HFRSV在Vero细胞上的传代适应及疫苗的初步研制

作者观察了肾综合症出血热病毒(HFRSV)Z_(10)株、HB_(55)株和L_(99)株在Vero细胞上的传代适应情况,并制备了3批灭活疫苗。试验结果表明,3批疫苗对家兔均有较好的免疫效果,动物经两次免疫后4周,血清中和抗体阳转率为100％。这一结果为应用Vero细胞制备HFRS灭活疫苗提供了有意义的科学数据。     

Adult Renal Stem/Progenitor Cells Can Modulate T Regulatory Cells and Double Negative T Cells

Adult Renal Stem/Progenitor Cells (ARPCs) have been recently identified in the human kidney and several studies show their active role in kidney repair processes during acute or chronic injury. However, little is known about their immunomodulatory properties and their capacity to regulate specific T cell subpopulations. We co-cultured ARPCs activated by triggering Toll-Like Receptor 2 (TLR2) with human peripheral blood mononuclear cells for 5 days and 15 days and studied their immunomodulatory capacity on T cell subpopulations. We found that activated-ARPCs were able to decrease T cell proliferation but did not affect CD8⁺ and CD4⁺ T cells. Instead, Tregs and CD3⁺ CD4^- CD8^- double-negative (DN) T cells decreased after 5 days and increased after 15 days of co-culture. In addition, we found that PAI1, MCP1, GM-CSF, and CXCL1 were significantly expressed by TLR2-activated ARPCs alone and were up-regulated in T cells co-cultured with activated ARPCs. The exogenous cocktail of cytokines was able to reproduce the immunomodulatory effects of the co-culture with activated ARPCs. These data showed that ARPCs can regulate immune response by inducing Tregs and DN T cells cell modulation, which are involved in the balance between immune tolerance and autoimmunity.     

The role of mass spectrometry in the study of non-enzymatic protein glycation in diabetes: an update

Recent studies on non-enzymatic protein glycation are reviewed, and results are critically discussed. Advanced glycation end products (AGE) levels in the body reflect a balance between their formation and catabolism. AGE proteolysis leads to the formation of low-molecular-weight AGE (AGE peptides) that are normally excreted in urine. In the case of diabetic disease and/or renal failure, AGE peptides accumulate in plasma. Because of their high reactivity, these compounds have been thought to play a role in the progression of chronic complications. The structural identification of these compounds is particularly important, and a strategy has been designed for their possible definition. A series of experiments has been devoted to the study of the enzymatic degradation products of in vitro glycated human serum albumin (HSA). This approach, based on different MS methods (LC/ESI/MS, LC/ESI/FTMS, MALDI), led to the detection of the glycated peptides generated by digestion of HSA. A further study was devoted to the possible identification of the peptides identified in the glycated HSA digestion products in the plasma of diabetic and nephropatic subjects. No glycated HSA digestion products were found in plasma samples of the subjects under investigation even if clear differences were found among the LC runs from populations of healthy, diabetic, and nephropatic subjects. Parallel investigations were devoted to the evaluation of glyoxal and methylglyoxal-dicarbonyl compounds that originate at the intermediate stage of the Maillard reaction. This evaluation was performed in diabetic patients, before and after the achievement of good metabolic control, and in nephropatic patients subjected to peritoneal dialysis (PD). In the latter case, results indicated that these dicarbonyl compounds, already present in the dialysis fluids, show a decrease in plasma and in dialysis fluids; those data suggested their reaction at peritoneal membrane level.     

Digital clubbing as an unusual complication associated with severe secondary hyperparathyroidism: report of two cases

Digital clubbing due to secondary hyperparathyroidism has been described as an unusual complication among patients with chronic kidney disease undergoing maintenance hemodialysis therapy. Although the pathogenesis of digital clubbing is unknown, certain growth factors such as platelet-derived growth factor and hepatocyte growth factor have been associated with this clinical syndrome. Two patients of our renal unit population presented this unique clinical feature bilaterally, among the other clinical findings of severe secondary hyperparathyroidism. Both patients were subjected to parathyroidectomy. Histological examination revealed diffuse hyperplasia of parathyroid glands. Despite the improvement of clinical symptoms and laboratory findings of secondary hyperparathyroism after parathyroidectomy, digital clubbing remained unchanged.     

Spontaneous retroperitoneal hemorrhage due to acquired cystic kidney disease

A patient with end-stage renal disease on maintenance hemodialysis developed sudden severe abdominal pain and distension. He suffered a decline in his hematocrit and subsequent abdominal imaging revealed a large left-sided retroperitoneal hemorrhage in the setting of atrophic, severely cystic kidneys. He underwent selective left renal artery angiography and embolization due to continued hemorrhage with stabilization in his condition. However, he became paraparetic within hours of the embolization procedure due to spinal cord infarct. Acquired cystic kidney disease is a very common entity in patients with chronic kidney disease. Complications include cystic hemorrhage or infection, erythrocytosis, and renal cell carcinoma. Screening of patients for cystic disease and malignant transformation remains a controversial topic; however, most advocate abdominal imaging after 3 to 5 years on dialysis.     

