bluuebunny/crossref_metadata_2025 huggingface dataset:
Paroxysmal Vagal Overactivity, Apparent Life-Threatening Event and Sudden Infant Death
Authors: Lucet V. , de Bethmann O. , Denjoy I.
Published: April 2003

The possibility of reversible cardiac asystoly due to paroxysmal vagal overactivity (VO) has been well studied, first in adults, then in children, and finally in breath-holding spells. Few studies deal with infants and the incidence of VO among preterm, apparent life-threatening event (ALTE) and sudden infant death syndrome (SIDS). In this review, we summarize data acquired during the past 20 years leading to the diagnosis of VO in infants. We describe the clinical aspects of VO in infants and young children such as Holter-ECG and oculocardiac reflex criteria. The familial aspect of VO and its possible link with SIDS (a new risk factor?) are discussed. Finally, whether or not to treat infants with symptomatic VO is discussed.
Effect of Follicle-Stimulating Hormone on Sertoli Cell Division in Cultures of Fetal Rat Testes
Authors: Sasaki Motoki , Yamamoto Masako , Arishima Kazuyoshi , Eguchi Yasunobu
Published: April 2003

The present study was performed to determine when follicle-stimulating hormone (FSH) begins to promote Sertoli cell division in fetal rats, and to determine whether the effect of FSH is mediated by cAMP-dependent protein kinase (PKA). When testes from 15- to 17-day fetuses were cultured with or without FSH for 48 h, FSH did not promote Sertoli cell division in 15-day testes, but did in 16- and 17-day testes. Anti-rat FSH was injected into 16-day fetuses in utero. Twenty-four hours later, the testes of the injected fetuses and those of their intact littermates were cultured with or without FSH for 48 h. Without FSH, the Sertoli cell division index was significantly lower in anti-FSH-treated fetuses than in intact fetuses. With FSH, however, the index increased. When PKA inhibitor was added to cultures of 16-day testes with FSH, the promotion of Sertoli cell division by FSH was inhibited. We conclude that between 16 and 17 days of gestation, fetal pituitary FSH stimulates the division of Sertoli cells by activating the PKA activity.
Effects of Feeding Colostrum and a Formula with Nutrient Contents as Colostrum on Metabolic and Endocrine Traits in Neonatal Calves
Authors: Rauprich A.B.E. , Hammon H.M. , Blum J.W.
Published: April 2003

Colostrum provides high amounts of nutrients and non-nutrient substances to neonates. To study differences between effects of nutritional and non-nutritional components on growth, health status and metabolic and endocrine traits, a formula was created based on bovine milk components which contained similar amounts of nutrients as bovine colostrum during the first 3 days of lactation, but only trace amounts of growth factors (such as insulin-like growth factor I) or hormones (such as insulin) in whey. Calves were fed either pooled colostrum of milkings 1 to 6, obtained during the first 3 days of lactation (GrC, n = 7) or a formula in the same amounts as colostrum (GrF, n = 7) for the first 3 days, followed by a milk replacer up to day 7. Pre- and postprandial blood samples were taken on days 1, 2, 3 and 7 for the determination of metabolic and endocrine traits and on day 5 we measured intestinal absorptive capacity by testing xylose absorption. Plasma concentrations of total protein and immunoglobulin G and γ-glutamyltransferase activity were lower (p < 0.05), whereas albumin and urea concentrations were higher (p < 0.05) in GrF than GrC during the first week of life. Plasma glucose concentrations were variably affected. Plasma triglyceride, phospholipid and cholesterol concentrations were higher (p < 0.05) in GrC than GrF on days 3 and 7. Insulin and growth hormone concentrations were higher (p < 0.05) in GrC than GrF on days 2 and 3 and on days 1 and 2, respectively, and glucagon concentrations were higher (p < 0.05) in GrC than GrF on day 1 and higher (p < 0.05) in GrF than GrC on day 3. Cortisol concentrations were higher (p < 0.05) on days 2 and 3 in GrF than GrC. Plasma xylose concentrations rose more markedly (p < 0.05) in GrC than GrF. In conclusion, feeding only trace amounts of bioactive substances appears to impair intestinal absorptive capacity and protein and fat metabolism and exert effects on endocrine systems in neonatal calves.
Postnatal Changes in Plasma Ceruloplasmin and Transferrin Antioxidant Activities in Preterm Babies
Authors: Lindeman Jan H.N. , Lentjes Eef G.W.M. , van Zoeren-Grobben Diny , Berger Howard M.
Published: April 2003

Postnatal changes in plasma ceruloplasmin ferroxidase and transferrin iron-binding antioxidant activity were studied in 10 healthy preterm babies during the first 6 weeks of life. Ceruloplasmin levels and ceruloplasmin ferroxidase activity were low at birth, remained stable for the first 3 weeks, and increased between 3 and 6 weeks. The transferrin levels were also low at birth, and this finding persisted throughout the 6-week study period. However, although the plasma iron-binding antioxidant activity was correspondingly low at birth, it thereafter rose and remained high. In four cord blood samples, but not in subsequent postnatal samples, peroxidation was actually stimulated in the assay measuring plasma iron-binding antioxidant activity. We have previously shown that this phenomenon is probably due to the presence of non-protein-bound iron.
Placental Transfer of Pyrimethamine Studied in an ex vivo Placental Perfusion Model
Authors: Peytavin Gilles , Leng Jean-Joël , Forestier François , Saux Marie-Claude , Hohlfeld Patrick , Farinotti Robert
Published: April 2003

