Eugenol Induces Phenotypic Alterations and Increases the Oxidative Burst in Cryptococcus.

Eugenol is a phenolic compound and the main constituent of the essential oil of clove India. Although there are reports of some pharmacological effects of eugenol, this study is the first that proposes to evaluate the antifungal effects of this phenol against both Cryptococcus gattii and C. neoformans cells. The effect of eugenol against yeast cells was analyzed for drug susceptibility, alterations in cell diameter, capsule properties, amounts of ergosterol, oxidative burst, and thermodynamics data. Data demonstrated that there is no interaction between eugenol and fluconazole and amphotericin B. Eugenol reduced the cell diameter and the capsule size, increased cell surface/volume, changed positively the cell surface charge of cryptococcal cells. We also verified increased levels of reactive oxygen species without activation of antioxidant enzymes, leading to increased lipid peroxidation, mitochondrial membrane depolarization and reduction of lysosomal integrity in cryptococcal cells. Additionally, the results showed that there is no significant molecular interaction between eugenol and C. neoformans. Morphological alterations, changes of cellular superficial charges and oxidative stress play an important role in antifungal activity of eugenol against C. gattii and C. neoformans that could be used as an auxiliary treatment to cutaneous cryptococcosis.

The Long-Term Follow-up and Support for Living Organ Donors: A Center-Based Initiative Founded on Developing a Community of Living Donors.

Transplant professionals recognize that the long-term follow-up of living organ donors is a priority, yet there has been no implemented solution to this problem. This critical gap is essential, because the transplant field is now emphasizing living donation as a means to address the organ shortage. We detail our living donor initiative, which sets several priorities we recognize as fundamental to persons who have donated organs at our transplant center. This intervention attempts to mitigate the donor and center factors that are known to contribute to the lack of long-term follow-up. Beyond that, our goals are aimed at providing ongoing engagement, wellness, clinical data accrual, laboratory follow-up, and social support for our living donors, in continuity. Our ultimate goal is to nurture the development of local living donor community networks by providing social engagement for current and past donors, which also serves as a platform for greater population education on the societal importance of living donation. This initiative is based on joint recognition by our transplant team and our hospital leadership that supporting the long-term welfare of living donors is essential to accomplishing the goal of expanding living donor transplantation. The transplant team and hospital missions are aligned, and both contribute resources to the initiative.

Annona glabra Flavonoids Act As Antimicrobials by Binding to Pseudomonas aeruginosa Cell Walls.

Pseudomonas aeruginosa is an important pathogen in opportunistic infections in humans. The increased incidence of antimicrobial-resistant P. aeruginosa isolates has highlighted the need for novel and more potent therapies against this microorganism. Annona glabra is known for presenting different compounds with diverse biological activities, such as anti-tumor and immunomodulatory activities. Although other species of the family display antimicrobial actions, this has not yet been reported for A. glabra. Here, we investigated the antimicrobial activity of the ethyl acetate fraction (EAF) obtained from the leaf hydroalcoholic extract of A. glabra. EAF was bactericidal against different strains of P. aeruginosa. EAF also presented with a time- and concentration-dependent effect on P. aeruginosa viability. Testing of different EAF sub-fractions showed that the sub-fraction 32-33 (SF32-33) was the most effective against P. aeruginosa. Analysis of the chemical constituents of SF32-33 demonstrated a high content of flavonoids. Incubation of this active sub-fraction with P. aeruginosa ATCC 27983 triggered an endothermic reaction, which was accompanied by an increased electric charge, suggesting a high binding of SF32-33 compounds to bacterial cell walls. Collectively, our results suggest that A. glabra-derived compounds, especially flavonoids, may be useful for treating infections caused by P. aeruginosa.

Controlling the alien hand through the mirror box. A single case study of alien hand syndrome.

Disruption of motor control in the alien hand syndrome might result from a dissociation between intentions and sensory information. We hypothesized that voluntary motor control in this condition could improve by restoring the congruency between motor intentions and visual feedback. The present study shows that, in one patient with right alien hand syndrome, the use of a mirror box paradigm improved motor speed. We speculate that the visual feedback provided by the mirror increases the sense of congruence between intention and sensory feedback, leading to motor improvement.

