Binding of teicoplanin to human serum albumin

Summary The interaction between the main components of the new glycopeptide antibiotic teicoplanin, A2–2, A2–3, A2–4, A2–5 and A3–1, and human serum albumin has been studied in vitro by equilibrium dialysis (pH 7.4, 37°C).From Scatchard analysis of the data, the calculated association constants (Ka) were: A2–2, 2.47×10⁴, A2–3, 2.86×10⁴, A2–4, 2.95×10⁴ and A2–5, 3.87×10⁴ mol·l^–1. The number of binding sites per albumin molecule ranged between 1.23 to 1.31. A3–1 had a lower affinity with a Ka of about 5×10³ mol·l^–1.Extrapolated to the in vivo situation, the data suggested that about 90–95% of A2 components will be bound to serum albumin, and about 68–72% of A3–1.The in vitro findings were confirmed by a pharmacokinetic study in volunteers given [¹⁴C] teicoplanin i.v., in whom the fraction of teicoplanin bound to serum protein ranged between 87.6 and 90.8%.     

Equol and other compounds from bovine urine as monoamine oxidase inhibitors

Summary Equol, its methylated derivative, and a carbazole, all isolated from bovine urine, are relatively potent inhibitors of monoamine oxidase with IC₅₀ values of 158, 28, and 16M respectively (using 83M tyramine as substrate). The probable dietary origin of these compounds suggests that natural monoamine oxidase inhibitors may be more widespread than had previously been suspected.     

Pharmacokinetic and pharmacodynamic study of the combination of furosemide retard and triamterene

Summary The pharmacodynamics and pharmacokinetics of the combination of furosemide retard (30 mg)/triamterene (50 mg) were compared with furosemide (30 mg) in 18 healthy male volunteers aged 39.3±6.3 years. After the administration of furosemide the onset of its effect was very rapid, reaching a maximum between 1.5 to 3 h, and followed by rebound after 9 to 10.5 h. In contrast the combination furosemide retard/triamterene showed a protracted course with a duration of effect up to 12 h. The general effect over 12 h of the two preparations was equivalent with respect to the excretion of urine, sodium, chloride and calcium, but the combination caused significantly less excretion of potassium (p0.05) than furosemide. After a lag-phase of 33.9±5.4 min the maximum plasma concentration of furosemide was reached after 3.47±0.66 h, and the elimination half-life was approximately 2 h. After a lag-phase of 33.0±17.8 min the maximum plasma concentration of the main metabolite of triamterene, the OH-TA sulphuric acid ester, was reached after 1.7±0.59 h, and its elimination half-life amounted to 1.25±0.37 h. Because of the sustained release of furosemide from the retard-formulation, its principal pharmacokinetic parameters were better adapted to those of triamterene. The consequences were not only a protracted effect but also an improved electrolyte profile, especially with regard to reduced loss of potassium. In the case of renal insufficiency, however, the potassium level in serum might be increased to an undesirable extent.     

Hyperosmolarity response of ocular standing potential as a clinical test for retinal pigment epithelium activity rhegmatogenous retinal detachment

The hyperosmolarity response of the ocular standing potential was recorded in unilateral rhegmatogenous retinal detachment (8 eyes) and in the fellow healthy eye (8 eyes). The hyperosmolarity response was greatly suppressed (M-4 SD: M and SD indicate respectively the mean and the standard deviation in normal subjects) in all affected eyes (p < 0.005), and slightly abnormal in 2 fellow eyes. The L/D ratio was normal in 2 affected eyes and in all fellow eyes. The hyperosmolarity response in the affected eyes was still greatly suppressed 14 months after successful surgical treatment.     

Combination of Quantitative Computed Tomography and Blood Biochemistry for Evaluating the Relationship Between Nutrition and Bone Mineral Density in Patients on Maintenance Hemodialysis

PurposeTo investigate the effect of nutritional factors on bone mineral density (BMD) using quantitative computed tomography combined with blood biochemistry in patients on maintenance hemodialysis (MHD).MethodsSixty patients on MHD were divided into osteopenia (n = 20) and nonosteopenia (n = 40) groups. BMD, fat, and muscle mass were measured by quantitative computed tomography. The calcification of coronary artery and hilar lymph node and computed tomography attenuation values of the liver and spleen were also analyzed. Differences between the two groups were compared, and the risk factors for osteopenia were analyzed by logistic regression analysis.ResultsPatients in the osteopenia group had lower albumin levels than those in the nonosteopenia group (37.84 ± 3.00 vs 42.03 ± 4.05 g/L; P < .001). Logistic regression showed that patients with lower albumin levels had a higher risk of osteopenia (odds ratio, 1.462; 95% confidence interval, 1.313–1.801; P = .003). BMD was negatively correlated with fat mass (r = ?0.365, P = .004) and positively correlated with the ratio of muscle mass to fat mass (r = 0.431, P = .001). There was no significant difference in the rate of calcification of coronary artery or hilar lymph nodes between the two groups. Computed tomography values of the liver and spleen were positively correlated with the duration of dialysis (r = 0.55, P = .001; r = 0.42, P < .001, respectively).ConclusionLow albumin levels are associated with an increased risk of osteopenia in patients on MHD. Abdominal fat is a risk factor for reduction in BMD in MHD patients, and the ratio of abdominal muscle mass to fat mass is a protective factor for BMD.     

