Chitosan–hyaluronic acid nanoparticles loaded with heparin for the treatment of asthma

The purpose of this study was to produce mucoadhesive nanocarriers made from chitosan (CS) and hyaluronic acid (HA), and containing the macromolecular drug heparin, suitable for pulmonary delivery. For the first time, this drug was tested in ex vivo experiments performed in mast cells, in order to investigate the potential of the heparin-loaded nanocarriers in antiasthmatic therapy. CS and mixtures of HA with unfractionated or low-molecular-weight heparin (UFH and LMWH, respectively) were combined to form nanoparticles by the ionotropic gelation technique. The resulting nanoparticles loaded with UFH were between 162 and 217 nm in size, and those prepared with LMWH were 152 nm. The zeta potential of the nanoparticle formulations ranged from +28.1 to +34.6 mV, and in selected nanosystems both types of heparin were associated with a high degree of efficiency, which was approximately 70%. The nanosystems were stable in phosphate buffered saline (PBS), pH 7.4, for at least 24 h, and released 10.8% of UFH and 79.7% of LMWH within 12 h of incubation. Confocal microscopy experiments showed that fluorescent heparin-loaded CS–HA nanoparticles were effectively internalized by rat mast cells. Ex vivo experiments aimed at evaluating the capacity of heparin to prevent histamine release in rat mast cells indicated that the free or encapsulated drug exhibited the same dose–response behaviour.     

Malaria: progress, perils, and prospects for eradication

There are still approximately 500 million cases of malaria and 1 million deaths from malaria each year. Yet recently, malaria incidence has been dramatically reduced in some parts of Africa by increasing deployment of anti-mosquito measures and new artemisinin-containing treatments, prompting renewed calls for global eradication. However, treatment and mosquito control currently depend on too few compounds and thus are vulnerable to the emergence of compound-resistant parasites and mosquitoes. As discussed in this Review, new drugs, vaccines, and insecticides, as well as improved surveillance methods, are research priorities. Insights into parasite biology, human immunity, and vector behavior will guide efforts to translate parasite and mosquito genome sequences into novel interventions.     

Sewage sludge applied to agricultural soil: Ecotoxicological effects on representative soil organisms

Application of sewage sludge to agricultural lands is a current practice in EU. European legislation permits its use when concentrations of metals in soil do not increase above the maximum permissible limits. In order to assess the fate and the effects on representative soil organisms of sewage sludge amendments on agricultural lands, a soil microcosm (multi-species soil system—MS 3) experiment was performed. The MS 3 columns were filled with spiked soil at three different doses: 30, 60 and 120 t ha^?1 fresh wt. Seed plants (Triticum aestivum, Vicia sativa and Brassica rapa) and earthworms (Eisenia fetida) were introduced into the systems. After a 21-d exposure period, a statistically significant increase for Cd, Cu, Zn and Hg concentrations was found for the soils treated with the highest application rate. Dose-related increase was observed for nickel concentrations in leachates. Plants and earthworm metal body burden offer much more information than metal concentrations and help to understand the potential for metal accumulation. Bioaccumulation factor (BAF_plant?soil) presented a different behavior among species and large differences for BAF_{earthworm?soil}, from control or sewage-amended soil, for Cd and Hg were found. B. rapa seed germination was reduced. Statistically significant decrease in fresh biomass was observed for T. aestivum and V. sativa at the highest application rate, whereas B. rapa biomass decreased at any application rate. Enzymatic activities (dehydrogenase and phosphatase) as well as respiration rate on soil microorganisms were enlarged.     

Liver Transplantation for Hepatocellular Carcinoma: Results of a Multicenter Study With Common Priorization Criteria

Objective

To evaluate the results of liver transplantation (OLT) performed for hepatocellular carcinoma (HCC) among a multicenter cohort of patients with predefined common inclusion and priorization criteria.

