Statistical Model for the Orientation of Nonspherical Particles Settling in Turbulence.

The orientation of small anisotropic particles settling in a turbulent fluid determines some essential properties of the suspension. We show that the orientation distribution of small heavy spheroids settling through turbulence can be accurately predicted by a simple Gaussian statistical model that takes into account particle inertia and provides a quantitative understanding of the orientation distribution on the problem parameters when fluid inertia is negligible. Our results open the way to a parametrization of the distribution of ice crystals in clouds, and potentially lead to an improved understanding of radiation reflection or particle aggregation through collisions in clouds.

Quantification of electrical field-induced flow reversal in a microchannel.

We characterize the electroosmotic flow in a microchannel with field effect flow control. High resolution measurements of the flow velocity, performed by micro particle image velocimetry, evidence the flow reversal induced by a local modification of the surface charge due to the presence of the gate. The shape of the microchannel cross-section is accurately extracted from these measurements. Experimental velocity profiles show a quantitative agreement with numerical results accounting for this exact shape. Analytical predictions assuming a rectangular cross-section are found to give a reasonable estimate of the velocity far enough from the walls.

Nitric oxide synthase in chick embryo retina during development.

High levels of nitric oxide synthase were found in the early stages of developing chick embryo retina. The enzyme activity sharply decreased up to 13-day-old chick embryo retina, when the level of the last embryonic day was reached. The results show that nitric oxide is synthesized in chick embryo retina prior to synaptogenesis. The incubation of chick embryo retinas in presence of NMDA increased the synthesis of nitric oxide, thus, the appearance of nitric oxide production before the synaptogenesis in the retina as well as in the brain may be considered as signal for the development and shaping of neuronal and non-neuronal cells.

Carnitine deficiency induced during hemodialysis and hyperlipidemia: effect of replacement therapy.

Plasma carnitine levels were studied in 14 uremic patients before, during, and after hemodialysis. The predialysis plasma carnitine levels were normal but fell during dialysis (half-life of 3.6 h). Plasma carnitine levels rose quickly in the first 6 h after dialysis, after which time the rise was more gradual. Muscle carnitine was significantly reduced in the dialyzed patients (p less than 0.005) compared with controls. In four patients lipid droplets were observed in muscle. Ten patients on maintenance hemodialysis exhibited plasma hyperlipidemia and low muscle carnitine. These individuals were given DL-carnitine (50 mg/kg body weight) intravenously after each dialysis. At the end of a 2-month carnitine treatment, plasma triglyceride levels were found to be reduced (p less than 0.001) and muscle carnitine content significantly increased (p less than 0.005). These findings suggest that carnitine may be useful in treatment of hypertriglyceridemia and muscle carnitine deficiency states induced during maintenance hemodialysis.

Reduction of homocysteine levels in coronary artery disease by low-dose folic acid combined with vitamins B6 and B12.

An increased plasma homocysteine concentration is a risk factor for atherosclerosis. Folic acid lowers homocysteine but the optimal dose in patients with coronary artery disease (CAD) is unclear. This placebo-controlled, single-blind, dose-ranging study evaluates the effect of low-dose folic acid on homocysteine levels in 95 patients aged 61 +/- 11 years (mean +/- SD) with documented CAD. Patients in each group were given either placebo or 1 of 3 daily supplements of folic acid (400 microg, 1 mg, or 5 mg) for 3 months. Each active treatment arm also received 500 microg vitamin B12 and 12.5 mg vitamin B6. Total plasma homocysteine levels were measured after 30 and 90 days. Folic acid 400 microg reduced homocysteine levels from 13.8 +/- 8.8 to 9.6 +/- 2.0 micromol/L at 90 days (p = 0.001). On 1- and 5-mg folic acid, levels decreased from 13.0 +/- 6.4 to 9.8 +/- 4.0 micromol/L (p = 0.001) and from 14.8 +/- 6.9 to 9.7 +/- 3.3 micromol/L (p < 0.001), respectively. The decrease was similar in all treatment groups. There was no significant change with placebo. Although the sample size is small, these findings suggest that daily administration of 400 microg/day folic acid combined with vitamin B12 and vitamin B6 may be equivalent to higher doses in reducing homocysteine levels in patients with CAD.