Pyrimethamine is used as and anti-infectious agent because of its antifolate properties. Its action is synergistic with that of dapsone and sulfamides on Toxoplasma gondii. The goal of the present study was to evaluate the placental transfer of pyrimethamine in an ex vivo model of perfused human placental cotyledon at term. Human placentas were perfused according to the slightly modified method of Schneider. The pyrimethamine fetal transfer rate was approximately 30%, while cotyledon clearance was about 1.8 ml/min. The placental transfer of pyrimethamine seems to be independent of the maternal concentrations of pyrimethamine, suggesting passive diffusion mechanisms or a nonsaturable active transport at the tested concentrations.
Effects of Correction of Hypocalcemia on Cardiac Function in the Newborn Lamb
Authors: Moon Anita J. , Milstein Jay M. , Goetzman Boyd W. , Bennett Stephen H.
Published: April 2003

The effect of correction of hypocalcemia on cardiac function in the neonate is unclear. Therefore, we evaluated changes in hemodynamic variables and cardiac contractility in a hypocalcemic neonatal lamb model. Baseline serum ionized hypocalcemia was induced via chelation with intravenous EGTA. Cardiac contractility, measured as end-systolic elastance, did not change with correction of hypocalcemia in this model. In contrast, the variable dP/dtmax, a load-dependent index of contractility, showed an increase with calcium administration while the end-diastolic volume decreased, suggesting that diastolic function or early systolic function had changed. Systemic vascular resistance, cardiac output, and heart rate did not change significantly with correction of hypocalcemia. The results of this study suggest that in our newborn lamb model, cardiac contractility is insensitive to ionized calcium and may reflect cardiac immaturity, but that there may be an effect of calcium administration on diastolic or early systolic function.
The Effect of Interleukin-12 and Interleukin-15 on CD69 Expression of T-Lymphocytes and Natural Killer Cells from Umbilical Cord Blood
Authors: Lin Syh-Jae , Chao Hsun-Chin , Kuo Ming-Ling
Published: April 2003

We investigated the effect of two immunoregulatory cytokines interleukin-12 (IL-12) and IL-15, alone or in combination, on CD69 expression of mononuclear cells (MNCs) obtained from umbilical cord blood (CB) and adult peripheral blood (APB). We established that (1) CD3/69, but not CD16/69, expression on CB MNCs could be increased with IL-12, IL-15 or both in 18-hour cultures, but to a lesser degree compared to that on corresponding APB MNCs, (2) CD3/69 expression on CB MNCs was significantly increased after 1 week’s culture with IL-12, especially with IL-15, exceeding that on APB MNCs similarly activated and (3) CD16/69 expression on CB MNCs, but not APB MNCs, was greatly increased after 1 week’s culture with IL-15. The combination of IL-12 + IL-15 resulted in greater CB CD3/69 expression than individual cytokines, while producing less of an effect on CD16/CD69 expression as compared to IL-15 alone. The results of our study indicate that neonatal T and NK cells readily respond to cytokine stimulation by upregulating CD69 expression, with a greater effect achieved using IL-15 compared to IL-12.
Role of Nitric Oxide in Hypoxia-Induced Changes in Newborn Rats
Authors: Kiliç İlknur , Kiliç B. Alper , Güven Cengiz , Demirpençe Ediz , Akşit M. Arif
Published: April 2003

In order to investigate the role of nitric oxide (NO) in hypoxic tissue damage in newborns, we studied the effects of systemic administration of an inhibitor of NO synthase, NG-nitro-L-arginine (L-NNA), and the precursor for the synthesis of NO, L-arginine (L-ARG), on the biochemical and histological changes in brain, heart, lung, liver, kidney, intestine, and skeletal muscle tissues. Four groups of 1-day-old Wistar rat pups were used: control, hypoxic, L-ARG, and L-NNA groups. L-ARG 100 mg/kg or L-NNA 2 mg/kg was administered as a bolus intraperitoneally 1.5 h before hypoxia. Hypoxia increased lipid peroxidation in all tissues except muscle; this increase was prevented by L-NNA and L-ARG in brain, heart, lung, kidney, and liver tissues. L-NNA in intestine and L-ARG in muscle tissue increased lipid peroxidation. The tissue-associated myeloperoxidase activity was decreased in the liver by L-NNA and L-ARG. Histopathological changes in intestines were villous epithelial separation and hyperemia in hypoxic and L-NNA groups which were not observed in control and L-ARG groups. In lungs, pulmonary hemorrhage was observed only in the hypoxic group. These data suggest that NO acts both as a destructive and a protective agent in the pathogenesis of hypoxia-reoxygenation injuries.
Plasminogen Did Not Affect Lung Function in Surfactant-Treated Preterm Lambs
Authors: Bhat Vishwanath , Jobe Alan H. , Wert Susan , Jesmok Gary J. , Ikegami Machiko
Published: April 2003

Preterm infants with respiratory distress syndrome develop fibrin-rich hyaline membranes within the alveoli and have depressed fibrinolytic activity, which is thought to be due to a relative deficiency of plasminogen. Local fibrin deposition inhibits surfactant function and amplifies inflammation. We hypothesized that plasminogen administration to surfactant-treated preterm lambs would prevent fibrin-rich hyaline membrane formation, resulting in the amelioration of lung pathology and improved lung function. We randomly treated preterm lambs (gestational age 127–129 days) with either 16 mg of lysine-plasminogen (n = 10) or saline (n = 10), and ventilated them for 5 h. There were no significant differences in physiologic measurements of lung function (ventilation efficiency index, oxygenation index, dynamic compliance, quasi-static pressure volume curve), measures of lung injury (alveolar wash protein content and 125I-albumin recovery) or surfactant pool size. The degree and extent of bronchiolar erosion and hyaline membrane formation were similar in the two groups. Plasminogen administration did not improve lung function or prevent hyaline membrane formation in surfactant-treated lambs.
Potential Hazards of Exposure to Di-(2-Ethylhexyl)-Phthalate in Babies
Authors: Latini G.
Published: April 2003

