Behavioural responses of beef cattle to different grazing systems and the influence of these responses on water productivity of livestock in a tropical savannah.

Environmental conditions and available forage on pastures greatly differ between different farming systems, which can affect the behaviour of grazing cattle. The interplay between environment-, forage-, and animal-related variables may affect the use of feed and water resources in grazing-based systems. Hence, our objectives were (i) to study the differences between grazing-based systems and seasons in environment- and pasture-related variables as well as the behaviour, feed intake, performance, and water productivity of Nellore heifers, and (ii) to understand the interrelationships between these variables. The measurements were performed in a conventional grazing system (CON), an integrated crop-livestock (ICL), and a crop-livestock-forestry (ICLF) systems in the Brazilian Cerrado during the rainy and dry seasons. Ambient temperature and relative air humidity were hourly measured in both seasons. Forage biomass and sward height were determined every month. Forage samples were taken to determine the proportions of alive leaves, alive stems, and dead plant material and to analyse their nutritive value. Forage intake, drinking water intake, and liveweight changes were quantified in 12 Nellore heifers per system and season. Feeding behaviour was recorded by chewing sensors on nine continuous days in each season. Drinking water intake was measured by water meters attached to drinking water troughs, whereby trial cameras at the troughs recorded the frequency of drinking events of individual animals. Feed conversion efficiency and water productivity were estimated. The ICLF reduced the exposure time to high ambient temperatures so that heifers even grazed during the hottest hours. Forage biomass in ICL and CON had greater proportions of stem and dead plant material than in ICLF. Forage intake rate was greater and grazing events were longer for animals in ICLF than those in CON, whereas the daily number of grazing events was greater in CON. Feed conversion efficiency and water productivity were greater in integrated systems than in CON. Amongst studied variables, thermal environment and forage canopy structure with its proportions of dead plant material are the main driving factors for animal behaviour, forage intake rate, and animal performance. These variables reduce feed conversion efficiency and water productivity in grazing cattle. Further research should analyse strategies for promoting thermal comfort for the animals, increasing the proportions of alive biomass, and enhancing the nutritional value of pastures for more efficient use of forage and water resources in grazing-based systems.

Presurgical setting of secondary hyperparathyroidism using high-resolution sonography and color Doppler.

PURPOSE: High-resolution sonography (US) with color Doppler imaging (CDI) is a simple, noninvasive, safe and repeatable technique able to highlight the presence of hyperplastic parathyroid glands and changes in their volume, structure, and vascularization during uremia. The primary aim of this study was to assess the diagnostic accuracy of US and the sensitivity for localizing parathyroid glands with a volume ≥ 500 mm(3). The secondary aim was to assess the parameters that define parathyroid glandular perfusion. MATERIALS AND METHODS: The diagnostic use of US was assessed in 40 consecutive uremic patients with severe secondary hyperparathyroidism (sHPT) who were receiving maintenance hemodialysis or conservative therapy with a hypoproteic-hypophosphoric diet and had undergone parathyroidectomy. Prior to surgery (99m)TC-sestamibi scintigraphy (SM) was performed in all patients. RESULTS: The sensitivity, specificity, positive predictive value and accuracy of US were 74 %, 75 %, 98 %, and 74 %, respectively. The sensitivity for localizing glands with a volume ≥ 500 mm(3) was 90 %. US and SM had a combined sensitivity of 83 %. The vascularization of parathyroid glands became more evident with increasing glandular volume. With CDI, the signs of hypervascularization (i. e. an enlarged feeding artery at the hilum, a peripheral arc of vascularity and/or ray-like endonodular vessels) were present in 77 % of glands with a volume ≥ 500 mm(3). CONCLUSION: The sensitivity of US is higher than that of SM, but it cannot be compared with that of parathyroidectomy (74 vs. 95 %). However, US/CDI is able to characterize glands with different volumes and vascular patterns. Since glandular volume and vascularization are indicative of the severity of sHPT, this study suggests that the main role of US/CDI in the setting of sHPT should be to complete the diagnosis and to evaluate the morphological changes of enlarged glands during uremia in order to define surgical timing, rather than to assess the presurgical location of glands.

Blood pressure phenotype reproducibility in CKD outpatients: a clinical practice report.

