Evaluation of therapeutic potency of human papillomavirus-16 E7 DNA vaccine alone and with interleukin-18 as a genetic adjuvant / Avaliação da potência terapêutica da vacina de DNA do papilomavírus humano-16 E7 isolada e com interleucina-18 como adjuvante genético

AIMS: Despite the existence of effective preventive vaccines for human papillomavirus (HPV), therapeutic vaccines that trigger cell-mediated immune responses are required to treat established infections and malignancies. The aim of this study was to evaluate the therapeutic potency of HPV-16 E7 deoxyribonucleic acid (DNA) vaccine alone and with interleukin (IL)-18. METHODS: In vitro expressions of IL-18 were performed on human embryonic kidney 293 cells and confirmed it by Western blotting methods. DNA vaccine was available from a previous study. A total of 45 female C57BL/6 mice divided into five groups (DNA vaccine, DNA vaccine adjuvanted with IL-18, pcDNA3.1, and phosphate buffer saline) were inoculated with murine tissue culture-1 cell line of HPV related carcinoma, expressing HPV-16 E6/E7 antigens. They were then immunized subcutaneously twice at a seven-day interval. The antitumor and antigen specific-cellular immunity were assessed by lymphocyte proliferation (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide: MTT) assay, lactate dehydrogenase release assay, IL-4 assay and interferon-gamma (IFN-γ) assay. Tumor size was followed for 62 days. RESULTS: MTT assay, which measures the lymphocyte proliferation in response to the specific antigen, increased in the co-administration and the DNA vaccine groups as compared to control and genetic adjuvant groups (p<0.001). The mice immunized with the co-administration generated significantly more IFN-γ and IL-4 than other immunized mice (p<0.001). Reduction of the tumor size in the co-administration and the DNA vaccine groups was significantly more pronounced than in the control and genetic adjuvant groups (p<0.001), but no statistically significant difference between DNA vaccine and co-administration groups (p=0.15) occurred. CONCLUSIONS: IL-18 as a genetic adjuvant and E7 DNA vaccine alone enhanced immune responses in mouse model systems against cervical cancer. However, using of IL-18 as a genetic adjuvant with E7 DNA vaccine had no significant synergistic effect on the immune responses in vivo.

OBJETIVOS: Apesar da existência de vacinas preventivas eficazes contra o papilomavírus humano (HPV), são necessárias vacinas terapêuticas que desencadeiem respostas imunes mediadas por células para tratar infecções e malignidades estabelecidas. O objetivo deste estudo foi avaliar a potência terapêutica da vacina de ácido desoxirribonucleico (DNA) HPV-16 E7 isolada e com interleucina (IL)-18. MÉTODOS: Expressões in vitro de IL-18 foram realizadas em células renais embrionárias humanas 293 e confirmadas por Western blotting. A vacina de DNA foi disponibilizada em um estudo anterior. Um total de 45 camundongos fêmeas C57BL/6 divididos em cinco grupos (vacina de DNA, vacina de DNA adjuvada com IL-18, pcDNA3.1 e solução salina tamponada com fosfato) e foram inoculados com linhagem murina-1 de carcinoma relacionado ao HPV, expressando antígenos E6 / E7 do HPV-16. Os animais foram então imunizados por via subcutânea duas vezes no intervalo de sete dias. A imunidade antitumoral e antígeno-celular específica foi avaliada pela proliferação de linfócitos (ensaio de brometo de 3- [4,5-dimetiltiazol-2-il] -2,5-difeniltetrazólio: MTT), ensaio de liberação de lactato desidrogenase, ensaio de IL-4 e ensaio de interferon-gama [IFN-γ]. O tamanho do tumor foi seguido por 62 dias. RESULTADOS: O ensaio MTT, que mede a proliferação de linfócitos em resposta ao antígeno específico, aumentou nos grupos de coadministração e de vacina de DNA em comparação aos grupos controle e adjuvante genético (p <0,001). Os camundongos imunizados com a coadministração geraram significativamente mais IFN-γ e IL-4 do que os outros camundongos imunizados (p<0,001). A redução do tamanho do tumor nos grupos de coadministração e de vacina de DNA foi significativamente mais acentuada do que nos grupos controle e adjuvante genético (p<0,001), mas não houve nenhuma diferença estatisticamente significativa entre os grupos vacina de DNA e coadministração (p=0,15). CONCLUSÕES: A IL-18 como adjuvante genético e a vacina de DNA E7 aumentaram as respostas imunes em sistemas modelo de camundongos contra o câncer cervical. No entanto, o uso de IL-18 como adjuvante genético com a vacina de DNA E7 não teve efeito sinérgico significativo nas respostas imunes in vivo.

