The effect of benzylpenicillin on the activity of antioxidative enzymes in the erythrocytes and on methemoglobin formation in children

Activity of erythrocyte antioxidative enzymes and the content of methemoglobin were studied in 36 healthy children under preventive treatment with benzylpenicillin and in 65 healthy children of the control group. It was shown that there was relationship between the changes in the activity of superoxidodismutase and catalase and the antibiotic dose and duration of the use. After benzylpenicillin intramuscular administration for 3-4 days (the total dose of 80,000-3000000 units) the catalase activity decreased to 65.6 per cent while the activity of superoxidodismutase did not change. When the antibiotic was used for 1-2.5 weeks (the total dose of 3000000-6000,000 units) the activity of catalase and superoxidodismutase decreased to 53.6 and 82 per cent respectively. Beginning from the 3rd week of the antibiotic use the catalase activity increased to 71.6 per cent while the superoxidodismutase activity did not change and remained at the level of 84.9 per cent. The content of methemoglobin in the children treated with benzylpenicillin was about 3 times higher than that in the controls. The correlation between the activity of the antioxidative enzymes and the content of erythrocyte methemoglobin was inverse: the lower was the enzyme activity, the higher was the content of methemoglobin and vice versa. It was concluded that benzylpenicillin impaired definite balance between single electron reduction of oxygen and antioxidative protection resulting in the antibiotic adverse action i. e. increased methemoglobin formation. The effects of benzylpenicillin should be considered when it is used in combination with oxidants in treatment of children.     

Effect of furosemide on the pharmacokinetics of benzylpenicillin and its penetration through the hematoencephalic barrier in experimental and clinical meningococcic meningitis]

Pharmacokinetics of sodium benzylpenicillin after intramuscular administration in a dose of 250 000 gamma/kg and simultaneous intramuscular injection of furosemid (lazix) in doses of 0.5--1--2 mg/kg was studied in experiments on a model of meningococcal meningitis of rabbits and in clinics on patients with meningococcal meningitis. A pronounced effect of furosemid on pharmacokinetics of benzylpenicillin as dependent on a number of factors was found. Furosemid and meningococcal endotoxin had a synergic effect and decreased benzylpenicillin excretion with urine resulting in prolongation of the antibiotic effect in the blood. An increase in benzylpenicillin blood levels and inflammation of the soft brain membranes increased permeability of the hemato-encephalic barrier for the antibiotic.     

Benzylpenicillin levels in the serum and bone tissue of the lower jaw in patients with chronic traumatic osteomyelitis after intraosseous and intramuscular administration

Penetration of benzylpenicillin into pathological foci was studied in 48 patients with chronic traumatic osteomyelitis of the lower jaw after intramuscular and intraosseous administration of the antibiotic. A group of 10 patients operated for congenital deformations of the lower jaw was used as the control. The results showed that after intramuscular administration benzylpenicillin penetration into the inflammation focus of the lower jaw was better than that into the intact bone only for the first 30 minutes. At later periods it was detected in both the cases as traces. After intraosseous administration of the drug in doses of 50,000 and 200,000 units its accumulation in the bone tissue of the patients with chronic traumatic osteomyelitis of the lower jaw in 30 minutes was respectively 75 and 160 times higher than that after the intramuscular injections. The period of its presence in the pathological focus as the therapeutic levels was also higher i. e. up to 2 hours. Intraosseous route of benzylpenicillin administration is likely to decrease the quantity of the drug needed for treating patients with chronic osteomyelitis of the lower jaw.     

