皮下注射低分子肝素局部按压与否对皮下出血的影响

目的探讨低分子肝素（LMWH）皮下注射经局部按压与否对皮下出血的关系。方法选择47例冠心病行皮下注射LMWH的患者,用自身对照法,即右腹部注射后局部压迫3-5min,左腹部注射后局部不压迫。观察皮下注射后1、3、7d局部皮下出血的例、性质及面积。结果观察组与对照组皮下出血例、性质、面积比较,P〈0.01,差异具有统计学意义。结论采用局部不按压方法可以显著降低皮下出血的发生率及皮下出血的程度。     

皮下注射低分子肝素更换针头与皮下出血关系的研究

目的:探讨低分子肝素皮下注射时更换针头与与皮下出血发生率及出血面积的关系。方法:选择脑梗死和T IA患者40例,将其随机分为实验组和对照组各20例。实验组皮下注射低分子肝素时注射前更换针头,对照组直接注射,两组各注射240例次,观察两组皮下出血发生率及出血面积。结果:实验组皮下出血面积及出血发生率显著低于对照组(P<0.05)。结论:注射前更换针头可以减少皮下出血发生率及出血面积。     

不同部位注射重组人促红素的减痛效果评价

目的 探讨不同部位注射重组人促红素的减痛效果.方法 按数字随机法随机抽取2016年5月份41名患者,选择上臂三角肌下缘注射为对照组(三角肌组),肘关节伸外侧无痛感区域皮下注射为观察组(肘关节组),同一工作人员执行注射重组人促红素,在同一患者每日注射不同的部位,即肘关节伸外侧区域与上臂三角肌下缘皮下注射交替进行,每次注射完毕都让患者在脸谱表情+评分的疼痛评估图上指出其感觉程度,并分别记录同一患者不同方法注射时患者的疼痛评分、患者满意度及护士操作方便程度并进行分析比较.结果 肘关节组的患者疼痛评分、患者满意度、护士操作方便程度均优于三角肌组,差异均有统计学意义(均P＜ 0.05).结论 经肘关节伸侧无痛感区域注射刺激性较强的重组人促红素可降低患者的疼痛程度、提高患者的满意度、方便护士操作.     

复方利多卡因乳膏在促红素注射中的应用

目的：观察复方利多卡因乳膏在重组人促红素注射液皮下注射中的镇痛作用。方法：29例慢性肾功能衰竭维持性血液透析患者采取自身前后对照的方法,使用直观模拟量表（VAS）评定值比较复方利多卡因乳膏与对照剂在促红素皮下注射中的镇痛作用。结果：常规组VAS评分值为55．64&#177;19．70,实验组的VAS评分值为30．27&#177;18．23,对照组VAS评分值为50．14&#177;18．51。实验组与常规组的VAS评分差值为25．37&#177;15．82（P〈0．05）。两组镇痛有效率比较差异有显著性（P〈0．01）。结论：复方利多卡因乳膏可明显降低皮下注射重组人促红素注射液时的疼痛,具有临床推广价值。     

左卡尼丁联合促红素治疗尿毒症血透患者的效果观察

目的观察左卡尼丁联合促红素治疗尿毒症血透患者的临床效果。方法入选2015年4月~2017年4月的尿毒症血透肾性贫血的患者80例,随机的分成对照组与观察组,各40例。对照组在血液透析后应用促红素皮下注射治疗,观察组在透析后采用左卡尼丁联合促红素治疗。治疗后,对两组的临床疗效进行评价与比较。结果治疗后,在血红蛋白和红细胞压积水平方面,观察组明显高于对照组,差异有统计学的意义(P0.05)。在不良反应发生率方面,观察组与对照组的分别为12.5%与17.5%,两组差异无统计学的意义(P0.05)。对比两组患者治疗前的NCT-A型下降时间、血氨浓度,差异均无统计学意义;对比两组患者治疗后的NCT-A型下降时间,观察组明显少于对照组,差异有统计学意义(P0.05);对比两组患者治疗后的血氨浓度,观察组明显低于对照组,差异有统计学意义(P0.05)。结论左卡尼丁联合促红素治疗尿毒症血透病人的肾性贫血的临床效果显著,值得在临床中推广应用。     