Out-of-office blood pressure (BP) measurement is encouraged by recent hypertension guidelines for assessing BP phenotypes. These showed acceptable reproducibility in the short term, but few data exist about long-term reproducibility, particularly for chronic kidney disease (CKD) patients. We evaluated changes of the BP phenotypes at 6 and 12 months in 280 consecutive non-dialysis CKD outpatients (186 males, age 71 ± 12 years, eGFR 38 ± 13 ml/min/1.73), without any change in drug therapy. Elevated BP is defined as office BP > 140/90 and home BP > 135/85 mmHg for defining the following BP phenotypes: sustained uncontrolled hypertension (SUCH); white-coat uncontrolled hypertension (WUCH); masked uncontrolled hypertension (MUCH); and controlled hypertension (CH). At baseline, the prevalence of the phenotypes was SUCH 36.6%, CH 30.1%, WUCH 25.4% and MUCH 7.9%, and it was similar at 6 months and 12 months. On the other hand, individual phenotype reproducibility at 12 months was poor both overall (38.0%) and across the different phenotypes (SUCH 53.9%, WUCH 32.4% and CH 32.1%, MUCH 9.1%). Patients who were not maintaining the same phenotype (non-concordant) were not distinguished by age, sex, BMI, eGFR, presence of diabetes or cardiovascular disease, or pharmacological therapy. When reproducibility of BP phenotypes both at 6 months and at 12 months was assessed, it was very low (19.6%), particularly for MUCH (0%), CH (14%) and WUCH (15.5%), while it was 31% for SUCH. In a CKD cohort, the overall prevalence of the different BP phenotypes defined by office and home BP remains constant over time. However, only 38% of patients maintained the same phenotype at 12 months, suggesting a poor reproducibility over time for the BP phenotypes.

[Living donor kidney transplant: the crossover modality]. / Il trapianto di rene da donatore vivente: la modalita' crossover.

Living donor kidney transplantation (LKD) has to be considered the best transplant choice for ESRD patients in terms of organ quality and survival. ABO incompatibility and positive cross-match frequently impede LKD. Recently, options based on stronger immunosuppression, apheresis techniques and Ig administration have been proposed to overcome the biological barriers. International guidelines on LKD advise paired exchange as the preferable transplant option to avoid the hazard of blood type or cross-match incompatibility. Since 1986 many paired exchange LKD programs have been started in the world including the USA, Japan, South Korea and, in Europe, the Netherlands, Switzerland, Romania, Germany and Italy. The first Italian paired exchange LKD was performed at the Pisa Transplant Center in November 2005 between three couples of spouses. One year later a National Program was established by the Italian National Transplant Center. The second experience in Italy was again in Pisa in December 2007 between two couples of spouses. International reports have shown that paired exchange LKD offers good clinical results comparable to direct LKD. In our experience paired exchange LKD is to be considered a quality choice for uremic patients, in that it allows them to obtain the benefit of an LKD that would otherwise not be practicable.

Kidney dimensions at sonography are correlated with glomerular filtration rate in renal transplant recipients and in kidney donors.

The gold standard to assess renal function is the measurement of glomerular filtration rate (GFR). For practical reasons, renal function is often evaluated from serum creatinine (S Cr) or cystatin C (S Cys), and GFR is predicted from SCr. Ultrasound scanning of the kidneys is used only to evaluate renal morphology. The aim of this study was to evaluate the relationship between sonographic renal dimensions and GFR in renal transplant recipients and in kidney donors. GFR (urinary clearance of (99m)Tc-DTPA), S Cr, and S Cys were measured in 33 donors (28 females [F], 5 males [M]; SCr, 0.81-1.90 mg/dL) and 30 recipients (8 F, 22 M; SCr, 0.96-2.42 mg/dL). GFR was also predicted using the Cockcroft and Gault (CG) formula and with the simplified Modification of Diet in Renal Disease (MDRD) formula. Length, width, and depth of kidneys and renal sinus were measured using renal sonography. Among sonographic measurements, kidney length showed the best correlation with GFR. A closer correlation with GFR was found in donors (r = 0.639; P < .00007) than in recipients (r = 0.511; P < .005). In either case, the correlation of kidney length with GFR was greater than that of S Cr or S Cys, and similar to that of CG or MDRD GFR. Accuracy of kidney length as an indicator of GFR impairment was not statistically different from laboratory tests. Only in donors did CG show better accuracy. In conclusion, renal dimensions at sonography closely correlated with GFR. Thus, renal sonography can give information also on the function of the renal graft and of the remaining kidney of living donors.

