Oxygen free radicals in volume overload heart failure

It has been suggested that oxygen free radicals (OFR) depress the excitation-contraction coupling in cardiac muscle. It is possible that a decrease in the cardiac contractility in the failing heart may be due to an increased OFR producing activity of polymorphonuclear (PMN) leukocytes. We studied the OFR producing activity (chemiluminescence) of PMN leukocytes from blood in dogs with heart failure due to chronic volume overload. The animals were divided into two groups: I) normal, (n = 10): II) dogs with mitral insufficiency (MI) of 6 to 9 months duration, (n = 10). Hemodynamic studies were done to establish the presence of heart failure. Blood samples were collected to measure PMN leukocyte chemiluminescence. There was a decrease in the cardiac index and index of myocardial contractility (dp/dt/IIP) and an increase in the left ventricular end-diastolic pressure in dogs with MI indicating left ventricular failure. The peak chemiluminescent activity of the PMN leukocytes in blood of dogs with failure was about four folds greater than that in the blood from normal dogs. These results suggest that there may be an increased OFR generation in dogs with volume overload heart failure. The decrease in the myocardial contractility in the failing heart might be due to an increase in the OFR produced by the PMN leukocytes.     

Plasmodium berghei: a mouse model for the "sudden death" and "malarial lung" syndromes

A mouse model for the "sudden death" and "malarial lung" syndromes is described. Mice of the C3H/z strain succumb suddenly approximately 7 days after an infection with Plasmodium berghei becomes patent, at a time when parasitemia is still moderate (6 to 8%). Death could be shown to be due to anaphylactoid shock, probably induced by soluble immune complexes. Increased vascular permeability caused transudation and leakage of serum proteins into the interstitium and the alveoli. The lungs were found to be edematous, with a fine granular precipitate in the alveoli and adherent to the vascular walls. The precipitates reacted with antiglobulins G and M, and could be shown to also contain malaria antigens and C3/4. A dramatic drop in hematocrit was recorded several hours before death, indicating the sudden release of malaria antigens. The myocardium of animals that had died very suddenly showed a patchy loss of phosphorylase activity. This loss of activity was much more extensive, and sometimes almost total, when there had been an agonal period of several (1 to 3) hours before death. In these cases the irreversibility of the myocardial damage was also indicated by the loss of activity of the dehydrogenases, as well as by typical inflammatory reactions of granulocytic and histiocytic infiltrations. The hearts thus presented a typical picture of the acute and peracute shock syndromes. In acute shock cardiac insufficiency develops so suddenly that death ensues before irreversible damage has occurred, and cardiac insufficiency can only be demonstrated by the most sensitive of enzyme histochemical means. In the present case shock was induced by the anaphylactoid activity of immune complexes with the lung as target organ. The described syndrome appears analogous to human "malarial lung."     

Treatment of Gaucher disease with an enzyme inhibitor

The hypothesis is offered predicting that Caucher patients could be treated with a drug that slows the synthesis of glucosylceramide, the lipid that accumulates in this disorder. The present therapeutic approach involves augmenting the defective enzyme, glucosylceramide -glucosidase, with exogenous -glucosidase isolated from human tissue. This spectacularly expensive mode of treatment should be replaceable with a suitable enzyme inhibitor that simply slows formation of the lipid and matches the rate of synthesis with the rate of the defective, slowly working -glucosidase. Several drugs that possess this ability are available, the best known of which is 1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP), a designer inhibitor that resembles the synthase's substrate and product. PDMP has been found to be effective in mice, rats, fish, and a wide variety of cultured cells. Its use, at suitable dosages, seems to be harmless, although long-term tests have not been made. The lack of suitable animal models of Gaucher disease has made it difficult to test the hypothesis adequately, but PDMP does rapidly lower the levels of glucosylceramide in normal animal tissues and the animals evidently do well with the lowered levels of glucosylceramide and its more complex glycolipid metabolites.Abbreviations PDMP 1-phenyl-2-decanoylamino-3-morpholino-1-propanol - GlcCer glucosylceramide - i.p. intraperitoneal     

Adoptive transfers of CD4+CD25+ Tregs partially alleviate mouse premature ovarian insufficiency