Many plastic items are made of polyvinylchloride (PVC) blended with plasticizers. The most frequently used plasticizer is di-(2-ethylhexyl)-phthalate (DEHP). DEHP migrates at a constant rate from plastics to the environment: it has been detected in water, soil and food and is therefore considered as a widespread environmental contaminant. Over the past several years, a number of publications concerning toxic effects of DEHP on animals and humans have been reported. Although DEHP is suggested to be of low acute toxicity, long-term exposure, especially in human beings at risk such as pregnant women and children, requires more in-depth studies. If DEHP toxicity in humans were to be confirmed, it would be advisable in the future to replace current PVC plasticizers, especially if they come into contact with babies, with better-quality materials.
Transient Effect of Granulocyte Colony-Stimulating Factor in Allo-Immune Neonatal Neutropenia
Authors: Girlando Pietro , Zuppa Antonio Alberto , Romagnoli Costantino , Tortorolo Giuseppe
Published: April 2003

The effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) administration at 10 μg/kg/day for 15–30 min over 3 consecutive days in 3 preterm neonates with allo-immune neonatal neutropenia (ANN) is reported. Patients 1 and 2 had antibodies against antigen NA2, while patient 3 had antibodies against NA1. All neonates developed a rapid increase in absolute neutrophil count which reached the normal range within 48 h (from 75–640/mm3 to 2,520–4,700/mm3). However, 23–25 days later, all 3 neonates relapsed into a second phase of severe neutropenia (408–870/mm3). Antibodies against neutrophil antigens were still positive during this period. This second-phase neutropenia persisted for 20–30 days and resolved spontaneously. It may be possible that when rhG-CSF is administered within a short time after birth in neonates with ANN, its effect is exhausted before the concentration of circulating antibodies decreases, with the result that a second phase of neutropenia can be expected.
Plasma Leptin Levels in Rat Mother and Offspring during Pregnancy and Lactation
Authors: Herrera E. , Lasunción M.A. , Huerta L. , Martín-Hidalgo A.
Published: April 2003

The profiles of plasma leptin levels in pregnant and lactating rats and their offspring were determined. The plasma leptin levels increased on days 12 and 20 of gestation and declined on day 21 of gestation, remaining at this level during lactation. These changes were similar for lumbar adipose tissue weight, and a significant correlation was found when both variables were plotted with individual values. During the last 2 days of intrauterine life, the plasma leptin levels in the fetuses were in the same range as in their mothers, declining from day 20 to day 21. On the 1st day of life, the leptin levels increased to decline in suckling newborns after 4 days, remaining stable until day 20 of life. The enhancement in maternal white adipose tissue mass that takes place during pregnancy and its decline around parturition and lactation are proposed to contribute actively to the changes in the plasma leptin profile detected at these stages. Besides the contribution of placental leptin for the fetus and milk leptin for the suckling newborn, it is proposed that brown adipose tissue, which is the first form of adipose tissue that appears during development in the rat, is responsible for most of the changes in plasma leptin levels seen around birth, whereas its later decline could be mediated by the hormonal changes occurring after birth.
Pharmacokinetics of Verapamil in New Zealand White Rabbits during Ontogeny
Authors: Solans Carlos , Bregante Miguel Angel , Aramayona José Javier , Fraile Lorenzo José , Garcia María Angeles
Published: April 2003

The pharmacokinetics of verapamil during ontogeny in rabbits and in vitro verapamil demethylase activity have been investigated in the liver and whole blood. In vivo experiments revealed that the slope of the postdistributive phase as well as the area under the curve and clearance showed significant differences when newborn and adult rabbits were compared. Other pharmacokinetic parameters, such as volume of distribution and plasma protein binding did not show any statistical differences. Liver microsomal preparation samples from 1-, 8- and 16-day-old rabbits displayed approximately 20% of the activity observed in adults. A significant verapamil demethylase activity in the whole blood of rabbits was also noted. The in vivo results show that newborn rabbits have a capacity to eliminate verapamil that is similar or even higher than that of adults. These findings could not be explained with regard to the in vitro liver metabolism of verapamil, although they could with respect to blood metabolism.
Enhanced Peritoneal Diffusion Capacity of 51Cr-EDTA during the Initial Phase of Peritoneal Dialysis Dwells: Role of Vasodilatation, Dialysate ‘Stirring’, and of Interstitial Factors
Authors: Carlsson Ola , Rippe Bengt
Published: April 2003