Exploring motor and visual imagery in Amyotrophic Lateral Sclerosis.

Amyotrophic Lateral Sclerosis (ALS) is a motor neuron disease characterized by the progressive atrophy of both the first and the second motor neurons. Although the cognitive profile of ALS patients has already been defined by the occurrence of language dysfunctions and frontal deficit symptoms, it is less clear whether the degeneration of upper and lower motor neurons affects motor imagery abilities. Here, we directly investigated motor imagery in ALS patients by means of an established task that allows to examine the presence of the effects of the biomechanical constraints. Twenty-three ALS patients and 23 neurologically unimpaired participants have been administered with the (1) hand laterality task (HLT) in which participants were asked to judge the laterality of a rotated hand and the (2) mirror letter discrimination task (MLD) in which participants were asked to judge whether a rotated alphanumeric character was in its canonical or mirror-reversed form (i.e. control task). Results show that patients present the same pattern of performance as unimpaired participants at the MLD, while at the HLT, they present only partially with the effects of biomechanical constraints. Taken together, our findings provide evidences that motor imagery abilities, related to the mental simulation of an action, are affected by this progressive disease.

Continuous ambulatory peritoneal dialysis and automated peritoneal dialysis: are there differences in outcome?

The proportion of peritoneal dialysis (PD) patients on automated peritoneal dialysis (APD) has been steadily increasing over the past decade. In the US, the percentage of PD patients on APD has steadily risen from 9% in 1993 to 54% in 2000. In continuous ambulatory peritoneal dialysis (CAPD), PD exchanges are performed manually, while in APD a mechanical device to assist the delivery and drainage of dialysate is employed. In CAPD, the patient or carer must perform at least 4-5 exchanges everyday. Many problems inherent to CAPD such as lack of sustained patient motivation over long periods of time, technique failure and recurrent peritonitis, led to a resurgence of interest in APD. APD has been reported to have several advantages over CAPD including lower incidence of peritonitis, better small solute clearances and reduced incidences of hernias. APD, especially in the form of nocturnal intermittent peritoneal dialysis (NIPD), has also been suggested to offer a number of psychosocial and physical benefits over CAPD mainly on account of fewer connections and being free of fluid in the abdomen during daytime. Such benefits relate to better dialysis acceptability for workers, school students or carers of elderly patients, pain and body image difficulties and reduced intra-abdominal pressures. APD is also considered to be more suitable form of PD in patients who have a rapid rate of solute transfer across their peritoneal membrane (high transporters) because of the ability to perform rapid frequent exchanges with shorter dwell times. It is not still clear if, with APD when compared to CAPD, a more rapid decline in residual renal function is present. Since the direct costs of APD are over 20% greater than CAPD and given this increasing trend towards greater use of APD, the aim of this paper is to understand if there are really differences in terms of quality of life and outcomes in favor of APD when compared to CAPD.

[Health-related quality of life in patients with chronic kidney disease]. / Qualita' della vita nei nefropatici.

Assessment of quality of life in patients with different degrees of chronic kidney disease is an important issue because of its impact on clinical decisions and financial resource management in the health-care system. The aim of this study was to assess whether a generic instrument like the SF-36 questionnaire is able to discriminate three different populations of patients with different degrees of renal disease (pre-ESRD, ESRD, TxR). Five hundred sixty-three patients from 12 Italian nephrology units completed the SF-36 scales by themselves. The results from these samples were compared with those from the general population. Univariate analysis and multivariate regression were used. The generic SF-36 questionnaire proved to be a powerful instrument to discriminate populations with different degrees of chronic renal failure. The quality of life of patients on dialysis is significantly worse than that of the normal population and other patients with less severe renal function impairment.

