Experimental and Computational Characterization of the Interaction between Gold Nanoparticles and Polyamidoamine Dendrimers.

Dendrimers provide a means to control the synthesis of gold nanoparticles and stabilize their suspensions. However, design of improved dendrimers for this application is hindered by a lack of understanding how the dendrimers and synthesis conditions determine nanoparticle morphology and suspension stability. In the present work, we evaluate the effect of polyamidoamine (PAMAM) dendrimers terminated with different functional groups (-OH or -NH3+) and different synthesis conditions on the morphology of the resulting gold nanoparticles and their stability in solution. We leverage molecular dynamics (MD) simulations to identify the atomic interactions that underlie adsorption of PAMAM dendrimers to gold surface and how the thermodynamics of this adsorption depends on the terminal functional groups of the dendrimers. We find that gold nanoparticles formed with hydroxyl-terminated PAMAM (PAMAM-OH) rapidly aggregate, whereas those formed with PAMAM-NH3+ are stable in solution for months of storage. Synthesis under ultrasound sonication is shown to be more rapid than that under agitation, with sonication producing smaller nanoparticles. Free-energy calculations in MD simulations show that all dendrimers have a high affinity for the gold surface, although PAMAM-OH and its oxidized aldehyde form (PAMAM-CHO) have a greater affinity for the nanoparticle surface than PAMAM-NH3+. Although adsorption of PAMAM-OH and PAMAM-CHO has both favorable entropy and enthalpy, adsorption of PAMAM-NH3+ is driven by a strong enthalpic component subject to an unfavorable entropic component.

Novel specific peptides as superior surface stabilizers for silver nano structures: role of peptide chain length.

Three new collagen mimetic peptides containing the CLK motif as anchoring arms were tested for silver nanoparticle surface stabilization. Our experimental and molecular dynamics data indicate that peptide length has an important effect not only in the resulting nanosilver's colloidal stability, but also in the biological performance of the composite.

Perspectives of TRPV1 Function on the Neurogenesis and Neural Plasticity.

The development of new strategies to renew and repair neuronal networks using neural plasticity induced by stem cell graft could enable new therapies to cure diseases that were considered lethal until now. In adequate microenvironment a neuronal progenitor must receive molecular signal of a specific cellular context to determine fate, differentiation, and location. TRPV1, a nonselective calcium channel, is expressed in neurogenic regions of the brain like the subgranular zone of the hippocampal dentate gyrus and the telencephalic subventricular zone, being valuable for neural differentiation and neural plasticity. Current data show that TRPV1 is involved in several neuronal functions as cytoskeleton dynamics, cell migration, survival, and regeneration of injured neurons, incorporating several stimuli in neurogenesis and network integration. The function of TRPV1 in the brain is under intensive investigation, due to multiple places where it has been detected and its sensitivity for different chemical and physical agonists, and a new role of TRPV1 in brain function is now emerging as a molecular tool for survival and control of neural stem cells.

Incidence and factors associated with delayed graft function in renal transplantation at Carlos Van Buren Hospital, January 2000 to June 2008.

Delayed graft function (DGF) is defined as the need for dialysis within the first week after renal transplantation, and slow graft function as persistence of serum creatinine concentration of at least 3 mg/dL on day 5 after the procedure. In the present study, we analyzed the incidence and risk factors for DGF at our center. This retrospective study included 106 patients who underwent renal transplantation between January 2000 and June 2008. Of these, 11 patients were excluded. Two of the remaining 95 patients received organs from living donors, and 93 received cadaver organs. Variables analyzed included donor age, cause of death, cause of chronic renal failure, recipient age, method and time of long-term renal replacement therapy, residual diuresis, panel of reactive antibodies (PRA), HLA mismatch, sex compatibility, cold and warm ischemia times, biopsy-confirmed episodes of acute rejection, urine output in the operating room and in the first 24 hours after the procedure, and intraoperative induction therapy. Data were analyzed using the chi(2) and Fisher exact tests and analysis of variance, and are given as mean (SD) and frequency. Variables associated with DGF at univariate analysis (P < .05) were divided between risk factors and predictors of DGF for inclusion in logistic regression models. The incidence of DGF was 32.6%; slow graft function, 16.8%; and immediate graft function, 50.5%. Cold ischemia time longer than 20 hours (P = .02) and donor age (P = .008) were directly associated with DGF. Twenty-four-hour urine output was a strong predictor of DGF. Patients with DGF demonstrated a 25% incidence of an episode of acute rejection before discharge from the hospital. No difference in DGF was observed for use of intraoperative induction therapy.

