诊治病毒性心肌炎及炎症性心肌病的最新进展

1 病原 　　心肌炎是心肌的一种炎症性病变,可分为感染性和非感染性两大类.非感染性包括过敏或变态反应性心肌炎,如风湿性心肌炎以及理化和药物引起的中毒性心肌炎等.感染可由各种病原体引起,但目前除个别国家尚有相当数量的白喉杆菌及南美洲锥虫病(Chagas)引起的心肌炎外,绝大多数属病毒性心肌炎类(VMC)[1]. 　　……     

Beyond bone biology: Lessons from team science

Today, research in biomedicine often requires the knowledge and technologies in diverse fields. Therefore, there is an increasing need for collaborative team science that crosses traditional disciplines. Here, we discuss our own lessons from both interdisciplinary and transdisciplinary teams, which ultimately ushered us to expand our research realm beyond bone biology.     

Intermittent catheterization with single- or multiple-reuse catheters: clinical study on safety and impact on quality of life

International Urology and Nephrology - Intermittent catheterization (IC) is a proven effective long-term bladder management strategy for individuals who have lower urinary tract dysfunction. This...     

硝酸甘油对狗的心表冠状动脉和心肌微循环血流的影响

目的：探讨硝酸甘油(NTG)对狗心表冠状动脉和心肌微血管血流量的影响。方法：对10只雄性杂种狗静脉注射NTG后,应用心肌对比超声心动图测量心肌微血管血流量,动脉血流仪测量冠状动脉前降支血流量,超声心动图测量心脏腔径和容积。结果：NTG对心表冠状动脉和心肌微血管的血流量均无明显影响,注射NTG前后,前降支血流量为(13．91±2．91)ml/min对(14．59±4,63m)1/min；A·β值为：45．57±14．27对80．13±36．63,P均＞0．05；NTG对心率、血压、平均动脉压、中心静脉压和冠状动脉血管阻力也无明显影响。但可明显减少心脏腔径和心腔容积,尤其右心腔径和容积减少更明显；与舒张末期容积比较,NTG对心脏收缩末期容积影响更大。结论：NTG对狗的心表大冠状动脉和心肌微血管的血流量无影响,其抗心绞痛的作用可能是通过减少心脏容积和心室壁张力,减少心肌耗氧量而实现的。     

Evidence for an unidentified ACTH-induced steroid hormone causing hypertension.

The hypothesis that hyperaldosteronism is not the sole cause of hypertension in dexamethasone-suppressible hyperaldosteronsim was tested in an 18-year-old male. After six years of little or no treatment, the hypertension and mild hyperaldosteronism were promptly decreased by a small dose of dexamethasone. During dexamethasone treatment, when aldosterone secretion was suppressed to less than normal and he was normotensive, steroids were given by constant infusion in an attempt to reproduce the hypertension of the dexamethasone-free state. Neither five days of aldosterone or 18-hydroxydesoxycorticosterone (18-OH-DOC) at 1 mg/day, nor desoxycorticosterone (DOC) at 30 mg/day caused hypertension. However, sodium retention and potassium loss was observed during aldosterone and DOC infusion. Hypertension was produced within five days during infusion with ACTH or oral metyrapone. The hypertensive effect of the latter was abolished by addition of aminoglutethimide treatment. These studies suggest that a steroid other than aldosterone, 18-OH-DOC, or DOC may be the cause of the ACTH-induced hypertension in this patient. The aminoglutethimide data suggest that the ACTH effect on blood pressure is due to a steroid, and the metyrapone studies suggest that the steroid may be an 11-desoxysteroid. Urine and blood collected under ACTH stimulation and metyrapone treatment may be a rich source from which we may characterize this hormone.     

Induction of heat shock protein 70 mRNA in adult hamster facial nuclear groups following axotomy of the facial nerve