An in vitro study on the free radical scavenging capacity of ergothioneine: comparison with reduced glutathione, uric acid and trolox.

BACKGROUND: Treatment of oxidative stress-related pathologies is a possible therapeutical strategy for the future. Natural product with antioxidant properties could trigger this goal. The aim of this in vitro study was to assess the antioxidant activity of the natural product ergothioneine (EGT), a compound of plant origin, which is assimilated and conserved by mammals in erythrocytes, kidney, seminal fluid and liver. METHODS: We measured the antioxidant activity of EGT as its ability to antagonize the oxidation of alpha-keto-gamma-methiolbutyric acid (KMBA) by hydroxyl radical, peroxyl radicals and peroxynitrite. The results are expressed as total oxyradical scavenging capacity (TOSC) units. Glutathione (GSH), uric acid and 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (trolox), the water-soluble analog of vitamin E, were used as the reference antioxidants. RESULTS: EGT was the most active scavenger of free radicals as compared to classic antioxidants as GSH, uric acid and trolox. In particular, the highest antioxidant capacity exhibited by EGT vs. peroxyl radicals (5.53 +/- 1.27 units) resulted 25% higher than the value obtained with the reference antioxidant trolox (4.4 +/- 0.6 units, P < 0.01). The scavenging capacity of EGT towards hydroxyl radicals (0.34 +/- 0.09 units) was 60% higher, as compared to uric acid (0.21 +/- 0.04 units, P < 0.001), which represent the reference antioxidant vs. hydroxyl radicals. Finally, EGT showed the highest antioxidant activity also towards peroxynitrite (5.2 +/- 1.0 units), with a scavenging capacity 10% higher than that of uric acid (4.7 +/- 0.9 units, P < 0.05). CONCLUSIONS: This study showed that EGT has potent intrinsic anti-hydroxyl, anti-peroxyl and anti-peroxynitrite radicals antioxidant activity, as compared to classic molecules with antioxidant capacity as GSH, trolox and uric acid. This appears of interest, given the increasing use of non-vitamins cocktails for therapeutical approaches to many oxidative-induced pathologies.

Binding properties of human albumin modified by covalent binding of penicillin.

Derivatisation of lysine residues in human albumin was performed in vitro by reaction with penicillin G. This modification reaction has been reported to occur in patients treated with high dosages of the antibiotic. The structure of the modified protein was characterised by mass spectrometry and circular dichroism. The number of the lysine residues involved depends on the time of incubation and on the drug/protein molar ratio. The secondary structure of the modified protein does not change significantly with respect to the native protein. Furthermore, the binding properties of the modified albumin were characterised by CD spectroscopy. Phenylbutazone, diazepam and bilirubin, known to bind to specific binding areas, were used as markers. A decrease of the affinity to the high-affinity binding sites was observed after the modification.

Pancreas transplants from donors aged 45 years or older.

AIMS: Since donor age of 45 years or more is considered a relative contraindication for pancreas transplantation (PTx), we herein report our experience with these donors. METHODS: Pancreases from donors aged 45 years or older were used in 16 of 147 PTx procedures (11%). The final decision to accept a graft for PTx was based mainly on the quality of visceral perfusion and the gross appearance of the pancreas and the vessels. There were 9 men and 7 women, ranging in age from 45 to 55 years (average, 48.9 years) who were donors, due to cerebrovascular accidents (n = 11; 68.7%). Among the donor group, 5 patients were receiving multiple vasopressor agents (31.2%), and 2 had a history of cardiac arrest (12.5%). Pancreases were transplanted either simultaneously with a cadaveric kidney (n = 6) or as solitary grafts (n = 10). RESULTS: After a mean period of cold preservation of 616 minutes (range, 475 to 844 min), delayed endocrine function occurred in 1 recipient (6%), who subsequently achieved insulin independence. Two recipients died suddenly, with functioning grafts. Two further grafts were lost due to portal vein thrombosis (6%) or late arterial thrombosis (6%). Three patients required repeat surgery (18.7%). After a mean follow-up period of 26.6 months, actuarial 1-year and 5-year patient survival rates were 87.5%, with insulin independence in 81.2% and 67.7%, respectively. CONCLUSIONS: Meticulous donor selection and short preservation times allow the safe use of pancreases procured from donors aged 45 years or older, thus expanding the donor pool for PTx procedures.