PD and HD in combination

Peritoneal dialysis (PD) and hemodialysis (HD) are the most used therapies for end stage renal disease (ESRD). Peritoneal dialysis offers the advantages of long, slow, continuous ultrafiltration and preserve residual renal function (RRF) one of the most important factors affecting outcomes in PD. In contrast, HD offers superior solute removal but with undesirable cardiovascular tolerance of high rates of sodium and water removal. Peritoneal dialysis (PD) represents an effective way to maintain residual renal function and should be the first choice dialysis technique. However, with the loss of RRF, some limitations of PD alone in controlling the uremic state appear. Combination of the two techniques therapies, PD + HD (also called bimodal dialysis BMD), is the simplest way to deal with these limitations. The general prescription for BMD should be 5-6 days of PD and 1 or 2HD sessions weekly. One of the most important controversy is how to evaluate the adequacy of the combined treatment: some Authors adopted the equivalent renal clearance (EKR), first transforming the weekly PD adequacy index (Kt/V), and then evaluating total clearance from both modalities. However, the EKR may overestimate the dialysis dose. Thus to accurately track dialysis dose some use the total effluent (PD, RRF, and HD) sampling method to yield Kt/Vef and creatinine clearance (CCref) (AU)

La diálisis peritoneal (DP) y la hemodiálisis (HD) son los tratamientos más utilizados para la nefropatía terminal (NT). La diálisis peritoneal ofrece la ventaja de una ultrafiltración prolongada, lenta y continua y conserva la función renal residual(FRR), uno de los factores más importantes que influyen en los resultados de la DP. En cambio, la HD elimina mejor los solutos pero con una tolerancia cardiovascular deficiente de los elevados porcentajes de eliminación de sodio y agua. La diálisis peritoneal(DP) representa un método eficaz para mantener la función renal residual y debe ser la técnica de diálisis de primera elección. Sin embargo, con la pérdida de la FRR, se manifiestan algunas limitaciones de la DP aislada para controlar el estado urémico. La combinación de las dos técnicas, DP + HD(también denominada diálisis bimodal, DBM), es la forma más sencilla para superar estas limitaciones. La prescripción general de la DBM debe ser 5-6 días de DP y 1 ó 2 sesiones de HD ala semana. Uno de los aspectos que suscitan más controversia es cómo se debe evaluar la idoneidad del tratamiento combinado: algunos autores han adoptado la depuración renal equivalente (EKR), primero transformando el índice de idoneidad de la DP semanal (Kt/V) y luego determinando la depuración total de ambas modalidades. Sin embargo, la EKR puede sobrevalorar la dosis de diálisis. Así pues, para determinar con exactitud dicha dosis algunos autores utilizan el método de muestreo del efluente total (DP, FRR y HD) para obtener el Kt/Vef y el aclaramiento de creatinina (CCref) (AU)

PD and HD in combination.

Peritoneal dialysis (PD) and hemodialysis (HD) are the most used therapies for endstage renal disease (ESRD). Peritoneal dialysis offers the advantages of long, slow, continuous ultrafiltration and preserve residual renal function (RRF) one of the most important factors affecting outcomes in PD. In contrast, HD offers superior solute removal but with undesirable cardiovascular tolerance of high rates of sodium and water removal. Peritoneal dialysis (PD) represents an effective way to maintain residual renal function and should be the first choice dialysis technique. However, with the loss of RRF, some limitations of PD alone in controlling the uremic state appear. Combination of the two techniques therapies, PD + HD (also called bimodal dialysis BMD), is the simplest way to deal with these limitations. The general prescription for BMD should be 5-6 days of PD and 1 or 2 HD sessions weekly. One of the most important controversy is how to evaluate the adequacy of the combined treatment: some Authors adopted the equivalent renal clearance (EKR), first transforming the weekly PD adequacy index (Kt/V), and then evaluating total clearance from both modalities. However, the EKR may overestimate the dialysis dose. Thus to accurately track dialysis dose some use the total effluent (PD, RRF, and HD) sampling method to yield Kt/Vef and creatinine clearance (CCref).

Successful use of sodium hypochlorite pack plus systemic and local antibiotic therapy for the treatment of pseudomonas infection of peritoneal dialysis catheter exit-site.