Successful multiple pregnancy (triplets) in a kidney transplant recipient: a case report.

Renal failure generally accompanies an alteration in reproduction function. Even though a renal transplantation does in fact improve this function, there are few cases described in medical literature of multiple pregnancies in transplant patients that ended in a successful manner. In addition, there is a greater incidence of complications such as hypertension, preeclampsia, and premature delivery. This article describes a 31-year-old patient who became pregnant with triplets at 3 years and 6 months after receiving a renal transplant from a cadaver. The patient received treatment with cyclosporine, azathioprine, and prednisolone. During the pregnancy, there was a increase in hypertension, proteinuria, cholestasia gravidic symptoms, and premature delivery. Pregnancy control included evaluation of the fetoplacental unit together with hypertensive management and adjustment of immunosuppressant treatment, especially the cyclosporine dose, seeking to facilitate greater fetal maturity. Three newborns of 840, 860, and 1020 were delivered by cesarean section. The newborns spent 6 to 8 weeks in the neonatal unit and were released without complications. The newborns have presented adequate psychomotor and physical development to date. The triplets are now 4 years old. The transplant recipient has a creatinine clearance of 81 mL/min at 7 years after transplantation.

[Survival of grafts in the first 100 renal transplants at the Carlos van Buren Hospital]. / Sobrevida del injerto en los primeros 100 trasplantes renales del Hospital Carlos van Buren.

BACKGROUND: Renal transplant is the best therapeutic alternative for chronic renal failure, although it is not exempt of risks. AIM: To report the survival of renal transplant recipients and grafts and the main complications at a public hospital in Chile. PATIENTS AND METHODS: This is a non experimental, open historical cohort study, with reposition of the first 100 transplants in 94 patients, performed at the Carlos van Buren Hospital between 1984 and 1998. Seventy grafts came from cadaveric donors and 30 from live donors. As immunosuppressive therapy, prednisone + azathioprine was used in 48 transplants and the same regimen plus cyclosporine in 52. RESULTS: Mean age of recipients was 36 +/- 23 years old. Ten years actuarial survival of patients was 80.5% in transplants from cadaveric donors and 86% in transplants from live donors. Ten years graft survival was 57.5% in transplants from cadaveric donors and 42% in transplants from live donors. The period in which the transplant was performed (first or second half of the observation period), type of donor, HLA B-DR compatibility and sensitization (% PRA) had no effect on survival. Twenty five subjects lost their graft, 12 due to acute steroid resistant rejection, 10 due to chronic graft nephropathy and three due to renal artery thrombosis. Fifteen subjects died with a functioning graft, 10 due to infections, two due to an acute myocardial infarction, two due to an acute pancreatitis and one due to a brain tumor. CONCLUSIONS: Survival of grafts and renal transplant recipients was not influenced by the type of donor, period of transplantation and immune variables. Main causes of recipient death were infections and the main cause of graft failure was acute rejection.

Latin American Registry of dialysis and renal transplantation: 1993 annual dialysis data report.