Neoral versus prograf in simultaneous pancreas-kidney transplantation with portal venous drainage: three-year results of a single-center, open-label, prospective, randomized pilot study.

BACKGROUND: The preferential use of tacrolimus (Prograf) over cyclosporine microemulsion (Neoral) in simultaneous pancreas-kidney transplantation (SPKTx) is mainly based on historical, retrospective studies. We herein report the 3-year results of a single-center, prospective, randomized comparison of the two calcineurin inhibitors in the setting of mycophenolate mofetil (MMF)-based immunosuppression and portal drainage of pancreas allografts. METHODS: Between May 2001 and August 2004, 47 SPKTx recipients who were stratified by recipient sex, were alternatively assigned to treatment with Neoral (n = 22) or Prograf (n = 25). Concurrent immunosuppression included induction treatment with basiliximab and maintenance with MMF and steroids. RESULTS: After a median follow-up of 24.0 months, all patients remained in the study arm into which they were initially enrolled. No pancreas rejection episode was observed. One acute kidney rejection was recorded in the Neoral arm (4.5%) as compared with 7 (28.0%) including one steroid-resistant episode, in the Prograf arm (P = .03). The cumulative incidence of adverse events was 31.8% (n = 7) in the Neoral arm compared with 92.0% (n = 23) in the Prograf arm (P < .0001). One patient died in each study arm. Patient, pancreas, and kidney survivals overlapped at 1- and 3-years posttransplant, namely all 95.4% for the Neoral arm compared with 95.8%, 91.8%, and 95.8%, respectively, for the Prograf arm (P > .05). CONCLUSIONS: We conclude that in MMF-based immunosuppression there is no convincing evidence that Prograf should be preferred to Neoral in SPKTx.

Surveillance and rescue of pancreas grafts.

BACKGROUND: Technical failure rates are higher for pancreas allografts (PA) compared with other solid organs. Posttransplant surveillance and prompt availability of rescue teams with multidisciplinary expertise both contribute to improve this result. We herein report a single institution's experience with posttransplant surveillance and rescue of PA. METHODS: A retrospective survey was performed of a consecutive series of 177 whole organ pancreas transplants in 173 patients. Antithrombotic prophylaxis was used in all recipients and tailored on anticipated individual risk of thrombosis. During the first posttransplant week, all PA were monitored with daily Doppler ultrasonography. Surgical complications were defined as all adverse events requiring relaparotomy during the initial hospital stay or the first 3 posttransplant months. RESULTS: A total of 26 relaparotomies were performed in 25 patients (14.7%). One recipient needed two relaparotomies (0.6%). Graft rescue was attempted in patients without permanent parenchymal damage at repeat surgery and in 12 recipients diagnosed with nonocclusive vascular thrombosis. Overall 25 grafts (96.3%) were rescued and one was lost. One-year recipient and graft survivals in patients with versus without complications potentially leading to allograft loss were 92.6% and 63.0% versus 94.4% and 94.3%, respectively. Excluding complications for which graft rescue was not possible, 1-year graft survival rate increased to 78.7%. CONCLUSIONS: Close posttransplant surveillance can allow rescue of a relevant proportion of PA developing nonocclusive venous thrombosis or other surgical complications. Further improvement awaits better understanding of biological reasons for posttransplant complications jeopardizing PA survival and the development of more effective preventive measures.

University of Wisconsin solution versus Celsior solution in clinical pancreas transplantation.