Peritoneal catheter exit-site and tunnel infections remain critical problems in patients undergoing peritoneal dialysis. Catheter-related peritonitis occurs in about 20% of patients and exit-site infections are responsible for catheter removal in more than one-fifth of the cases. For the last 2 years in the Department of Nephrology, San Bortolo Hospital, Vicenza, Italy, we have been treating exit-site infections caused by Pseudomonas with sodium hypochlorite packs as well as systemic and local antibiotic therapy. Considering the encouraging results obtained on Pseudomonas infection, we decided to utilize the same schedule for the treatment of exit-site infections caused by other germs which are generally difficult to eradicate to prevent peritonitis and catheter removal. Between 2003 and 2004, 10 patients contracted infection of the exit-site. All patients underwent a swab test because of the reddening and the purulent secretion of the exit-site. The swab resulted positive for Pseudomonas in 7 patients, Corynebacterium sp. in 2 patients, and Candida albicans in 1 patient. All patients were treated with systemic antibiotic therapy or antifungal therapy, local sodium hypochlorite 50% packs. After 15 days all patients were submitted to a swab test of the exit site. In all patients, the swab test resulted negative after 15 days and 1 month, and they could continue peritoneal dialysis. This procedure avoided peritoneal catheter removal and temporary switch to hemodialysis in all patients with exit site infection. The mechanism of action is related to the wide antimicrobial spectrum and the rapid action of sodium hypochlorite possibly creating a protective barrier on the exit-site.

Acid-base balance in peritoneal dialysis.

In patients without functioning kidneys, alkali replenishment is accomplished by the addition, via dialysis solution, of either HCO 3 - itself or a metabolic precursor of this anion, such as lactate. The body base balance in peritoneal dialysis (PD) patients is self-regulated by the feedback between plasma bicarbonate concentration and dialytic base gain. Dialytic base gain is the only source of buffer for PD patients and this gain should counteract the metabolic acid production. Dialytic base gain depends on peritoneal buffer fluxes (lactate reabsorption minus bicarbonate lost). The plasma bicarbonate level is determined by the dialytic base gain and the metabolic acid production. Bicarbonate buffered PD solution provides some advantages over the conventional lactate buffered PD solution.

The ''Ronco'' catheter for continuous flow peritoneal dialysis.

To perform CFPD, a two way access must be available in order to allow continuous inflow and outflow of the solution. This is most likely achieved with a double lumen peritoneal catheter. To design a double lumen catheter does not necessarily mean to increase the size of the tube or to increase the discomfort of the patient. However, the real challenge is to find a design in which minimal re-circulation is experienced. The two tips of the catheter must be positioned such that a maximal exposure of the peritoneal surface to the fluid is guaranteed during one single passage of the fluid from one lumen to another. Double lumen catheters with one short branch and another long of straight and of spiral shape were originally designed. Ash and coworkers have designed a catheter with a t-shape configuration in order to distantiate to the maximum the tips of the two lumens. Recently we have designed a novel catheter for CFPD equipped with a thin walled silicone diffuser used to gently diffuse the inflow dialysate into the peritoneum. The holes on the round tapered diffuser are positioned to allow dialysate to perpendicularly exit 360 degrees from the diffuser. The diffuser design and hole locations disperse the high-flow dialysate fluid at 360 degrees, reducing trauma to the peritoneal walls and allowing the dialysate to mix into the peritoneum. The dispersed fluid infused into the peritoneal cavity is then drained through the second lumen whose tip is placed into the lower Douglas cavity. The new catheter with diffuser is also equipped with a special removable hub that allows for easy creation of the subcutaneous tunnel without increasing the size of the skin exit site. The results so far achieved seems to offer advantages in terms of high flows, minimal pressure regimes and negligible recirculation.

The Vicenza ''Short'' peritoneal catheter: a twenty year experience.

Dislocation of peritoneal dialysis catheters is one of the major causes of technique failure. We evaluated 701 Vicenza catheters, implanted since 1985 in 365 males, mean age 53 +/- 16 yrs, range 24 - 87, and 336 females, mean age 51 +/- 17 yrs, range 21 - 82. The Vicenza catheter is defined "short" since it consists of a classic straight double cuff PD catheter having however an inner segment (the portion located in the peritoneal cavity) much shorter than any other type of catheter. It is implanted in the lower abdomen, just a few centimeters above the pubis. The analysis of our results obtained in a large PD population displayed good device survival at 2 and 5 years (94.3% and 91.5% respectively), a low dislocation rate (4%) and an exit-site infection rate similar to other double cuffed catheters. There was no selection of patients receiving this catheter since from 1985 we have used this catheter in every incident patient. Due to its lower implantation site this catheter demonstrates excellent wearability and good body image acceptance.