Mass transfer area coefficients (PS) to small solutes are usually markedly increased during the first 0–15 min of peritoneal dialysis (PD) dwells. This phenomenon may be due to, for example, initial arteriolar vasodilatation and, hence, recruitment of capillary surface area. Other possibilities are an initial discharge (or saturation) of solutes from (in) the interstitium or an increased mixing, i.e., ‘macrostirring’ caused by the exchange procedure per se. We have investigated these possibilities during acute PD in rats, by assessing PS for 51Cr-EDTA as a function of time [PS(t)]. The discharge effect was studied by saturating the peritoneal interstitium with 51Cr-EDTA by intravenous tracer infusion prior to each dwell and the results compared to those obtained in rats when tracer infusion and dwells were started simultaneously. The potential effect of initial vasodilatation was studied by adding isoproterenol to the dialysis fluid. Finally, the potential influence of an increased interstitial ‘microstirring’, induced by high glucose concentrations, was investigated by comparison of results for 1.36% Dianeal® with those for 3.86% Dianeal. In nonvasodilated rats there was a significant drop in PS(t) between 2.5 and 15 min regardless of whether the rats were preloaded with tracer or not. However, there were no significant changes in PS(t) within the isoproterenol-treated group, indicating that vasodilatation plays a crucial role for the high PS initially. Furthermore, there was no difference in overall PS for 51Cr-EDTA among 1.36 and 3.86% Dianeal dwells. In conclusion, we have found that vasodilatation, but not interstitial discharge (or loading), may explain the inflation of PS occurring during the initial part of PD dwells. In addition, ‘macrostirring’, induced by the exchange procedure per se, may also be important.
Modulation of Neutrophil Apoptosis by Uremic Plasma during Hemodialysis
Authors: Jaber Bertrand L. , Balakrishnan V.S. , Cendoroglo Miguel N. , Perianayagam Mary C. , King Andrew J. , Pereira Brian J.G.
Published: April 2003

During hemodialysis (HD), blood-membrane interactions lead to activation of several circulating cells and plasma proteins. The resultant activation and/or release of mediators can modulate the structure, function and survival of circulating neutrophils. Little is known of plasma factors that influence apoptosis of neutrophils in hemodialyzed patients. Hence, we investigated the effect of uremic plasma obtained during HD on the survival of neutrophils obtained from healthy volunteers. Neutrophils harvested from healthy volunteers were incubated in ultrafiltered culture medium supplemented with either 50% heterologous normal plasma obtained from healthy volunteers (n = 15) or 50% uremic plasma collected from long-term HD patients dialyzed with cuprophan (CU) (n = 8), cellulose triacetate (CTA) (n = 8) or polysulfone (PS) (n = 8) dialyzers. Plasma samples were drawn predialysis, 15 min after starting dialysis, and postdialysis. After 24-hour incubation, neutrophil aliquots were processed for quantification of apoptosis by flow cytometry, using propidium iodide DNA staining. In addition, tumor necrosis factor α (TNFα) and interleukin-10 (IL-10) were measured in normal and predialysis uremic plasma samples. Neutrophils from healthy volunteers exposed to heterologous normal plasma samples exhibited 10.3 ± 1.2% apoptosis. In contrast, the proportion of apoptosis was significantly higher among neutrophils exposed to predialysis (28.5 ± 2.3%, p < 0.0001), 15 min (23.0 ± 2.4%, p < 0.0001), or postdialysis uremic plasma samples (25.7 ± 2.3%, p < 0.0001). Compared to neutrophils exposed to predialysis uremic plasma samples, a significantly lower proportion of apoptosis was observed in neutrophils exposed to the 15-min plasma samples among patients dialyzed with CU (26.4 ± 2.9 vs. 18.2 ± 3.5%; p < 0.001) but not with CTA or PS dialyzers. Futher, CU membranes induced the greatest percentage decrease in neutrophil apoptosis at 15 min. There was a direct correlation between neutrophil apoptosis and plasma levels of TNFα (r = 0.424, p = 0.02) and IL-10 (r = 0.744, p < 0.0001). The results of the study suggest that normal neutrophils exposed to uremic plasma undergo accelerated in vitro apoptosis compared to those incubated with normal plasma. Further, during HD, the apoptosis-inducing activity of uremic plasma is modulated by the use of dialyzers with different degrees of biocompatibility. The identification of soluble factors that are responsible for the increased apoptosis-inducing activity of uremic plasma needs to be further investigated.
The Involvement of Oxidative Stress in the Progression of Renal Injury
Authors: Haugen Eric , Nath Karl A.
Published: April 2003

That reactive oxygen species are involved in progressive renal injury is supported by several lines of evidence: increased generation of oxidants occurs in chronic renal injury; various antioxidant strategies exert beneficial effects in models of chronic renal injury; and, oxidative stress can induce changes in the otherwise unmanipulated kidney that resemble those seen in chronic renal disease. Oxidants may contribute to progressive renal disease by virtue of their renal haemodynamic actions, by impairing glomerular permselective properties, by inducing inordinate or aberrant growth responses, by inducing loss of cellular phenotype and apoptosis, and finally, by promoting acute and chronic inflammatory responses. Certain adhesion molecules and proinflammatory mediators, and the transcription factor NFκB, can be upregulated by oxidants. Oxidants can also induce the fibrogenic cytokine, TGFβ1, one that is widely incriminated in progressive renal injury. Reduction in renal oxidative stress by dietary or pharmacologic approaches provides an appealing target for therapies directed towards the retardation of progressive renal injury.
Imbalance of Oxidants and Antioxidants in Haemodialysis Patients
Authors: Canaud B. , Cristol J.-P. , Morena M. , Leray-Moragues H. , Bosc J.-Y. , Vaussenat F.
Published: April 2003