INTRODUCTION: This study compared the safety and efficacy of University of Wisconsin solution (UW) and Celsior solution (C) in pancreas transplantation (PTx). METHODS: A retrospective review of 154 PTx performed over a 61-month period included 77 grafts preserved with UW and 77 with C. The two groups were comparable for both donor and recipient characteristics. RESULTS: After a mean cold ischemia time of 624 minutes (range 360 to 945 minutes) for UW versus 672 minutes (range 415 to 1005 minutes) for C (P = NS), no primary endocrine nonfunction occurred. Delayed endocrine function was diagnosed in two grafts in the UW group (2.6%) versus none in the C group (P = NS). After a minimum follow-up of 4 months (mean 26.5 +/- 15.2 months), 22 recipients (UW = 11 vs C = 11; P = NS) required relaparotomy. Overall, 18 pancreata were lost due to either patient death with functioning graft (UW = 4 vs C = 1; P = NS) or graft loss due to other reasons (UW = 8 vs C = 5; P = NS). Actuarial 1- and 5-year patient survival rates were 93.5% and 86.8% for UW compared with 98.7% and 98.7% for C (P = .04). Actuarial graft survival rates at the same times were 88.3% and 75.0% for UW compared with 90.4% and 90.4% for C (P = NS). CONCLUSIONS: Within the range of cold ischemia times reported in this study, UW and C show similar safety and efficacy profiles for PTx.

Kidney transplantation from donors aged 65 years or more as single or dual grafts.

AIM: The organ shortage and aging donor population force transplant centers to accept donors previously considered unusable for kidney transplantation. We report the experience of two Italian transplant centers with single (SKTx) and dual (DKTx) kidney transplantation from donors aged 65 years or more. METHODS: The study population comprised 75 SKTx (mean donor age 70.5 years) and 28 DKTx (mean donor age 75.0 years). Kidneys from donors with a calculated admission creatinine clearance <50 mL/min, a Karpinski's score on kidney biopsy between 5 and 7, or both were allocated to DKTx. Grafts with better function or lower biopsy scores were employed for SKTx. RESULTS: Delayed graft function occurred in 45.3% of SKTx and in 39.3% of DKTx. After a mean follow-up period of 30.0 +/- 19.5 months, the acute rejection rate was 24.0% in SKTx and 7.1% in DKTx. Mean serum creatinine was 1.8 +/- 0.9 and 1.8 +/- 1.3 mg/dL in SKTx, and 1.8 +/- 1.6 mg/dL and 1.3 +/- 0.2 mg/dL in DKTx at 1 and 5 years, respectively. Patient survival was 93.3% and 91.2% in SKTx, and 92.9% and 92.9% in DKTx at 1 and 5 years, respectively. Graft survival was 92.0% and 88.3% in SKTx, and 89.3% and 89.3% in DKTx at the same time intervals. Keeping preservation time below 16 hours and avoiding calcineurin inhibitors were both associated with improved graft survival and function. CONCLUSION: Careful donor selection, short preservation time, and tailored immunosuppression allow safe and efficient use of elderly donor kidneys.

Thyrotoxicosis, hypercalcemia, and secondary hyperparathyroidism.

Two patients with hypercalcemia and hyperthyroidism had elevated levels of parathyroid hormone (PTH). When the patients were made euthyroid with appropriate medical therapy, both the levels of PTH and calcium returned to normal. Since thyroid hormone can increase tissue responsiveness to catecholamines, and since catecholamines can stimulate PTH secretion, we postulate that the elevated levels of PTH were secondary to thyrotoxicosis. In patients with coexisting hyperthyroidism and hyperparathyroidism, primary hyperparathyroidism should only be diagnosed when the patient is eumetabolic.

The source of protein in the aqueous humor of the normal monkey eye.

In vivo aqueous fluorophotometry, morphology, and computational modeling were combined to examine the source of protein and the pathway by which protein enters the aqueous humor of monkeys. A computational model was developed to determine the likelihood of a diffusional route for delivering plasma proteins from ciliary body capillaries via the iris to anterior chamber aqueous humor, bypassing the posterior chamber. Model predictions were compared to aqueous fluorophotometric data obtained from monkeys following a single intravenous injection of fluoresceinated horseradish peroxidase (F-HRP, 250 mg/kg body mass). Model predictions of the magnitude and time course of anterior chamber F-HRP concentration agree with the fluorophotometric measurements. For example, of anterior chamber F-HRP concentration as a percentage of initial plasma F-HRP concentration at 90 min and 180 min post-injection was predicted to be 0.02% and 0.05%, respectively, and was measured to be 0.01-0.03% and 0.03-0.06%, respectively. In addition, model predictions in the case of a constant plasma protein level also are consistent with experimental data. The steady-state anterior chamber total protein concentration as a percentage of plasma protein concentration was predicted to be 0.2% and was assayed to be 0.05-0.2%. As in our previous study of the normal rabbit eye, morphologic and tracer localization evidence combined with the good agreement between model predictions and experimental data lead to the conclusion that a significant amount of the plasma protein normally present in monkey aqueous humor originates in ciliary body capillaries and diffuses anteriorly through the iris and into the anterior chamber.