血清RBP4、NGAL、Klotho蛋白在慢性肾脏病病情监测及预后评估中的价值

目的:探讨血清视黄醇结合蛋白4(retinol binding protein 4,RBP4)、中性粒细胞明胶酶相关脂质运载蛋白(neutrophil gelatinase-associated lipocalin,NGAL)、Klotho蛋白在慢性肾脏病病情监测及预后评估中的价值。方法:收集我院2017年5月～2019年2月收治的297例慢性肾脏病患者为研究对象,依据肾小球滤过率(GFR)分为1期24例、2期46例、3期128例、4期66例、5期33例,并依据临床转归情况分为肾功能稳定组104例和肾功能恶化组193例;同期选择门诊健康体检者251例作为对照组。比较各组血清RBP4、NGAL、Klotho蛋白表达情况,并分析慢性肾脏病患者血清RBP4、NGAL、Klotho蛋白和GFR的相关性。结果:慢性肾脏病组血清RBP4、NGAL水平高于对照组,Klotho蛋白低于慢性肾脏病组(P0.05)。慢性肾脏病5期者血清RBP4、NGAL水平高于4期、3期、2期及1期者,Klotho蛋白低于4期、3期、2期及1期者,差异有统计学意义(P0.05)。慢性肾脏病患者血清RBP4、NGAL和GFR呈负相关,Klotho蛋白和GFR呈正相关(P0.05)。肾功能恶化组血清RBP4、NGAL水平高于肾功能稳定组,Klotho蛋白低于肾功能稳定组,差异有统计学意义(P0.05)。结论:血清RBP4、NGAL及Klotho蛋白表达水平的变化对了解慢性肾脏病患者病情程度及预后评估中有重要的参考价值,建议临床予以重视。     

Effect of sulfalene and furosemide on benzylpenicillin kinetics in rats with aseptic inflammation

The effect of sulfalen and furosemide on benzylpenicillin kinetics in blood serum, intact tissues and aseptic inflammation foci was studied on rats. It was shown that under the action of sulfalen and furosemide protein binding of benzylpenicillin lowered by 30 per cent. The changes in the antibiotic kinetics after combined use with sulfalen and furosemide were of the same type: markedly increased concentrations in blood serum and tissues and retarded elimination.     

Effect of antibiotics on the resistance of white mice to infection caused by antibiotic-resistant Staphylococcus strains]

The effect of benzylpenicillin, streptomycin and tetracycline on the animal resistance to infection caused by the antibiotic resistant staphylococci was studied. It was found that the effect of the antibiotics on the infectious process outcome was not limited by their antibacterial properties. Changes in the natural resistance of the host under the effect of the antibiotics were not always the same and depended on both the antibiotic type and the moment of its administration.     

肾脏肿瘤患者CT灌注参数与肾功能生化检测指标的相关性研究

目的:探讨肾脏肿瘤患者CT灌注参数与肾功能生化检测指标的相关性。方法:选取河北省第六人民医院2013年3月至2018年1月期间收治的35例肾脏肿瘤患者作为观察组,另选取同期来我院体检的35例健康者作为对照组,均对两组受试者实施CT灌注成像,获取等效血容量(Equiv BV)、表面渗透性(Ps)、血流量(BF)等CT灌注参数,并检测两组受试者血尿素氮(BUN)、血肌酐(Scr)、总胆固醇(TC)、甘油三酯(TG)等肾功能生化指标,对比两组受试者上述指标检测结果,采用Pearson相关分析CT灌注参数与肾功能生化指标的相关性。结果:与对照组相比,观察组CT灌注参数Equiv BV、Ps、BF均降低,肾功能生化指标BUN、Scr、TC、TG水平均升高,有统计学差异(P0.05)。Pearson相关分析结果显示,CT灌注参数Equiv BV、Ps、BF与肾功能生化指标TC、BUN均呈负相关(P0.05),与Scr、TG无相关性(P0.05)。结论:肾脏肿瘤患者的CT灌注参数Equiv BV、Ps、BF均较低,BUN、Scr、TC、TG水平均较高,且CT灌注参数与BUN、TC水平呈负相关性,可作为评估肾脏肿瘤患者肾功能的辅助方法。     

Magnetic resonance tomography in the diagnosis of renovascular hypertension]

MR tomography was used for investigation of 38 patients with renovascular hypertension (RVH) and 26 healthy persons. A possibility of the use and practical value of the method in the diagnosis and evaluation of renal function and renal arteries (RA) were under study. Some quantitative MRT indices were calculated both for the patients and healthy persons. They included spin-spin relaxation time, proton density, and signal intensity. These data can provide important information on renal function in RVH with relation to kidney sizes and the state of the renal parenchyma (evaluation of the cortical substance and medulla and the border between them). In some cases MRT ensures noninvasive diagnosis of PA stenosis.     