Comparison of the PROMIS Preference Score (PROPr) and EQ-5D-5L Index Value in General Population Samples in the United Kingdom,France, and Germany

ObjectivesThe Patient-Reported Outcome Measurement Information System (PROMIS) Preference score (PROPr) can be used to assess health state utility (HSU) and estimate quality-adjusted life-years in cost-effectiveness analyses. It is based on item response theory and promises to overcome limitations of existing HSU scores such as ceiling effects. The PROPr contains 7 PROMIS domains: cognitive abilities, depression, fatigue, pain, physical function, sleep disturbance, and ability to participate in social roles and activities. We aimed to compare the PROPr with the 5-level EQ-5D (EQ-5D-5L) in terms of psychometric properties using data from 3 countries.MethodsWe collected PROMIS-29 profile and EQ-5D-5L data from 3 general population samples (United Kingdom = 1509, France = 1501, Germany = 1502). Given that cognition is not assessed by the PROMIS-29, it was predicted by the recommended linear regression model. We compared the convergent validity, known-groups construct validity, and ceiling and floor effects of the PROPr and EQ-5D-5L.ResultsThe mean PROPr (0.48, 0.53, 0.48; P<.01) and EQ-5D-5L scores (0.82, 0.85, 0.83; P<.01) showed significant differences of similar magnitudes (d = 0.34; d = 0.32; d = 0.35; P<.01) across all samples. The differences were invariant to sex, income, occupation, education, and most conditions but not for age. The Pearson correlation coefficients between both scores were r = 0.74, r = 0.69, and r = 0.72. PROPr’s ceiling and floor effects both were minor to moderate. The EQ-5D-5L’s ceiling (floor) effects were major (negligible).ConclusionsBoth the EQ-5D-5L and the PROPr assessed by the PROMIS-29 show high validity. The PROPr yields considerably lower HSU values than the EQ-5D-5L. Consequences for quality-adjusted life-year measurements should be investigated in future research.     

A Log Ratio-Based Analysis of Individual Changes in the Composition of the Oral Microbiota in Different Dietary Phases

Background: Investigating the influence of nutrition on oral health has a long scientific history. Due to recent technical advances like sequencing techniques for the oral microbiota, this topic has gained scientific interest again. A basic challenge is to understand the influence of nutrition on the oral microbiota and on the interaction between the oral bacteria, which is also statistically challenging. Methods: Log-transformed ratios of two bacteria concentrations are introduced as the basic analytic tool. The framework is illustrated by application in an experimental study exposing eleven participants to different nutrition schemes in five consecutive phases. Results: The method could be sufficiently used to analyse the interrelation between the bacteria and to identify some bacterial groups with the same as well as different reactions to additional dietary components. It was found that the strongest changes in bacterial concentrations were achieved by the additional consumption of dairy products. Conclusion: A log ratio-based analysis offers insights into the relation of different bacteria while taking specific features of compositional data into account. The presented methods allow becoming independent of the behaviour of other bacteria, which is a disadvantage of common analysis methods of compositions. The results indicate that modulations of the oral biofilm microbiota due to nutrition change can be attained.     

Maternal Quercetin Consumption during Pregnancy May Help Regulate Total Cholesterol/HDL-Cholesterol Ratio without Effect on Cholesterol Levels in Male Progeny Consuming High-Fat Diet

Quercetin has been shown to have anti-obesity effects, but it is unknown whether these effects can be transmitted from mothers to their progeny. In this study, we investigated whether maternal quercetin consumption during pregnancy has a protective effect on high-fat diet–induced hyper lipid levels and overweight in progeny. Female mice consumed a control diet or a diet containing 1.0% quercetin during breeding. The male progeny were then divided into four groups that were (1) sacrificed at postnatal day 3; (2) born to dams fed the control diet and also fed the control diet (C-C), (3) born to dams fed the control diet and then fed a 30% high-fat diet (C-HF), or (4) born to dams fed the Q-diet and then fed the HF diet (Q-HF). Maternal consumption of quercetin did not affect body weight or blood lipid parameters in either dams or neonates at postnatal day 3. After 13 weeks, the Q-HF group exhibited greater body and liver weights, and higher blood cholesterol levels than the C-HF group. However, the total cholesterol/ high density lipoprotein (HDL)-cholesterol ratios in the Q-HF and C-C groups remained similar. In conclusion, maternal quercetin consumption does not appear to protect the next generation from high-fat diet–induced hyper cholesterol level in the blood and liver, and consequently overweight, but may help regulate the total cholesterol/HDL-cholesterol ratio.     

