The distribution of erythrocyte phospholipids in hereditary spherocytosis demonstrates a minimal role for erythrocyte spectrin on phospholipid diffusion and asymmetry

In the human erythrocyte membrane phosphatidylcholine and sphingomyelin reside mainly in the outer leaflet, whereas the aminophospholipids, phosphatidylethanolamine and phosphatidylserine, are mainly found in the inner leaflet. Maintenance of phospholipid asymmetry has been assumed to involve interactions between the aminophospholipids and the membrane skeleton, in particular spectrin. To investigate whether spectrin contributes to maintaining the phospholipid transbilayer distribution and kinetics of redistribution, we studied erythrocytes from hereditary spherocytosis patients whose spectrin levels ranged from 34% to 82% of normal. The phospholipid composition and the accessibility of membrane phospholipids to hydrolysis by phospholipases were in the normal range. Spin-labeled phosphatidylserine and phosphatidylethanolamine analogues that had been introduced into the outer leaflet were rapidly transported at 37 degrees C to the inner leaflet, whereas the redistribution of spin-labeled phosphatidylcholine was slower. The kinetics of transbilayer movement of these spin-labeled phospholipid in all samples was in the normal range and was not affected by the level of spectrin. Although these erythrocyte membranes contained as little as 34% of the normal level of spectrin and were characterized by several physical abnormalities, the composition, distribution, and transbilayer kinetics of the phospholipids were found to be normal. We therefore conclude that spectrin plays, at best, only a minor role in maintaining the distribution of erythrocyte membrane phospholipid.     

Alpha-receptor restriction of coronary blood flow during atrial fibrillation

The effects of atrial fibrillation (AF) on coronary circulation before and after alpha-receptor blockade were studied in 14 anesthetized, open-chest dogs. AF was induced by electrical stimulation of the left atrial appendage; identical rhythmic heart rates were adjusted by left atrial pacing. During atrial pacing, coronary vascular resistance (CVR) was 0.97 +/- 0.10 mm Hg X min X 100 g/ml (resistance units [RU]), coronary blood flow (CBF) 125 +/- 14 ml/min X 100 g, and oxygen saturation 30 +/- 2%; plasma epinephrine was 193 +/- 42 pg/ml and norepinephrine 584 +/- 111 pg/ml. During AF, CVR was higher (1.16 +/- 0.11 RU, p less than 0.0005), whereas CBF (92 +/- 9 ml/min X 100 g, p less than 0.001) and coronary sinus oxygen saturation (24 +/- 2%, p less than 0.0025) were lower than during atrial pacing. When AF was induced, epinephrine increased to 333 +/- 98 pg/ml (p less than 0.05) and norepinephrine to 1,005 +/- 214 pg/ml (p less than 0.005). The large increase in plasma catecholamines suggested an activation of the sympathoadrenal system during AF. In addition, the alpha-receptor blocker phenoxybenzamine (10 mg/kg, intravenously) abolished the differences in CVR, CBF and oxygen saturation between AF and atrial pacing. The data suggest that the decrease in CBF and increase in CVR during experimentally induced AF are caused by coronary vasoconstriction, mediated by sympathetic activation of alpha receptors in the coronary vascular bed.     

Phospholipase A2 levels in acute chest syndrome of sickle cell disease

Acute chest syndrome (ACS) is associated with significant morbidity and is the leading cause of death in patients with sickle cell disease (SCD). Recent reports suggest that bone marrow fat embolism can be detected in many cases of severe ACS. Secretory phospholipase A2 (sPLA2) is an important inflammatory mediator and liberates free fatty acids, which are felt to be responsible for the acute lung injury of the fat embolism syndrome. We measured SPLA2 levels in 35 SCD patients during 20 admissions for ACS, 10 admissions for vaso-occlusive crisis, and during 12 clinic visits when patients were at the steady state. Eleven non-SCD patients with pneumonia were also evaluated. To determine if there was a relationship between sPLA2 and the severity of ACS we correlated SPLA2 levels with the clinical course of the patient. In comparison with normal controls (mean = 3.1 +/- 1.1 ng/mL), the non- SCD patients with pneumonia (mean = 68.6 +/- 82.9 ng/mL) and all three SCD patient groups had an elevation of SPLA2 (steady state mean = 10.0 +/- 8.4 ng/mL; vaso-occlusive crisis mean = 23.7 +/- 40.5 ng/mL; ACS mean = 336 +/- 209 ng/mL). In patients with ACS sPLA2 levels were 100- fold greater than normal control values, 35 times greater than values in SCD patients at baseline, and five times greater than non-SCD patients with pneumonia. The degree of SPLA2 elevation in ACS correlated with three different measures of clinical severity and, in patients followed sequentially, the rise in SPLA2 coincided with the onset of ACS. The dramatic elevation of SPLA2 in patients with ACS but not in patients with vaso-occlusive crisis or non-SCD patients with pneumonia and the correlation between levels of SPLA2 and clinical severity suggest a role for SPLA2 in the diagnosis and, perhaps, in the pathophysiology of patients with ACS.     

