Characterization of the DialGuard device for endotoxin removal in hemodialysis

Bacterial pyrogens, capable of penetrating dialyzer membranes, are responsible for a systemic inflammatory reaction in hemodialysis patients. Dialyzer reuse, involving rinsing of the dialyzer with pyrogen-containing water, may exacerbate this situation. Studies of the mechanism of action of endotoxin suggest that it irreversibly damages the vascular endothelium. The novel endotoxin removal method described here, is based on affinity-binding of endotoxin by the adsorbent ClarEtox, a USP Class VI-certified resin that is the active component of the medical device DialGuard. Under standard hemodialysis operating conditions, challenge of DialGuard with Pseudomonas maltophilia supernatant-spiked dialysate, containing 35-193 EU/ml endotoxin, resulted in endotoxin levels below 0.05 EU/ml in the treated dialysate. DialGuard was able to decrease endotoxin concentrations in the dialysate from a range of 2.39-8.49 to <0.005 EU/ml. DialGuard supports high fluid velocities at low back pressures and can be sanitized using the heat sanitization cycle of hemodialysis machines. DialGuard offers a simple, user-friendly way to reduce the concentration of endotoxin in dialysate and water for dialysis at a low cost.     

Compliance measurement in respiratory distress syndrome: the prediction of outcome

Dynamic compliance (Cdyn) measurements within the first three days of life predicted survival in 60 preterm infants suffering from respiratory distress syndrome. Cdyn was measured in 47 survivors at 2.3 +/- 1.4 days of life and in 13 nonsurvivors on 2.7 +/- 1.7 days. All nonsurvivors died from respiratory failure within the first two weeks of life. Mean Cdyn of the survivors was 0.83 +/- 0.33 ml/cm H2O and of the nonsurvivors 0.35 +/- 0.19 ml/cm H2O (p less than 0.001). Cdyn values below 0.45 ml/cm H2O predicted 11 of 13 deaths in infants, and Cdyn measurements above this value predicted 45 of 47 survivals, with a specificity of 81% and a sensitivity of 89%. Eleven of the survivors, who subsequently developed bronchopulmonary dysplasia (BPD), had a mean Cdyn of 0.56 +/- 0.23 ml/cm H2O. When these infants were matched with infants of comparable weight without evidence of BPD, the BPD group had a significantly lower Cdyn (p less than 0.05). Cdyn measurements during the first three days of life are useful in predicting outcome of respiratory failure secondary to respiratory distress syndrome.     

Insulin is necessary for the hypertrophic effect of cholecystokinin-octapeptide following acute necrotizing experimental pancreatitis

AIM: In previous experiments we have demonstrated that by administering low doses of cholecystokinin-octapeptide (CCK-8), the process of regeneration following L-arginine (Arg)-induced pancreatitis is accelerated. In rats that were also diabetic (induced by streptozotocin, STZ), pancreatic regeneration was not observed. The aim of this study was to deduce whether the administration of exogenous insulin could in fact restore the hypertrophic effect of CCK-8 in diabetic-pancreatitic rats.METHODS: Male Wistar rats were used for the experiments.Diabetes mellitus was induced by administering 60 mg/kg body mass of STZ intraperitoneally (i.p.), then, on d 8, pancreatitis was induced by 200 mg/100 g body mass Argi.p. twice at an interval of 1 h. The animals were injected subcutaneously twice daily (at 7 a.m. and 7 p.m.) with 1 μglkg of CCK-8 and/or 2 IU mixed insulin (300 g/L shortaction and 700 g/L intermediate-action insulin) for 14 d after pancreatitis induction. Following this the animals were killed and the serum amylase, glucose and insulin levels as well as the plasma glucagon levels, the pancreatic mass/body mass ratio (pm/bm), the pancreatic contents of DNA, protein, amylase, lipase and trypsinogen were measured. Pancreatic tissue samples were examined by light microscopy on paraffin-embedded sections.RESULTS: In the diabetic-pancreatitic rats treatment with insulin and CCK-8 significantly elevated pw/bm and the pancreatic contents of protein, amylase and lipase vs the rats receiving only CCK-8 treatment. CCK-8 administered in combination with insulin also elevated the number of acinar cells with mitotic activities, whereas CCK-8 alone had no effect on laboratory parameters or the mitotic activities in diabetic-pancreatitic rats.CONCLUSION: Despite the hypertrophic effect of CCK-8 being absent following acute pancreatitis in diabetic-rats,the simultaneous administration of exogenous insulin restored this effect. Our results clearly demonstrate that insulin is necessary for the hypertrophic effect of low-doses of CCK-8 following acute pancreatitis.     

Ross procedure using pulmonary autograft with a previous prosthetic patch

The case described is of a 7-year-old boy with recurrent long-segment left ventricular outflow tract obstruction. Due to previous pulmonary artery band stenosis and subsequent repair with a prosthetic patch, the pulmonary root was not intact. In this complicated Ross-Konno operation, the prosthetic patch was replaced with autologous tissue and the repaired pulmonary root was used successfully as an autograft.     