Morphologic correlations with fluorophotometric data from monkey eyes with anterior uveitis.

Acute anterior uveitis was induced in monkeys by unilateral intravitreal injection of 1.0 ng of Escherichia coli endotoxin. Twenty-four hours later, each animal received an intravenous injection of 250 mg/kg body weight of fluoresceinated horseradish peroxidase (F-HRP), and fluorophotometric measurements were taken for 90 min. The animals were killed, and both eyes were processed for HRP demonstration. In the anterior chamber aqueous humor of normal control eyes, F-HRP concentrations were less than 0.002 mg/ml at 90 min. The F-HRP concentration was elevated consistently in the endotoxin-injected eyes; however, the magnitude of the effect varied. By fluorophotometry, inflamed eyes fell into two distinct groups. At 90 min, most had an anterior chamber F-HRP concentration of 0.014-0.06 mg/ml, although others had 0.39 mg/ml. In the latter group, an appreciably shorter latency was observed between the time of tracer injection and its detection in the anterior chamber. Aqueous humor protein concentrations, although highest in the most F-HRP-permeable eyes, followed more of a continuum in their distribution and identified less clearly the subpopulations seen by fluorophotometry. Normal eyes had no tracer leakage across either the ciliary epithelial or iris vascular endothelial barriers. All inflamed eyes had HRP leakage across the ciliary epithelium, but the subpopulation of eyes with shorter latencies and higher F-HRP concentrations by fluorophotometry also had iris vascular leakage.

The source of proteins in the aqueous humor of the normal rabbit.

Aqueous fluorophotometric, tracer localization and modeling methods were combined to document the existence of a pathway in the normal rabbit for the diffusion of proteins from the ciliary and iridial process stromas through the iris stroma into the aqueous humor of the anterior chamber. A new custom-conjugated tracer, fluoresceinated horseradish peroxidase (F-HRP), was used. Anesthetized rabbits were injected intravenously with F-HRP (250 mg/kg). In some animals, aqueous fluorophotometric and tracer localization studies were performed on the same eyes. Anterior chamber fluorescence was detected 2-10 min post-injection and rose to concentrations of 0.01-0.05 mg/ml 60 min post-injection. Subsequent tracer localization studies of these eyes revealed that the morphologic components of the blood-aqueous barrier were intact, that is, no leakage of F-HRP from the iris vasculature or across the ciliary epithelium was observed. Separate tracer localization studies were performed to examine the time course of the route(s) by which tracer entered the anterior chamber. These studies revealed a "wave" of tracer that migrated from the ciliary and iridial process stromas, through the iris, and arrived at the anterior iris surface approximately 8 min post-injection. A pharmacokinetic model based on the diffusional pathway was developed to describe the time course of the concentration of plasma macromolecules in the ciliary body, iris and anterior chamber. Model predictions were consistent with aqueous fluorophotometric and tracer localization results. The diffusion model can account for a major fraction of protein entering the aqueous humor of normal rabbit eyes.

Background-protein effects on fluorophotometric data.

Fluorescent tracers are commonly used in fluorophotometric studies of ocular fluids and tissues that contain background protein. Background-protein concentrations were found to decrease or increase significantly the measure of fluorescence emitted from solutions containing sodium fluorescein, fluorescein-labeled dextran, or fluorescein-labeled horseradish peroxidase. The effect of background protein on fluorescence was expressed as a function of the specific fluorescent tracer, tracer concentration, and background-protein concentration; it can be corrected in the analysis of fluorophotometric data. Fluorophotometric studies--particularly those in which the background-protein level is expected to be abnormally high, such as postoperative and pathologic studies--may need to include either a data correction based on measured effects of background protein on tracer fluorescence or, in the case of clinical investigations, recognize at least the potential for a range of possible interpretations.

Transferrin modifies surfactant responsiveness in acute respiratory failure: role of iron-free transferrin as an antioxidant.

