Debate: "How low should LDL cholesterol be lowered for optimum prevention of vascular disease?" Viewpoint: "Below 100 mg/dl"

Arteriosclerotic vascular disease manifests as heart disease, stroke, aortic aneurysms, and peripheral vascular disease, and is a growing problem world-wide. The preventive efforts made so far have demonstrated that lowering LDL-C is one action that individuals and populations can do with significant success in delaying the onset of clinical events. Epidemiological studies and small clinical trials suggest that more aggressive and sustained lowering to LDL-C below 100 mg/dl could result in 50 to 70% reductions in vascular death. The full benefit of reducing LDL-C is only now being tested in adequate clinical trials.     

A Review of the Adverse Effects of Peripheral Alpha-1 Antagonists in Hypertension Therapy

Background  

Doxazosin and its role as an antihypertensive agent have come under recent scrutiny as a result of the early termination of that treatment arm in ALLHAT. It is unclear why the cardiovascular (CV) event rate in this randomized, controlled trial (RCT), especially heart failure, is higher in those treated with a doxazosin-based regimen than with a chlorthalidone based-regimen. There has been little work in the past to summarize information on peripheral alpha-1 antagonists that may be helpful in evaluating the results of this randomized controlled trial.     

两株采自惠州的细鞘丝藻亚科(Leptolyngbyaceae)嗜热蓝细菌的分离鉴定及细胞组分分析

【背景】随着CO_2排放增加,全球变暖愈发严峻,嗜热蓝细菌作为能够在45°C及以上环境中生长并实现生物固碳的微生物,具有重要的研究意义。【目的】对从广东惠州地区采集的藻种进行分离鉴定,并筛选出2株嗜热蓝细菌,研究其生长特性,为嗜热蓝细菌的后续应用提供依据。【方法】通过16SrRNA基因、藻蓝蛋白链A基因(PhycoA)序列分析确定从惠州地区采集到的菌株的分类学位置。对PKUAC-GDTS1-24和PKUAC-GDTS1-29两株嗜热蓝细菌进行形态观察和主要细胞成分(灰分、糖类、脂质、蛋白质和色素)分析。【结果】共分离出12株嗜热蓝细菌,其中PKUAC-GDTS1-24和PKUAC-GDTS1-29菌株,形态上呈蓝绿色球形毛状体,是由细胞形成密集的簇,彼此附着形成的。两株嗜热蓝细菌的主要细胞成分是糖类,分别占细胞干重的36.42%和28.46%。PKUAC-GDTS1-24的灰分、脂质和蛋白质含量分别为24.41%、21.40%和26.64%。PKUAC-GDTS1-29的细胞中,灰分、脂质和蛋白质含量分别为24.72%、23.92%和12.93%。藻蓝蛋白(Phycocyanin,PC)在PKUAC-GDTS1-24和PKUAC-GDTS1-29中的含量分别为157.29 mg/g DW和374.86 mg/g DW,类胡萝卜素分别为65.13 mg/g DW和18.87 mg/g DW。【结论】基于系统发育树研究,本实验的2个分离株属于细鞘丝藻亚科(Leptolyngbyaceae),与研究较少的纤发鞘丝蓝细菌属(Leptolyngbya)菌株相近,可能是广东和四川温泉中存在的一种新型丝状轻度嗜热蓝细菌属或Leptolyngbya新种。嗜热菌株PKUAC-GDTS1-24和PKUAC-GDTS1-29的形态和细胞组成相似,通过比较,2个菌株的藻胆蛋白含量远远高于其他研究报道的Leptolyngbya蓝细菌,尤其是PKUAC-GDTS1-29可以作为藻蓝蛋白生产的潜在菌株。     

Immunohistochemical characterization of mononuclear cells in delayed hypersensitivity reactions toParacoccidiodes brasiliensis (paracoccidioidin test)