In this study, the effects of axotomy on heat shock protein 70 (hsp70) mRNA levels were analyzed by northern blot hybridization with a mouse-inducible hsp70 cDNA probe. The right facial nerve of adult golden hamsters was axotomized external to the skull, with the left nerve serving as sham-operated and internal control. Postoperative survival times were 0.5, 2, 6, 12, and 24 hr, with three to six animals per time point. Total RNA in the axotomized and control facial nuclear groups, dissected from the brain stem, was isolated by guanidinium-thiocyanate extraction and analyzed by northern hybridization and scanning densitometry. For normalization, the blots were rehybridized with a genomic cDNA probe complementary to the 28 S rRNA. At 0.5 hr postoperative, there was a 68% induction of hsp70 mRNA levels as compared to control. This increase peaked at 2 hr postoperative with a 280% induction and declined subsequently to 160% at 6 hr, 33% at 12 hr, and — 56% at 24 hr, relative to control levels. As a positive control, hyperthermia-induced hsp70 expression was established in hamster whole brain using northern blot hybridization and the mouse-inducible hsp70 cDNA probe. There was a 126% increase in hsp70 mRNA levels relative to control at 1.5 hr following hyperthermia. By 6.5 hr after the 1.5-hr hyperthermic period, there was a 40% decrease in hsp70 mRNA levels below control. The results provide the first evidence that peripheral axotomy acts as a cell stressor to induce the expression of hsp70 mRNA. Within our current understanding of the nerve cell body response to injury, the data represent the earliest changes in gene expression following axotomy reported thus far.     

Structure of human steroid 21-hydroxylase genes.

We have determined the structure of cDNA and two genomic genes encoding steroid 21-hydroxylase [21-OHase; steroid 21-monooxygenase; steroid, hydrogen-donor:oxygen oxidoreductase (21-hydroxylating); EC 1.14.99.10]. If this cytochrome P-450 enzyme is defective, cortisol cannot be synthesized, resulting in congenital adrenal hyperplasia. The cDNA encoding this enzyme is 2.0 kilobases long, and the encoded protein is predicted to contain 494 amino acid residues with a molecular weight of 55,000. This enzyme is at most 28% homologous to other P-450 enzymes that have been studied. The 21-OHase genomic genes, which are located in the HLA major histocompatibility complex on chromosome 6, each contain 10 exons. This structure is distinct from other characterized P-450 genes, which contain 7 or 9 exons. Studies of individuals with homozygous deletions of the 21-OHase A or B genes suggest that only the B gene encodes an active enzyme. This is confirmed by the finding that the A gene has an 8-base deletion within codons 110-112, resulting in a frameshift that brings a stop codon into the reading frame at codon 130. A second frameshift and a nonsense mutation occur downstream. In contrast, the sequence of the exons of the B gene is identical to the cDNA sequence. The 21-OHase A gene is, therefore, a pseudogene.     

Estrogen-eluting, phosphorylcholine-coated stent implantation is associated with reduced neointimal formation but no delay in vascular repair in a porcine coronary model.

Estrogen can inhibit intimal proliferation and accelerate endothelial regeneration after angioplasty. This suggests that estrogen may prevent in-stent restenosis. Unlike other therapies to prevent restenosis, estrogen may also not delay endothelial regrowth, thereby avoiding the risk of late stent thrombosis. The purpose of this work was to determine the effect of a 17beta-estradiol-eluting stent on neointimal formation in a porcine model. Each artery of six pigs was randomized to either a control, low-dose, or high-dose 17beta-estradiol-eluting stent. All animals were sacrificed at 30 days for histopathological analysis. There was a 40% reduction in intimal area in the high-dose stents compared with control stents (2.54 +/- 1.0 vs. 4.13 +/- 1.1 mm(2), for high dose vs. control, respectively; P < 0.05). There was complete endothelial regeneration at 30 days and similar inflammatory response to stenting on histopathology in all the stent groups. This is the first study to show that 17beta-estradiol-eluting stents are associated with reduced neointimal formation without affecting endothelial regeneration in the pig model of in-stent restenosis. Estrogen-coated stents may have a potential benefit in the prevention and treatment of in-stent restenosis.     