Elevated antibody levels against Chlamydia pneumoniae, human HSP60 and mycobacterial HSP65 are independent risk factors in myocardial infarction and ischaemic heart disease

The relative significance of traditional risk factors, chronic infections and autoimmune processes in the development of acute myocardial infarction (AMI) has not been fully elucidated. We compared serum IgG antibody titres to various pathogens, i.e. Chlamydia pneumoniae (Cpn), cytomegalovirus (CMV) and herpes simplex virus type 1 (HSV-1), and to the potential autoantigens human heat shock protein 60 (hHSP60) and mycobacterial heat shock protein 65 (mHSP65), in serum samples obtained from patients 3-48 h after AMI (n = 40) or stable effort angina (SEA, n = 43), and from controls (n = 46). The strongest association was observed between AMI and the elevated level of hHSP60 antibodies. The association between AMI and the level of Cpn antibodies was also significant. High levels of hHSP60 and Cpn antibodies represented independent risk factors for the development of AMI, but the simultaneous presence of high levels of antibodies to Cpn and hHSP60 suggested a joint effect on the relative risk of AMI (OR = 12.0-21.1). The antibody titres to mHSP65 were higher in the SEA group than in the controls, and the simultaneous presence of high levels of Cpn and mHSP65 antibodies meant an increased risk among the SEA patients. The antibody titres to CMV or HSV-1 were similar in the three groups. In conclusion, these results demonstrate associations of AMI with high levels of anti-hHSP60 and anti-Cpn antibodies, and of SEA with the level of anti-mHSP65 antibodies, these being independent risk factors.     

Polymorphism of the heat-shock protein gene Hsp70-2, but not polymorphisms of the IL-10 and CD14 genes, is associated with the outcome of Crohn's disease

OBJECTIVE: In Crohn's disease (CD) a Th-1 dominant immune reaction is induced, which could be associated with genetic predisposition. Several previous studies have investigated the roles of CD14, heat-shock protein (Hsp)70 and IL-10 gene polymorphisms in the development of the disease. The results are contradictory and inter-racial differences are implicated. Therefore, this phenomenon was evaluated in well-documented Caucasian patients with CD in order to verify the clinical importance of these polymorphisms. MATERIAL AND METHODS: The genomic DNA of 133 patients with CD and that of 75 healthy controls were examined. CD was divided into subgroups according to the Vienna classification. An arbitrary classification system based on disease severity was also applied, which was determined according to the therapeutic intervention. The CD14 (-159 C-->T) promoter gene polymorphism was investigated by melting-point analysis. The IL-10 (-1082 G-->A) and Hsp70-2 (1267 A-->G) gene polymorphisms were detected by RFLP (restriction fragment length polymorphism). RESULTS: None of the allele frequencies of the examined polymorphisms differed significantly between the patient and control populations. Neither the CD14 nor the IL-10 polymorphisms exhibited any correlation with the development or with the progression of the disease. With regard to Hsp70-2 gene polymorphism, those patients who carry at least one A allele have a significantly lower probability of the need for surgical intervention. CONCLUSIONS: Allele A of the Hsp70-2 gene may be associated with a less severe form of CD, suggesting the clinical value of the genotype assessment. The genetic determination of the defense mechanisms in CD appears to be associated with the polymorphism of the Hsp70-2 gene rather than that of the CD14 or IL-10 genes.     

Study of the effect of instant controlled pressure drop (DIC) treatment on IgE-reactive legume-protein patterns by electrophoresis and immunoblot

Détente Instantanée Contrôlée (DIC) technology was used to reduce immunoglobulin E (IgE) reactivity of legume proteins. Soybean, roasted peanut, chickpea and lentil seeds were treated at three or six bars for 60 or 180s. The effect of this treatment on the IgE-binding pattern of the legume proteins – separated by sodium-dodecyl-sulphate polyacrylamide gel electrophoresis – was monitored by five individual paediatric legume allergic and – two individual negative control human sera. A highly cross-reactive legume positive serum was selected for the two-dimensional electrophoreses immunoblots to compare the IgE reactive protein patterns, before and after the DIC treatment. The number of the identified IgE reactive spots was highly reduced for soybean (0/7) and chickpea (2/7), and moderately reduced for lentil (4/7) when the seeds were treated at a higher pressure (6 bar) and for a longer time (180 s), but this treatment was not effective for roasted peanut (6/8) where the intensity of the IgE reactive resistant spots were even stronger.     

Scope and limitation of propylene carbonate as a sustainable solvent in the Suzuki–Miyaura reaction

The Suzuki–Miyaura reaction is one of the most used transformations in drug research. Thus making this reaction more sustainable is of considerable current interest. Here we show that propylene carbonate (PC) can be used as a solvent for the Suzuki–Miyaura reaction. PC is one of the greenest solvents since it is synthesized under green conditions by the use of carbon dioxide in the air. All reactions proceeded well and good or excellent yields were observed for the biaryl products. Nonetheless in the case of pyridazinones, 2-hydroxypropyl- chain containing side-products were observed. Importantly, this fact allowed the isolation of several novel compounds which were generated under prominently green conditions.

The Suzuki–Miyaura reaction was carried out in propylene carbonate yielding an interesting side-product besides the biphenyl derivative.