Tissue factor pathway inhibitor (TFPI) activity in uremic patients during hemodialysis.

We studied tissue factor pathway inhibitor (TFPI) activity during hemodialysis in 10 uremic patients who were not receiving anticoagulant for at least 120 minutes. TFPI activity before dialysis was normal (patients 107 +/- 5.8%, controls 104 +/- 4.5%). During extracorporeal circuit it rose progressively with a statistically significant difference, reaching a plateau between 60 and 120 minutes. Since thrombin induces a marked redistribution and release of TFPI from stimulated endothelial cells and platelets contain about 10% of TFPI activity that is secreted following activation it is possible that thrombin-induced release of TFPI by endothelium and platelets could account for the increased TFPI we found during hemodialysis. To investigate this possibility we measured during dialysis beta-thromboglobulin (beta-TG), thrombin-antithrombin complex (TAT) and prothrombin fragment 1.2 (F 1.2). The increased levels of beta-TG, TAT and F1.2 we noted during extracorporeal circuit are in keeping with this concept. One hundred eighty minutes after initiation of dialysis, by which time all patients were receiving heparin there was a further increase in TFPI (to more than 200% of baseline), due to the presence of the glycosaminoglycan. This was due the previously reported displacement by heparin of the major intravascular pool of TFPI, from endothelial cell surfaces.

Beneficial effects of L-carnitine in dialysis patients with impaired left ventricular function: an observational study.

BACKGROUND: Recent studies have shown that L-carnitine may improve clinical status and reduce the need for erythropoietin in dialysis patients with cardiovascular diseases. In this observational study, we investigated whether the addition of L-carnitine to conventional therapy might improve cardiac function (as assessed by M-mode and two-dimensional echocardiography) and clinical status in dialysis patients with left ventricular dysfunction. METHODS: Eleven dialysis patients with reduced left ventricular function (EF < 45%) were treated with L-carnitine for 8 months. Two-dimensional (2-D) echocardiography was performed at baseline and every 2 months up to the end of the treatment period. The dosage of erythropoietin was also monitored during the study and the patients' clinical status was assessed by a questionnaire. RESULTS: Carnitine increased mean LV ejection fraction from 32.0% to 41.8% (p < 0.05 vs baseline). There was also a slight reduction of erythropoietin dosage and an improvement of clinical status. CONCLUSIONS: Eight months' therapy with carnitine appears to improve LV function and clinical status in dialysis patients with impaired LVF.

Vitamin E-coated dialyzers reduce oxidative stress related proteins and markers in hemodialysis--a molecular biological approach.

BACKGROUND: Hemodialysis patients (HD) are exposed to oxidative stress which contributes to cardiovascular disease and accelerated atherosclerosis, major causes of mortality in these patients. A new dialysis membrane coated with vitamin E has been proposed against oxidative stress and atherosclerosis due to their ability to inhibit lipid peroxidation by interacting with scavengers. The mechanisms however are not completely clarified. This study evaluated, using a molecular biology approach, the effect of 6 months treatment with vitamin E-modified dialyzers, CL-E, on the gene expression of oxidative stress related proteins and markers. PATIENTS AND METHODS: To this end, the gene expression of p22phox, a NAD(P)H oxidase subunit closely linked with the generation of superoxide anions and of Heme oxygenase-1 (HO-1), induced by and protective from oxidative stress, were evaluated by RT-PCR in mononuclear cells from 5 patients under 3 times a week chronic bicarbonate dialysis. Hydroperoxide (HPO) and total antioxidant power (AOP) plasma levels were evaluated at 3 and 6 months of treatment. HPO was also evaluated in 8 patients under CL-E treatment for 1 year and compared with 8 patients treated with cuprammonium-ryon filter (TAF). RESULTS: p22phox mRNA decreased from 0.61 +/- 0.05 d.u. to 0.48 +/- 0.03, p < 0.01 while HO-1 increased from 0.55 +/- 0.04 d.u. to 0.62 +/- 0.03, p < 0.01. HPO decreased in CL-E treated patients: from 2.72 +/- 0.26 microM to 1.45 +/- 0.27 at 3 months (p < 0.001) to 0.87 +/- 0.11, p < 0.001 at 6 months, while AOP increased: from 752 +/- 90 mmol/L to 1057 +/- 105, p < 0.001 at 6 months. HPO was also reduced in 1 year Excebrane CL-E treated patients compared with cuprammonium treated patients: 2.25 +/- 0.3 vs. 1.42 +/- 0.11 microM, p < 0.001. CONCLUSION: The reduced expression of oxidative stress related proteins and markers gives further support to the efficacy of the use of Vitamin E coated dialysers for the prevention or slowing progression of cardiovascular disease and atherosclerosis, major complications and causes of mortality in these patients in which oxidative stress plays a pivotal role.