Patients and Methods

Over a 5-year period (January 2002-December 2006), 199 HCC patients underwent OLT in four centers in Andalusia. The morphological (Milan) inclusion criteria were priorized in two consecutive periods, according to the Model for End-stage Liver Disease score: group I, 53 patients (HCC < 2 cm = 24 points; ≥ 2 cm or multinodular = 29 points) and group II, 146 cases (HCC < 3 cm without priorization; HCC ≥ 3 cm or multinodular = 18 points).

Results

Among the 199 HCCs, 186 (93.5%) subjects were transplanted and 13 (6.5%) were excluded. There were 18 cases (9.7%) where the diagnosis was incidental and 168 were known HCC cases; 144 (85.7%) complied with the Milan criteria (Milan+); 24 (14.3%) exceeded there criteria (Milan−). According to preoperative imaging, the number of nodules and tumor mean sizes among the excluded—Milan+ and Milan− groups—were 1.8/5.3 cm, 1.4/3.5 cm, and 2.3/6.7 cm, respectively (P < .001). Percutaneous treatment during listing was delivered to 55% of the excluded cases: 49% of Milan+ and 96% of Milan−. The median time on the list was 88 days for known HCC (53 days for group I, and 97 days for group II), and 172 days for the incidental HCCs. Staging (pTNM) was correct in 64% of cases: 23% were understaged and 13% were overstaged. Overall mortality within the first 90 days was 9%, and transplant patient survival at 5 years was 61%. No differences were observed in survival rates between both study periods, although there were differences between the Milan+ (65%) and Milan− (23%) groups (P < .04). In addition, the difference in the recurrence rates was also significant between the Milan+ (7%), Milan− (24%), and the incidental (25%) groups (P < .02).

Conclusions

A common priorization policy of HCC for OLT based on morphological criteria results in a low exclusion rate on the waiting lists (6.5%). The Milan criteria are still a good cutoff to stratify the risk of recurrence, despite preoperative tumor staging being correct in only two-thirds of cases.     

Adenocarcinoma vesical primario en extrofia vesical no corregida

We report a 60 years old patient with a not repaired exstrophic bladder, who develops an adenocarcinoma on his bladder and review of the literature.     

Donante vivo renal. experiencia de cirugía abierta y laparoscópica. hospital la paz

Laparoscopic live donor nephrectomy is a rare operation in our country because the complexity of the technique and the expansion of the cadaveric donor. We present our open and laparoscopic live donor nephrectomy from 1984.Material and MethodsFrom 1984 to 2007 we have done 84 live donor nephrectomies; 64 open, 20 laparoscopic surgeries. The transperitoneal approach is preferred in laparoscopy and lumbotomy for the open surgery.ResultsIn the open technique the operating time is 112min (70-155), ischaemia time 20 seconds (15-47) and postoperative hospital stay 4,8 days (3-9). Laparoscopic cases, the operating time is 146 min (90-210), ischaemia time 3 min 15 sec (2-3,25 min) and postoperative hospital stay 3,4 days (2-9).ConclusionsThe laparoscopic live donor nephrectomy is a difficult and demanding technique. It should be done by experienced team in laparoscopic renal surgery. The kidney from a live donor is a very good alternative for the cronic renal failure. It should be offered in our main hospitals.     