Dialysis-related pathology (DRP) observed in long-term haemodialysis patients is increasingly reported. Among DRP manifestations, cardiovascular disease is the most frequent, being the first cause of mortality in haemodialysis patients. Alterations in lipid metabolism and oxidative stress are recognised as major risk factors that could be prevented or reduced by optimal therapy.In order to evaluate the rationale for preventive intervention against oxidative damage we review the factors that are implied and may be responsible for the imbalance between prooxidative and antioxidative mechanisms in haemodialysis patients. Oxidative stress resulting from this imbalance is responsible for increasing stress markers and enhancing susceptibility to LDL oxidation. Factors implied in this prooxidative state belong to four groups: (1) uremia and comorbid status of the end stage renal disease (ESRD) patient; (2) losses of antioxidant substances via the dialysis; (3) haemoincompatibility of the dialysis system; (4) adjuvant therapy. Such prooxidant status could have further deleterious consequences since it has been recently shown that antioxidant status could modulate cell functions such as reactive oxygen species (ROS) production, adhesive molecule expression and/or cell proliferation.Preventive modalities, including use of biocompatible membrane, ultrapure dialysate, exogenous supplementation of antioxidant vitamins, extracorporeal removal of ROS and oxidatively-modified substances, would appear highly desirable to reduce complications of long-term dialysis patients.
An Overview of Haemodialysis and Oxidant Stress
Authors: Tetta C. , Biasioli S. , Schiavon R. , Inguaggiato P. , David S. , Panichi V. , Wratten M.L.
Published: April 2003

Today’s patient population is increasingly older. Patients with chronic renal failure therefore start extracorporeal substitutive treatment having congestive heart failure, chronic liver disease, diabetes and so forth. In these patients, however, long-term haemodialytic treatment may add further aggravation on their pre-existing pathological conditions. Oxidative stress and alterations in lipid metabolism are caused by haemodialysis mainly due to (1) bioincompatibility type of reactions such as production of reactive oxygen species by inflammatory cells due to complement-mediated or -independent pathways, and (2) the imbalance between oxidants and antioxidants due to the diffusive loss of hydrophilic vitamins such as ascorbic acid. The events related to the oxidant stress may sustain a state of chronic inflammation. Recent advances suggest that atherosclerosis and proliferation of the smooth muscle are initiated and sustained by inflammatory mechanisms. Therefore, attempts to counterbalance the prooxidant effect of haemodialysis and to reduce the chronic inflammatory state will be presented.
Trace Elements in End-Stage Renal Disease
Authors: Zima Tomáš , Tesař Vladimír , Mestek Oto , Němeček Karel
Published: April 2003

For human beings trace elements are essential nutrients with a gamut of functions. They are for instance indispensable components of many enzymes, so they have some regulatory functions and they may affect immune reactions and free radical generation. Altered blood levels of different trace elements have been described in patients with advanced renal failure and especially in those treated by different kinds of renal replacement therapy. Altered renal function may result in impaired renal excretion of trace elements and their accumulation or depletion in the body. The dialysate concentrate and water used for preparing the dialysate may be an important source of the accumulation or depletion of trace elements in dialyzed patients. The gain or loss of trace elements during dialysis depends on the gradient between the ultrafiltrable fraction of a particular element in serum and its concentration in the dialysis fluid, and also on the type and permeability of the dialysis membrane. There are some methodological problems concerning the handling and storing of blood samples and measurement techniques leading to the rather inconsistent results of different studies concerning trace elements in renal disease. Geographical variations and environmental contamination of soil and water and different dietary habits may significantly influence trace elements in these patients. The abnormalities of trace elements are primarily the result of uremia, and they may be further modified and sometimes greatly exacerbated by the dialysis procedure.
Plasma C-Reactive Protein in Hemodialysis Patients: A Cross-Sectional, Longitudinal Clinical Survey1
Authors: Panichi Vincenzo , Migliori Massimiliano , De Pietro Stefano , Metelli Maria Rita , Taccola Daniele , Perez Rafael , Palla Roberto , Rindi Paolo , Cristofani Renza , Tetta Ciro
Published: April 2003

In hemodialysis patients, C-reactive protein (CRP), an acute-phase reactant, is a sensitive and independent marker of malnutrition, anemia, and amyloidosis. The aim of the present studies was to evaluate CRP and interleukin 6 levels in plasma samples from long-term hemodialysis patients on different extracorporeal modalities associated with or without backfiltration. Two hundred and forty-seven patients were recruited in eight hospital-based centers. All patients had been on their dialytic modality for at least 6 months. At enrollment, 46 hemodialysis patients out of 247 (18.6%) had clinical evidence of pathologies known to be associated with high CRP values. The 201 remaining patients were defined as clinically stable and were on conventional hemodialysis (34%), hemodiafiltration with infusion volumes <10 liters/session (10%), hemodiafiltration with infusion volumes <20 liters/session (32%), and double-chamber hemodiafiltration with infusion volumes <10 liters/session (22%). Analysis of CRP values in the clinically stable patients showed that an unexpectedly high proportion (47%) of the patients had CRP values higher than 5 mg/l (taken as the upper limit in normal human subjects). The values of CRP and interleukin 6 were significantly higher in hemodiafiltration with infusion volumes <10 liters/session than in hemodiafiltration with infusion volumes >20 liters/session, in hemodialysis and in double-chamber hemodiafiltration. The same pattern occurred after 6 months of follow-up in 171 out of 201 clinically stable patients. Hemodialytic conditions that expose to the risk of backfiltration such as low exchange volume hemodiafiltration may induce a chronic inflammatory state as reflected by increased plasma values of both CRP and interleukin 6, thus suggesting the need for hemodialytic strategies that reduce (hemodialysis with low-permeability membranes or hemodiafiltration with infusion volumes >20 liters) or eliminate (double-chamber hemodiafiltration) backfiltration of bacteria-derived contaminants.
Hemodiafiltration with On-Line Endogenous Reinfusion
Authors: de Francisco Angel L.M. , Piñera Celestino , Heras Milagros , Rodrigo Emilio , Fresnedo Gema Fernandez , Ruiz Juan Carlos , Tetta Ciro , Arias Manuel
Published: April 2003

