Physiologic Insulin Resensitization as a Treatment Modality for Insulin Resistance Pathophysiology

Prevalence of type 2 diabetes increased from 2.5% of the US population in 1990 to 10.5% in 2018. This creates a major public health problem, due to increases in long-term complications of diabetes, including neuropathy, retinopathy, nephropathy, skin ulcers, amputations, and atherosclerotic cardiovascular disease. In this review, we evaluated the scientific basis that supports the use of physiologic insulin resensitization. Insulin resistance is the primary cause of type 2 diabetes. Insulin resistance leads to increasing insulin secretion, leading to beta-cell exhaustion or burnout. This triggers a cascade leading to islet cell destruction and the long-term complications of type 2 diabetes. Concurrent with insulin resistance, the regular bursts of insulin from the pancreas become irregular. This has been treated by the precise administration of insulin more physiologically. There is consistent evidence that this treatment modality can reverse the diabetes-associated complications of neuropathy, diabetic ulcers, nephropathy, and retinopathy, and that it lowers HbA1c. In conclusion, physiologic insulin resensitization has a persuasive scientific basis, significant treatment potential, and likely cost benefits.     

窑灰与粉煤灰复合作为混凝土掺合料的研究

以粉煤灰和窑灰与普通硅酸盐水泥组成的复合体为试验对象,采用新型水泥水化过程测定方法（仪器为非接触式电阻率测定仪）以及水化热测试方法,对粉煤灰一窑灰一水泥的水化过程进行了研究,结果表明：窑灰与粉煤灰有着良好的复合效应,且粉煤灰能有效固化和吸附窑灰中的有害离子,克服过量碱对混凝土的有害作用。通过SEM研究了该浆体微观结构的发展,并测定了砂浆的抗折及抗压强度,结果进一步证明了上述结论。     

The Signaling Pathway of TNF Receptors: Linking Animal Models of Renal Disease to Human CKD

Chronic kidney disease (CKD) has been recognized as a global public health problem. Despite the current advances in medicine, CKD-associated morbidity and mortality remain unacceptably high. Several studies have highlighted the contribution of inflammation and inflammatory mediators to the development and/or progression of CKD, such as tumor necrosis factor (TNF)-related biomarkers. The inflammation pathway driven by TNF-α, through TNF receptors 1 (TNFR1) and 2 (TNFR2), involves important mediators in the pathogenesis of CKD. Circulating levels of TNFRs were associated with changes in other biomarkers of kidney function and injury, and were described as predictors of disease progression, cardiovascular morbidity, and mortality in several cohorts of patients. Experimental studies describe the possible downstream signaling pathways induced upon TNFR activation and the resulting biological responses. This review will focus on the available data on TNFR1 and TNFR2, and illustrates their contributions to the pathophysiology of kidney diseases, their cellular and molecular roles, as well as their potential as CKD biomarkers. The emerging evidence shows that TNF receptors could act as biomarkers of renal damage and as mediators of the disease. Furthermore, it has been suggested that these biomarkers could significantly improve the discrimination of clinical CKD prognostic models.     

CKD8G型内燃机车

介绍了出口刚果(布)的CKD8G型内燃机车的运用条件、主要技术参数、总体布置和主要部件的结构、性能、特点以及线路牵引试验情况。     

The long path towards implementation of clinical proteomics: Exemplified based on CKD273

Clinical proteomics aims at the development and the implementation of novel biomarkers that demonstrate a clear clinical benefit in the management of diseases. However, though the attention in the field is increasing and multiple articles on biomarker research are published, clinical implementation of these biomarkers is scarce. In this paper, we aim towards identifying the hurdles on the path towards implementation, and present one successful approach, based on capillary electrophoresis coupled with mass spectrometry. A panel of biomarkers identified and assessed using this approach, termed CKD273, has recently received a Letter‐of‐Support from the US‐Food and Drug Administration (FDA), and is now implemented in the (early) management of chronic kidney disease. Based on this experience in the process towards implementation of CKD273, issues associated with implementation and suggestions how to meet these challenges are given.     