This study was designed to investigate the protective effect of CD4⁺CD25⁺ regulatory T cells (Tregs) against zona pellucida glycoprotein 3 peptide (pZP3) immunization‐induced premature ovarian insufficiency (POI) in mice. A mouse POI model was induced by two subcutaneous injections of pZP3 (50 nmol/L). Mice in the pZP3‐Treg group were intraperitoneally injected with 5 × 10⁵ CD4⁺CD25⁺ Tregs after the POI model was established. Sex hormone levels, follicle numbers, apoptotic events, and the Akt/FOXO3a signaling pathway molecules in the ovaries were assessed. Compared with control group, the weight of ovaries in both pZP3 group and pZP3‐Treg group was decreased and no difference was found between them. The number of follicles in the Treg transferred mice, like in pZP3 group, was significantly reduced compared to the control group, but showed a modest improvement when compared the pZP3 group alone. Significantly lower serum concentrations of follicle‐stimulating hormone, luteinizing hormone, and anti‐zona pellucida antibodies (AZPAbs) were found, while the concentrations of estradiol and anti‐Mullerian hormone increased. In mechanism, Treg cell transfer to ZP3 treated mice restored the levels of Caspase3 to control levels, and partially restored Bax, however, had no effect on Bcl‐2. Moreover, Treg cell transfer to ZP3 treated mice partially restored the levels of Akt and FOXO3a, and partially restored the ratios of p‐Akt/Akt and p‐FOXO3a/FOXO3a. In conclusion, Treg cells improved some aspects of ZP3‐induced POI which may be mediate by suppressing ovarian cells apoptosis and involving the Akt/FOXO3a signaling pathway. Therefore, Treg cells may be protective against autoimmune POI.     

苓桂术甘汤联合电针风池供血穴治疗椎基底动脉供血不足性眩晕的临床研究

目的:探讨苓桂术甘汤联合电针风池供血穴治疗椎基底动脉供血不足(VBI)性眩晕的临床疗效。方法:选择2017年11月-2019年8月我院收治的VBI性眩晕患者145例为研究对象,采用随机数字表法分成联合组(75例)和对照组(70例)。在基础治疗的前提下,联合组采用苓桂术甘汤联合电针风池供血穴治疗,对照组采用西比灵治疗。比较两组临床疗效、眩晕改善情况、脑动脉血流速度指标、动脉硬化指数(AI)以及血液流变学指标。结果:治疗后联合组总有效率为89.33%,高于对照组的75.71%(P<0.05);治疗后联合组眩晕症状积分、欧洲眩晕评分量表(EEV)评分和眩晕障碍量表(DHI)评分低于对照组(P<0.05);联合组治疗后左侧动脉、基底动脉峰值流速(Vp)、左右侧动脉、基底动脉平均血流速度(Vm)均高于对照组,左侧动脉、基底动脉血管搏动指数(PI)、右侧动脉血管阻力指数(RI)、AI、高切全血黏度、中切全血黏度、低切全血黏度、血浆黏度、红细胞压积均低于对照组(P<0.05)。结论:苓桂术甘汤联合电针风池供血穴治疗VBI性眩晕,能够缓解患者的眩晕状况,疗效确切,改善脑动脉血流速度和脑动脉硬化程度,降低血液黏度。     

Seasonality of dizziness and vertigo in a tropical region

Vertigo and dizziness are among the most common medical complaints in the emergency room, and are associated with a considerable personal and health care burden. Scarce and conflicting reports indicate those symptoms may present a seasonal distribution. This study aimed at investigating the existence of a seasonal distribution of vertigo/dizziness in a tropical region, and the correlations of these findings with climatic variables. The charts of all patients consecutively admitted between 2009 and 2012 in the emergency room of a Brazilian general hospital were reviewed. A total of 4920 cases containing these terms were sorted from a sample of 276?076 emergency records. Seasonality was assessed using Cosinor Analysis. Pearson's correlations were performed between the incidence of consultations, considering separately dizziness and vertigo and each of the predictor climatic variables of that index month. Significant seasonal patterns were observed for dizziness and vertigo in the emergency room. Vertigo was more frequent in late winter–spring, negatively correlating to humidity (r?=??0.374; p?=?0.013) and rainfall (r?=??0.334; p?=?0.020). Dizziness peaked on summer months, and positively correlated to average temperatures (r?=?0.520; p?<?0.001) and rainfall (r?=?0.297; p?=?0.040), but negatively to atmospheric pressure (r?=??0.424; p?=?0.003). The different seasonal patterns evidenced for dizziness and vertigo indicate possible distinct underlying mechanisms of how seasons may influence the occurrence of those symptoms.     

