1、喜树碱类衍生物抗HIV构效关系与作用机制研究2、HIV/AIDS患者疱疹病毒感染状况及性病患者的HIV感染状况分析

1、喜树碱类衍生物抗HIV构效关系与作用机制研究 喜树碱为传统的抗肿瘤药物。本研究对经过化学结构修饰的喜树碱类衍生物进行抗HIV活性及作用机制的研究，并初步探讨了其抗HIV构效关系。 我们对喜树碱类衍生物A系列化合物A1(喜树碱)、A2(10-羟基喜树碱)及A3(7-羟基喜树碱)进行了抗HIV活性检测。化合物A1和A3有较好的抗HIV-1和抗HIV-2活性，化合物A2没有显示抗HIV活性。表明化合物A1的C-10位上-OH基团修饰可能会降低抗HIV活性，化合物A1的C-7位上-CH2OH基团修饰和C-20位-CH3缺失可能会提高其抗HIV活性。对化合物A3和A1的抗HIV机制研究发现：二者对整合酶有一定的结合活性，对慢性感染H9/HIV-1ⅢB 和Jurkat/HIV-1ⅢB细胞中病毒复制没有抑制活性、不能阻断H9/HIV-1ⅢB与正常细胞间的融合，对重组的HIV-1蛋白酶和逆转录酶没有抑制活性。化合物A1和A3不具有选择性杀伤HIV-1ⅢB慢性感染的H9和Jurkat细胞系的作用。进一步进行化合物A3诱导 H9和H9/HIV-1ⅢB、Jurkat和Jurkat/HIV-1ⅢB的凋亡实验显示，化合物A3诱导感染HIV-1ⅢB和未感染病毒细胞的凋亡没有选择性。据此我们初步认为化合物A3和A1的抗HIV作用可能与抑制整合酶活性有关，该化合物可能还作用于其它靶点。 喜树碱类衍生物B系列中化合物B1为20(S)-O - [-O-( 1'-氧基-2',2',6',6'-四甲基哌啶-4'-丁二酸)]-20-喜树碱酯，化合物B2为20(S)-O - [-N-( 1'-氧基-2',2',6',6'-四甲基-1',2',5',6'-四氢吡啶酰胺)-4'-丙氨酸)]-20-喜树碱酯)。我们对化合物B1和B2进行了抗HIV活性检测。结果显示：化合物B2有较好的抗HIV-1和抗HIV-21、喜树碱类衍生物抗HIV构效关系与作用机制研究 喜树碱为传统的抗肿瘤药物。本研究对经过化学结构修饰的喜树碱类衍生物进行抗HIV活性及作用机制的研究，并初步探讨了其抗HIV构效关系。 我们对喜树碱类衍生物A系列化合物A1(喜树碱)、A2(10-羟基喜树碱)及A3(7-羟基喜树碱)进行了抗HIV活性检测。化合物A1和A3有较好的抗HIV-1和抗HIV-2活性，化合物A2没有显示抗HIV活性。表明化合物A1的C-10位上-OH基团修饰可能会降低抗HIV活性，化合物A1的C-7位上-CH2OH基团修饰和C-20位-CH3缺失可能会提高其抗HIV活性。对化合物A3和A1的抗HIV机制研究发现：二者对整合酶有一定的结合活性，对慢性感染H9/HIV-1ⅢB 和Jurkat/HIV-1ⅢB细胞中病毒复制没有抑制活性、不能阻断H9/HIV-1ⅢB与正常细胞间的融合，对重组的HIV-1蛋白酶和逆转录酶没有抑制活性。化合物A1和A3不具有选择性杀伤HIV-1ⅢB慢性感染的H9和Jurkat细胞系的作用。进一步进行化合物A3诱导 H9和H9/HIV-1ⅢB、Jurkat和Jurkat/HIV-1ⅢB的凋亡实验显示，化合物A3诱导感染HIV-1ⅢB和未感染病毒细胞的凋亡没有选择性。