Cardiac apoptosis: from organ failure to allograft rejection

Cardiac myocyte apoptosis has been extensively studied in the last few years. Increased interest in the field stems from the hope that pharmacological manipulation of apoptosis may become a valuable tool for preventing excessive cell death observed in different pathological conditions. This paper is not intended as a comprehensive overview of current research about life and death in the cardiovascular system, but rather as a concise update on new developments in areas that were highlighted in a recent series of excellent reviews. A short inventory of unsolved issues concerning the significance of cardiac myocyte loss through apoptosis in both physiological and pathological circumstances is addressed.     

Bone aluminum uptake in uremic rats receiving intraperitoneal iron

To assess the effect of concomitant iron and aluminum loads on bone aluminum accumulation and on the response to the deferoxamine test in rats with the same aluminum surcharge, Wistar rats with chronic renal failure were divided into three groups: iron-overloaded rats (N=6) (intraperitoneal iron); iron-depleted rats (N=6) (blood withdrawal two to three times per week); control rats (N=4) (no manipulation). All groups received intraperitoneal aluminum simultaneously. After 6 wk, a deferoxamine challenge test was performed. Thereafter, bone aluminum and iron were measured. The iron-overloaded rats showed higher bone iron content (iron overloaded: 147.7±55.4 μg/g; iron depleted: 7.9±1.0, and controls 13.3±9.9 μg/g, p<0.010) and lower bone aluminum content (iron overloaded: 14.2±4.0 μg/g; iron depleted: 70.9±35.1 μg/g; controls: 72.7±28.3 μg/g p<0.005). No differences were found between the iron-depleted and control rats. After the deferoxamine infusion, the iron-depleted rats tended to have higher serum aluminum increments (p=NS) and higher urinary aluminum excretion (p<0.012, p<0.020) than control rats despite similar amounts of aluminum in bone of the two groups. Aluminum bone accumulation was minor if iron and aluminum loads were given concomitantly. The iron depletion influenced the results of the deferoxamine challenge test in rats with similar bone aluminum burden.     

压力超负荷心肌肥大晚期和心衰大鼠心肌力学及Ca2+反应性的改变

目的 :观测比较肥大心肌和衰竭心肌在基础力学性能、[Ca2 ]o 正性变力作用和Ca2 通道阻滞剂负性变力作用三方面的变化和差别。方法 :大鼠升主动脉缩窄法建立左心室肥大 (LVH)和充血性心衰 (CHF)模型 ,记录离体灌流乳头肌的长度 张力曲线 ,比较基础状态和nifidipine处理后 [Ca2 ]o 与峰张力的量效关系。结果 :①CHF组长度 张力曲线较LVH组和假手术对照组 (Sham)明显下移 ;基础状态下 ([Ca2 ]o=0 .5mmo1/L) ,LVH等长收缩峰张力 (PT)尚能维持 ,但CHF组PT分别低于LVH组和Sham组 37.9%和 43 .7% (P均 <0 .0 1) ;±dT/dtmax也较LVH组进一步下降 (P <0 .0 1) ;②各组峰张力随 [Ca2 ]o 的升高而增强 ,但CHF组 [Ca2 ]o 作用的量效曲线较LVH和Sham明显下移 ;③nifedjpine的负性肌力作用具明显剂量依赖性 ,但其抑制程度在三组间没有明显差异 (P>0 .0 5 )。结论 :肥大心肌以收缩强度不变区别于衰竭心肌的收缩低抑。两组收缩速度、舒张速率和 [Ca2 ]o 正变力效应的下降程度递增 ,但Ca2 通道阻滞剂的负变力效应均无改变。     

Reproductive physiology of female tilapia broodstock

Tilapiine fish have become one of the mostcommercially important groups of cultured freshwaterfish with in excess of 850 000 tonnes producedannually in a range of countries (e.g. Thailand,Taiwan, China, Philippines, Belgium and the USA).However, poor broodstock productivity, owing to lowfecundity and asynchronous spawning cycles, remainsone of the most significant outstanding constraintsupon commercial tilapia production and its futureexpansion. This paper reviews current understanding ofthe reproductive physiology of tilapia with particularemphasis upon those factors deemed critical tosuccessful broodstock management. Special emphasis isplaced upon factors such as fecundity, egg size,spawning periodicity, ovarian development and theexogenous and endogenous regulatory mechanismsinvolved in their control. Mouthbrooding speciesexhibit higher levels of parental care but fecundityis lower and egg size larger than insubstrate-spawning species. Fecundity, the number ofeggs oviposited per spawning act, can be < 350 inmouthbrooders such as Oreochromis mossambicus(Peters) but can exceed 12 000 in substrate-spawnerssuch as Tilapia zillii (Gervais). Eggs producedby mouthbrooders normally exceed 2 mm in diameterwhilst those of substrate spawners average only 1.5 mm.Interspawning intervals of mouthbrooders generallyaverage 30–50 days whether the fish are held in natural orartificial conditions, although substrate-spawningspecies such as Tilapia zillii can re-spawnafter only 6 or 7 days. The dynamics of theasynchronous pattern of ovarian development adopted bytilapiines are complex and result in the ovary beingdominated by late-vitellogenic/maturing oocytes asearly as 8–10 days after spawning. Advancement ofour understanding of these key areas will be essentialif the present constraints on tilapia culture are tobe overcome.     

