Insulin-like growth factor system components in hyperparathyroidism and renal osteodystrophy

BACKGROUND: The insulin-like growth factor (IGF) system plays a key role in regulation of bone formation. In patients with renal osteodystrophy, an elevation of some IGF binding proteins (IGFBPs) has been described, but there is no study measuring serum levels of both IGF-I and IGF-II as well as IGFBP-1 to -6 in different forms of renal osteodystrophy and hyperparathyroidism. METHODS: In a cross-sectional study, we investigated 319 patients with mild (N = 29), moderate (N = 48), preuremic (N = 37), and end-stage renal failure (ESRF; N = 205). The ESRF group was treated by hemodialysis (HD; N = 148), peritoneal dialysis (PD; N = 27), or renal transplantation (RTX; N = 30). As controls without renal failure, we recruited age-matched healthy subjects (N = 87) and patients with primary hyperparathyroidism (pHPT; N = 25). Serum levels of total and free IGF-I, IGF-II, IGFBP-1 to -6, and biochemical bone markers including intact parathyroid hormone (PTH), bone alkaline phosphatase (B-ALP), and osteocalcin (OSC) were measured by specific immunometric assays. IGF system components and bone markers were correlated with clinical and bone histologic findings. Mean values +/- SEM are given. RESULTS: With declining renal function a significant increase was measured for IGFBP-1 (range 7- to 14-fold), IGFBP-2 (3- to 8-fold), IGFBP-3 (1.5- to 3-fold), IGFBP-4 (3- to 19-fold), and IGFBP-6 (8- to 25-fold), whereas IGFBP-5 levels tended to decrease (1.3- to 1. 6-fold). In contrast, serum levels of IGF-I, free IGF-I, and IGF-II remained constant in most patients. Compared with renal failure patients, pHPT patients showed a similar decline in IGFBP-5 levels and less elevated levels of IGFBP-1 (3.5-fold), IGFBP-2 (2-fold), IGFBP-3 (1.2-fold), and IGFBP-6 (4-fold) but no elevation of IGFBP-4 levels. In all subjects, free and total IGF-I levels showed significant negative correlations with IGFBP-1, IGFBP-2, and IGFBP-4 (that is, inhibitory IGF system components) and significant positive correlations with IGFBP-3 and IGFBP-5 (that is, stimulatory IGF system components). A positive correlation was observed between IGF-II and IGFBP-6. ESRF patients with mixed uremic bone disease and histologic evidence for osteopenia revealed significantly (P < 0.05) higher levels of IGFBP-2 and IGFBP-4 but lower IGFBP-5 levels. Histologic parameters of bone formation showed significant positive correlations with serum levels of IGF-I, IGF-II, and IGFBP-5. In contrast, IGFBP-2 and IGFBP-4 correlated positively with indices of bone loss. Moreover, dialysis patients with low bone turnover (N = 24) showed significantly (P < 0.05) lower levels of IGFBP-5, PTH, B-ALP, and OSC than patients with high bone turnover. CONCLUSION: Patients with primary and secondary hyperparathyroidism showed lower levels of the putative stimulatory IGFBP-5 but higher levels of IGFBP-1, -2, -3, and -6, whereas total IGF-I and IGF-II levels were not or only moderately increased. The marked increase in serum levels of IGFBP-4 appeared to be characteristic for chronic renal failure. IGFBP-5 correlated with biochemical markers and histologic indices of bone formation in renal osteodystrophy patients and was not influenced by renal function. Therefore, IGFBP-5 may gain significance as a serological marker for osteopenia and low bone turnover in long-term dialysis patients.     

Respiratory syncytial virus genotypes and disease severity among children in hospital

OBJECTIVES: To determine the spectrum of N and G genotypes of respiratory syncytial virus (RSV) causing respiratory tract infection and whether particular genotypes are associated with severity of infection. PATIENTS AND METHODS: Nasopharyngeal aspirates (NPAs) were obtained from 114 infants with acute respiratory tract infection due to RSV over two seasons. Viral mRNA was extracted from NPAs or cultured virus, reverse transcribed, and the cDNA amplified by the polymerase chain reaction using primers directed to parts of the N and G gene respectively. Amplicons were separately digested with four different restriction endonucleases for each gene. The fragments were separated by agarose gel, electrophoresis, and the electrophoretic patterns used to assign the various genotypes. Disease severity was assessed as very mild (upper respiratory tract signs only), mild (coryza and signs of lower respiratory tract infection), moderate (requiring nasogastric or intravenous fluids), and severe (requiring oxygen or ventilation). RESULTS: Five of the six known N genotypes were detected, but NP4 and NP2 were found most frequently. There was no association between N genotype and disease severity. Six G (SHL) genotypes were detected. Significantly (p = 0.04) more of the infants infected with the SHL2 genotype had severe or moderate disease. CONCLUSIONS: During the seasonal peaks of RSV respiratory tract infection at least 10 different RSV genotypes cocirculated. While there is no association between N genotypes and disease severity, infection with the SHL2 G genotype appears to result in moderate to severe disease.     