尼可地尔联合冠状动脉心脏介入治疗冠心病合并肾功能不全的疗效及对NGAL、Cys-C的影响

摘要 目的：探析冠心病（CHD）合并肾功能不全（RI）应用冠状动脉心脏介入治疗（PCI）联合尼可地尔的临床疗效及对胱抑素C（Cys-C）、中性粒细胞明胶酶相关脂质运载蛋白（NGAL）影响。方法：选择本院2019年6月~2021年6月就诊的86例CHD合并RI患者,随机数字表法分为两组各43例。 两组均实施PCI治疗,对照组实施常规静脉水化处理,观察组联合尼可地尔治疗。对比两组PCI治疗前后24 h肾功能指标（Cys-C、NGAL）、血清炎性因子指标（高敏C反应蛋白 (hs-CRP)、白细胞介素 6 (IL-6)）、心肌损伤指标（心肌肌钙蛋白I（cTnI）及肌酸激酶同工酶（CK-MB））、并发症发生率。结果：观察组CIN发生率（2.33%）、MACE率（2.33%）均明显低于对照组（16.28%、13.95%）,有统计学差异（P<0.05）。两组PCI治疗前Cys-C、NGAL、hs-CRP、IL-6、cTnI、CK- MB无统计学差异（P<0.05）。治疗后观察组Cys-C、NGAL、hs-CRP、IL-6升高幅度、组cTnI、CK- MB明显低于对照组（P<0.05）。结论：PCI 联合尼可地尔应用于CHD合并RI临床治疗效果显著,可有效改善患者肾功能,降低炎症反应、心肌损伤,预防CIN发生。     

早发性卵巢功能不全患者血清25-OH-VD、DBP、SIRT1与性激素和氧化应激的关系研究

摘要 目的：探讨早发性卵巢功能不全（POI）患者血清25-羟基维生素D（25-OH-VD）、邻苯二甲酸二丁酯（DBP）、沉默信息调节因子2相关酶1（SIRT1）与性激素和氧化应激的关系。方法：选取2019年1月～2020年12月攀枝花学院附属医院妇产科收治的97例POI患者（POI组）,另选取同期54名体检健康女性（对照组）。检测两组血清性激素[卵泡刺激素（FSH）、黄体生成素（LH）、雌二醇（E2）、抗缪勒管激素（AMH）]、氧化应激[超氧化物岐化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）、丙二醛（MDA）]、25-OH-VD、DBP、SIRT1水平。采用Pearson/Spearman相关系数分析POI患者血清25-OH-VD、DBP、SIRT1与性激素、氧化应激指标的相关性,Logistic回归分析血清25-OH-VD、DBP、SIRT1与POI的关系。结果：POI组FSH、LH、MDA、DBP水平高于对照组,E2、AMH、SOD、GSH-Px、25-OH-VD、SIRT1水平低于对照组（P＜0.05）。Pearson/Spearman相关系数显示,POI患者血清25-OH-VD、SIRT1与FSH、LH、MDA呈负相关,与E2、AMH、SOD、GSH-Px呈正相关（P＜0.05）;血清DBP与FSH、LH、MDA呈正相关,与E2、AMH、SOD、GSH-Px呈负相关（P＜0.05）。Logistic回归分析显示,调整混杂因素后,25-OH-VD（OR＝0.825,95％CI：0.741～0.919）、SIRT1（OR＝0.872,95％CI：0.810～0.938）是POI发生的保护因素,DBP（OR＝1.173,95％CI：1.074～1.282）是危险因素（P＜0.05）。结论：POI患者血清25-OH-VD、SIRT1水平下调,DBP水平上调,与性激素和氧化应激相关,可能成为POI的辅助预测因子。     

The effect of high protein diet on urea and guanidino compound levels in renal insufficient mice

Summary. Nephrectomy in mice provokes a decrease in creatinine clearance (CTN_Cl) and an increase in urea and specific guanidino compound (GC) concentrations in blood and other tissues. Our purpose was to investigate the influence of high protein diet (HPD) on CTN_Cl, urea and GC levels in NX mice. Mice were nephrectomized or sham-operated and subdivided in groups to study five diet conditions. At the end of each experiment, 10 days and 30 days postsurgery, urine and blood were collected for determination of urea and GCs, including creatinine. HPD resulted in significantly higher CTN_Cl values in sham-operated mice than those observed in mice under normal protein diet, 10 days as well as 30 days postnephrectomy. HPD induced significant increases in plasma urea, guanidinosuccinic acid, argininic acid and α-keto-δ-guanidinovaleric acid concentration 10 days postsurgery but not 30 days postsurgery. HPD coincided with significantly higher excretion of urea, guanidinosuccinic acid, α-keto-δ-guanidinovaleric acid, creatine, argininic acid and γ-guanidinobutyric acid in sham-operated and nephrectomized mice 10 days postsurgery. Our results show that HPD induces supplementary (to nephrectomy) increases of urea and GCs in the early postsurgery period but not in the later phase. Received June 13, 2000 Accepted January 9, 2001