Over-exploitation of a broadcast spawning marine invertebrate: Decline of the white abalone

Marine invertebrates have long been consideredto be resistant to overfishing. However, agrowing number of exploited taxa have declinedsubstantially and even disappeared from partsof their former range. We consider the case ofthe white abalone (Haliotis sorenseni);the first marine invertebrate proposed for theUS endangered species list. This high-valuespecies was one of five abalones targeted inthe California and Mexico fisheries; it is nowrare and protected from fishing. The biologicalcharacteristics of this deep-living abaloneindicate that it was particularly vulnerable toover-exploitation; reduction of density orgroup size is now known to lead to declines infertilization success and recruitment failure.Warning signs of potential problems existedboth pre- and post-exploitation but were notrecognized. In particular, serial depletion wasnot detected because catch was not analyzedspatially, perhaps because total landings werereasonably stable for the short period ofexploitation. Recent submersible surveys led toestimates that white abalone now number lessthan 2,600 animals or 0.1% of the estimatedpre-exploitation population size. Densities andestimated population sizes are less than 100animals, at all but one location. Alternateexplanations for the decline in abundance wereconsidered and only exploitation-linkedfactors, such as sub-legal mortality andillegal fishing, were likely contributors.Episodic recruitment appears to be acharacteristic of broadcast-spawning,long-lived species and may make themparticularly vulnerable to over-exploitation.Management strategies based on size limits thatallow a few years of spawning prior to reachingminimum legal size are insufficient.Sustainable fisheries will require multipleprotected areas to preserve brood stockaggregations necessary for successfulfertilization.     

Expression of nm23-H1 gene product in thyroid,ovary, and breast cancers

The nm23 gene product is one of several possible mediators of cancer invasion and metastasis. As the amounts of nm23-H1 mRNA and gene product are reduced in metastatic lymph nodes from patients with papillary carcinoma of the thyroid, we examined the expression of nm23 gene product in 115 thyroid cancers, 78 ovarian cancers, 63 breast cancers, and metastatic lymph node tissues by immunohistochemistry. It was found that nm23-H1, but not nm23-H2 gene product, was expressed in primary sites of thyroid, ovarian, and breast cancers, except for medullary and anaplastic carcinomas of the thyroid, but expressed only weakly or poorly in metastatic lymph nodes. Although nm23-H1 gene product expression was lower in anaplastic and medullary carcinomas of the thyroid, there was no significant difference in nm23-H1 gene product expression among histological types of ovarian and breast cancers. Our data indicate that the nm23-H1 gene product may play a role in metastasis in these hormone-producing organs and that other factors may be involved in metastasis of anaplastic and medullary carcinomas of the thyroid.     

Induced pluripotent stem cells as a tool for gaining new insights into Fanconi anemia

Induced pluripotent stem cells (iPSC) hold significant promise for advancing biomedical research. In the case of monogenic diseases, patient-iPSC and their derivatives contain the disease-causing mutation, suggesting the possibility of recapitulating salient disease features in vitro. Fanconi anemia (FA) is the most common inherited bone marrow failure syndrome. The etiology of bone marrow failure in FA remains largely unclear, but limited studies on patient bone marrow cells indicate cell intrinsic defects as causative. We examined the feasibility of modeling FA in a system based on hematopoietic differentiation of patient-specific iPSC. An informative iPSC-based model is predicated on the ability to derive disease-specific (uncorrected) patient iPSC that contain the disease-causing mutation, are pluripotent, maintain a normal karyotype and are capable of hematopoietic differentiation. Careful analysis of hematopoietic differentiation of such iPSC holds the promise of uncovering new insights into bone marrow failure and may enable high-throughput screening with the goal of identifying compounds that ameliorate hematopoietic failure. Ultimately, genetic correction, molecular characterization and successful engraftment of iPSC-derived cells may provide an attractive alternative to current hematopoietic stem cell-targeted gene therapy in some monogenic diseases, including FA.     

Physiology and development of the M and S molecular forms of Anopheles gambiae in Burkina Faso (West Africa)

In West Africa, M and S molecular forms of Anopheles gambiae sensu stricto (Diptera: Culicidae) Giles, frequently occur together, although with different population bionomics. The S form typically breeds in rain‐dependant water collections and is present during the rainy season only whereas the M form can thrive all year long in areas with permanent breeding opportunities. In the present study, we explored physiological and developmental trade‐offs at play in laboratory colonies and field populations of the M and S forms that originated from an area of sympatry in Burkina Faso, where M and S larvae exhibit such habitat segregation. In the laboratory, larvae of the M form developed slower than the S form (mean values 9.51 and 8.85 days, respectively, Wilcoxon's test, P < 0.001). Although wing length and dry weight at emergence showed large variations, M females were on average 8% heavier than S females of similar wing length. Higher nutritional reserves (proteins and lipids) in teneral adults explained part of this weight difference, reflecting a better ability of the M form to garner resources at the larval stage. Furthermore, a higher rate of ovarian maturation was observed in the M form after a single bloodmeal. The relevance of these findings for parasite transmission is discussed.     

Mitochondria in the human heart

The heart relies mainly on mitochondrial metabolism to provide the energy needed for pumping blood to oxygenate the organs of the body. The study of mitochondrial function in the human heart faces many obstacles and elucidation of the role of mitochondria in cardiac diseases has relied mainly on studies with animal models. Cardiac diseases are the leading cause of mortality worldwide. With the emergence of new therapies to treat and prevent heart disease, some aiming at metabolic modulation, a need for acquiring a better understanding of mitochondrial function in the human heart becomes apparent. Our review is aimed at specific evaluation of the human heart in terms of (1) methods to understand mitochondrial function, with particular emphasis on integrated function, (2) data on the role of mitochondrial dysfunction in cardiovascular disease, and (3) possible applications of this knowledge in the treatment of patients with cardiac disease.