The density and distribution of T cells, T helper cells, macrophages and B cells at the site of skin tests with a cytoplasmicParacoccidioides brasiliensis antigen (paracoccidioidin) was studied at 24 and 48 h post-challenge in 10 patients with the chronic form of paracoccidioidomycosis and in 5 non-infected individuals. The in situ study was carried out using immunoperoxidase techniques and monoclonal antibodies. The controls showed negative skin test. In the patients, the great majority of the cells in the perivascular foci were T cells (CD43-positive cells) making up 47% and 48.6% of the total number of cells at 24 and 48 h respectively. Most of the T cells showed a T helper phenotype (CD45RO-positive cells). Approximately 25% of the cells were macrophages (CD68-positive cells) and there were very few B lymphocytes (CD20-positive cells). The present data on the microanatomy of paracoccidioidin skin test sites were consistent with a delayed type hypersensitivity pattern. Our results were comparable to those reported on skin tests for other granulomatous chronic diseases.     

Corticosteroid reduces blood flow to femoral heads in rabbits

Avascular necrosis of the femoral head is one of the common problems in orthopedic practice in Taiwan. The subchondral bone loses its blood supply which weakens its biomechanical support. Steroid overuse is one of many possible etiologies in reducing blood flow to the femoral head. Laser Doppler velocimeter is a precise monitor of regional blood flow of bone which is expressed in perfusion units (PU). In the control group the rabbits were injected with normal saline and there were no statistical differences between blood flow to the right hip (39.26±5.64 PU) and left hip (38.58±4.35 PU). In group B a weekly injection of methylprednisolone into rabbits for 6 weeks demonstrated the reduction of blood flow of femoral head (24.74±3.13 PU) by the laser Doppler velocimeter. The flow decreased further (15.93±2.33 PU) by 12 weeks of steroid treatment. In group C after a weekly injection of steroid for 6 weeks the flow became 31.63±4.79 PU. The steroid was then discontinued for 3 weeks and the flow was 34.6±1.34 PU. In group D the blood flow was 25.89±4.01 PU after 6 weeks of steroid treatment and we stopped the steroid for 6 weeks, the blood flow became 29.86±2.59 PU. The merit of our experiment established a model of study in avascular necrosis of the femoral head in rabbits.     

Improvement of long-term prognosis in patients with ovarian cancers by adjuvant sizofiran immunotherapy: a prospective randomized controlled study

The effect of immunotherapy using sizofiran (SPG) on the prognosis of patients with ovarian cancers was prospectively studied in a total of 68 patients, who were randomly assigned to either a cisplatin, adriamycin and cyclophosphamide (PAC) therapy group or a PAC plus SPG combination therapy group.The survival rate was significantly higher in patients with stage Ic, II or III cancers treated with the PAC plus SPG combination, compared with the patients treated with PAC alone. In the SPG-receiving patients with stage Ic or more advanced cancers who were treated with four cycles or more of PAC, the outcome was improved (Cox-Mantel, p=0.074; generalized Kruskal-Wallis, p=0.032). Similar improvement was also observed in the patients with non-serous adenocarcinomas (Cox-Mantel, p-0.076; generalized Krukal-Wallis, p=0.045). No side effects attributable to SPG were recorded.The present results suggest that the use of SPG in combination with long-term chemotherapy improves the postoperative prognosis in ovarian cancer patients.Abbreviations SPG sizofiran     

Improved analyses of human mtDNA sequences support a recent African origin for Homo sapiens