民办医学院校专科教学改革的探讨

该研究以山东万杰医学院为例,针对目前招生规模越来越大,生源质量不断下滑,大面积学生逃学、厌学、考试成绩不及格的严峻现实,提出有关教学方法、教学内容和考核方式的教学三项改革,这三项改革举措顺应了当前高校教育(特别是民办高校教育)形势的发展趋势。通过改革实践,已初见成效,进一步验证了只有坚定不移地搞好教学三项改革,才能保证和提高教学质量,从而使广大学生及其家长的利益得到充分保障;也只有大张旗鼓地继续搞好教学三项改革,学校才有生存和可持续发展的空间。     

Coronary collateral flow: effect of drugs and perfusion pressure

Summary In 35 mongrel dogs acute myocardial infarction was produced by ligating the anterior descending branch of the left coronary artery and subsequent embolization of the peripheral area of the descending branch with microspheres. Retrograde flow and coronary retrograde pressure were measured before and after embolization as well as after embolization before and during the action of coronary dilating drugs. After embolization, the mean retrograde flow represented the whole coronary collateral flow, and the retrograde pressure equalled the true coronary collateral perfusion pressure. Following embolization, the mean retrograde pressure significantly increased from 20±2 to 69±3 mm Hg, i.e. to 73% of the mean aortic pressure. There was a simultaneous rise in retrograde flow from 3.99±0.78 to 6.19±1.16 ml/(min · 100 g), i.e. 12% of the antegrade perfusion. A significant correlation between coronary collateral flow and collateral perfusion pressure could be demonstrated. The average increase in collateral flow was 1.14 ml/(min · 100 g), i.e. 21 %, when the perfusion pressure rose from 70 to 80 mm Hg.After drug infusions, a slight increase in coronary collateral flow was observed, provided that the perfusion pressure remained unchanged. This increase was significant after nitroglycerine (+ 13±3 %) and after papaverine (+ 11±5%). When the perfusion pressure decreased, there was a decrease in collateral flow. When, however, under isoproterenol the decreased perfusion pressure was brought back to control level my means of a blood infusion, the collateral flow also increased and was then slightly, but significantly, above control (+ 4%).It can be concluded that, provided the perfusion pressure remains constant, the application of coronary dilating drugs can slightly improve the coronary collateral flow. This small effect might be of vital importance for the treatment of myocardial infarction. Myocardial steal only appeared when the perfusion pressure decreased.

---

Über den Einfluß von Pharmaka und des Perfusionsdruckes auf die Kollateraldurchblutung des Herzens

Zusammenfassung Bei 35 narkotisierten Hunden wurde der Ramus descendens der linken Koronararterie akut unterbunden und das zugehörige Stromgebiet mit Latexpartikeln embolisiert. Der retrograde Fluß und der retrograde Druck wurden vor und nach Embolisation sowie nach der Embolisation vor und während des Einflusses von Koronardilatatoren gemessen. Der retrograde Fluß nach Mikroembolisation entspricht dem wahren Kollateralfluß und der retrograde Druck dem wahren Perfusionsdruck der Kollateralgefäße. Nach Mikroembolisation stieg der retrograde Druck signifikant von 20±2 auf 69±3 mm Hg, das entspricht 73% des mittleren Aortendruckes. Gleichzeitig stieg der retrograde Fluß von 3,99±0,78 auf 6,19±1,16 ml/(min · 100 g), das sind 12% der antegraden Durchblutung. Der durchschnittliche Anstieg der Kollateraldurchblutung betrug 1,14 ml/(min. · 100 g), das sind + 21%, bei einer Zunahme des Perfusionsdruckes von 70 auf 80 mm Hg.Unter der Applikation von Koronardilatatoren konnte ein geringer Anstieg der Kollateraldurchblutung beobachtet werden, vorausgesetzt, daß der Perfusionsdruck unverändert blieb. Dieser Anstieg war unter Nitroglycerin, (+ 13 ±3%) und unter Papaverin (+11±5%) signifikant. Die Kollateraldurchblutung nahm ab, wenn der Perfusionsdruck unter dem Einfluß des Pharmakons abfiel. Wurde der unter Isoproterenol gesunkene Perfusionsdruck mittels Bluttransfusion wieder auf den Ausgangswert angehoben, so stieg die Kollateraldurchblutung wieder an und lag dann mit +4% gering, aber signifikant über dem Ausgangswert.Aufgrund dieser Befunde kann geschlossen werden, daß Koronardilatatoren die Kollateraldurchblutung geringgradig verbessern können unter der Voraussetzung, daß der Perfusionsdruck nicht absinkt. Dieser geringe pharmakologische Effekt könnte jedoch von entscheidender Bedeutung bei der Behandlung des Myokardinfarktes sein. Ein myocardial steal tritt nur bei einem Abfall des Perfusionsdruckes ein.