Paired filtration dialysis is a modified form of hemodiafiltration with a double-chamber hollow fiber. Convection is separated from diffusion, eliminating the potential risk of backfiltration (which can contain endotoxin or cytokine-inducing substances).The regeneration of high volumes of plasma ultrafiltrate obtained in the first filter allows a large plasma volume to be treated, and at the same time enables the return of many beneficial substances such as hormones, small peptides and many vitamins. Ultrafiltrate is regenerated with a charcoal-resin device and reinfused to the patient. Hemodiafiltration with on-line endogenous reinfusion is an easy and safe procedure. In addition, the method avoids risks associated with exogenous fluid infusion (endotoxin, pyrogens), allows exchange at no extra costs of large volumes of fluids and reduction in storage of fluid bags. Clinical advantages also include infusion of physiological fluid containing bicarbonate and calcium, good clinical tolerance and cardiovascular stability.
Plasma Amino Acid Profile on Nocturnal Hemodialysis
Authors: Raj Dominic S.C. , Ouwendyk Michaelene , Francoeur Robert , Pierratos Andreas
Published: April 2003

Background/Aims: The purpose of this study was to examine the effect of nocturnal hemodialysis (NHD) on serum amino acid (AA) profile. Methods: In a cross-over trial, we studied the AA profile in 11 patients who were switched from conventional hemodialysis to NHD. Plasma levels of AA were measured at monthly intervals for a period of 1 year. Results: Concentrations of AA isoleucine, threonine, phenylalanine, valine, glycine, glutamine and taurine increased on switch to NHD. Total AA (2,907.2 ± 542.2 vs. 3,870.2 ± 715.2 μmol/l, p = 0.03), essential AA (EAA, 842.2 ± 259.4 vs. 1,125.8 ± 235.3 μmol/l, p = 0.03), nonessential AA (NEAA, 2,307.2 ± 399.1 vs. 2,879.5 ± 581.2 μmol/l, p = 0.03), and branched chain AA (315.5 ± 90.8 vs. 386.0 ± 114.3 μmol/l, p = 0.05) concentrations were significantly higher on NHD. However, abnormalities in the ratios of EAA/NEAA, valine/glycine and tyrosine/phenylalanine persisted during NHD. Conclusions: NHD alleviated some abnormalities in the aminogram of uremia, but other metabolic derangements lingered.
Measurement of Fluid Volume Shifts during Hemodialysis by A-Mode Ultrasonography
Authors: Schumacher Jan , Rob Peter , Kreft Burkhard , Engelke Anke , Heringlake Matthias , Klotz Karl-F.
Published: April 2003

Background: The rate of intercompartmental fluid volume changes during hemodialysis (HD) is a major determinant of dialysis-induced hypotension and lacks direct monitoring. The aim of the study was to evaluate the feasibility of tissue thickness (TT) measurement in monitoring the mobilization of interstitial fluids during HD. Methods: We studied the intradialytic changes in forehead TT and inferior vena cava diameter (IVCD) in 20 patients. Plasma refilling was calculated from changes in hematocrit (Hct) and ultrafiltration rates. Results: During ultrafiltration of 2,437 ± 117 ml (mean ± SEM), Hct increased significantly from 27.9 ± 0.7 to 30.0 ± 0.9%. IVCD decreased significantly from 9.7 ± 0.2 to 6.1 ± 0.4 mm/m2. We found a simultaneously pronounced reduction in TT from 4.46 ± 0.12 to 3.78 ± 0.12 mm (≥15.3%) with a significant correlation to plasma refilling (0.613). Conclusion: Volume changes in the peripheral shell tissues during HD can be monitored directly and noninvasively by A-mode ultrasound.
Leukocyte Sequestration in Isolated Guinea Pig Lungs during Extracorporeal Circulation: Effects on Microvascular Function
Authors: Nyhlén K. , Hultkvist-Bengtsson U. , Nilsson M. , Rippe B.
Published: April 2003

Neutrophils accumulate in patient lungs during clinical hemodialysis and in isolated blood-perfused guinea pig lungs due to the contact between blood and extracorporeal system. However, it is unclear how these sequestered and partly activated neutrophils affect the lung microvasculature. We, therefore, studied pulmonary vascular resistance, vascular permeability, gas exchange, and oxygen free radical production in isolated guinea pig lungs during perfusion with whole blood containing partly ‘activated’ neutrophils in comparison with perfusions using leukopenic blood. We also connected a Cuprophan hemodialysis membrane to the whole-blood perfusion system in order to investigate whether a dialyzer, which may further activate leukocytes, affects lung microvascular permeability, vascular resistances, and reactive oxygen species production. The sequestered neutrophils did not seem to markedly affect the lung microvascular function, since neither the leukocyte-free perfusion nor the hemodialysis membrane altered any of the measured variables as compared with whole-blood perfusion in a system without a dialyzer. We conclude that neutrophils, whether activated by a perfusion system or by a dialysis membrane, can accumulate in isolated lungs without adversely affecting the microvascular function.
Inflammatory and Atherosclerotic Interactions in the Depleted Uremic Patient
Authors: Stenvinkel Peter
Published: April 2003

