CpG oligonucleotide as an adjuvant for the treatment of prostate cancer

The use of an adenovirus transduced to express a prostate cancer antigen (PSA) as a vaccine for the treatment of prostate cancer has been shown to be active in the destruction of antigen-expressing prostate tumor cells in a pre-clinical model, using Balb/C or PSA transgenic mice. The destruction of PSA-secreting mouse prostate tumors was observed in Ad/PSA immunized mice in a prophylaxis study with 70% of the mice surviving long term tumor free. This successful immunotherapy was not observed in therapeutic studies in which tumors were established before vaccination and the development of anti-PSA immune response was not as easily generated in PSA transgenic mice. Immunization of conventional and transgenic animals was enhanced by incorporating a collagen matrix into the immunizing injection. Therefore the need to strengthen anti-PSA and anti-prostate cancer immunity was an obvious next step in developing a successful prostate cancer immunotherapy. Because the use of immunostimulatory CpG motifs was shown to enhance immune responses to a wide variety of antigens, our studies incorporated CpG into the Ad/PSA vaccine experimental plans. The results of the subsequent studies demonstrated a dichotomy where Ad/PSA plus CpG enhanced the in vivo destruction of PSA-secreting tumors and the survival of experimental animals, but revealed that the number and in vitro activities of antigen specific CD8+ T cells was decreased as compared to the values observed when the vaccine alone was used for immunization. The dichotomous observations were confirmed using another antigen system, OVA also incorporated into a replication defective adenovirus. Despite the reduction in antigen-specific CD8+ cells after vaccine plus CpG immunization the enhanced destruction of sc and systemic tumors was shown to be mediated entirely by CD8+ T cells. Finally, the reduction of the CD8+ T cells was the result of an observed decrease in the proliferation of the antigen specific cell population.     

Synthesis and anti-inflammatory evaluation of some pyrazolo[3,4-b]pyridines

Novel series of pyrazolo[3,4-b]pyridines with basic skeleton different from the known COX inhibitors were synthesized from 5-amino-1-[4-(aminosulfonyl)phenyl]-3-phenyl-1H-pyrazole, which in turn was prepared by the condensation of (4-sulfamoylphenyl)hydrazine with α-cyanoacetophenone. All the newly synthesized compounds were tested for their in vivo anti-inflammatory activity by carrageenan-induced rat paw edema assay. Some of the most potent compounds were evaluated in different COX and LOX assays. Some of the new compounds were found to possess moderate anti-inflammatory activity.     

Reducing out-of-pocket expenditures to reduce poverty: a disaggregated analysis at rural-urban and state level in India

Out-of-pocket (OOP) expenditure on health care has significantimplications for poverty in many developing countries. Thispaper aims to assess the differential impact of OOP expenditureand its components, such as expenditure on inpatient care, outpatientcare and on drugs, across different income quintiles, betweendeveloped and less developed regions in India. It also attemptsto measure poverty at disaggregated rural-urban and state levels. Based on Consumer Expenditure Survey (CES) data from the NationalSample Survey (NSS), conducted in 1999–2000, the shareof households’ expenditure on health services and drugswas calculated. The number of individuals below the state-specificrural and urban poverty line in 17 major states, with and withoutnetting out OOP expenditure, was determined. This also enabledthe calculation of the poverty gap or poverty deepening in eachregion. Estimates show that OOP expenditure is about 5% of total householdexpenditure (ranging from about 2% in Assam to almost 7% inKerala) with a higher proportion being recorded in rural areasand affluent states. Purchase of drugs constitutes 70% of thetotal OOP expenditure. Approximately 32.5 million persons fellbelow the poverty line in 1999–2000 through OOP payments,implying that the overall poverty increase after accountingfor OOP expenditure is 3.2% (as against a rise of 2.2% shownin earlier literature). Also, the poverty headcount increaseand poverty deepening is much higher in poorer states and ruralareas compared with affluent states and urban areas, exceptin the case of Maharashtra. High OOP payment share in totalhealth expenditures did not always imply a high poverty headcount;state-specific economic and social factors played a role. The paper argues for better methods of capturing drugs expenditurein household surveys and recommends that special attention bepaid to expenditures on drugs, in particular for the poor. Targetedpolicies in just five poor states to reduce OOP expenditurecould help to prevent almost 60% of the poverty headcount increasethrough OOP payments.     

Reduced expansion rate of abdominal aortic aneurysms in patients with diabetes may be related to aberrant monocyte-matrix interactions

Aims: Diabetes increases the risk of atherothrombosis, but reducesthe risk of abdominal aortic aneurysm (AAA). The reason forthis difference is unknown. We examined the role of diabetesand glycation on AAA expansion and extracellular matrix–monocyteinteractions. Methods and results: We followed 198 patients (20 with diabetes) who had 30–45mm AAAs with yearly aortic ultrasound for 3 years. Diabeteswas independently associated with reduced AAA growth (β= –0.17, P = 0.01; OR for expansion above median 0.18,95% confidence interval 0.06–0.57). In vitro incubationof resting human monocytes with glycated bovine serum albuminor monomeric type I collagen increased matrix metalloproteinase(MMP) secretion. In contrast, exposure of activated monocytesto glycated type I collagen lattices induced a marked reductionin MMP and interleukin-6 secretion. This de-activating effectwas also demonstrated in cross-linked non-glycated collagenlattices, healthy decellularized aortic media, and decellularizedaortic media from diabetes patients with atherosclerosis. Incontrast, decellularized aortic media from patients with atherosclerosis,but no diabetes, induced increased MMP secretion. Conclusion: These findings confirm that the progression of AAA is slowerin patients with diabetes and suggest a mechanism by which theaortic media may be protected from degradation in these individuals.     

枳■子黄酮类成分研究

从北枳（ＨｏｖｅｎｉａｄｕｌｃｉｓＴｈｕｎｂ）种子中首次分离并鉴定了４个黄酮类化合物，即双氢山奈酚（ｄｉｈｙｄｒｏｋａｅｍｐｆｅｒｏｌＩ）、槲皮素（ｑｕｅｒｃｅｔｉｎＩＩ）、（＋）３，３′，５′，５，７五羟基双氢黄酮［（＋）３，３′，５′，５，７ｐｅｎｔａｈｙｄｒｏｆｌａｖａｎｏｎｅＩＩ］和（＋）双氢杨梅黄素［（＋）ｄｉｈｙｄｒｏｍｙｒｉｃｅｔｉｎＩＶ］。其中ＩＩ为新化合物，Ｉ和ＩＶ为首次从该属植物中分到。