In respiratory failure, transferrin (TF) with variable iron saturation accumulates in the alveolar space. Binding free iron to TF may inhibit metal-catalyzed formation of free radicals. The aim of this study was to evaluate whether the degree of the iron-saturation of TF influences the severity of respiratory failure and surfactant responsiveness. Surfactant deficiency and lung edema was induced in 42 paralyzed and ventilated young rabbits by bronchoalveolar lavage (BAL); 19 of these animals were preexposed to 100% O2 for 40 hours. The animals received (1) exogenous surfactant intratracheally (100 mg/kg in 4 ml/kg saline); (2) surfactant and Fe(3+)-TF (50 or 25 mg/kg); or (3) surfactant and iron-free TF (50 mg/kg). One hour after administration of TF, 13-25% of exogenous TF was recovered by BAL. Administration of Iron-free TF significantly decreased the iron saturation of TF in BAL. In acute respiratory failure induced by BAL, Fe(3+)-TF decreased the efficacy of exogenous surfactant in improving the gas exchange, and increased surfactant inhibition, while iron-free TF had no effect. By contrast, in respiratory failure induced by hyperoxia and BAL, iron-free TF improved the efficacy of exogenous surfactant, but Fe(2+)-TF had no effect. After administration of iron-free TF, surfactant isolated from BAL was more surface-active than surfactant from BAL of the other hyperoxia-treated animals. In animals exposed to hyperoxia, treatment with iron-free TF decreased malondialdehyde content of BAL. We propose that low iron saturation of TF decreases oxidant stress and favors the recovery from respiratory failure.

Uremic medium increases cytokine-induced PAI-1 secretion by cultured endothelial cells.

The overall fibrinolytic activity is depressed in patients with chronic renal failure where a prothrombotic state is described, thereby enhancing the risk of vascular occlusive events. The mechanism responsible for fibrinolysis derangement has not yet been elucidated. To evaluate the effect of the uremic environment on the fibrinolytic activity of endothelial cells, we studied plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) production by human umbilical vein endothelial cells (HUVEC) in culture, exposed either to uremic or normal sera, before and after cytokine stimulation. Twenty uremics were studied: 11 were on conservative dietary treatment and nine were on maintenance hemodialysis. Eight healthy subjects served as controls. Before cytokine stimulation, no difference in the HUVEC supernatant concentration of t-PA and PAI-1 was found among the groups studied. After stimulation with interleukin (IL)-1 and tumor necrosis factor (TNF)-alpha, the HUVEC supernatant levels of PAI-1 in the uremics were higher than in the controls, whereas the supernatant levels of t-PA did not differ. Our data provide evidence that uremic serum, in concert with IL-1 or TNF-alpha, can enhance PAI-1 secretion by endothelial cells, thereby depressing the fibrinolytic system. This impaired endothelial fibrinolytic response to hypercoagulation could favor vascular events, which are the major cause of morbidity and mortality in patients with chronic uremia.

Color-Doppler in the imaging work-up of primary hyperparathyroidism.

Primary hyperparathyroidism (PHP) is a rare disease that must be suspected in all the cases of recurrent calcium nephrolithiasis, and that may be totally corrected by surgery. The imaging techniques permit to locate the hyperplastic gland or adenoma before intervention, but their usefulness in patients without a history of previous neck surgery is still debated. Several imaging techniques have been proposed with the aim of locating parathyroid hyperfunctioning glands, including high resolution sonography (US) with color-Doppler (CD), scintigraphy, computed tomography (CT) and magnetic resonance imaging (MRI). We report here a case of recurrent calcium oxalate nephrolithiasis sustained by PHP, which demonstrates how US coupled with CD and echocontrast enhancement is useful in the preoperative location of parathyroid glands. US is the first choice technique in the evaluation of PHP because it is less expensive and useful in detailing lesions of the neck when carried out by a skilled operator. CD should be regarded as a useful complement of US enhancing its sensitivity (80 vs 90%) especially in the cases of associated thyroid gland diseases. Tc-99m SESTAMIBI scintigraphy coupled with MRI is mandatory in high risk surgical patients, namely in those undergoing repeated neck surgery. In conclusion, considering that surgeon must explore all the four parathyroid glands (because of the possibility of multiple adenomas or hyperplasia) a well definite location of the adenomatous lesion may reduce the risks and the time of intervention, and allow the use of alternative procedures, such as videoscopic surgery. On this view and in terms of economy, only US and CD coupled with Tc-99 SESTAMIBI scintigraphy should be considered before surgery.