Liver-kidney-transplantation in type 1 primary hyperoxaluria: description and comments on a case.

BACKGROUND: Primary hyperoxaluria leads to oxalosis, a systemic illness with fatal prognosis in uremic youngsters because of systemic complications. CASE REPORT: A 14-year old boy with primary type 1 hyperoxaluria who had a long-lasting history of nephrolithiasis and passed from normal renal function to end-stage renal disease within 7 months. MEASUREMENT of alanine: glyoxylate aminotransferase (AGT) catalytic activity in the liver biopsy disclosed very low activity which was not. responsive to pyridoxin., thus the patient entered onto a priority national waiting list for liver-kidney transplantation and a week later received a combined transplant. In order to increase body clearance of oxalate, the patient underwent medical treatment to increase urine oxalate solubility (sodium and potassium citrate oral therapy, magnesium supplementation and increase of diuresis) and intensive dialysis both before and after transplantation. COMMENT: The medical approach to the treatment of this rare illness is discussed. Since the major risk for the grafted kidney is related to the oxalate burden, i.e. oxalate deposition from the body deposits to the kidney that becomes irreversibly damaged, treatment consists of increasing the body clearance of oxalate both by increasing oxalate solubility in the urine and with intensive dialysis performed both before and after combined transplantation. To the same extent (by limiting body oxalate deposits), a relatively early (native GFR 20-25 ml/minute) transplantation is advisable.

Biofiltration vs. bicarbonate dialysis: influence on plasma volume changes and extravascular fluid mobilization.

The present study compares the effects of bicarbonate hemodialysis (Bic. HD) and biofiltration (BF), a new hemodiafiltration technique, on plasma volume (PV) changes and extravascular fluid mobilization (Vfm). Ten uremic patients underwent one experimental session of Bic. HD and, one week later, one of BF, both on the second dialysis of the week. Net ultrafiltration rate was limited to 700 ml/min. At the start of each session, whole blood volume (WBV), PV and red cell volume (RCV) were determined using 5 mu Ci of radioiodinated serum albumin (RISA). PV and Vfm were calculated at hourly intervals using a serial hematocrit method. On Bic. HD, PV increased at 60 min. then decreased at 120 and 180 min., with efficient Vfm only during the first hour. On BF, PV increased throughout treatment, with greater Vfm. It would appear that PV is better preserved in BF, on account of more efficient Vfm.

ALEX (artificial liver for extracorporeal xenoassistance): a new bioreactor containing a porcine autologous biomatrix as hepatocyte support. Preliminary results in an ex vivo experimental model.

Long-term maintenance of viability and expression of differentiated hepatocyte function is crucial for bioartificial liver support. We developed a new bioreactor design (ALEX), associated with a new extracellular autologous hepatocyte biomatrix (Porcine Autologous Biomatrix - PBM) support. To test this new bioreactor, we compared it to a standard BAL (BioArtificial Liver) cartridge in a ex vivo model using human plasma added to bilirubin, ammonium and lidocaine. A pathology study was performed on both bioreactors. The results suggest that ALEX allows a maximal contact between the perfusing plasma and the liver cells and a proper hepatocyte support by a cell-to-matrix attachment. ALEX is a suitable cell support bioreactor, guaranteeing long-term maintenance of the metabolic activity of hepatocytes when compared to a standard BAL cartridge.