Ventricular arrhythmia in dialysis patients: A link with higher hemoglobin levels?

We investigated the frequencies and associated risk factors of cardiac arrhythmias and heart rate variability (HRV) in hemodialysis (HD) patients. One hundred fifty prevalent HD patients underwent 48-hour Holter monitoring. Holter monitoring was analyzed in 4 phases: early post-HD phase (12 hours), late post-HD phase (20 hours), pre-HD phase (12 hours), and HD phase (4 hours). Echocardiography was applied to measure the left ventricular mass index in a subgroup of patients (n: 52). Patients with ventricular premature contraction (VPC) were significantly older, had a longer HD duration, and higher hemoglobin (Hb) levels. Left ventricular mass index was significantly correlated with the frequency of VPC, during the HD and pre HD phases (r: 0.435, 0.312, respectively). In logistic regression analysis, patients with Hb level >11.9 g/dL (high tertile) had a 4.5-fold increased risk of VPC compared with those with Hb levels <10.8 g/dL (P: 0.04). In HRV analysis, age (P<0.001), and diabetes (P: 0.03) were found to be independent predictors of low standard deviation of all mean normal-to-normal RR intervals. Increased left ventricular mass index is associated with a high frequency of VPC in the pre-HD and HD periods. The occurrence of VPC is predicted by older age, longer dialysis duration, and higher Hb levels, while older age and diabetes are the determinants of HRV. The relation between higher Hb levels and the frequency of VPC might provide a clue for the explanation of the detrimental effect of higher Hb levels on HD patients.     

Hemodialysis does not impair ventricular functions over 2 years

We aimed to evaluate the long-term effect of hemodialysis (HD) treatment on left and right ventricular (LV and RV) functions in patients with end-stage renal disease. The study population consisted of 22 patients with newly diagnosed end-stage renal disease. Before an arteriovenous fistula was surgically created for HD, the patients were evaluated by echocardiography for systolic and diastolic functions. After the first HD session (mean 24.22 ± 2.14 months), the second echocardiographic evaluations were performed. Left ventricular and RV functions before and after long-term HD treatment were compared. The mean age was 55 ± 13 years and 10 (45%) of the patients were female. After long-term HD treatment, the isovolumic relaxation time was significantly decreased; however, the peak early (E) and late (A) diastolic mitral inflow velocities, E/A ratio, and deceleration time of E wave were not significantly different from the baseline measurements. Also, there was no significantly change in the early diastolic velocity (Ea) of the lateral mitral anulus and the E/Ea ratio. Pulmonary vein peak diastolic velocity, peak atrial reversal velocity, and peak atrial reversal velocity duration remained almost unchanged even though the pulmonary vein peak systolic velocity and the pulmonary vein peak systolic velocity/pulmonary vein peak diastolic velocity ratio were significantly lower after long-term HD treatment. In addition, LV systolic functions, LV diameters, LV mass index, left atrium size, and RV diastolic functions were not statistically different after long-term HD treatment. The myocardium is exposed to hemodynamic, metabolic, and neuro-humoral abnormalities during HD treatment; however, the long-term effects of HD on ventricular functions are not clearly known. The present study showed that the long-term effects of HD on LV and RV functions were insignificant in patients with end-stage renal disease. We have demonstrated that the LV and RV functions did not change significantly after long-term HD treatment. We suggest that this result may be due to regulated blood pressure levels of the patients, treatment of anemia and other metabolic disorders during the HD period and the prevention of weight gain and hypervolemia.     

Genetic polymorphisms and the risk of progressive renal failure in elderly Hungarian patients

The relationship between renal disease progression and genetic polymorphism of enzymes influencing endothelial function remains incompletely understood. We genotyped three cohorts of elderly Hungarian patients: 245 patients with end‐stage renal disease (ESRD) on chronic hemodialysis (HD), 88 patients with mild chronic kidney disease (CKD), and 200 healthy controls. The underlying diagnoses of renal diseases were primary glomerulonephritis, interstitial nephritis, hypertension, diabetic nephropathy, and hereditary diseases. We examined genetic polymorphisms of eight candidate genes associated with endothelial function: endothelial constitutive nitric oxide synthase (ecNOS) T‐786C, endothelin‐1 G5727T, methylenetetrahydrofolate reductase (MTHFR) C677T, paraoxonase‐1 Q192R and M55L, angiotensinogen M235T, angiotensin‐converting enzyme (ACE) I/D and angiotensin II type 1 receptor A1166C gene. Six gene polymorphisms were detected by real‐time polymerase chain reaction with melting‐point analysis, and two via allele‐specific amplification and gel electrophoresis. Control group patients were in Hardy‐Weinberg equilibrium for all tested genotypes. In ESRD patients attributed to hypertension, the endothelin gene G5727T GG genotype occurred significantly less but GT genotype more frequently (P < 0.01 for both). In ESRD patients attributed to primary glomerulonephritis, more ACE DD and less ID genotypes were found (P < 0.02 for both) than in the controls. The underlying diagnosis may modify the association of genetic polymorphism and dialysis‐dependent ESRD.