据此我们初步认为化合物A3和A1的抗HIV作用可能与抑制整合酶活性有关，该化合物可能还作用于其它靶点。 喜树碱类衍生物B系列中化合物B1为20(S)-O - [-O-( 1'-氧基-2',2',6',6'-四甲基哌啶-4'-丁二酸)]-20-喜树碱酯，化合物B2为20(S)-O - [-N-( 1'-氧基-2',2',6',6'-四甲基-1',2',5',6'-四氢吡啶酰胺)-4'-丙氨酸)]-20-喜树碱酯)。我们对化合物B1和B2进行了抗HIV活性检测。结果显示：化合物B2有较好的抗HIV-1和抗HIV-2活性，而化合物B1的抗HIV活性差。表明化合物B1的C-4’位-CH2被-NH取代，同时C-3’位-CH3修饰可能会提高其抗HIV活性。对化合物B2的抗HIV机制研究发现，化合物B2对慢性感染H9/HIV-1ⅢB细胞中病毒复制没有抑制活性、不能阻断H9/HIV-1ⅢB与正常细胞间的融合，对HIV-1蛋白酶、重组的HIV-1逆转录酶及整合酶没有抑制活性。化合物B2不具有选择性杀伤HIV-1ⅢB慢性感染的H9细胞系的作用。化合物B2抗HIV的作用机制还需进一步研究。 2、HIV/AIDS患者疱疹病毒感染状况及性病患者的HIV感染状况分析 疱疹病毒是AIDS患者合并感染的常见病原体。引起人类疾病的8种疱疹病毒与HIV感染及AIDS进展、机会性感染、恶性肿瘤密切相关。为了解HIV/AIDS患者人类8型疱疹病毒感染状况，我们检测了30例AIDS患者、40例HIV携带者及70例正常对照的液标本中8型疱疹病毒感染状况。采用ELISA法检测单纯疱疹病毒1型(HSV-1)、单纯疱疹病毒2型(HSV-2)、水痘-带状疱疹病毒(VZV)和巨细胞病毒(CMV)；采用PCR法检测EB病毒(EBV)、疱疹病毒6型(HHV-6)、疱疹病毒7型(HHV-7)及疱疹病毒8型(HHV-8)。结果显示，HIV/AIDS患者中HSV-1、HSV-2、VZV、CMV、HHV-6、HHV-8 阳性率均高于健康体检者，其中AIDS患者VZV感染率与HIV携带者有显著性差异；在AIDS患者中多种疱疹病毒共感染普遍存在，必须重视HIV/AIDS患者合并疱疹病毒感染的防治。 性病可促进HIV的传播，了解性病患者的HIV感染状况及临床特征具有重要的意义。在自愿接受HIV咨询检测的基础上，对临床确诊的412例性病患者进行HIV-1/2抗体检测，并对其临床特征进行分析研究。结果显示412例性病患者的HIV检出率为2.9%。性病患者中检出HIV阳性率依次为：尖锐湿疣(6.2%)、生殖器疱疹(4.2%)、梅毒(3.4%)、淋病(1.5%)及非淋菌性尿道炎(1.0%)。83.3%合并感染HIV的性病患者存在多性伴，商业性行为普遍存在，安全套使用率极低现象。感染HIV的尖锐湿疣及生殖器疱疹患者以频繁复发为突出表现，1例合并感染HIV的梅毒患者半年即进展为神经梅毒。性病患者是HIV感染的重要高危人群，危险性行为是其感染HIV和其它性病的主要原因，应该加强性病患者的HIV检测。对临床上频繁复发的尖锐湿疣及生殖器疱疹患者、快速进展的梅毒患者应高度怀疑合并HIV感染的可能。