Despite the improvements in dialysis technology, the cardiovascular mortality rate is still unacceptably high among dialysis patients. It is obvious that traditional risk factors, such as hypertension, chronic heart failure (CHF), dyslipidemia and diabetes mellitus, may account for a large part of the increased cardiovascular mortality rate in these patients. However, based on recent research it could be speculated that other, non-traditional risk factors might also contribute to the high cardiovascular mortality rate in dialysis patients. Chronic inflammation, as evidenced by increased levels of pro-inflammatory cytokines and C-reactive protein (CRP), is a common feature in dialysis patients and is associated with an increased cardiovascular morbidity and mortality. Indeed, elevated levels of pro-inflammatory cytokines (such as TNF-α, IL-1 and IL-6) may cause malnutrition and progressive atherosclerotic cardiovascular disease by several pathogenetic mechanisms, which will be discussed in this review. Based on the strong associations observed between malnutrition, inflammation and atherosclerosis in patients with chronic renal failure (CRF) we have proposed that these features constitute a specific syndrome (MIA), which carries a high mortality rate. As elevated levels of pro-inflammatory cytokines may play a central part in the vicious circle of malnutrition, inflammation and atherosclerosis, further research is needed to investigate whether or not different anti-cytokine treatment strategies may improve survival in dialysis patients.
An in vitro Bacterial Touch Contamination Risk Assessment of Two CAPD Twinbag Systems
Authors: Kubey W. , Straka P. , Holmes C.J.
Published: April 2003

The objective of this study was to compare, using in vitro quantitative microbiology, the ability of two commercially available peritoneal dialysis solution delivery systems to prevent and remove, via convective fluid flow, intralumenal fluid path bacterial contamination. The two systems (A and B) differed in both the configuration of their flow control, or Y-junction and the method of fluid flow control and also in the design of their Luer tubing connectors. System A had a tubing type Y-junction that requires clamps to control fluid flow and uses a connector with a male Luer that is deeply recessed within a shroud. System B has a dial-type rigid Y-junction with in-line flow control and a connector with a male Luer that is shrouded but not recessed. System A connectors allowed significantly (p < 0.0001) fewer bacteria to be transferred into the fluid path than System B after simulated touch contamination. Also, when an equivalent number of bacteria were deliberately placed into the fluid paths of both systems, System A was more effective in removal of the bacterial contamination by convective fluid flow than System B (p < 0.0001), resulting in fewer organisms infused into the simulated peritoneum. Specific design features of System A, such as a recessed male Luer, and a Y-junction fluid flow path with low turbulence were likely explanations for its superior results. This study emphasizes the importance of connector and fluid path flow design in the aseptic performance of peritoneal dialysis delivery systems.
ZOO-FISH analysis in insectivores: “Evolution extols the virtue of the status quo”
Authors: Dixkens C. , Klett C. , Bruch J. , Kollak A. , Serov O.L. , Zhdanova N. , Vogel W. , Hameister H.
Published: April 2003

In evolutionary terms, insectivores are thought to be close to primates. Through ZOO-FISH analysis using human chromosome-specific painting probes, the syntenic relationship between the human and common shrew, Sorex araneus, karyotypes was studied. The human karyotype was found to be conserved in the shrew, with 32 autosomal segments of common synteny. Special arrangements, already known from similar studies on other species, were noted: fusions of HSA 16 and 19, HSA 3 and 21, and HSA 14 and 15. Only 10 breaks are necessary to transform the human karyotype into the karyotype of the common shrew. Together with known ZOO-FISH data from species belonging to other orders, this puts the human karyotype arrangement near the basis of all mammalian karyotypes. Human chromosome 2 was found to be conserved in its entirety as a single chromosome arm in the shrew. Evidence is presented that the same fusion of two original chromosomal segments formed the shrew chromosome ortholog of HSA 2 as the fusion that occurred during primate evolution to form human chromosome 2. This is a remarkable example of chromosomal coevolution.
Direct and mediated effects of testosterone: analysis of sex reversed mosaic mice heterozygous for testicular feminization
Authors: Drews U.
Published: April 2003

Sex reversed mice are XX males carrying on one of their X chromosomes a translocation of the sex determining region of the Y (Cattanach’s Sxr factor). The phenotype corresponds to the Klinefelter syndrome in man. The X linked Tfm (testicular feminization) mutation in the mouse is a frame shift in the androgen receptor gene leading to complete androgen insensitivity. Due to random X inactivation, sex reversed mice heterozygous for Tfm, are mosaics composed of a variable proportion of androgen insensitive XTfm and androgen sensitive X+ wildtype cells. In the intersexual genital tract, Tfm cells are maintained as undifferentiated cells in the epididymal duct. To the distorted prostate lobes and bulbourethral glands they contribute some lobules of indifferent urethral glands. A large contribution of Tfm cells allows downgrowth of Wolffian and Müllerian ducts to form a vagina. In the external genitalia the stimulatory effect of testosterone is reduced leading to various degrees of feminization correlating with the proportion of Tfm cells present. In the mosaics effects of testosterone, mediated by local growth factors from the wildtype to the Tfm cells, can be distinguished from direct effects expressed only in the wildtype cells. Mediated effects are embryonic induction and morphogenesis of male organs and postnatal maintenance of organ structure and proliferation. The direct effect is cellular differentiation.
Chromosomal rearrangements in a Somali wild ass pedigree, Equus africanus somaliensis (Perissodactyla, Equidae)
Authors: Houck M.L. , Kumamoto A.T. , Cabrera R.M. , Benirschke K.
Published: April 2003