Inhibition of cell wall synthesis and acylation of the penicillin binding proteins during prolonged exposure of growing Streptococcus pneumoniae to benzylpenicillin

Growing cultures of an autolysis-defective pneumococcal mutant were exposed to [3H]benzylpenicillin at various multiples of the minimal inhibitory concentration and incubated until the growth of the cultures was halted. During the process of growth inhibition, we determined the rates and degree of acylation of the five penicillin-binding proteins (PBPs) and the rates of peptidoglycan incorporation, protein synthesis, and turbidity increase. The time required for the onset of the inhibitory effects of benzylpenicillin was inversely related to the concentration of the antibiotic, and inhibition of peptidoglycan incorporation always preceded inhibition of protein synthesis and growth. When cultures first started to show the onset of growth inhibition, the same characteristic fraction of each PBP was in the acylated form in all cases, irrespective of the antibiotic concentration. Apparently, saturation of one or more PBPs with the antibiotic beyond these threshold levels is needed to bring about interference with normal peptidoglycan production and cellular growth. Although it was not possible to correlate the inhibition of cell wall synthesis or cell growth with the degree of acylation (percentage saturation) of any single PBP, there was a correlation between the amount of peptidoglycan synthesized and the actual amount of PBP 2b that was not acylated. In cultures exposed to benzylpenicillin concentrations greater than eight times the minimal inhibitory concentration, the rates of peptidoglycan incorporation underwent a rapid decline when bacterial growth stopped. However, in cultures exposed to lower concentrations of benzylpenicillin (one to six times the minimal inhibitory concentration) peptidoglycan synthesis continued at constant rate for prolonged periods, after the turbidity had ceased to increase. We conclude that inhibition of bacterial growth does not require a complete inhibition or even a major decline in the rate of peptidoglycan incorporation. Rather, inhibition of growth must be caused by an as yet undefined process that stops cell division when the rate of incorporation of peptidoglycan (or synthesis of protein) falls below a critical value.     

糖尿病肾病患者NT-proBNP,Hcy和cTnI的水平变化及其临床意义

目的:观察糖尿病肾病患者血清NT-proBNP,Hcy和cTnI的水平变化情况,分析其与心血管疾病发生的关系,为临床提供指导依据。方法:选择我院2012年3月至2013年9月收治的152例糖尿病肾病患者,根据合并心血管疾病的情况,将所选患者分为并发症组(83例)和无并发症组(69例),另选择同期在我院接受健康体检的志愿者(72例)作为对照组。检测三组对象血清中NT-proBNP,Hcy与cTnI的水平,以及糖尿病肾病患者的肾功能指标。结果:对照组NT-proBNP,Hcy与cTnI水平显著低于其他两组,并发症组患者NT-proBNP,Hcy与cTnI水平高于无并发症组,差异有统计学意义(P0.05)。并发症组患者的BUN,UA及CysC水平显著高于无并发症组,差异有统计学意义(P0.05)。结论:NT-proBNP,Hcy和cTnI在合并心血管疾病的糖尿病肾病患者血清中显著升高,并在一定程度上影响患者的肾功能。     

Effectiveness of the intramuscular administration of high doses of penicillin in treating pneumonia]

Clinical tolerance of benzylpenicillin administered intramuscularly in doses of 2000000--3000000 units every 4--6hours (12000000 units a day) was studied in 253 patients with pneumonia. Satisfactory tolerance of sodium benzylpenicillin and pronounced painfulness at the site of injection of potassium benzylpenicillin were noted. General toxic side effects in the form of asthenia, dizziness, pain in the heart region were observed in a part of elderly patients. The benzylpenicillin serum levels after administration of 2000000 units were 6--10 times higher than those after administration of 200000 units. The efficiency of benzylpenicillin elevated doses was studied in 193 patients. In 101 of them the previous treatment with usual doses of benzylpenicillin, i. e. 200000 units every 4 hours was not sufficiently effective. The elevated doses of benzylpenicillin proved to be effective in 78 per cent of the cases, the effect being observed in all the cases with acute pneumonia, in 88.5 per cent of the cases with neglected state and in 83 per cent of the cases with chronic pneumonia. The therapeutic effect was also observed in most of the patients with benzylpenicillin resistant microflora in the sputum. On the basis of high efficiency of penicillin therapy it was concluded that gram-positive cocci played the main role in pneumonia etiology.     