Functions of vasopressin and oxytocin in bone mass regulation

Prior studies show that oxytocin (Oxt) and vasopressin (Avp) have opposing actions on the skeleton exerted through high-affinity G protein-coupled receptors. We explored whether Avp and Oxtr can share their receptors in the regulation of bone formation by osteoblasts. We show that the Avp receptor 1α (Avpr1α) and the Oxt receptor (Oxtr) have opposing effects on bone mass: Oxtr^−/− mice have osteopenia, and Avpr1α^−/− mice display a high bone mass phenotype. More notably, this high bone mass phenotype is reversed by the deletion of Oxtr in Oxtr^−/−:Avpr1α^−/− double-mutant mice. However, although Oxtr is not indispensable for Avp action in inhibiting osteoblastogenesis and gene expression, Avp-stimulated gene expression is inhibited when the Oxtr is deleted in Avpr1α^−/− cells. In contrast, Oxt does not interact with Avprs in vivo in a model of lactation-induced bone loss in which Oxt levels are high. Immunofluorescence microscopy of isolated nucleoplasts and Western blotting and MALDI-TOF of nuclear extracts show that Avp triggers Avpr1α localization to the nucleus. Finally, a specific Avpr2 inhibitor, tolvaptan, does not affect bone formation or bone mass, suggesting that Avpr2, which primarily functions in the kidney, does not have a significant role in bone remodeling.Over the past decade, we have described direct actions of anterior and posterior pituitary hormones on the skeleton (1–8). We have shown that these actions are exerted via G protein-coupled receptors resident on both osteoblasts and osteoclasts. We also find that the skeleton is highly sensitive to the action of posterior pituitary hormones; for example, mice haploinsufficient in oxytocin (Oxt) have osteopenic bones, but lactation is normal; lactation is impaired only in Oxt^−/− mice (2). Likewise, Tshr haploinsufficient mice are completely euthyroid with normal thyroid follicles but display significant osteopenia (4). The exquisite sensitivity of the skeleton to pituitary hormones comes as no surprise, considering that the pituitary gland and the skeleton are both evolutionarily more primitive than target endocrine organs (7).Apart from the known actions of growth hormone on the skeleton, Tsh, Fsh, Acth, Oxt, and vasopressin (Avp) have all been shown to regulate the formation and/or function of both osteoblasts and osteoclasts and thus to control bone remodeling in vivo (2–4, 6–8). The two neurohypophyseal hormones Oxt and Avp have opposing functions (2, 3). Oxt stimulates and Avp inhibits osteoblast formation. Consequently, the genetic deletion of the Oxt receptor (Oxtr) and Avp receptor 1α (Avpr1α) yields opposing phenotypes, notably osteopenia in Oxtr^−/− mice and high bone mass in Avpr1α^−/− mice (2, 3). These findings may explain the rapid recovery of bone loss at weaning when plasma Oxt levels are high (9) and also the profound loss of bone noted in chronic hyponatremic states, such as the syndrome of inappropriate antidiuretic hormone secretion (SIADH), in which serum Avp levels are elevated (3).We find high levels of Oxtr expression on both osteoclasts and osteoblasts (2, 10), in addition to their abundant expression in breast and uterine tissue, where they regulate lactation and parturition, respectively (11). Avpr1αs, in contrast, are distributed more ubiquitously, whereas Avpr2s are localized mainly in the kidney, where they regulate free water excretion (12). Osteoblasts express both Avpr1α and Avrpr2 (3). The only other known isoform, Avpr1β, is expressed predominantly in the pancreas and pituitary; it regulates ACTH secretion from pituitary corticotrophs (13). Sequence alignment shows that the binding sites of the Oxtr and Avprs are highly conserved, with specific amino acids within the predicted binding pocket providing ligand selectivity (14–16). The respective ligands Oxt and Avp also are homologous nonapeptides, differing in only two amino acids, and are known to interact with the other’s receptor with different affinities (17).To our knowledge, osteoblasts and osteoclasts are the only cells in which Oxtr, Avpr1α, and Avpr2 are coexpressed. We also have shown that osteoblastic Oxtrs undergo internalization and nuclear translocation upon binding to Oxt and that this action is independent of cytosolic Erk phosphorylation (18). Avpr1α activation by Avp also activates Erk phosphorylation within minutes (3). The homology between the ligands and their respective receptors and converging downstream signals suggest that Avp and Oxtr may share receptors with opposing or convergent signals. Here, we have explored these interactions in the regulation of osteoblastic bone formation by using mice lacking one or both receptors, chemical inhibitors, and physiological models of high bone turnover.     

Washed red cells: theory and practice

Washing of red cells is sometimes performed to reduce allergic reactions due to contaminating plasma proteins or to reduce the concentration of potassium accumulating in the supernatant of red cells during storage as an alternative to transfusion of fresher red cells in patients at risk of hyperkalaemia. There are a variety of methods for washing red cells, and the laboratory data suggest that variables such as age of red cell before washing, washing method and solution, storage medium and length of storage time after washing can all effect the final red cell quality. Studies suggest that washing removes 90–95% plasma, but the proportion of units below 0·05 mg/dl IgA (equivalent to IgA deficient) is variable dependent upon methods used. Although potassium levels are reduced immediately following washing, the rate of leakage following subsequent storage is method-dependent, requiring careful consideration of shelf life if potassium reduction is the goal. Other markers of red cell quality such as haemolysis are negatively impacted by washing so a reduced shelf life compared to standard red cells is appropriate, especially following irradiation. Data from animal models and clinical studies on possible additional benefits of washing, such as reduced lung or kidney injury, are mixed, ranging from some benefit to some harm, and further studies are warranted.