Levantamento do Uso e Cobertura da Terra de Seis Áreas Amostrais Relacionadas ao Projeto BiosBrasil (Conservation and Sustainable Management of Below-Ground Biodiversity:Phase I), Município de Benjamin Constant (AM).

2005

Análisis de calidad de páginas web en español relacionadas con la nutrición y los TCA

SIN FINANCIACIÓN

HIV/AIDS and national security

McInnes, C., 'HIV/AIDS and national security', in: AIDS and Governance, N. Poku, A. Whiteside and B. Sandkjaer (eds.),(Aldershot: Ashgate, 2007), pp.93-111 RAE2008

Sinusite odontogénica

Monografia apresentada à Universidade Fernando Pessoa para obtenção do grau de Licenciada em Medicina Dentária.

Informe Final de actividades relacionadas en el plan de trabajo del contrato interinstitucional suscrito entre Artesanías de Colombia S. A. y la Alcaldía de Palmira, Valle del Cauca.

40 hojas : ilustraciones fotografías.

Shifting the Burden of HIV/AIDS

As the economic burden of HIV/AIDS increases in sub-Saharan Africa, the allocation of the burden among levels and sectors of societies is changing. The private sector has greater scope than government, households, or NGOs to avoid the economic burden of AIDS, and a systematic shifting of the burden away from the private sector is underway. Common practices that shift the AIDS burden from businesses to households and government include pre-employment screening, reduced employee benefits, restructured employment contracts, outsourcing of less skilled jobs, selective retrenchments, and changes in production technologies. In South Africa, more than two thirds of large employers have reduced health care benefits or required larger contributions by employees. Most firms have replaced defined benefit retirement funds, which expose the firm to large annual costs but provide long-term support for families, with defined contribution funds, which eliminate firm risk but provide little to families of younger workers who die of AIDS. Contracting out of previously permanent jobs also shields firms from costs while leaving households and government to care for affected workers and their families. Many of these changes are responses to globalization and would have occurred in the absence of AIDS, but they are devastating for employees with HIV/AIDS. This paper argues that the shifting of the economic burden of AIDS is a predictable response by business to which a thoughtful public policy response is needed. Countries should make explicit decisions about each sector’s responsibilities if a socially desirable allocation is to be achieved.

Why do Nigerian manufacturing firms take action on AIDS?

Objective: To identify differences between manufacturing firms in Nigeria that have undertaken HIV/AIDS prevention activities and those that have not as a step toward improving the targeting of HIV policies and interventions. Methods: A survey of a representative sample of registered manufacturing firms in Nigeria, stratified by location, workforce size, and industrial sector. The survey was administered to managers of 232 firms representing most major industrial areas and sectors in March-April 2001. Results: 45.3 percent of the firms’ managers received information about HIV/AIDS from a source outside the firm in 2000; 7.7 percent knew of an employee who was HIV-positive at the time of the survey; and 13.6 percent knew of an employee who had left the firm and/or died in service due to AIDS. Only 31.7 percent of firms took any action to prevent HIV among employees in 2000, and 23.9 percent had discussed the epidemic as a potential business concern. The best correlates of having taken action on HIV were knowledge of an HIV-positive employee or having lost an employee to AIDS (odds ratio [OR] 6.36, 95% confidence interval [CI]: 2.30, 17.57) and receiving information about the disease from an outside source (OR 7.83, 95% CI: 3.46, 17.69). Conclusions: Despite a nationwide HIV seroprevalence of 5.8 percent, as of 2001 most Nigerian manufacturing firm managers did not regard HIV/AIDS as a serious problem and had neither taken any action on it nor discussed it as a business issue. Providing managers with accurate, relevant information about the epidemic and practical prevention interventions might strengthen the business response to AIDS in countries like Nigeria.