皮下注射低分子肝素后按压时间对皮下出血的影响

目的:探讨皮下注射低分子肝素后按压时间对皮下出血的影响。方法:选取2013年11月到2015年5月于我院进行低分子肝素皮下注射的75例患者作为本次研究的对象,将全部患者随机分成甲、乙、丙三组,三组各有25例患者,甲组注射后按压3min,乙组注射后按压5min,丙组注射后按压10min,对比三组患者的皮下出血情况。结果:甲组25例患者的出血例数与皮下出血点要明显大于乙组、丙组,具有统计学差异(P0.05);而乙组与丙组患者的出血例数与皮下出血点对比无明显差异,不具统计学意义(P0.05)。结论:患者皮下注射低分子肝素后按压时间5min以上能够有效降低注射部位的皮下出血率,缩小皮下出血点大小,值得在临床上进一步推广研究。     

促红素不同注射方式的临床疗效比较

目的观察用不同的皮下注射法注射促红素对患者局部疼痛程度的影响以及临床疗效的比较。方法采用对照法,100例行皮下注射EPO治疗的患者分别采用常规斜刺法和垂直注射法,观察并比较效果,包括局部疼痛程度、血常规结果(血红蛋白+红细胞计数+红细胞压积)。结果采用垂直注射法患者的局部疼痛程度低于常规斜刺法(P<0.05)。结论采用垂直注射法皮下注射促红素可减轻患者局部疼痛程度,优于常规斜刺注射法,并且治疗效果没有显著差异。     

血液透析患者血C反应蛋白水平与促红素疗效关系的临床研究

人类重组促红细胞生成素(EPO)在治疗肾性贫血中取得令人满意的效果,绝大多数患者治疗反应良好,生活质量提高,发病率及病死率下降。但5％～10％的患者出现EPO抵抗,一般认为主要与铁缺乏、甲状旁腺机能亢进、感染及炎症反应有关[1-5]。本文观察不同血C-反应蛋白(CRP)水平透析患者的EPO治疗效果,分析CRP升高与EPO低反应性的关系。     

注射依诺肝素钠后局部压迫时间对消瘦患者皮下出血的影响

目的：寻找适合消瘦患者的皮下注射依诺肝素钠的方法,探讨注射后局部压迫时间对消瘦患者皮下出血的影响。方法以体重指数〈18.5 kg·m-2标准选取该科注射依诺肝素钠的消瘦患者50例,同一患者在每天的两次注射时分别采用同样的注射方法和两种不同的按压方式,分为试验组与对照组,试验组注射后按压10 min,对照组注射后按压3 min,对注射后12 h的皮下出血情况作出记录与分析,通过对结果的分析找出按压时间与皮下出血发生率的关系。结果在该实验中,试验组发生皮下出血6例,对照组发生皮下出血15例,二者经字2检验差异有统计学意义。结论用统一的标准方法注射依诺肝素钠后按压时间大于10 min可有效降低消瘦患者的皮下出血发生率。     

Erythropoietin, erythropoiesis and beyond

Erythropoietin (EPO) is a glycoprotein that is mainly produced in the adult kidney, and it was initially highlighted for its action on the hematopoietic system. Moreover, EPO is also expressed in several non-hematopoietic tissues, where it plays a role in the protection from apoptosis and inflammation due to hypoxia, toxicity or injury. These protective effects are mainly known and studied in cardioprotection and neuroprotection but are also reported in retina degeneration, auditory injury and pancreatic-related diseases. The tissue protective effect of EPO is mainly mediated through the interaction with the heterodimeric receptor EPOR/βcR. Human recombinant EPO (HuREPO), which has been developed to treat anemia, is not adequate for tissue protection. The low affinity of the alternative receptor for EPO involves the injection of excessive concentration of erythropoiesis-stimulating agents (ESAs), implicating side effects due to the cross-talk with hematopoietic activity. For these reasons, EPO derivatives with less affinity for the EPO homodimeric receptor are under development. In this review, we provide an overview of the erythroid and non-erythroid functions of EPO by detailing the molecular mechanisms activated by the binding of EPO to its receptors in different tissues.     

Studies on the Subcutaneous Absorption in Mice VIII: Influence of Connective Tissue Ground Substance on the Absorption of Subcutaneously Injected Depots of Sodium and Chloride

A standard volume of 80 μl of physiological saline or of pure water was injected subcutaneously in mice. In both cases the electrolyte composition of the depots was the same 15 minutes later, at which time the injected volumes had not been significantly reduced. The sodium concentration in the depot corresponded to that of the plasma, while the chloride concentration corresponded to approximately 50 per cent of that of the plasma. The missing anions could probably be accounted for by the non-diffusible polyanions of the connective tissue ground substance. Radioactive sodium ions were cleared significantly more slowly than radioactive chloride ions, these in turn being significantly slower than the radioactive water molecules, after the subcutaneous injection of physiological saline or water depots containing the radioactive ions in tracer concentrations.     