Daytime sleepiness and polysomnography in obstructive sleep apnea patients

BackgroundExcessive daytime sleepiness (EDS) is the major complaint in subjects with obstructive sleep apnea syndrome (OSAS). However, EDS is not universally present in all patients with OSAS. The mechanisms explaining why some patients with OSAS complain of EDS whereas others do not are unknown.ObjectiveTo investigate polysomnographic determinants of excessive daytime sleepiness (EDS) in a large multicenter cohort of patients with obstructive sleep apnea (OSAS).MethodsAll consecutive patients with an apnea–hypopnea index greater than 5 h⁻¹ who were evaluated between 2003 and 2005. EDS was assessed using the Epworth Sleepiness Scale (ESS), and patients were considered to have EDS if the ESS was >10.ResultsA total of 1649 patients with EDS ((mean [±SD] Epworth 15 ± 3) and 1233 without EDS (Epworth 7 ± 3) were studied. Patients with EDS were slightly younger than patients without EDS (51 ± 12 vs 54 ± 13 years, p < 0.0001), had longer total sleep time (p < 0.007), shorter sleep latency (p < 0001), greater sleep efficiency (p < 0.0001) and less NREM sleep in stages 1 and 2 (p < 0.007) than those without EDS. Furthermore, patients with EDS had slightly higher AHI (p < 0.005) and arousal index (p < 0.001) and lower nadir oxygen saturation (p < 0.01).ConclusionsPatients with OSAS and EDS are characterized by longer sleep duration and increased slow wave sleep compared to those without EDS. Although patients with EDS showed a mild worsening of respiratory disturbance and sleep fragmentation, these results suggest that sleep apnea and sleep disruption are not the primary determinants of EDS in all of these patients.     

Personality dimensions in obsessive-compulsive disorder: relation to clinical variables

Research on the relationship between personality factors and obsessive-compulsive disorder (OCD) has proved difficult to interpret due to conceptual problems including a lack of consensus on the model of personality employed as a framework as well as a failure to consider the clinical heterogeneity of the disorder. The aim of this study was to examine the dimensional personality profile associated with OCD and to determine whether any relationship exists between personality factors and clinical variables in a sample of 60 OCD outpatients who were administered Cloninger's Temperament and Character Inventory (TCI). The Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), the Hamilton Depression Rating Scale (HDRS) and the Y-BOCS symptom checklist were used to assess the severity of obsessive-compulsive and depressive symptoms and the presence of the main OCD symptom dimensions. OCD patients showed significantly higher scores in harm avoidance and lower scores in novelty-seeking, self-directedness and cooperativeness than healthy subjects. These results remained unchanged when only pure OCD patients without comorbid psychiatric conditions were considered. Comorbid depressive symptoms and hoarding obsessions and compulsions were significantly associated with high harm avoidance scores. These results support the existence of a dimensional personality profile associated with OCD and characterized by high harm avoidance and low novelty-seeking, self-directedness and cooperativeness scores, but also emphasize the importance of considering the influence of comorbid clinical conditions or symptom subtypes in addressing the role of personality factors in OCD.     

Dehydroepiandrosterone affects Trypanosoma cruzi tissue parasite burdens in rats

Dehydroepiandrosterone (DHEA), the predominant steroid hormone produced by adrenal glands has significant effects on the immune system. DHEA enhances immune responses against a wide range of viral, bacterial, and parasitic pathogens. In the present study, we investigated the effects of DHEA treatment during the acute phase of experimental Trypanosoma cruzi infection. Male and female Wistar rats were infected with the Y strain of T. cruzi and treated subcutaneously with 40 mg/kg body weight/day of DHEA. Myocardial parasitism and inflammation were always present in the heart during the acute phase, in male and female infected animals, regardless of DHEA treatment, but the numbers of amastigote nests in cardiomyocytes were significantly lower in DHEA-treated rats. At the end of the acute phase, the nests became rare or virtually absent in all experimental infections. Histological analysis of the adrenal glands showed that treated males displayed an absence of parasites. DHEA treatment also resulted in reduced parasitisim of heart and adrenal glands, as indicated by fewer and smaller amastigote burdens, and less inflammatory infiltrate and tissue disorganization. DHEA treatment also resulted in thymic atrophy as measured both by reduced weight and by a reduction in the number of cultured activated thymocytes. In vitro analysis showed the number of activated macrophages was higher in treated animals. Antibody levels were monitored by complement-mediated lysis. Higher titers were observed in females when compared to males; but DHEA treatment enhanced the percentage of lysis for both sexes. These findings suggest that DHEA can play a role in the control of parasite multiplication.