---

---

With 2 figures and 3 tables

---

Supported by a grant of the Deutsche Forschungsgemeinschaft, Sonderforschungsbereich 30, Kardiologie, Düsseldorf.     

Dilution of candidates: the case of iron-related genes in restless legs syndrome

Restless legs syndrome (RLS) is a common multifactorial disease. Some genetic risk factors have been identified. RLS susceptibility also has been related to iron. We therefore asked whether known iron-related genes are candidates for association with RLS and, vice versa, whether known RLS-associated loci influence iron parameters in serum. RLS/control samples (n=954/1814 in the discovery step, 735/736 in replication 1, and 736/735 in replication 2) were tested for association with SNPs located within 4 Mb intervals surrounding each gene from a list of 111 iron-related genes using a discovery threshold of P=5 × 10⁻⁴. Two population cohorts (KORA F3 and F4 with together n=3447) were tested for association of six known RLS loci with iron, ferritin, transferrin, transferrin-saturation, and soluble transferrin receptor. Results were negative. None of the candidate SNPs at the iron-related gene loci was confirmed significantly. An intronic SNP, rs2576036, of KATNAL2 at 18q21.1 was significant in the first (P=0.00085) but not in the second replication step (joint nominal P-value=0.044). Especially, rs1800652 (C282Y) in the HFE gene did not associate with RLS. Moreover, SNPs at the known RLS loci did not significantly affect serum iron parameters in the KORA cohorts. In conclusion, the correlation between RLS and iron parameters in serum may be weaker than assumed. Moreover, in a general power analysis, we show that genetic effects are diluted if they are transmitted via an intermediate trait to an end-phenotype. Sample size formulas are provided for small effect sizes.     

美学区软组织水平和骨水平植体周围骨丧失和牙龈生物型的分析

目的: 植体周围一定程度的骨丧失可能会给牙种植治疗的美观效果带来不利影响。这种情况可能更容易影响软组织水平（Tissue-Level, TL）设计,因此,当强调形态的美观自然性时,骨组织水平（Bone-Level, BL）设计可能更有优势。除了植体的设计,牙龈生物型也被认为是维持牙槽骨稳定的重要因素。本研究拟针对具有不同牙龈生物型的患者,在其美学区域行软组织水平和骨水平牙种植治疗,探究其骨丧失的程度。材料和方法: 对41位患者行20个TL和22个BL种植治疗,术后即刻、术后随访对这42个位点行口内影像学检查;运用计算机技术行牙槽骨高度测量分析;运用TRAN法鉴定患者的牙龈生物型。结果: TL组平均4.9年的存留期里,厚龈型的12颗植体周围平均骨丧失0.21mm（SD：0.43mm）;薄龈型的8颗植体周围平均骨丧失0.05mm（SD：0.47mm;P=0.31）。BL组平均1.9年的存留期里,厚龈型的14颗植体周围骨丧失为-0.03mm（SD：0.38mm）,薄龈型的8颗植体周围骨丧失为+0.09mm（SD：0.32mm;P=0.84）。结论: 分析得到的数据发现,牙槽骨高度的变化与种植设计或是牙龈生物型并无直接相关性。然而在选择种植设计之前,评价软组织的厚度是有利的,其中BL种植设计更能获得自然的外形。为实现以上评价目的,TRAN法是最快速、简易的方法。