促红细胞生成素对大鼠肢体缺血再灌注后肾血流的影响

【摘要】目的探讨促红细胞生成素（EPO）对大鼠肢体缺血再灌注（LIR）后肾血流的影响及可能作用机制。方法 30只雄性SD大鼠随机分为Control组、LIR组和EPO+LIR组,每组10只;检测各组动物肾血流量、血浆肌酐（Cr）、尿素氮（BUN）含量、肾组织湿干比（W/D）、NO、一氧化氮能合成酶（NOS）及内皮素-1（ET-1）含量,采用免疫组织化学法检测肾组织细胞间黏附分子（ICAM-1）和血管细胞黏附分子（VCAM-1）的表达,光镜下观察肾组织形态学改变。结果LIR组较Control组肾血流量减少,血浆Cr、BUN、肾组织W/D、NO、ET-1、NOS活性、ICAM-1和VCAM-1的表达增高(P<0.05),镜下可见肾组织间隙增宽和炎细胞浸润等病理改变。EPO+LIR组较LIR组肾血流量增加,血浆Cr、 BUN、肾组织W/D、NO、ET-1和NOS活性、ICAM-1和VCAM-1的表达均降低(P<0.05),肾组织病理学变化有所减轻。结论EPO可改善LIR后大鼠的肾功能,增加肾血流量,其机制可能与减轻肾水肿、调节肾血管舒缩功能、减轻炎症反应有关。     

Pharmacokinetic and Pharmacological Profiles of Free and Liposomal Recombinant Human Erythropoietin After Intravenous and Subcutaneous Administrations in Rats

Purpose. Recombinant human erythropoietin (Epo) is used frequently through intravenous (i.v.) and subcutaneous (s.c.) administration for the clinical treatment of the last stage of renal anemia. We encapsulated Epo in liposomes to develop an alternative administration route. The purpose of our study was to evaluate the pharmacokinetics and the pharmacological effects of liposomal Epo in comparison with the Epo after i.v. and s.c. administration to rats. Methods. Epo was encapsulated in liposomes composed of dipalmitoylphosphatidylcholine (DPPC) and soybean-derived sterol mixture (SS) prepared by the reversed-phase evaporation vesicle method. After filtration through a 0.1 m polycarbonate membrane, liposomes were gel filtered (Epo/liposomes). Results. Epo/liposomes showed higher pharmacological activity than Epo/liposomes before gel filtration after i.v. administration to rats. Non-encapsulated Epo lost its activity, whereas encapsulated Epo in liposomes retained it. The pharmacological effects of Epo/liposomes were greater than those of Epo after i.v. administration. Epo/liposomes afforded 3–9 times higher AUC, lower clearance and lower steady-state volume of distribution than Epo after both i.v. and s.c. administrations. Epo/liposomes had an improved pharmacokinetic profile compared with Epo. S.c. administration of Epo/liposomes at 7 h may penetrate primarily (40% of dose) through the blood as a liposome and partly (7% of dose) in lymph. Conclusions. Epo/liposomes may reduce the frequency of injections required for a certain reticulocyte effect in comparison to Epo. The lower clearance of Epo/liposomes may increase the plasma concentrations of Epo, which increases the efficacy.     