Continuous flow peritoneal dialysis: a new double lumen catheter.

Continuous flow peritoneal dialysis (CFPD) is a therapy originally utilized in the sixties. It was then abandoned because of technical reasons, but, today, a new interest in this technique is emerging, because of new technical solutions and new hardware capabilities. CFPD is a peritoneal dialysis technique in which a certain amount of fluid is maintained in the peritoneal cavity, while a continuous inflow and outflow is provided via twin catheters or through a double lumen catheter. In this paper a new double lumen catheter is presented. The catheter is characterized by the presence of a diffuser in the inflow lumen, while a standard coiled shape characterizes the outflow lumen. The diffuser allows the use of high dialysate flows without peritoneal damage and with an excellent distribution of the fluid. The other feature of the catheter is the removable hub which allows for an easy subcutaneous tunneling of the catheter with a subsequent connection to the y segment. The special shape also guarantees a minimum recirculation during treatment. Data obtained in the first implanted catheter showed a progressive increase in small solute clearances in relation to an increase of the flow and the tidal volume in the peritoneal cavity. In particular, urea clearances up to 48 ml/min and creatinine clearances up to 39 ml/min were obtained. No major complications were observed after one year of use of the catheter.

[Prevalence of pre-obesity and obesity in uremic hemodialysis patients from Puglia and Lucania]. / Prevalenza dei preobesi e degli obesi negli uremici in trattamento emodialitico in Puglia e Lucania.

BACKGROUND: Obesity is a well-known cause of increased morbidity and mortality in the general population, while its influence on the hemodialysis population is yet to be defined. Obesity probably has a protective effect on survival in hemodialysis. In this study, we evaluated the prevalence of obesity in the hemodialysis population of Puglia and Lucania, two regions of Southern Italy, by using simple and easily accessible parameters collected by the participating centres. METHODS: One thousand five hundred and forty-six patients on stable hemodialysis for at least 6 months from 23 Centres were studied. One hundred and sixty patients had a body mass index (BMI) more than 25 kg/m2; "preobesity" was defined as a BMI ranging between 25 and 30 kg/mq, while "obesity" as a BMI > 30. All data regarding the underlying renal disease, the use of low-protein diet before beginning hemodialysis, weight and height at the beginning of treatment and the different kinds of treatment were collected. A careful analysis of the last dialysis treatment by means of biochemical data was carried out. RESULTS: The prevalence of preobesity and obesity was 3.1 and 7.3%, respectively. Eighty-three percent of patients in the preobesity group and seventy-two percent in the obesity group were female (p<0.001). The prevalence of diabetes was 19 and 24% in the preobesity and obesity groups, respectively, while it was 8% in patient with normal BMI (p<0.0001). Age and duration of low-protein diet were similar to those observed in the general population, while dialytic age was greater in preobesity group (p<0.01). Conclusions. Our study has shown that the prevalence of obese people undergoing hemodialysis is increasing. It is therefore necessary to introduce new measures to obtain a good nutritional status in end stage renal disease patients; in particular fat free mass is to be increased, since an improvement in the patient's nutritional status acts as a protecting factor against morbidity and mortality.

[Prevalence of malnutrition in uremic patients undergoing hemodialysis therapy in Puglia and Lucania]. / Prevalenza della malnutrizione negli uremici in trattamento emodialitico di Puglia e Lucania.