Rationing Antiretroviral Therapy for HIV/AIDS in Africa: Efficiency, Equity, and Reality

Background: Rationing of access to antiretroviral therapy already exists in sub-Saharan Africa and will intensify as national treatment programs develop. The number of people who are medically eligible for therapy will far exceed the human, infrastructural, and financial resources available, making rationing of public treatment services inevitable. Methods: We identified 15 criteria by which antiretroviral therapy could be rationed in African countries and analyzed the resulting rationing systems across 5 domains: clinical effectiveness, implementation feasibility, cost, economic efficiency, and social equity. Findings: Rationing can be explicit or implicit. Access to treatment can be explicitly targeted to priority subpopulations such as mothers of newborns, skilled workers, students, or poor people. Explicit conditions can also be set that cause differential access, such as residence in a designated geographic area, co-payment, access to testing, or a demonstrated commitment to adhere to therapy. Implicit rationing on the basis of first-come, first-served or queuing will arise when no explicit system is enforced; implicit systems almost always allow a high degree of queue-jumping by the elite. There is a direct tradeoff between economic efficiency and social equity. Interpretation: Rationing is inevitable in most countries for some period of time. Without deliberate social policy decisions, implicit rationing systems that are neither efficient nor equitable will prevail. Governments that make deliberate choices, and then explain and defend those choices to their constituencies, are more likely to achieve a socially desirable outcome from the large investments now being made than are those that allow queuing and queue-jumping to dominate.

Treatment of HIV/AIDS at South Africa's Largest Employers: Myth and Reality

Background: In the past three years, many large employers in South Africa have announced publicly their intention of making antiretroviral treatment (ART) available to employees. Reports of the scope and success of these programs have been mostly anecdotal. This study surveyed the largest private sector employers in South Africa to determine the proportion of employees with access to ART through employer-sponsored HIV/AIDS treatment programs. Methods: All 64 private sector and parastatal employers in South Africa with more than 6,000 employees were identified and contacted. Those that agreed to participate were interviewed by telephone using a structured questionnaire. Results: 52 companies agreed to participate. Among these companies, 63% of employees had access to employer-sponsored care and treatment for HIV/AIDS. Access varied widely by sector, however. Approximately 27% of suspected HIV-positive employees were enrolled in HIV/AIDS disease management programs, or 4.4% of the workforce overall. Fewer than 4,000 employees in the entire sample were receiving antiretroviral therapy. In-house (employer) disease management programs and independent disease management programs achieved higher uptake of services than did medical aid schemes. Conclusions: Publicity by large employers about their treatment programs should be interpreted cautiously. While there is a high level of access to treatment, uptake of services is low and only a small fraction of employees medically eligible for antiretroviral therapy are receiving it.

The Private Sector and HIV/AIDS in Africa: Taking Stock of Six Years of Applied Research

Background: Until recently, little was known about the costs of the HIV/AIDS epidemic to businesses in Africa and business responses to the epidemic. This paper synthesizes the results of a set of studies conducted between 1999 and 2006 and draws conclusions about the role of the private sector in Africa’s response to AIDS. Methods: Detailed human resource, financial, and medical data were collected from 14 large private and parastatal companies in South Africa, Uganda, Kenya, Zambia, and Ethiopia. Surveys of small and medium-sized enterprises (SMEs) were conducted in South Africa, Kenya, and Zambia. Large companies’ responses or potential responses to the epidemic were investigated in South Africa, Uganda, Kenya, Zambia, and Rwanda. Results: Among the large companies, estimated workforce HIV prevalence ranged from 5%¬37%. The average cost per employee lost to AIDS varied from 0.5-5.6 times the average annual compensation of the employee affected. Labor cost increases as a result of AIDS were estimated at anywhere from 0.6%-10.8% but exceeded 3% at only 2 of 14 companies. Treatment of eligible employees with ART at a cost of $360/patient/year was shown to have positive financial returns for most but not all companies. Uptake of employer-provided testing and treatment services varied widely. Among SMEs, HIV prevalence in the workforce was estimated at 10%-26%. SME managers consistently reported low AIDS-related employee attrition, little concern about the impacts of AIDS on their companies, and relatively little interest in taking action, and fewer than half had ever discussed AIDS with their senior staff. AIDS was estimated to increase the average operating costs of small tourism companies in Zambia by less than 1%; labor cost increases in other sectors were probably smaller. Conclusions: Although there was wide variation among the firms studied, clear patterns emerged that will permit some prediction of impacts and responses in the future.