Chromosome analyses were conducted on 15 animals in a pedigree of Somali wild ass, Equus africanus somaliensis. G- and C-banded karyotypes are presented for the first time on this endangered species. The diploid number ranged from 62 to 64. Numerical chromosomal variation was the result of a centric fission which was accompanied by a heterochromatic deletion. The fission polymorphism involved acrocentric elements 19 and 21 as determined by G-banding. These autosomes are homologous to those involved in centric fission/fusion polymorphisms in other equids: E. asinus (domestic donkey), E. hemionus (onager), E. kiang (kiang), and E. burchelli (common zebra). Banding analyses also revealed a paracentric inversion polymorphism in submetacentric chromosome pair 2 of E. a. somaliensis. Both the centric fission and paracentric inversion polymorphisms involved heterochromatic regions. One individual was found to be heterozygous for two de novo chromosomal rearrangements: a centric fission (involving acrocentric elements 19 and 21) and a heterochromatic deletion of chromosome 2.
Chromosomal localization of rDNA in the gorilla
Authors: Schempp W. , Zeitler S. , Rietschel W.
Published: April 2003

Twenty-five specimens of lowland gorilla, including 24 specimens of the western lowland gorilla (Gorilla gorilla gorilla) and 1 specimen of the eastern lowland gorilla (G. gorilla graueri), were investigated by fluorescence in situ hybridization with a human-derived 18S + 28S rDNA probe. Specific hybridization was constitutively seen on the short arms of gorilla acrocentric chromosome pairs 22 and 23, corresponding to human pairs 21 and 22. Only one specimen of western lowland gorilla investigated showed an additional hybridization site at the telomeric short arm of one chromosome 1. From our own results and those in the literature, it is clear that the additional rDNA site on chromosome 1 must be regarded as a rare polymorphism in the subspecies of western lowland gorilla, possibly going back to a founder translocation event.
Three novel SRY mutations in XY gonadal dysgenesis and the enigma of XY gonadal dysgenesis cases without SRY mutations
Authors: Scherer G. , Held M. , Erdel M. , Meschede D. , Horst J. , Lesniewicz R. , Midro A.T.
Published: April 2003

Mutations in the Y-located testis-determining gene SRY are one cause for XY sex reversal. We have previously identified four SRY mutations in a total of 45 sex-reversed females with XY gonadal dysgenesis (XY GD). In a new sample of 16 XY GD cases, three previously undescribed SRY mutations were identified. Two are point mutations that lead to amino acid substitutions in the HMG domain of SRY, M64R, and F67V. The third SRY mutation is a single base insertion 5′ to the HMG box within codon 43, converting this lysine codon to a stop codon (K43X). A total of 33 SRY mutations have so far been described that account for only 10–15% of XY GD females. A further 10–15% of these cases result from deletion of SRY due to aberrant X/Y interchange. The etiology of the remaining 70–80% of XY GD cases is still enigmatic. Possible explanations for these XY sex-reversal cases are discussed.
Evolution by fusion and amplification: the murine Sp100-rs gene cluster
Authors: Weichenhan D. , Kunze B. , Traut W. , Winking H.
Published: April 2003

Abstract. Sp100 is a single-copy gene in the human and the mouse. A related gene, Sp100-rs, occurs in multiple copies and forms a conspicuous cluster in the mouse chromosome 1. Murine Sp100 and Sp100-rs are homologous from the promoter up to a position in intron 3, but they differ 3′ of that position. In the genus Mus, Sp100-rs is present in one phylogenetic branch, represented by the house mouse, M. musculus, but probably does not exist in another branch, represented by M. caroli. Thus, Sp100-rs arose relatively late in the evolution of the genus Mus, whereas Sp100 existed in the common ancestor of the human and the mouse. The Sp100-rs gene cluster probably evolved by gene fusion followed by amplification and diversification.
Localisation of the imprinted gene neuronatin, Nnat, confirms and refines the location of a second imprinting region on mouse chromosome 2
Authors: Williamson C.M. , Beechey C.V. , Ball S.T. , Dutton E.R. , Cattanach B.M. , Tease C. , Ishino F. , Peters J.
Published: April 2003

Nine regions on six mouse autosomes are subject to imprinting and uniparental inheritance of any one of these regions results in mice with phenotypic anomalies. So far on distal Chromosome (Chr) 2 there is a unique imprinting region between 2H3 and 2H4 associated with two behavioural disorders and neonatal lethality. A maternally imprinted gene, Nnat, has been identified which is expressed in the nervous system and maps to distal Chr 2. Nnat has been excluded as a candidate for either or both the behavioural phenotypes as it lies proximal to the 2H3–2H4 imprinting region. Here we have mapped Nnat to band 2H1 which is at least 18 Mb proximal to the previously described imprinting region. It maps close to agouti, some alleles of which show differential expression according to parental origin. The localisation of Nnat to band H1 confirms and refines the map location of a second imprinting region on mouse Chr 2.
Identification and in situ hybridization mapping of a mouse Tpd52l1 (D53) orthologue to chromosome 10A4–B2
Authors: Byrne J.A. , Mattei M.G. , Basset P. , Gunning P.
Published: April 2003

We report the identification of a mouse cDNA Tpd52l1 (tumor protein D52-like 1), which represents the first demonstrated orthologue of the human TPD52L1 (alias D53) gene, a member of the breast carcinoma-associated TPD52 (alias D52) gene family. In situ hybridization mapping located the Tpd52l1 gene to chromosome 10A4–10B2. Since the TPD52L1 gene is found at human chromosome 6q22→q23, the mouse and human TPD52L1 loci are syntenically conserved.