Total but not resting energy expenditure is increased in infants with ventricular septal defects

OBJECTIVE: The purpose of this study was to determine the effect of left-to-right shunting on the resting energy expenditure (REE), total energy expenditure (TEE), and energy intake in a group of 3- to 5-month-old infants with moderate to large unrepaired ventricular septal defects (VSDs) compared with age-matched, healthy infants. METHODS: Eight infants with VSDs and 10 healthy controls between 3 to 5 months of age participated in the study. Indirect calorimetry was used to measure REE and the doubly-labeled water method was used to measure TEE and energy intake. An echocardiogram and anthropometric measurements were performed on all study participants. Daily urine samples were collected at home for 7 days. Samples were analyzed by isotope ratio mass spectrometry. Data were compared using analysis of variance. RESULTS: No significant differences were found in REE (VSD, 42.2 +/- 8.7 kcal/kg/d; control, 43.9 +/- 14.1 kcal/kg/d) or energy intake (VSD, 90.8 +/- 19.9 kcal/kg/d; control, 87.1 +/- 11.7 kcal/kg/d) between the groups. The percent total body water was significantly higher in the VSD infants and the percent fat mass was significantly lower. TEE was 40% higher in the VSD group (VSD, 87.6 +/- 10.8 kcal/kg/d; control, 61.9 +/- 10.3 kcal/kg/d). The difference between TEE and REE, reflecting the energy of activity, was 2.5 times greater in the VSD group. CONCLUSIONS: REE and energy intake are virtually identical between the two groups. Despite this, infants with VSDs have substantially higher TEE than age-matched healthy infants. The large difference between TEE and REE in VSD infants suggests a substantially elevated energy cost of physical activity in these infants. These results demonstrate that, although infants with VSDs may match the energy intake of healthy infants, they are unable to meet their increased energy demands, resulting in growth retardation.     

VEGF对缺血/再灌注损伤胰腺细胞凋亡的影响

目的 研究血管内皮生长因子(VEGF)对缺血/再灌注损伤胰腺组织细胞凋亡的影响.方法 将雄性sD大鼠30只随机分为3组(n=10),A组为假手术组,B组为缺血/再灌注损伤组,C组为缺血/再灌注损伤+VEGF反义寡核苷酸组.通过血管夹阻断大鼠腹腔干及肠系膜上动脉30 min,然后去除血管夹再灌注6 h,建立大鼠胰腺缺血/再灌注损伤模型.对各组胰腺组织进行VEGF免疫组化染色及TUNEL法细胞凋亡检测.结果 缺血/再灌注损伤后胰腺组织出现细胞凋亡,同时VEGF蛋白表达上调.缺血/再灌注损伤+VEGF反义寡核苷酸组的胰腺组织VEGF蛋白表达较缺血/再灌注损伤组显著减少(P<0.05),前者细胞凋亡指数较后者明显升高(P<0.05).结论 VEGF能抑制缺血/再灌注损伤胰腺细胞凋亡,可能对胰腺缺血再灌注损伤具有保护作用.     

系膜细胞来源的白细胞介素-13对系膜细胞细胞因子基因表达的研究(英文)

目的　白细胞介素 1 3(IL 1 3)是新近发现的一种抗炎性细胞因子 ,其在肾小球肾炎中的作用尚不清楚 ,该研究探讨脂多糖 (LPS)对体外培养的人肾小球系膜细胞 (HMC)表达IL 1 3作用以及IL 1 3对HMC促炎性细胞因子、趋化因子和促纤维化因子基因表达的影响。方法　体外培养HMC ,加入不同浓度的LPS和 (或 )IL 1 3后 ,用逆转录 -聚合酶链反应和ELISA检测HMCIL 1 3mRNA表达和细胞培养上清液中IL 1 3蛋白含量 ;应用核酸酶保护法检测HMC肿瘤坏死因子 α(TNF α)、白介素 - 1α(IL 1α)、白介素 - 1 β(IL 1 β)、单核细胞趋化蛋白 1(MCP 1 )、白介素 8(IL 8)、转化生长因子 - β1 (TGF β1 )mRNA的表达。 结果　未予LPS刺激的HMC不表达IL 1 3mRNA和蛋白 ;LPS呈剂量依赖性和时间依赖性诱导HMC表达IL 1 3mRNA和分泌IL 1 3蛋白。HMC受LPS刺激后 1 2h即可表达IL 1 3mRNA ,4 8h达高峰 ,72h仍维持在较高的水平。HMC受LPS刺激后 2 4h ,其培养上清液中检测到IL 1 3蛋白 ,4 8h和 72h进一步增加。外源性IL 1 3呈剂量依赖性地抑制LPS诱导的系膜细胞TNF α ,IL 1α ,IL 1 β ,MCP 1 ,IL 8,TGF β1mRNA的表达。应用抗IL 1 3抗体中和内源性IL 1 3后 ,上述炎症因子表达增强。结论　IL 1 3是HMC自分泌因子。IL 1 3可抑制LPS诱导     

Rolle der Diabetesberatung im digitalen Zeitalter

Digitization has long since taken hold in the diabetes sector. Digital support including pumps, rtCGM (CGM: continuous glucose monitoring, rtCGM: real time CGM), iscCGM (intermittent scanning CGM), apps as well as measuring devices with pattern recognition and a reminder function has become commonplace in many areas. Training to become a diabetes advisor provides diabetes professionals with appropriate basic knowledge to advise the patient in self-management with technical support. Continuous medical training to empower and support patients in health literacy, data protection and the use of telemedicine is imperative.