血浆hs-CRP和Hcy水平与血管性痴呆患者认知功能的关系

目的:探讨血浆超敏C反应蛋白(hs-CRP)和同型半胱氨酸(Hcy)水平与血管性痴呆(VD)患者认知功能的相关性。方法:回顾性分析2011年12月-2014年7月间我院100例脑梗死住院患者的临床资料,按诊断结果,将患者分为VD组55例和非VD组45例,另选取同期50例健康体检者为对照组。检测并比较3组血浆hs-CRP和Hcy水平,采用简易精神状态速检表(MMSE)对VD组进行痴呆程度分类,分析其与血浆hs-CRP和Hcy的相关性。结果:血浆Hcy与hs-CRP在3组间差异有统计学意义(P0.05),且VD组、非VD组均显著高于对照组,VD组显著高于非VD组,差异均有统计学意义(P0.05)。随着痴呆程度的加重,MMSE评分逐渐降低,血浆hs-CRP与Hcy水平则逐渐升高,差异有统计学意义(P0.05)。经相关性分析发现,MMSE评分和血浆hs-CRP与Hcy水平均呈负相关(r=-0.672,-0.703,P0.05)。结论:血浆hs-CRP与Hcy水平与VD患者的认知功能负相关,临床加强对两指标的检测对VD的诊断及防治有着重要的临床意义。     

The inhibition of mucopeptide synthesis by benzylpenicillin in relation to irreversible fixation of the antibiotic by staphylococci

1. Benzylpenicillin is irreversibly fixed to staphyloccoci by a reaction that obeys second-order kinetics, whereas the progress of inhibition of mucopeptide synthesis obeys first-order kinetics after a short lag during which the antibiotic has no effect. 2. When the micro-organisms are saturated with benzylpenicillin they can still make mucopeptide in solutions containing chloramphenicol at a normal rate after a lag period. 3. About 90% of the benzylpenicillin stays fixed to the cells after mucopeptide synthesis has reached its maximum and constant rate. 4. During the phase when mucopeptide synthesis by cells saturated with benzylpenicillin is accelerating, a small number of additional sites that fix benzylpenicillin is revealed. The number of these sites reaches a maximum and constant value at about the same time as mucopeptide biosynthesis reaches a maximum and constant rate. 5. Staphylococci saturated with benzylpenicillin are exceedingly sensitive to fresh additions of the antibiotic. 6. The degree of inhibition of mucopeptide synthesis caused by these small amounts of antibiotic agrees with the degree of substitution by benzylpenicillin of the newly revealed or `sensitive' sites. 7. Since these sensitive sites are revealed during incubation of the bacteria with chloramphenicol it is unlikely that they are due to newly formed protein. 8. On the basis of these results, a hypothesis for the inhibition by penicillin of the cross-linking reaction in the terminal stages of mucopeptide synthesis is suggested.     

血清肌钙蛋白I、N端前体脑钠肽和高敏C反应蛋白水平在充血性心力衰竭中的临床意义

目的：探讨血清肌钙蛋白I（cTnI）、N端前体脑钠肽（NT-proBNP）和高敏c反应蛋白（hs—CRP）水平在充血性心力衰竭（CHF）中的临床意义。方法：选取2010年1月-2012年12月在我院诊治的CHF患者210例（CHF组）,心功能按纽约心脏病协会（NYHA）分级：Ⅱ级88例、Ⅲ级96例和Ⅳ级26例。同时选取同期在我院行健康体检的自愿者30例为健康对照组。观察和比较两组血清hs．CRP、cTnI和NT．proBNP水平的差异及其与CHF患者心功能的心功能分级的相关系。结果：CHF组患者的血清hs-CRP．cTnI和NT．proBNP水平均较对照组明显增高,差异均有统计学意义（P〈0．0t）,且CHF患者的血清hs—CRP、cTnI和NT—proBNP水平随着心功能分级的增加而升高,差异有统计学意义（P〈0．01）。血浆hs—cI冲（F0．694,P〈0．01）水平,cTnI（r=0．782,P〈0．01）水平均与NT—proBNP水平呈显著正相关,血浆hs．CRP和cTnI水平也呈显著正相关（r==0．649,P〈0．01）。结论：CHF患者的血清hs—CRP、cTnI和NT-proBNP水平与其心功能分级显著相关,有助于评估CHF患者心功能不全的严重程度,可能与CHF患者的预后相关。     