[Study of the arrhythmia in patients with chronic uremia in periodic hemodialysis with Holter dynamic electrocardiography]. / Studio delle aritmie negli uremici cronici in emodialisi periodica mediante elettrocardiografia dinamica secondo Holter.

For the purpose of evaluating cause, frequency, type and seriousness of arrhythmias in dialysis patients, 14 chronic uremics, 8 on bicarbonate-dialysis, 6 on acetate-dialysis underwent a basal ECG, echocardiography and a Holter dynamic electrocardiography (ECGD) for a duration of 96 hours. Before and after dialysis PAO, body weight, serum electrolytes and arterial pH were controlled. In 11 patients (78%) supraventricular and ventricular arrhythmias were discovered of equal frequency and seriousness both in the inter and intra dialytic phase, even if more frequent in ventricular hypertrophic patients (IVSn) the complex ventricular arrhythmias (Lown greater than 2). The seriousness and frequency of ventricular and supraventricular arrhythmias in the dialytic phase did not seem to depend either on the type of tampon or on the presence or absence of cardiopathies while in the inter-dialytic phase the seriousness of ventricular arrhythmias seems to depend upon the presence of cardiopathies. The Authors conclude that the pathogenesis of arrhythmias in uremic patients on dialysis is multifactorial and that their elevated incidence makes the use of a Holter in these patients recommendable.

[Relationship between late ventricular potentials and ventricular arrhythmias in patients in chronic dialysis treatment]. / Relazione tra potenziali tardivi ventricolari e aritmie ventricolari nei pazienti in trattamento dialitico cronico.

BACKGROUND: Arrhythmias are frequent pathology in patients with chronic hemodialysis. We evaluated whether a relatively new technique, signal averaging, could be useful in predicting the development of complex arrhythmias in these patients. METHODS: Thirty-three patients, 18 male and 15 female, subjected to thrice weekly chronic hemodialytic treatment with various dialysis techniques, were studied. Exclusion criteria were the presence of antiarrhythmic and inotropic treatment. The following examinations were carried out in all patients: a Holter dynamic electrocardiography for a duration of 24 hours, begun on the day of dialysis, high resolution ECG pre- and post-dialysis to find out if there were any ventricular late potential (VLP). Four hundred beats were examined in order to obtain a background noise of less than 0.7 microV and a better definition of the signal. The following parameters were considered significant for the presence of VLP: a) filtered QRS duration > 120 msec; b) the root mean square of the signal expressed in the terminal portion of QRS (RMS) < 25 microV) high frequency low amplitude signals duration (HFLA) > 40 msec. A positive value in two of these parameters was considered indicative of the presence of VLP. In addition various pre and post-dialysis indices of dialytic efficiency and a mono and two-dimensional echocardiogram with pulsed and color Doppler were carried out. Of the 33 patients studied, ten were excluded because they presented too high a background noise at the high resolution ECG. Of the remaining 23 patients, 13 (56%) presented VLP and nine of these (69%) presented complex arrhythmias. Of the ten patients without VLP, 5 (50%) presented complex arrhythmias. The incidence of arrhythmias was highest during the last two hours of dialysis and in the two hours following it. The patients were then divided into two groups (A and B) according to the ejection fraction (EF) found at the echocardiogram. Group A was composed of 17 patients of whom 8 (47%) presented complex arrhythmias; group B (EF < 45%) was composed of the remaining six patients, who all presented complex arrhythmias. In group A nine patients (53%) out of 17 had LVP, in group B four out of six (66%) had it. All the patients except one presented an increase in the thickness of the ventricular wall and alterations of Doppler transmitral filling rate. Left ventricular hypertrophy was diagnosed in 22 out of the 23 patients. Four patients also had chronic ischaemic heart disease; of these three had LVP. There was no correlation between the presence of LVP and the hemodialytic indices and between the latter and complex arrhythmias. CONCLUSIONS: Our study showed that arrhythmias are more frequent in patients with LVP before dialysis than in those without. The difference was statistically significant (p < 0.006); the incidence of arrhythmias was higher in patients with FE < 45% (p < 0.001). The majority of patients (95%) had left ventricular hypertrophy; only four (17%) had ischaemic heart disease too. It is highly probable that the presence of LVP in our patients can be attributed to hypertension and subsequent left ventricular hypertrophy. As patients with LVP at the end of dialysis had a greater incidence of arrhythmias than those without LVP, we suggest that this method could be useful as a first screening in dialysed patients.