Association between Reduced Serum Zinc and Diastolic Dysfunction in Maintenance Hemodialysis Patients

Diastolic dysfunction is an emerging challenge among hemodialysis (HD) patients, and the associations between serum zinc with echocardiographic parameters and diastolic function remain uncertain. A total of 185 maintenance HD patients were stratified by the tertiles of serum zinc level to compare their clinical characteristics and echocardiography. Correlations of serum zinc levels with echocardiographic parameters were examined using Pearson’s analysis. Univariate and multivariate logistic regression analyses were performed to investigate the determinants of E/e’ ratio >15 and left atrial volume index (LAVI) > 34 mL/m², both indicators of diastolic dysfunction. Patients belonging to the first tertile of serum zinc level had a significantly higher E/e’ ratio and LAVI. Serum zinc levels were negatively correlated with E (r = −0.204, p = 0.005), E/e’ ratio (r = −0.217, p = 0.003), and LAVI (r = −0.197, p = 0.007). In a multivariate analysis, older age, diabetes, coronary artery disease, and lower serum zinc levels (OR = 0.974, 95% CI = 0.950–0.999, p = 0.039) were significantly associated with E/e’ ratio >15. Furthermore, diabetes and lower serum zinc levels (OR = 0.978, 95% CI = 0.958–0.999, p = 0.041) were significantly associated with LAVI >34 mL/m². Reduced serum zinc level was significantly associated with diastolic dysfunction among HD patients. Further prospective studies are warranted to investigate whether zinc supplementation can attenuate cardiac dysfunction in maintenance HD patients.     

全国细菌耐药监测网2014—2019年尿标本细菌耐药监测报告

目的探讨全国尿标本分离细菌菌种分布及耐药变迁。方法按照全国细菌耐药监测网(CARSS)技术方案,应用WHONET5.6软件对2014—2019年所有CARSS成员单位上报的尿标本分离细菌及药敏结果数据进行分析。结果男性患者尿标本分离细菌居前5位者分别为大肠埃希菌(33.1%~34.6%)、粪肠球菌(9.2%~10.2%)、肺炎克雷伯菌(9.0%~9.4%)、屎肠球菌(7.8%~10.2%)和铜绿假单胞菌(5.6%~6.9%),女性患者尿标本分离细菌居前5位者分别为大肠埃希菌(57.0%~57.4%)、肺炎克雷伯菌(7.5%~8.3%)、屎肠球菌(6.8%~8.7%)、粪肠球菌(5.5%~6.0%)和奇异变形杆菌(3.3%~3.5%)。男性和女性患者尿标本分离粪肠球菌对氨苄西林和呋喃妥因耐药率分别<12%和7%,对万古霉素耐药率<3%;屎肠球菌对氨苄西林、左氧氟沙星耐药率均为90%左右,对万古霉素耐药率<4%。大肠埃希菌对头孢曲松耐药率>47%,对头孢哌酮/舒巴坦、哌拉西林/他唑巴坦、呋喃妥因耐药率≤8%,对于β-内酰胺类耐药率男性比女性高,其中头孢曲松的耐药率高12个百分点左右。男性患者分离肺炎克雷伯菌对头孢曲松耐药率为58%左右,女性患者耐药率为45%左右。男性和女性患者尿标本分离铜绿假单胞菌对头孢哌酮/舒巴坦和哌拉西林/他唑巴坦的耐药率均<14%,对碳青霉烯类耐药率为15%左右。鲍曼不动杆菌对头孢哌酮/舒巴坦和米诺环素耐药率分别<27%和22%,对碳青霉烯类耐药率,男性为31.7%~47.7%,女性为26.5%~41.2%。结论尿标本分离细菌在不同性别构成上有所不同,且部分肠杆菌目细菌耐药率不同性别间也有一定差异,不同年度间部分细菌的耐药率也有一定变化。尿标本分离细菌的耐药监测,可为尿路感染抗菌药物合理应用提供参考数据。