Action of penicillin on the erythrocyte membrane

The effect of the therapeutic concentrations of benzylpenicillin on potassium release and osmotic resistance of the red blood cells in healthy children was investigated potentiometrically with the use of a K+-selective electrode. In a concentration of 0.66 mM (370 units/ml) benzylpenicillin increased the total content of potassium in the cells and their resistance to osmotic lysis and lowered the rate of K+ release induced by valinomycin. The membrane stabilizing effect of benzylpenicillin observed in these studies could to some extent stipulate its nonspecific antiinflammatory effect. In a concentration of 1.32 mM (740 units/ml) it had no significant effect on the indices studied. Under the effect of the maximum concentrations of the antibiotic (3.3 mM) the signs of lowered stability of the red blood cell membranes were observed, i.e. an increased rate of the valinomycin induced release of K+ and a tendency for the decreasing of the osmotic resistance.     

Insulin-like growth factor binding protein-1 levels are increased in patients with IgA nephropathy

The mechanisms underlying the pathogenesis of immunoglobulin A (IgA) nephropathy (IgAN) are not well understood. In this study, we examined gene expression profiles in kidneys obtained from mice with high serum IgA levels (HIGA mice), which exhibit features of human IgAN. Female inbred HIGA, established from the ddY line, were used in these experiments. Serum IgA levels, renal IgA deposition, mesangial proliferation, and glomerulosclerosis were increased in 32-week-old HIGA mice in comparison to ddY animals. By microarray analysis, five genes were observed to be increased by more than 2.5-fold in 32-week-old HIGA in comparison to 16-week-old HIGA; these same five genes were decreased more than 2.5-fold in 32-week-old ddY in comparison to 16-week-old ddY mice. Of these five genes, insulin-like growth factor (IGF) binding protein (IGFBP)-1 exhibited differential expression between these mouse lines, as confirmed by quantitative RT-PCR. In addition, serum IGFBP-1 levels were significantly higher in patients with IgAN than in healthy controls. In patients with IgAN, these levels correlated with measures of renal function, such as estimated glomerular filtration rate (eGFR), but not with sex, age, serum IgA, C3 levels, or IGF-1 levels. Pathologically, serum IGFBP-1 levels were significantly associated with the severity of renal injury, as assessed by mesangial cell proliferation and interstitial fibrosis. These results suggest that increased IGFBP-1 levels are associated with the severity of renal pathology in patients with IgAN.     

Polyamines in renal failure

Summary. The levels of polyamines (putrescine, spermidine and spermine) and polyamine oxidase in plasma of patients with chronic renal failure were determined. The level of putrescine was increased but the level of spermine was decreased in the plasma of these patients. The patients also had increased plasma polyamine oxidase activity leading to increased degradation of spermine. As acrolein was a major toxic compound produced from spermine by polyamine oxidase, the levels of free and protein-conjugated acrolein in plasma were also measured. Acrolein levels were enhanced in plasma of patients with chronic renal failure. The accumulated acrolein found as protein conjugates was equivalent to 170 μM, which was about 5-fold higher than in plasma of normal subjects. It was found that acrolein is mainly produced by spermine oxidase in plasma. An increase in putrescine, spermine oxidase and acrolein in plasma was observed in all cases such as diabetic nephropathy, chronic glomerulonephritis and nephrosclerosis. After patients with chronic renal failure had undergone hemodialysis, their levels of plasma polyamines, spermine oxidase and acrolein returned towards normal. It is likely that acrolein produced from spermine accumulates in the blood due to decreased excretion into urine and may function as a uremic “toxin”.     

