The role of inflammation and infection in acute coronary syndrome

INFLAMMATORY PROCESS: Within the vessel wall is considered to be crucial for initiation and progression of atherosclerosis. As response to endothelial injury a focal inflammatory response arises which can lead to plaque vulnerability and rupture and a consecutive acute coronary syndrome. Systemic markers of inflammation like C-reactive protein (CRP) or interleukin (IL) 6 are elevated in stable angina and acute coronary syndrome and are associated with future cardiovascular events even in initially healthy people. Alongside classical risk factors infectious agents like cytomegalovirus or Chlamydia pneumoniae are discussed to be involved in the local and systemic inflammatory response. Seroepidemiological studies revealed disparate results of the association between antibody titers against Chlamydia pneumoniae or cytomegalovirus and prevalence of coronary artery disease or future cardiovascular events. In animal models Chlamydia pneumoniae and cytomegalovirus increase accelerated neointimal response, however, molecular mechanisms are not entirely clear. CONCLUSION: Whereas local and systemic inflammatory processes play a crucial role in atherogenesis and prognosis the causal role of infection in atherogenesis remains controversial.     

Die Radiofrequenzablation des weichen Gaumens (Somnoplastik)

Twenty-nine patients (26 male and 3 female) with habitual or obstructive snoring and socially disturbing character were followed over a ten week period. All patients were treated with radiofrequency volumetric tissue reduction (RFVTR) of the soft palate. In 21 patients this operation was combined with other surgery of the upper airway, eight patients had soft palate reduction with RFVTR exclusively. With this method an electrode is positioned in the musculature of the soft palate submucosally. RFVTR may be performed under local anesthesia and has to be repeated if necessary. Ten weeks postoperatively 24 of 29 patients, respectively their social-partners, reported subjective reduction of snoring after the first treatment. Markable improvement of snoring was seen in 20 of 29 patients postoperatively and reduction of the respiratory-disturbance-index (RDI) for more than 10 was noticed in 7/29 patients polysomnographically. 5/8 patients who were treated with RFVTR exclusively, showed reduction of snoring and 3/8 patients had RDI-reduction for more than 10. We conclude, that RFVTR of the soft palate is successful in the treatment of snoring and may be helpful in the treatment of mild obstructive-sleep-apnea-syndrome (OSAS).     

添加谷氨酰胺的全胃肠外营养对造血干细胞移植术后常见并发症的防治作用

目的:严重的黏膜损伤是诱发造血干细胞移植后出现并发症的一常见原因,已有证据显示谷氨酰胺能降低接受化疗患儿黏膜炎的发生率。观察谷氨酰胺对异基因外周造血干细胞移植患者并发症及恢复的影响。方法:选择于2002-03/2006-11在河南省血液病研究所接受同胞异基因外周造血干细胞移植的48例血液系统肿瘤患者。所有患者及其家属对治疗和实验均知情同意,并经医院伦理委员会批准。所有患者移植前均处于完全缓解状态,营养中等或良好,心、肝、肾功能正常,将48例患者随机分为标准化全胃肠外营养液组(标准组,n=13)和加用谷氨酰胺的全胃肠外营养液组(谷氨酰胺组,n=35)。待患者中性粒细胞升至1.0×109L-1,且无任何感染指征,进行异基因外周造血干细胞移植。造血干细胞输注后第1天开始给予全胃肠外营养与胃肠外营养联合谷氨酰胺双肽,至中性粒细胞≥1.0×109L-1,且无消化道症状时停用。观察两组患者中性粒细胞恢复时间、出层流室时间以及关于感染、急性移植物抗宿主病等情况有无差异。结果:48例患者均进入结果分析。两组患者营养物质的摄入基本相同,谷氨酰胺组有6例发生黏膜炎,标准组有11例,差异显著(P<0.05);谷氨酰胺组有1例发生严重腹泻,标准组有5例,差异显著(P<0.05);谷氨酰胺组有3例发生临床感染,标准组有7例,差异显著(P<0.05);标准组中性粒细胞≥0.5×109L-1的持续时间短于谷氨酰胺组(P>0.05);谷氨酰胺组抗生素治疗时间及无菌病房居住时间较标准组短(P<0.05);两组急性移植物抗宿主病发生率差异无统计学意义(P>0.05)。结论:添加谷氨酰胺的全胃肠外营养可改善异基因造血干细胞移植患者的营养状态,减少感染及肠损害,减少急性移植物抗宿主病的发生,有利于异基因移植患者恢复。     

Uterine artery Doppler and placental volume in the first trimester in the prediction of pregnancy complications.

