The goal of the present paper was to optimize the encapsulation of beta-lactoglobulin (BLG) within poly(lactide-co-glycolide) (PLGA) microparticles prepared by the multiple emulsion solvent evaporation method. The role of the pH of the external phase and the introduction of the surfactant Tween 20, in the modulation of the entrapment and release of BLG from microparticles, was studied. Reducing the solubility of BLG by decreasing the pH of the external phase to a value close to the pI of BLG resulted in a better encapsulation with, however, a larger burst release effect. By contrast, Tween 20 was shown to increase the encapsulation efficiency of BLG and reduce considerably the burst release effect. In fact, Tween 20 was shown to be responsible for removing the BLG molecules that were adsorbed on the particle surface. In addition, Tween 20 reduced the number of aqueous channels between the internal aqueous droplets as well as those communicating with the external medium. Thus, the more dense structure of BLG microspheres could explain the decrease in the burst release. These results constitute a step ahead in the improvement of an existing technology in controlling protein encapsulation and delivery from microspheres prepared by the multiple emulsion solvent evaporation method.

Hydrogen-Ion Concentration↗

PubMed1999

Isolated noncompaction of the myocardium.

Explore the source record for details and available documents.

Adult↗

PubMed1999

Angiopoietins 3 and 4: diverging gene counterparts in mice and humans.

The angiopoietins have recently joined the members of the vascular endothelial growth factor family as the only known growth factors largely specific for vascular endothelium. The angiopoietins include a naturally occurring agonist, angiopoietin-1, as well as a naturally occurring antagonist, angiopoietin-2, both of which act by means of the Tie2 receptor. We now report our attempts to use homology-based cloning approaches to identify new members of the angiopoietin family. These efforts have led to the identification of two new angiopoietins, angiopoietin-3 in mouse and angiopoietin-4 in human; we have also identified several more distantly related sequences that do not seem to be true angiopoietins, in that they do not bind to the Tie receptors. Although angiopoietin-3 and angiopoietin-4 are strikingly more structurally diverged from each other than are the mouse and human versions of angiopoietin-1 and angiopoietin-2, they appear to represent the mouse and human counterparts of the same gene locus, as revealed in our chromosomal localization studies of all of the angiopoietins in mouse and human. The structural divergence of angiopoietin-3 and angiopoietin-4 appears to underlie diverging functions of these counterparts. Angiopoietin-3 and angiopoietin-4 have very different distributions in their respective species, and angiopoietin-3 appears to act as an antagonist, whereas angiopoietin-4 appears to function as an agonist.

Amino Acid Sequence↗

PubMed1999

Improved outcome for acute lymphoblastic leukemia in children of a developing country: results of the Chilean National Trial PINDA 87.

BACKGROUND: The National Chilean Pediatric Oncology Group, PINDA, reports the first prospective, nonrandomized trial for acute lymphoblastic leukemia (ALL), using a modified version of the Berlin-Frankfurt-Munster protocol (ALL BFM 86). The aim of this study was to classify immunophenotypes, to decrease cranial irradiation, and to assess whether this protocol would improve the survival rate. PROCEDURE: From June, 1987, to June, 1992, 444 unselected children were diagnosed with ALL. Of them, 425 were evaluable. Therapy was stratified by risk. Standard-risk (SR) and high-risk (HR) patients received protocols I, M, II, and maintenance therapy. Very-high-risk (VHR) patients received protocol E instead of protocol M. All patients received a prephase treatment consisting of prednisone and intrathecal methotrexate (MTX). HR and VHR patients received cranial irradiation (12-18 Gy). The following changes were made to the ALL BFM 86 protocol: in protocol M, MTX 1 g/m2 instead of 5 g/m2; in protocol E, citarabine 1 g/m2 instead of 2 g/m2; mithoxantrone and ifosfamide were substituted by teniposide and cyclophosphamide. RESULTS: Immunophenotypes: pro-B-ALL, 14%; common ALL, 67.4%; pre-B-ALL, 4.3%; T-ALL, 10%; undifferentiated leukemia (AUL), 4.3%. The overall 5-year event-free survival (EFS) rate was 60% +/- 2% (SE). The 5-year EFS rate for each risk group was: SR 75%, HR 62%, VHR 28%, with a median follow-up of 6.5 years (range 4.5-9.5 years). The cumulative incidence of central nervous system (CNS) relapse was 5.4%. CONCLUSIONS: We have been able successfully to perform a nationwide study. Our strategy to adapt the BFM protocol to our population of patients trial was effective in improving the EFS. The immunophenotype distribution is similar to that in other reported series.