尿微量蛋白联合血凝在冠心病诊断中的检测价值

目的:探讨尿微量蛋白联合血清纤维蛋白原在冠心病的诊断价值。方法:选取同期在我院治疗的24例稳定型心绞痛的患者,36例诊断为不稳定型心绞痛的患者和30例诊断为急性心肌梗死的患者,并选择同期30例来我院体检健康志愿者为对照组。分析以上4组患者发病时尿微量蛋白及血清纤维蛋白原的变化情况。结果:与对照组比,3个冠心病组的尿微量蛋白及血清纤维蛋白原的含量显著升高(P<0.05),与稳定型心绞痛组比,不稳定型心绞痛组的尿微量蛋白及血清纤维蛋白原的含量显著升高(P<0.05);与不稳定型心绞痛组比,急性心梗的尿微量蛋白及血清纤维蛋白原的含量显著升高(P<0.05)。3组病患的尿微量蛋白及血清纤维蛋白原之间呈正相关关系(r=0.852,P<0.05)。结论:心肌梗死和心绞痛患者尿微量蛋白及血清纤维蛋白原含量较健康成人含量高,提示尿微量蛋白及血清纤维蛋白原的含量有助于对心肌梗死和心绞痛的诊断,对急性心肌梗死的诊断价值较高。     

肾移植术后患者同型半胱氨酸、肾功能和血脂水平的变化及其相关性分析

目的:分析肾移植术后患者血清的同型半胱氨酸(Hcy)、肾功能和血脂水平的变化和相关性,探讨其在肾移植术后评价肾功能的应用价值。方法:将2013年10月~2016年9月就诊于我院确诊慢性肾衰并进行肾移植手术的300例术后随访患者作为观察组,选择同期健康志愿者100例作为对照组。检测并比较两组Hcy、总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)水平。根据观察组患者Hcy水平的不同将其分成Hcy正常组与Hcy异常组,并对比两组患者的血脂指标水平;测定半胱氨酸蛋白抑制剂C(CysC)的水平并计算肾小球滤过率(eGFR);对观察组血清Hcy与eGFR值、血脂指标水平进行相关性分析,并采用Logistic回归分析分析观察组肾移植术后eGFR下降的影响因素。结果:观察组患者的血清Hcy、TC、TG、HDL-C、LDL-C水平均明显高于对照组(P0.05)。Hcy异常组血清LDL-C水平明显高于Hcy正常组,而HDL-C水平明显低于Hcy正常组(P0.05)。观察组患者血清Hcy与eGFR、HDL-C水平呈负相关关系(r=-0.573、-0.414,P0.05);与TG水平呈正相关(r=0.432,P0.05),与TC、LDL-C无相关(P0.05)。多元Logistic回归分析显示,Hcy、TG、LDL-C水平均与患者eGFR下降有关(P0.05)。结论:在肾移植术后,慢性肾衰患者的TG、LDL-C、Hcy水平均升高,且伴有eGFR水平的降低;肾移植术后肾功能的改变与血清TG、LDL-C、Hcy水平相关;检测肾移植患者血脂指标、Hcy的水平可以评估移植肾功能受损情况。     

Effect of water immersion on levels of atrial natriuretic peptide in patients with chronic renal failure

An effect of a 2-hour water immersion on the blood serum ANP was investigated in 20 haemodialysed patients with chronic renal failure and in 15 healthy individuals. Water immersion produced an increase in volume in both healthy individuals and the patients of similar degree. Baseline ANP concentration (290.0 +/- 21.9 pg/mL) was significantly higher in the dialysed patients than that in healthy individuals (66.0 +/- 5.5 pg/mL). Water immersion decreased mean arterial pressure (previously significantly higher in the patients) in both healthy individuals and examined patients, significantly increased secretory renal function (significantly higher in healthy individuals than in the examined patients), and increased ANP (previously significantly higher in healthy subjects). A significant correlation between ANP level in blood serum and changes in volume was seen only in healthy individuals. The obtained results suggest a contribution of other than changed volume factors of ANP release regulation and other than ANP factors to pathomechanism of post-immersion drop of the arteria blood pressure and increased secretory renal function in both healthy individuals and patients with renal failure.