OBJECTIVE: To evaluate placental volume and uterine artery Doppler in the first trimester in the prediction of pregnancies that subsequently develop pre-eclampsia, pregnancy-induced hypertension, preterm placental abruption or fetal growth restriction. METHODS: In 380 singleton pregnancies attending our center for nuchal translucency screening at 11-14 weeks of gestation, Doppler assessment of both uterine arteries was carried out for measurement of the pulsatility index and the mean pulsatility index of the two vessels was calculated. In addition, three-dimensional ultrasound was used to obtain images for subsequent measurement of placental volume. The 90th centile of the uterine artery mean pulsatility index and the 10th centile of the placental volume for crown-rump length (placental quotient) were calculated. These cut-offs were used for the prediction of pregnancy complications. RESULTS: Complications occurred in 36 (9.5%) of the 380 pregnancies, including 31 cases of fetal growth restriction, two of pregnancy-induced hypertension and abruption, two of pregnancy-induced hypertension, and one of abruption. The uterine artery mean pulsatility index was > or =90th centile in 38 (10%) pregnancies and this group contained nine (25%) of those that developed complications. The placental quotient was < or =10th centile in 39 (10%) pregnancies and this group contained eight (22%) of those that developed complications. In eight (2%) pregnancies the uterine artery mean pulsatility index was > or =90th centile and the placental quotient was < or =10th centile and this group contained six (17%) of those that developed complications. CONCLUSION: The combination of placental volume measurement and uterine artery Doppler in the first trimester may identify women at risk for subsequent development of pregnancy complications.     

Crkl is constitutively tyrosine phosphorylated in platelets from chronic myelogenous leukemia patients and inducibly phosphorylated in normal platelets stimulated by thrombopoietin

Platelet functions such as aggregation and clot retraction are often abnormal in chronic mylogenous leukemia (CML) patients. However, the molecular mechanisms of these altered functions are unknown. As expression of the p210bcr-abl oncogene product, a constitutively active tyrosine kinase, is known to have an essential role in the pathogenesis of CML and tyrosine phosphorylation is intimately involved in various aspects of platelet activation, we examined the pattern of protein tyrosine phosphorylation in platelets from 15 CML patients by immunoblotting with a monoclonal antiphosphotyrosine antibody (4G10). Before and after stimulation with thrombin, the only consistent difference between normal and CML platelets was the presence of a tyrosine phosphorylated protein with a relative molecular weight of 39 kD. This tyrosine phosphorylated protein was identified as crid, an SH2, SH3 containing adapter protein. Thus, as previously demonstrated for neutrophils from CML patients, tyrosine phosphorylation of p39crkl persists in mature platelets. No tyrosine phosphorylation of crid was detected following stimulation with thrombin in normal platelets. However, crkl became incorporated into the Triton X-100 insoluble residue following thrombin stimulation in a manner dependent on platelet aggregation. Further, we found that crkl is an endogenous substrate for calpain, a protease that may be involved in postaggregation signaling processes. This suggests that crkl may be involved in the reorganization of the cytoskeleton during normal platelet aggregation and its tyrosine phosphorylation in CML platelets may contribute to the abnormal platelet function in CML patients. Finally, we found that thrombopoietin induces tyrosine phosphorylation of crk1 in normal platelets and FDCP cells genetically engineered to express human c-Mpl. This suggests that crk1 can be phosphorylated by a kinase other than p210bcr-abl and that crk1 may have a role in signaling by thrombopoietin.     

Proceedings of the Symposium ‘Angiotensin AT1 Receptors: From Molecular Physiology to Therapeutics’: PHYSIOLOGICAL ACTIONS OF ANGIOTENSIN II MEDIATED BY AT1 AND AT2 RECEPTORS IN THE BRAIN

• 1 Autoradiographic binding studies have shown that the AT₁ receptor is the predominant angiotensin II (AngII) receptor subtype in the central nervous system (CNS). Major sites of AT₁ receptors are the lamina terminalis, hypothalamic paraventricular nucleus, the lateral parabrachial nucleus, rostral and caudal ventrolateral medulla, nucleus of the solitary tract and the intermediolateral cell column of the thoraco-lumbar spinal cord.
• 2 While there are differences between species, AT₂ receptors are found mainly in the cerebellum, inferior olive and locus coeruleus of the rat.
• 3 Circulating AngII acts on AT₁ receptors in the subfornical organ and organum vasculosum of the lamina terminalis (OVLT) to stimulate neurons that may have a role in initiating water drinking.
• 4 Centrally administered AngII may act on AT₁ receptors in the median preoptic nucleus and elsewhere to induce drinking, sodium appetite, a sympathetic vasoconstrictor response and vasopressin secretion.
• 5 Recent evidence shows that centrally administered AT₁ antagonists inhibit dipsogenic, natriuretic, pressor and vasopressin secretory responses to intracerebroventricular infusion of hypertonic saline. This suggests that an angiotensinergic neural pathway has a role in osmoregulatory responses.
• 6 Central angiotensinergic pathways which include neural inputs to the rostral ventrolateral medulla may use AT₁ receptors and play a role in the function of sympathetic pathways maintaining arterial pressure.