New quantitative methods are applied to the 135 human mitochondrial sequences from the Vigilant et al. data set. General problems in analyzing large numbers of short sequences are discussed, and an improved strategy is suggested. A key feature is to focus not on individual trees but on the general "landscape" of trees. Over 1,000 searches were made from random starting trees with only one tree (a local optimum) being retained each time, thereby ensuring optima were found independently. A new tree comparison metric was developed that is unaffected by rearrangements of trees around many very short internal edges. Use of this metric showed that downweighting hypervariable sites revealed more evolutionary structure than studies that weighted all sites equally. Our results are consistent with convergence toward a global optimum. Crucial features are that the best optima show very strong regional differentiation, a common group of 49 African sequences is found in all the best optima, and the best optima contain the 16 !Kung sequences in a separate group of San people. The other 86 sequences form a heterogeneous mixture of Africans, Europeans, Australopapuans, and Asians. Thus all major human lineages occur in Africa, but only a subset occurs in the rest of the world. The existence of these African-only groups strongly contradicts multiregional theories for the origin of Homo sapiens that require widespread migration and interbreeding over the entire range of H. erectus. Only when the multiregional model is rejected is it appropriate to consider the root, based on a single locus, to be the center of origin of a population (otherwise different loci could give alternative geographic positions for the root). For this data, several methods locate the root within the group of 49 African sequences and are thus consistent with the recent African origin of H. sapiens. We demonstrate that the time of the last common ancestor cannot be the time of major expansion in human numbers, and our results are thus also consistent with recent models that differentiate between the last common ancestor, expansion out of Africa, and the major expansion in human populations. Such a two-phase model is consistent with a wide range of molecular and archeological evidence.      

Growth conditions differentially affect the constitutive expression of primary response genes in cultured cereballar granule cells

Cultured cerebellar granule cells underwent apoptotic degeneration when grown in medium containing 10 instead of 25 mM K⁺. Knowing that apoptosis is associated with changes in the expression of primary response genes, we have measured c-fos, zif/268, and c-jun mRNA levels during maturation of cultured granule cells grown in 10 or 25 mM K⁺. The constitutive expression of c-fos and zif/268 was differentially regulated by extracellular K⁺ concentration at 5 days of maturation in vitro (DIV), when cells grown under suboptimal conditions (i.e. in 10 mM K⁺) are committed to degenerate. At this stage, c-fos mRNA levels were detectable only in cultures grown in 25 mM K⁺, whereas zif/268 mRNA levels were dramatically elevated in cultures grown in 10 mM K⁺. This provides one of the few conditions in which c-fos and zif/268 are differentially regulated in nerve cells. Substantial changes in c-jun, or -actin mRNA levels were detectable only at 7 DIV, when the percentage of apoptotic cells had already reached a plateau in ultures grown in 10 mM K⁺. We speculate that changes in the expression of zif/268 are important in the gene program associated with the induction of apoptosis by trophic deprivation in cultured neurons.Special issue dedicated to Dr. Robert Balázs     

Intensive hemodialysis and hemoperfusion treatment of Amanita mushroom poisoning

Over a period of fifteen years, 41 patients including 23 males and 18 females with Amanita mushroom poisoning were treated at the University Hospital of Lund, Sweden. The intensity of poisoning was graded according to serum transaminase elevations and prothrombin time reductions. Severity was mild in 16 patients (Group A), moderate in 14 (Group B) and severe in 11 (Group C). Members of Group C reported shorter latency periods before the onset of symptoms, (10±1 hours,p<0.05) and longer delays in treatment, (34±4 hours), than did the other patients. Intensive treatment was begun before the results of urine amatoxin assays were reported. Treatment consisted of: fluid and electrolyte replacement, oral activated charcoal and lactulose, IV penicillin, combined hemodialysis and hemoperfusion in two 8 hour sessions, some received IV thioctic acid, others IV silibinin, all received a special diet. This combination of treatment modalities was used to accelerate the elimination of amatoxin from the patients' bodies. The longest period of hospitalization, 13±2 days, was required by the patients of Group C (p<0.01). All patients improved and were discharged from the hospital asymptomatic. No sequelae were later reported for the majority of those moderately and severely poisoned. We have concluded that intensive combined treatment applied in these cases is effective in relieving patients with both moderate and severe amanitin poisoning.