OSAHS患者正压通气治疗后促红细胞生成素及血液流变学的变化

【摘要】目的 观察中重度阻塞性睡眠呼吸暂停低通气综合征（obstructive sleep apnea hypopnea syndrome, OSAHS）患者经无创正压通气(noninvasive positive pressure ventilation,NPPV)治疗后血清促红细胞生成素（erythropoietin, EPO）及血液流变学变化的情况;进一步了解睡眠呼吸暂停低通气综合征对人体的影响。方法 选择32例诊断为中重度OSAHS患者在经无创正压通气治疗前、治疗1月及治疗3月后行多导睡眠监测、血清EPO及血流变检测,分析治疗前后不同时间夜间最低血氧饱和度（LSaO2）、患者血清EPO及血流变水平变化,并对其临床意义进行探讨。 结果 ①治疗3月后OSAHS患者全血粘度、血浆粘度、全血还原粘度、红细胞积聚指数、RBC、Hgb、HCT、MCH、MCV、血清EPO、LSaO2比治疗前均有差异,有统计学意义（P﹤0.05）,而与对照组比较均无显著性差异（P＞0.05）,上述所有指标治疗前与正常对照组均有明显差异,有统计学意义（P﹤0.05）。②治疗1月后OSAHS患者全血粘度、血浆粘度、全血还原粘度、红细胞积聚指数与治疗前比较无显著差异（P＞0.05）;而患者RBC、Hgb、HCT、MCH、MCV、LSaO2及血清EPO与治疗前相比有明显差异,有统计学意义（P﹤0.05）,与治疗3月及对照组比较无显著差异（P＞0.05）。③相关性分析显示OSAHS患者治疗前后血清EPO水平与Hgb浓度、RBC均呈正相关(均P<0. 01) 。治疗前后AHI与血清EPO水平呈正相关(均P<0. 01) ,夜间LSaO2与血清EPO水平呈负相关（P＜0.05)。结论 OSAHS患者缺氧可诱发促红细胞生成素升高,血液粘度增加,通过无创正压通气治疗可以明显改善患者缺氧程度,使促红细胞生成素降低,降低血液粘度,所以早期检测并应用无创正压通气治疗以缓解气道阻塞对于防治OSAHS及其并发症具有重要的临床意义。      

Enhanced Bioavailability of Subcutaneously Injected Insulin Coadministered with Collagen in Rats and Humans

The present study was undertaken to develop an agent that stabilizes insulin injected subcutaneously. ¹²⁵I-Porcine insulin with 0.2 U/kg unlabeled porcine insulin was subcutaneously injected with or without collagen in the rat under the depilated skin of the back. At various times, the radioactivity in subcutaneous tissue was assayed for insulin and its metabolites by gel filtration. The degradation and absorption rate constants of insulin at the subcutaneous injection site were estimated according to a one-compartment model. The degradation rate constant of insulin in the presence of collagen at the injection site was less than half of the control rate. The inhibition was confirmed by increases in the immunoreactive insulin plasma levels and the hypoglycemic effect in rats and healthy volunteers. We postulate that collagen prevents insulin from being degraded by inhibiting proteolytic enzymes, mainly collagenase-like peptidase, in subcutaneous tissue.     

Comparison of dose requirement,serum erythropoietin and blood pressure following intravenous and subcutaneous erythropoietin treatment of dialysis patients IV and SC erythropoietin

Objective: The purpose of the study was to investigate the effect of route of administration of erythropoietin (EPO) on the dose requirement in dialysis patients after intravenous (IV) and subcutaneous (SC) therapy. Methods: The study was performed as a single centre, prospective, open, combined parallel and cross-over study of 50 dialysis patients, consecutively randomised to IV or SC treatment with EPO. The initial dose was 40 U⋅kg⁻¹ 3-times weekly, adjusted to increase haemoglobin (Hgb) from a median 5.3 mmol⋅l⁻¹ to a target of haemoglobin 6.5–7.5 mmol⋅l⁻¹. After reaching the target level, the haemoglobin was maintained for 4 months (Period 1). Then IV and SC treatment was switched for a further 4 months (Period 2). The study included high risk patients. The adjustment period was completed by 38 patients, Period one by 32 patients (IV/SC = 15/17; male/female = 19/13; age = 54 (24– 71) y), and Period two by 22 patients. Results: No significant difference was found between the two groups in the reticulocyte response, the rate of Hgb increase (IV 0.7 versus SC 0.5, mmol⋅l⁻¹⋅ month⁻¹), time to reach target level (IV 43 versus SC 60 days), or total EPO dose per increase in haemoglobin to target level (IV 663 versus SC 946 (U⋅kg⁻¹) per (mmol Hgb⋅l⁻¹). The overall median maintenance dose during the last month of the two four month periods was 105 (range IV 51–336) U⋅kg⁻¹⋅w⁻¹ and SC 104 (range 21–321) U⋅kg⁻¹⋅w⁻¹. Trough serum EPO levels were significantly higher during SC treatment. The blood pressure did not change significantly from the base level after either route of administration; start 133/80 versus 143/80 mmHg, target 127/78 versus 154/85 mmHg, and maintenance period 140/84 versus 142/85 mmHg. Thus, three-times weekly IV or SC EPO did not differ significantly in efficacy or in the effect on blood pressure in dialysis patients. Received: 13 June 1995/Accepted in revised form: 30 October 1995     