Analysis of Informal Payments Among Hospitals Covered Under Tehran University of Medical Sciences[TUMS]2009

Informal health payment in several middle and low income countries is a serious impediment to health care reform. This payment is effectively a form of systemic corruption. Informal health payments have adverse impact on access and utilization of health services, efficiency, quality and equity. Informal payments lead to false information about the real costs of disease and the patient share of these costs and consequently wrong government policies. The objective of this paper is analyses of informal payments among hospitals covered under Tehran University of medical sciences [TUMS] 2009. In this cross- sectional study, we used random sampling and selected finally 3 hospitals. Then in a simple random sampling, we recruited 300 discharged patients from general, surgery, emergency, ICU and CCU wards. All of the data are collected by interview and questionnaire. We analyzed data with Chi- Square, T-test, Annova, Bonferroni. According to the findings, Of the total 300 respondents in the study sample, about 3.7% had requested informal payment. 21% of respondents reported at least one informal payment. Cash payments constituted the bulk of total informal payment [88.8%]. In the majority of the cases, the Patient paid for appreciation [55.6%]. All of the people who had paid informal payment, it has been paid to the servant and maid, Only in one case, in addition to the servant and maid, the Guardian has also been paid. None of the socio-economic characteristics of the family, Insurance status, type of referral, payment form [voluntary or solicited] were related to the size of informal payments. And there is a relationship between length of stay and size of informal payment [p-value=0.015]. There isn't relationship between these factors- except marital status [p-value=0.042] - and frequency of informal payments. It seems that training about informal payments properly, increasing health sector resources, increasing official income levels, improving quantity and quality of health services and Trying to change the opinions which believes informal payments are necessary [changing culture] can be effective in controlling informal payments

Risk factors of breast cancer in north of Iran: a case-control in Mazandaran Province.

INTRODUCTION: Breast cancer is the most common cancer among Iranian women. This study aimed to determine risk factors for breast cancer in the north of Iran. METHOD: A matched case-control study was conducted in Mazandaran province of Iran in 2004 of 250 biopsy proven cases of breast cancer and 500 neighbor controls that were matched by age within a 3 year period. Statistical analysis was carried out using conditional logistic regression with the backward elimination method and crude and adjusted odds ratios with related 95% CIs were estimated with Stata 8.0 software RESULTS: Multivariate analysis showed that higher education (OR=4.70, 95%CI: 1.71-12.88), late menopause (OR=4.18, 95%CI: 2.54-6.88), history of induced abortion (OR=1.62, 95%CI: 1.13-2.31), positive first-degree family history of breast cancer (OR=3.14, 95%CI: 1.37-7.20), and BMI (OR=1.02, 95%CI: 1.01-1.03) were risk factors for breast cancer. Furthermore, having more episodes of full term pregnancy (OR=0.87, 95%CI: 0.80-0.95), longer duration of breast feeding (OR=0.993, 95%CI: 0.989-0.997) and parity more than 2 were shown to be protective factors. CONCLUSIONS: Our study revealed the role of some modifiable determinants of breast cancer that can be focused by public health intervention in the northern community of Iran. Accordingly, the women who have one or more of the following risk factors should take the special attention to risk of breast cancer: obesity, being menopause, positive family history of breast cancer and history of induced abortion. The protective effect of longer duration of breast feeding should be encouraged too.