Investigation of the Aortic Pulse Wave Velocity in Patients with Gilbert’s Syndrome

Arterial stiffness is currently the “gold standard” measure of aortic (carotid-femoral) pulse wave velocity (PWV), which is an important independent predictor of risk of developing a cardiovascular event. Gilbert’s syndrome is a congenital disorder characterized by intermittent and non-hemolytic elevation of indirect bilirubin levels due to the deficiency of the enzyme UDP-glucuronyl transferase in the liver and many prospective studies found an inverse relationship between bilirubin levels and cardiovascular events in these patients. We aimed to investigate serum bilirubin levels and arterial stiffness parameters in patients with Gilbert’s syndrome in this study. A total of 53 cases, consisting of 26 patients with a diagnosis of Gilbert’s syndrome and 27 healthy control subjects, were included in the study. Serum bilirubin levels, other routine blood chemistry, and arterial stiffness measurements were recorded. The mean ages of Gilbert’s syndrome and the control group were 31.5 ± 9.7 and 36.8 ± 11.1 years, respectively. PWV measurements were significantly lower in Gilbert syndrome patients (6.68 and 7.3 m/s in patients and controls; respectively) (P < .05). In correlation analysis in Gilbert’s syndrome patients, PWV had a significant correlation with total and indirect bilirubin levels (r = ?0.370, P = .009/r = ?0.495, P = .003, respectively). Gilbert’s syndrome patients have lower PWV measurements compared to healthy subjects, and the total and indirect bilirubin levels are also associated with PWV measurements. These findings may indicate the decreased atherosclerotic disease incidence in Gilbert’s syndrome patients.     

UGT1A1基因复合杂合突变致吉尔伯特综合征一例

一例吉尔伯特综合征患儿自幼反复出现巩膜黄染,无其他自觉症状;血清胆红素水平升高,以非结合胆红素为主;排除胆道梗阻、溶血等其他引起黄疸的因素;基因检测发现患儿尿苷二磷酸葡糖苷酸转移酶1A1（UGT1A1）基因存在UGT1A1*28和c.211G>A杂合突变。     

Effect of nicotine upon uterine blood flow in the pregnant rhesus monkey

Acute effects of nicotine upon the uterine blood flow, blood pressure, maternal and fetal acid-base state, and oxygenation were determined in eight pregnant rhesus monkeys near term. Nicotine was infused intravenously to the mother in a dose of 100 microgram/kg per body weight/minute over 20 minutes. The flow rate was measured with the use of the electromagnetic flowmeter. Significant decrease in the uterine arterial blood flow rate, as much as 38% of the control value, was observed during the first 15 minutes of the infusion while aortic pressure increased by 14%. Acidosis and hypoxia resulted in the fetus. Considered together with our previously reported data, the present investigation appears to indicate that the adverse effects of nicotine to the fetus are due to the combined effects of the reduced uterine blood flow and the transmitted nicotine to the fetus.     

云南省婴儿期不同民族高非结合性胆红素血症UGT1A1基因多态性研究

目的研究云南省婴儿期不同民族高非结合性胆红素血症UGT1A1基因多态性研究。方法收集怒江、保山、临沧、迪庆云南边界地区2018年1月至2019年11月就诊于本院新生儿科及消化内科门诊确诊的GS和CNS患儿67例(观察组,基因检测均阳性),并选取同期健康体检婴儿67例作为对照组。比较两组UGT1A1基因突变位点基因型与等位基因频率分布,采用Spearman分析UGT1A1基因突变与非溶血性非结合型高胆红素血症的相关性,比较不同性别、民族患儿UGT1A1基因变异谱。结果观察组c.211G>A、c.1456T>G、c.1061C>T位点突变率分别为62.69%、62.69%、47.77%,高于对照组的14.93%、2.99%、7.46%(P<0.05),组间基因型频率和等位基因频率比较,差异具有统计学意义(P<0.05)。c.211G>A、c.1456T>G、c.1061C>T杂合与纯合突变均与非溶血性非结合型高胆红素血症呈正相关(P<0.05);汉族患儿c.211G>A、c.1456T>G、c.1061C>T杂合突变型均高于少数民族患儿,汉族患儿c.1456T>G纯合突变型频率低于少数民族患儿(P<0.05)。结论云南地区婴儿期高非结合性胆红素血症发病与UGT1A1基因c.211G>A、c.1456T>G、c.1061C>T位点突变有关,c.1456T>G纯合突变集中体现在少数民族中,c.211G>A、c.1456T>G、c.1061C>T复合杂合突变致病主要集中在汉族人群。     

Enterohepatic cycling of bilirubin as a cause of 'black' pigment gallstones in adult life

In contrast to bile salts, which undergo a highly efficient enterohepatic circulation with multiple regulatory and physiologic functions, glucuronic acid conjugates of bilirubin are biliary excretory molecules that in health do not have a continuing biologic life. Intestinal absorptive cells are devoid of recapture transporters for bilirubin conjugates, and their large size and polarity prevent absorption by passive diffusion. However, unconjugated bilirubin, the beta-glucuronidase hydrolysis product of bilirubin glucuronides can be absorbed passively from any part of the small and large intestines. This can occur only if unconjugated bilirubin is kept in solution and does not undergo rapid bacterial reduction to form urobilinoids. Here we collect, and in some cases reinterpret, experimental and clinical evidence to show that in addition to the well-known occurrence in newborns, enterohepatic cycling of unconjugated bilirubin can reappear in adult life. This happens as a result of several common conditions, particularly associated with bile salt leakage from the small intestine, the most notable ileal dysfunction resulting from any medical or surgical cause. We propose that when present in excess, colonic bile salts solubilize unconjugated bilirubin, delay urobilinoid formation, prevent calcium complexing of unconjugated bilirubin and promote passive absorption of unconjugated bilirubin from the large intestine. Following uptake, reconjugation, and resecretion into bile, this source of 'hyperbilirubinbilia' may be the important pathophysiological risk factor for 'black' pigment gallstone formation in predisposed adult humans.     

遗传性高胆红素血症1例报道并文献回顾

目的探讨遗传性高胆红素血症的发病机制及临床特点。方法本文报告了一例较为罕见的遗传性高胆红素血症的病例,并进行了相关的文献复习。结果本例13岁的患几经多次的生化学、血液学、影像学、组织学检查,并进行苯巴比妥的诊断性治疗有效,提示该患儿为遗传性高胆红素血症：1．Gilbert综合症？2．Crigler-Najjar综合症（Ⅱ型）？结论遗传性高胆红素血症在临床上较为罕见,需要对患者的病史、家族史、临床特征及实验室检查做仔细分析,并可结合诊断性治疗,如苯巴比妥等进行诊断,早期治疗对患者的预后有一定的帮助,基因检测可进一步明确诊断。