA-induced Inhibition of Human Telomerase RNA (hTR)

BACKGROUND: We have determined the effects of human telomerase RNA inhibiton using siRNA in tumor cells and human embryonic and mesenchymal stem cells. METHODS: We selected the sequences against the predicted loop; these sequneces were comprised of nucleotides from 76 to 94 residues and from 143 to 163 residues as the target sequences, and we cloned these sequences into pU6sh75 and pU6sh143 cells. Three different kinds of cell lines were used: HeLa, SNUhES3, and human mesenchymal stem cells. The degree of inhibition of telomerase activity was assessed by TRAP assay and RT-PCR. RESULTS: The telomerase activity of the HeLa and SNUhES3 cells were 135.3+/-14.5 and 109.0+/-18.2; these cells showed higher activity than human mesenchymal stem cells and Wi38 cells (46.3+/-5.0 and 26.0+/-12.0), which were control cells. When each of the types of cells was treated with siRNA-hTR, the transfection efficiency of pU6sh75 for the HeLa, SNUhES3, and human mesenchymal stem cells was 91.0+/-8.4%, 83.3+/-16.0% and 81.9+/-12.3%, respectively. In the case of pU6sh143, its transfection efficiency was similar to pU6sh75; the HeLa, SNUhES3 and human mesenchymal stem cells tranfection efficiency was 90.1+/-9.0%, 79.9+/-18.2% and 79.4+/-15.1%, respectively. After two days of transfection, the level of telomerase activity in the pU6sh75 transfected cells decreased to 64.3+/-10.1% and 56.0+/-11.0% in the HeLa and SNUhES3 cells, respectively. When the cells were transfected with pU6sh143, the telomerase activity also decreased in the HeLa and SNUhES3 cells (71.3+/-9.1% and 61.6+/-8.3%, respectively). However, the difference of telomerase activity was not significant in the human mesenchymal stem cells: 43.0+/-7.2% with pU6sh75 and 46.0+/-9.0% with pU6sh143. CONCLUSION: Telomerase RNA inhibiton with siRNA may be a feasible way to inhibit the telomerase activity of human tumor and embryonic stem cells.

Selection of Antihypertensive Drugs in Hypertensive Patients with Diabetes Mellitus: In Pohang-Gyeongju Primary Care Research Network

BACKGROUND: Angiotensin converting enzyme inhibitor or Angiotensin II type 1 receptor blocker is usually recommended for hypertensive patients with diabetes mellitus. No reports have been made on antihypertensive agents prescribed for these patients in private practice. METHODS: During a one month period of December 2004, 169 hypertensive patients with diabetes mellitus on their prescribed antihypertensive agents by ten family physicians were analyzed. The influencing factors for such prescriptions were analyzed by directly visiting each physicians who prescribed them. RESULTS: A total of 21 antihypertensive agents were prescribed by these family physicians. Single calcium channel blocker therapy was the most common with 55 cases (32.5%), followed by 20 cases (11.8%) of single angiotensin converting enzyme inhibitor therapy and 16 cases of single therapy of Angiotensin II type 1 receptor blocker. The low frequency of prescribing the Angiotensin II type 1 receptor blocker was due to insufficient effect (7), lack of information (5), resistance from the patients from changing the medications (4) and expensive costs (4). CONCLUSION: In prescribing antihypertensive agents for patients with diabetes mellitus, angiotensin converting enzyme inhibitor or Angiotensin II type 1 receptor blocker were chosen less. In order to decrease the incidence of complications in these patients, such agents should be prescribed more.

Inhibition of Melanoma Cell Lines Using Antisense Sequence Expressing Adenovirus and Cisplatin

PURPOSE: Telomerase is known to play a role of adding repetitive parts to chromosomal ending and to be involved in carcinogenic process through cell immortalization. The purpose of this study is to evaluate that restraining of telomerase activation can have killing effect on cancer cell and enhance susceptibility of cancer cells to anticancer substance. METHODS: The killing effect on melanoma cells was studied by using recombinant adenovirus that makes it possible to inhibit telomerase from getting activated, with such targets as two types of melanoma cell lines. This recombinant adenovirus was used combined with cisplatin, one of the most representative anticancer medicine to evaluate enhancement in susceptibility of cancer cells to anticancer substance. RESULTS: From the result of cytotoxic assay, it is found that melanoma cells have much resistance to cisplatin on the whole. In the case of using Ad-OA of recombinant virus alone, killing effect on melanoma cells was insignificant. On the other hand, when Ad-OA was used in combination with cisplatin, susceptibility of melanoma cell lines to cisplatin was enhanced. CONCLUSIONS: Ad-OA, recombinant adenovirus, could be used as a supplementary medicine in the targeted cancer gene therapy against cancer cell lines resistant to cisplatin.

Treatment and Prognosis of Retinoblastoma: Clinicopathologic Analysis of 101 Cases

The clinicopathologic characteristics, treatments and prognosis of retinoblastoma, the most common intraocular tumor in children, were studied retrospectively in 101 cases(128eyes) who visited our clinic from 1987 to 1996. All patients were followed for 2 years or longer. Twenty seven cases were bilateral and seventy four cases were unilateral,. Eihgty four eyes were enucleated. Twenty one eyes were successfully treated by conservative modality. The rest refused any type of treatment. Orbital recurrence or distant metastasis were observed in 5 cases after enucleation without systemic treatment, and one died in spite of irradiation and aggressive chemotherapy. It is widely recognized that the prognosis for survival of retinoblastoma patients, especially unilateral, is excellent, however the authors emphasize the importance of careful postoperative histopathologic review and long term periodic follow-up to improve long-term prognosis.

Four Families of Hereditary Retinoblastoma

We analysed the clinical findings in four families of hereditary retinoblastoma. All four children with retinoblastoma were male. Two of them were diagnosed after two years of age and the remainder were before seven months of age. The relatives affected with retinoblastoma were one father, one mother, one sibling, and one second cousin of patients respectively. To our knowledge, this is the first report of hereditary retinoblastoma with family history in Korea.

Severe Head Injury:Clinical Prognostic Factors

A clinical analysis was carried out retrospectively with 54 cases of severe head injured patients(Glasgow Coma Scale score 3 to 8) to identify prognostic factors. Unawareness for over 1 month, abnormal papillary reaction, abnormal motor response pattern, and diffuse head injury with basal cisternal compression prove to be the most reliable predictors. Individual predictions of outcome provide a powerful too for assessing the relative efficacy of alternative treatments.