BACKGROUND: Calorie-protein malnutrition is associated with increased morbidity and mortality in hemodialysis patients. The aim of this study was to evaluate the prevalence of malnutrition in uremic patients treated with hemodialysis in two areas of Southern Italy. METHODS: A questionnaire was sent out to all Dialysis Centers in the two regions to select and enrol eligible patients by considering these parameters: Body Mass Index (BMI), serum albumin, serum creatinine, urea, calcium, phosphate, triglycerides, cholesterol, body weight. Enrolment criteria were patients on dialysis for at least six months and BMI less than 21 kg/m2. The dialytic dose was evaluated by reporting the hours of dialysis and filter surfaces. The number of weekly sessions (n. 3) remained unchanged over time. RESULTS: Twenty-three Dialysis Centers in the two Regions replied to our questionnaire and 149 patients were enrolled in the study out of the 1546 patients examined. The overall prevalence of calorie-protein malnutrition was observed in 9.6% of the patients. The prevalence of malnutrition was found to be higher in males and in patients on dialysis for longer time. We observed no correlation with the hypoproteic diet administered in the pre-dialysis phase. Malnourished patients showing progressive weight loss were older and had undergone dialysis for a longer time. CONCLUSIONS: This retrospective study indicates low prevalence of malnutrition in the two regions examined. The lack of correlation between the hypoproteic diet and dialytic dose suggests the need for further studies to evaluate if increased dialytic dose or early start of dialysis could improve the nutritional status and quality of life in elderly patients.

Associations of CCR5, CCR2, and stromal cell-derived factor 1 genotypes with human immunodeficiency virus disease progression in patients receiving nucleoside therapy.

Genotype data for CCR5, CCR2, and stromal cell-derived factor 1 (SDF-1) were obtained from 354 human immunodeficiency virus type 1 (HIV-1)-positive subjects who were being treated with nucleosides. Associations with HIV-1 load, HIV syncytium-inducing (SI) phenotype, CD4 cell count, and disease progression were analyzed. No differences in HIV-1 load or CD4 cell count were observed between wild type (+) and variant genotypes. Changes from non-SI to SI viral phenotype were more frequent in heterozygotes with a 32-bp deletion (Delta32) in the CCR5 gene than in + homozygotes (40% vs. 7%; P=.01). In a multivariate analysis, heterozygous CCR5 Delta32 was associated with reduced hazard of progression (hazard ratio, 0.32; P=.02). Subjects homozygous for the SDF-1 3'A variant had more-rapid disease progression (P=.008). The SDF-1 homozygous 3'A variant was related to more-rapid disease progression, and CCR5 Delta32 was associated with reduced rates of hazard for disease progression in nucleoside-treated subjects.

Human immunodeficiency virus type 1 hypersusceptibility to amprenavir in vitro can be associated with virus load response to treatment in vivo.

The human immunodeficiency virus type 1 protease mutation N88S, which is occasionally selected by treatment with nelfinavir or indinavir, confers hypersusceptibility to amprenavir in vitro. The clinical relevance of this observation is unclear. We report a case of N88S developing after virologic failure of both indinavir- and nelfinavir-containing regimens that was managed successfully with a regimen that contained amprenavir.

Practice pattern and treatment options for kidney patients in a single North Italian nephrology center.

The experience and the current practice of a single center located in northern Italy is reported. The center of Vicenza is a self-standing nephrologic unit serving a population of about 300,000 individuals. The overall province counts approximately 800,000 individuals and some of them are referred to our center from peripheral hospitals for renal transplantation and/or particular pathologic conditions. The center offers an integrated approach to the treatment of uremia including hemodialysis (HD), peritoneal dialysis (PD), and renal transplantation. In HD and PD, the most peculiar aspect is the treatment personalization that leads to numerous types of applied therapies and technologies. The policy of the center is based on the belief that the nephrology team has a substantial influence on the outcomes of dialysis patients. A large number of treatment options are available. Special care is placed on the delivery of an adequate amount of dialysis, but the fractional clearance of urea in relation to volume (Kt/V) is seen as a prerequisite and other factors are considered important. Reduction in mortality and morbidity is largely dependent on beginning therapy early in the course of renal treatment. The attainment of appropriate hemoglobin concentrations, good nutrition, good control of calcium and phosphorus metabolism, lipids, and blood pressure, is considered of great importance. Beyond all these factors the time spent by the physician with the patient is considered one of the major factors influencing quality of care. The particularly low mortality of the center (6%/yr) may also be ascribed to a lower incidence of diabetes and other comorbidities.