BACKGROUND: The Latin American Registry of Dialysis and Transplantation was created in October 1991 and comprises the National Societies of Nephrology from 21 countries with a total population of 468.56 million inhabitants. METHODS: This report includes data from 21,181 patients from Argentina, Brazil, Chile, El Salvador, Panama, Paraguay, Peru, Puerto Rico, Uruguay, and Venezuela who were receiving chronic dialysis treatment during 1993. Data was collected by individual patient questionnaires except from Chile and Brazil where the data was obtained from a local centre questionnaire. RESULTS: The prevalence rate averaged 131.1 per million population. The mean age of the 8972 incident patients was 50.5 years, with 58.2% males. The more frequent causes of renal failure were glomerulopathies (22.6%), vascular nephropathy (20.9%) and diabetes (16.9%). Haemodialysis was the most used treatment (88.3%). Gross mortality was 21.1% and the more frequent causes of death were cardiac complications and infections. The analysis of mortality risk factors using a logistic regression model showed that diabetics patients older than 65 years had the highest probability of death (43.0%) and patients with glomerulonephritis, younger than 65 years had the lowest (8.0%). The adjusted mortality rate was 241 deaths/1000 patient-years at risk when the USRDS 1987-1989 white mortality rate by age groups and primary diseases was used as standard. CONCLUSION: In spite of the economic difficulties, very important efforts have been made to treat ESRD patients and gross mortality statistics in some countries are similar to those reported by other regional registries.

Modulation of human muscle sodium channels by intracellular fatty acids is dependent on the channel isoform.

Free fatty acids (FFAs), including arachidonic acid (AA), are implicated in the direct and indirect modulation of a spectrum of voltage-gated ion channels. Skeletal muscle sodium channels can be either activated or inhibited by FFA exposure; the response is dependent on both FFA structure and site of exposure. Recombinant human skeletal muscle sodium channels (hSkM1) were transfected into heterologous human renal epithelium HEK293t cells. Cytoplasmic delivery of 5 microM AA augmented the voltage-activated sodium current of hSkM1 channels by 190% (+/-54 S.E., n = 7) over a 20-min period. Similar results were seen with 5 microM oleic acid. Sodium currents in HEK293t cells transfected with human cardiac muscle sodium channels (hH1) were insensitive to AA treatment, and exposure to oleic acid inhibited the hH1 currents over a 20-min period by 29% (+/-13 S.E., n = 5). The increase in hSkM1 current was not accompanied by shifts in voltage dependence of activation, steady-state inactivation, or markedly altered kinetics of inactivation of the macroscopic current. The FFA-induced increase in sodium currents was not dependent on protein kinase C activity. In contrast, both isoforms were reversibly inhibited by external application of unsaturated FFA. Thus, the differential effects of FFA on skeletal muscle sodium channels first noted in cultured muscle cells can be reproduced by expressing recombinant sodium channels in epithelial cells. Although the responses to applied FFAs could be direct or indirect, we suggest that: 1) SkM1 has two classes of response to FFA, one which produces augmentation of macroscopic currents with intracellular FFA, and a second which produces inhibition with extracellular FFA; 2) H1 has only one class of response, which produces inhibition with extracellular FFA. A testable hypothesis is that the presence or absence of each response is due to a specific structure in SkM1 or H1. These specific structures may directly interact with FFA or may interact with intermediate components.

[Nocardiosis in a renal transplant recipient]. / Nocardiosis en un paciente con transplante renal.

We report a unilateral pulmonary nocardiosis in a 51 years old male that received a renal allograft. The clinical picture appeared 68 days after transplantation and the culture of a bronchoalveolar lavage showed the presence of Nocardia asteroides. Cyclos-porine and azathioprine were discontinued and trimethoprim-sulphamethoxazole was started with a good clinical response. Afterwards, azathioprine was restarted and the patient is asymptomatic at the present moment.

Hábito de fumar y su relación con el embarazo y la lactancia en Arica: Chile / Cigarette smoking and its relation to pregnancy and lactation in Arica: Chile

El objetivo de este trabajo fue clasificar a las madres según su condición de fumadora, durante el embarazo y la lactancia en Arica, y determinar la influencia de este hábito en el peso del recién nacido y en la duración de la lactancia. La muestra comprendió 240 madres, de las cuales 36,3% declararon ser fumadoras activas. De este grupo, 42,5% fumaron durante el embarazo y 85% durante la lactancia. El peso y la talla de los recién nacidos de madres fumadoras activas fueron significativamente menores, en 370 g y 1,1 cm, respectivamente, que entre los de madres no fumadoras, siendo también, en las primeras, significativamente menor la duración de la lactancia natural exclusiva -2,6 vs. 3,5 meses -P < 0,05 y en la duración total de ésta -4,2 vs. 5,3 meses -p < 0,01