Thymosin-alpha 1 (Zadaxin) enhances the immunogenicity of an adjuvated pandemic H1N1v influenza vaccine (Focetria) in hemodialyzed patients: a pilot study.

BACKGROUND: Although influenza vaccination is widely recommended for immunosuppressed people, the same immune dysfunction that can increase the risk of contracting influenza might also compromise vaccine effectiveness, especially during pandemics. Clinical data have highlighted the role of adjuvants in improving vaccine efficacy. As uremic patients are especially vulnerable to infections, it is recommended that they should be vaccinated yearly against influenza. This paper presents the results of a pilot clinical trial, conducted in hemodialyzed patients with an adjuvated pandemic H1N1v influenza vaccine alone and combined with Thymosin-alpha 1. METHODS: Subjects were subdivided into 3 treatment groups receiving: the adjuvated pandemic influenza vaccine (Focetria) only (first treatment group), and the Vaccine+Thymosin alpha 1 (Zadaxin) at a dose of 3.2 and 6.4 mg (second and third treatment groups respectively). The immunoresponse was assessed on days 0, 21, 42, 84 and 168 after vaccine administration by means of Hemagglutination Inhibition (HI), Microneutralization (MN) and Single Radial Hemolysis (SRH) assays. The CHMP regards HI as the gold standard test to evaluate the immune response to influenza vaccines before influenza vaccines are licensed. The CHMP criteria are slightly different in adults (18-60-year-old subjects) and the elderly (>60 years old). Indeed, 40% of seroconversion, 70% of subjects seroprotected 21 days after vaccination, and a 2.5-fold increase in GMR (Geometric Mean Ratio) are required in adults, while in the elderly, the corresponding threshold values are: 30%, 60% and a 2-fold increase. All these criteria must be met for the licensing of a pandemic influenza vaccine. Safety evaluation was performed by means of Adverse Event (AE) recording, laboratory assays (hematology and chemistry), electrocardiogram, and assessment of vital signs. RESULTS: Three populations were considered: Intention-To-Treat (ITT) (94 patients), Per Protocol (PP) (82 patients), and Safety population (99 patients). With regard to the Geometric Mean Titer (GMT) and the Geometric Mean Ratio (GMR) of HI on Day 21 in the ITT population, both "Vaccine+Thymosin alpha 1" groups presented better results than the "Vaccine only" group. A large proportion of ITT patients in the two Vaccine+Thymosin alpha 1 groups achieved seroconversion by Day 21. On Day 42, the decrease in the GMT of HI was greater in the Vaccine+Thymosin alpha 1 groups than in the vaccine only group. Similar results were obtained in the PP population. The CHMP criteria were fully met in the groups treated with Vaccine+Thymosin alpha 1. No AE was found to be related to Thymosin alpha 1 nor to the Focetria vaccine. CONCLUSIONS: Although further studies in larger hemodialyzed populations are necessary, it can be concluded that Thymosin alpha 1 enhanced the immunogenicity of the pandemic influenza vaccine used. Moreover, it proved safe and well tolerated, and did not affect hematology or blood-chemistry values.

Increased platelet aggregation and decreased high-density lipoprotein cholesterol in women on oral contraceptives.

In vivo platelet function, serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL), and serum triglycerides (TG) were determined in 26 women starting oral contraceptives (OCA). Studies were run prior to, and after one and two months of therapy. Platelet aggregation time decreased by 50 percent or more in eight of the 26 women from a pre-experimental mean value of 387 +/- 136 seconds. TC did not vary but after the women were on medication for two months, HDL decreased from 56 +/- 14.4 mg/dl to 52 +/- 12.3 mg/dl (p less than 0.05). There was a progressive increase in TG under treatment, 74 +/- 23.3 mg/dl on the pre-experimental measurement to 93 +/- 31.0 mg/dl after two months of therapy (p less than 0.005). Women planning to use OCA might best be advised to have aggregation and serum lipid studies done before and early in usage.