Toxicity of Subcutaneously Administered Recombinant Human lnterleukin-2 in Rats

Recombinant human interleukin-2 (rIL-2) was administered subcutaneouslyto rats at doses of 0.3–10 mg/kg/day in a rangefindingstudy and 0.03–0.3 mg/kg/day in a 4-week toxicity study.Treatment-related effects were assessed by hematology, clinicalchemistry, anti-rIL-2 antibody production, and gross and histopathologicevaluations. Doses of 1 mg/kg/day or above were not tolerated,resulting in death or moribund termination by Day 7. Slightdecreases in red blood cell counts (including hematocrit andhemoglobin) were observed at 0.1 mg/kg/day. White blood cellscounts increased in a dose-dependent manner; increases wereprimarily due to increases in lymphocytes and eosinophils. Hepaticabnormalities, including increases in aspartate aminotransferaseand bilirubin, were noted at 0.3 mg/ kg/day. Histologic findingswere evident primarily in the spleen, liver, lung, and injectionsites, with dose-related increases in inflammatory cell foci/infiltratesnoted in these sites. Findings in the liver also included biliaryhyperplasia, hepatocellular degeneration, necrosis, vascularmural thickening in the portal triads, and fibrosis. Red andwhite pulp hyperplasia and capsular fibrosis occurred in thespleen. Most clinical and histopathologic findings were reversiblewithin 4 weeks after termination of treatment. Anti-rIL-2 antibodieswere detected beginning on Day 19 and were still present onDay 56. The pharmacological and toxicological effects associatedwith subcutaneous administration of rIL-2 are comparable tothose reported after intravenous administration, indicatingthat subcutaneous dosing may be an alternative to the currentclinical iv regimens.     

Subcutaneous pharmacokinetics of the cardiac hormone vessel dilator

Vessel dilator, a hormone synthesized in the heart, eliminates 71% of human small‐cell lung cancers and 67% of human breast cancers growing in mice when given subcutaneously (s.c.) via osmotic pumps. The pharmacokinetics of s.c. administered vessel dilator have not been evaluated previously. In the present study, the pharmacokinetics of vessel dilator following s.c. bolus (ScB) or 3 h s.c. infusion (ScI) were compared with those following i.v. bolus (IvB) administration in male Fischer 344 rats. The half‐life (t_½) of vessel dilator after ScI, IvB and ScB was 54, 43 and 30 min, respectively. The t_max for vessel dilator after IvB, ScB and ScI administration was 1.5, 23 and 156 min, respectively, whereas the corresponding C_max values were 3749, 887 and 471 ng/L (normalized against the dose used for ScB and IvB). The area under the curve (AUC_0–∞) for vessel dilator was 1166, 880 and 1652 ng h/mL (normalized) following IvB, ScB and ScI administration, respectively. The volume of distribution for vessel dilator was 2.38, 0.92 and 1.08 L following IvB, ScB and SCI administration, respectively; corresponding clearance values were 1.69, 1.50 and 0.78 L/h, respectively. Plasma concentrations of vessel dilator after each of the three methods of administration mirrored their predicted concentration–time profiles. We conclude that vessel dilator administered via ScI has a significantly greater AUC and t_½ and slowed clearance compared with IvB or ScB administration (P < 0.001), suggesting that s.c. infusion is the preferred method of administration, based on pharmacokinetics, to treat cancers.     

Enhanced Bioavailability of Subcutaneously Injected Insulin by Pretreatment with Ointment Containing Protease Inhibitors

The present study was undertaken to develop an ointment preparation containing a protease inhibitor for stabilizing subcutaneously injected insulin. The ointment containing the protease inhibitor, gabexate mesilate or nafamostat mesilate, was applied to the skin around the insulin injection site. Three results were obtained. First, gabexate and nafamostat inhibited insulin degradation in subcutaneous tissue homogenates in vitro. Second, after application of gabexate or nafamostat ointment, an appreciable amount of gabexate or nafamostat appeared in the subcutaneous tissue of rats or hairless mice and their concentrations were comparable to those seen in the in vitro experiment. Third, insulin degradation at the subcutaneous injection site in the rat was depressed after pretreatment with gabexate or nafamostat ointment. Pretreatment with gabexate or nafamostat ointment increased the plasma immunoreactive insulin (IRI) levels and the hypoglycemic effect of insulin in healthy volunteers. These results indicate that gabexate or nafamostat ointments stabilize subcutaneously injected insulin.