The Impact of AIDS on Government Service Delivery: The Case of the Zambia Wildlife Authority

Background: The loss of working-aged adults to HIV/AIDS has been shown to increase the costs of labor to the private sector in Africa. There is little corresponding evidence for the public sector. This study evaluated the impact of AIDS on the capacity of a government agency, the Zambia Wildlife Authority (ZAWA), to patrol Zambia’s national parks. Methods: Data were collected from ZAWA on workforce characteristics, recent mortality, costs, and the number of days spent on patrol between 2003 and 2005 by a sample of 76 current patrol officers (reference subjects) and 11 patrol officers who died of AIDS or suspected AIDS (index subjects). An estimate was made of the impact of AIDS on service delivery capacity and labor costs and the potential net benefits of providing treatment. Results: Reference subjects spent an average of 197.4 days on patrol per year. After adjusting for age, years of service, and worksite, index subjects spent 62.8 days on patrol in their last year of service (68% decrease, p<0.0001), 96.8 days on patrol in their second to last year of service (51% decrease, p<0.0001), and 123.7 days on patrol in their third to last year of service (37% decrease, p<0.0001). For each employee who died, ZAWA lost an additional 111 person-days for management, funeral attendance, vacancy, and recruitment and training of a replacement, resulting in a total productivity loss per death of 2.0 person-years. Each AIDS-related death also imposed budgetary costs for care, benefits, recruitment, and training equivalent to 3.3 years’ annual compensation. In 2005, AIDS reduced service delivery capacity by 6.2% and increased labor costs by 9.7%. If antiretroviral therapy could be provided for $500/patient/year, net savings to ZAWA would approach $285,000/year. Conclusion: AIDS is constraining ZAWA’s ability to protect Zambia’s wildlife and parks. Impacts on this government agency are substantially larger than have been observed in the private sector. Provision of ART would result in net budgetary savings to ZAWA and greatly increase its service delivery capacity.

How Much Does It Cost to Provide Antiretroviral Therapy for HIV/AIDS in Africa?

Background: Many African countries are rapidly expanding HIV/AIDS treatment programs. Empirical information on the cost of delivering antiretroviral therapy (ART) for HIV/AIDS is needed for program planning and budgeting. Methods: We searched published and gray sources for estimates of the cost of providing ART in service delivery (non-research) settings in sub-Saharan Africa. Estimates were included if they were based on primary local data for input prices. Results: 17 eligible cost estimates were found. Of these, 10 were from South Africa. The cost per patient per year ranged from $396 to $2,761. It averaged approximately $850/patient/year in countries outside South Africa and $1,700/patient/year in South Africa. The most recent estimates for South Africa averaged $1,200/patient/year. Specific cost items included in the average cost per patient per year varied, making comparison across studies problematic. All estimates included the cost of antiretroviral drugs and laboratory tests, but many excluded the cost of inpatient care, treatment of opportunistic infections, and/or clinic infrastructure. Antiretroviral drugs comprised an average of one third of the cost of treatment in South Africa and one half to three quarters of the cost in other countries. Conclusions: There is very little empirical information available about the cost of providing antiretroviral therapy in non-research settings in Africa. Methods for estimating costs are inconsistent, and many estimates combine data drawn from disparate sources. Cost analysis should become a routine part of operational research on the treatment rollout in Africa.

Children Affected by AIDS: A Review of the Literature on Orphaned and Vulnerable Children

This paper presents a systematic review of the literature pertaining to orphans and vulnerable children in sub-Saharan Africa, with a particular focus on research in countries heavily impacted by HIV/AIDS. Despite study and data limitations, the literature provides evidence of growing orphan-based disparities, difficulties within households providing care, and insufficient capacity among social services. Still, additional research is urgently needed, including better OVC surveillance methods, qualitative data than answers persisting questions, the inclusion of more useful indicators in national household surveys, and longitudinal studies to determine the mechanisms by which parental HIV status and death impacts children, caregiving impacts households, and the orphan epidemic impacts communities and social systems.