Effect of pharmacological suppression of secondary hyperparathyroidism on cardiovascular hemodynamics in predialysis CKD patients: A preliminary observation

Cardiovascular events are the principal cause of mortality in patients with chronic kidney disease (CKD). Secondary hyperparathyroidism (SHPT), a common complication of CKD, contributes to cardiac dysfunction. This study is an attempt to demonstrate the effects of parathyroid hormone suppression with oral calcitriol on cardiovascular hemodynamics. Twenty predialysis CKD patients with SHPT were given calcitriol therapy for 12 weeks. Ten similar patients received placebo. Echocardiographic assessment of cardiac function was performed at baseline and after 12 weeks of treatment. Calcitriol therapy effectively suppressed SHPT. Baseline left ventricular (LV) end diastolic diameter and LV end systolic diameter were 4.86+/-0.48 and 2.86+/-0.33 cm, and the mean FS was 41.02+/-4.79%. Left ventricular end systolic and end diastolic volumes were normal (42.30+/-9.07 and 91.40+/-19.68 mL). The ejection fraction was slightly reduced (53.54+/-3.57%). Pretreatment Doppler indices including E velocity (0.816+/-0.087 m/s), A velocity (0.696+/-0.089 m/s), and E/A ratio (1.193+/-0.210) were significantly impaired. After 12 weeks of calcitriol therapy, there was no significant change in the LV dimensions or ejection fraction, but there was a significant improvement in the diastolic parameters, namely the A velocity (0.680+/-0.084) and E/A ratio (1.238+/-0.180). Secondary hyperparathyroidism is an important factor in the pathogenesis of cardiovascular complications in CKD. There is evidence to support that correction of hyperparathyroidism can improve the systolic dysfunction seen in advanced kidney disease. This study shows that diastolic dysfunction seen in predialysis CKD patients may also be possibly improved with calcitriol therapy.     

Understanding the Renal Fibrotic Process in Leptospirosis

Leptospirosis is a neglected infectious disease caused by pathogenic species of the genus Leptospira. The acute disease is well-described, and, although it resembles other tropical diseases, it can be diagnosed through the use of serological and molecular methods. While the chronic renal disease, carrier state, and kidney fibrosis due to Leptospira infection in humans have been the subject of discussion by researchers, the mechanisms involved in these processes are still overlooked, and relatively little is known about the establishment and maintenance of the chronic status underlying this infectious disease. In this review, we highlight recent findings regarding the cellular communication pathways involved in the renal fibrotic process, as well as the relationship between renal fibrosis due to leptospirosis and CKD/CKDu.     

CKD8E型内燃机车交流电传动系统分析

介绍了CKD8E型内燃机车电气系统的技术特点,各主要部件的功能和技术参数,以及交流控制系统的特点,较详尽地分析了该系统中采用的一些新技术,阐述了牵引工况和制动工况的工作过程。     

Evolution of strength, microstructure and mineralogical composition of a CKD–GGBFS binder

Characterization of a nontraditional binding material containing cement kiln dust (CKD) and ground granulated blast furnace slag (GGBFS) is discussed in this paper. Significant compressive strength was obtained for a CKD–GGBFS blend with 70% CKD and 30% GGBFS at a water-to-binder ratio of 0.40 after 2 days of curing at elevated temperature. Similar strength was also obtained for the samples subjected to normal moisture curing over a period of 28 days. The compressive strength increased with additional moist curing in both the cases. The microstructural and the mineralogical examinations show that the strength development was mainly due to the formation of calcium silicate hydrate (C-S-H). In addition to normal C-S-H, aluminum and magnesium incorporated C-S-H phases were also present in the CKD–GGBFS blends. The formation of ettringite appears to be a contributing factor in early age strength development of CKD–GGBFS binder.     

Mineralocorticoid Receptor Antagonists—Use in Chronic Kidney Disease

Mineralocorticoid receptor antagonists (MRA) are drugs with a potentially broad spectrum of action. They have been reported to have healing effects in many diseases, such as chronic heart failure, hypertension, or nephrotic syndrome. Numerous studies suggest that mineralocorticoid receptor activation is pathogenic and a progression factor of chronic kidney disease (CKD); however, results of studies on the use of MRA in the treatment of CKD are inconclusive. Current guidelines recommend against the use of MRA in patients with advanced CKD. Although, there is growing interest on their use in this population due to treatment benefits. In this review, we summarize studies which were purposed to evaluate the impact of MRA therapy on CKD patients. Despite many benefits of this treatment e.g., reducing cardiovascular mortality or alleviating proteinuria, steroidal MRA (such as spironolactone or eplerenone) have a low safety profile. They often lead to hyperkalemia complications which are dangerous in patients with CKD, and diabetic nephropathy, especially in hemodialysis patients. Studies on recently developed nonsteroidal MRA showed that they have fewer side effects. In our review, we discuss steroidal and nonsteroidal MRA treatment effects on the estimated glomerular filtration rate (eGFR), proteinuria, the cardiovascular system, and hyperkalemia in CKD patients. We present new content and recent publications in this field.