Adolescent↗

PubMed1999

A polysorbate-based non-ionic surfactant can modulate loading and release of beta-lactoglobulin entrapped in multiphase poly(DL-lactide-co-glycolide) microspheres.

PURPOSE: The goal of the present paper was to investigate the role of a surfactant, Tween 20, in the modulation of the entrapment and release of beta-lactoglobulin (BLG) from poly (DL-lactide-co-glycolide) microspheres. METHODS: Poly(DL-lactide-co-glycolide) microspheres containing BLG were prepared by a water-in-oil-in-water emulsion solvent procedure. Tween 20 was used as a surfactant in the internal aqueous phase of the primary emulsion. BLG entrapment efficiency and burst release were determined. Displacement of BLG from microsphere surface was followed by confocal microscopy observations and zeta potential measurements, whereas morphological changes were observed by freeze-fracture electron microscopy. RESULTS: Tween 20 was shown to increase 2.8 fold the encapsulation efficiency of BLG without any modification of the stability of the first emulsion and the viscosity of the internal aqueous phase. In fact, Tween 20 was shown to be responsible for removing the BLG molecules that were adsorbed on the particle surface or very close to the surface as shown by confocal microscopy and zeta potential measurements. Tween 20 reduced the number of aqueous channels between the internal aqueous droplets as well as those communications with the external medium. Thus, the more dense structure of BLG microspheres could explain the decrease of the burst release. CONCLUSIONS: These results constitute a step forward in the improvement of existing technology in controlling protein encapsulation and delivery from microspheres prepared by the multiple emulsion solvent evaporation method.

Chemistry, Pharmaceutical↗

PubMed1999

Plasma-electrolytes in natives to hypoxia after marathon races at different altitudes.

PURPOSE: It is well known that altitude natives differ from sea level natives in aspects of fluid and electrolyte homeostasis. METHODS: To evaluate exercise and environmental influences on the electrolyte and water status in hypoxia adapted subjects, we investigated 11 well-trained marathon runners (33.7 +/- 0.7 yr, 60.5 +/- 1.9 kg), native to an altitude above 2600 m, before and after two marathon races. One competition was held at moderate altitude (AM, 2650 m, 14 degrees C, 55% RH, running time 3 h 6 min +/- 22 min) and another under tropical conditions (HM, 470 m, 28 degrees C, 70% RH, running time 2 h 54 min +/- 30 min). Blood samples were taken 3 d before, immediately after, 1 h after, and 24 h after the races. RESULTS: The loss in body fluid was calculated to be 2.15 L during AM and 5.05 L during HM, respectively. It was compensated mostly by ingested fluids without electrolyte content and by metabolically produced water, which led to hyponatremia during AM (plasma [Na+] from 144.3 +/- 0.7 to 131.7 +/- 2.1 mmol x L(-1)). Severe dehydration without significant changes in plasma [Na+] could be detected after HM. Serum antidiuretic hormone concentrations and serum aldosterone concentrations significantly increased during both races and remained at a high level for at least 1h after both competitions. Serum atrial natriuretic peptide (ANP) concentrations were at a high level at rest, increasing during HM, and decreasing during AM. CONCLUSION: Under tropical conditions, we found a severe state of dehydration characterized by an extended ANP-response, which was not prevented by water intake during the race. Under hypoxic conditions, however, we found that hyponatremia had developed. This can be partly explained by pure water intake and metabolically produced water, and also, possibly, by a special hypoxia-induced effect.

Adult↗

PubMed1999

Humoral immune response and antigenemia in sheep experimentally infected with Schistosoma bovis. Cross-reactivity with Fasciola hepatica antigens.

Circulating antigen level, IgG antibody response to worm antigens and to excretory/secretory products (ES), and specificity to Fasciola hepatica antigens were determined in 6 Schistosoma bovis-infected sheep at weekly intervals for 15 wk. A noninfected control group was included. An enzyme-linked immunosorbent assay (ELISA) sandwich and a double-antibody ELISA test was used for antibody and antigen detection, respectively. The infection induced an early and relatively low IgG response to adult worm extract. This response was significantly elevated by 3 wk postinfection (PI), reached its maximum level at 9 wk PI, and was followed by a subsequent decrease. The response to ES antigens was slightly higher than that to adult worms, although the response started later, at 8 wk PI, and remained at its maximum level until 15 wk. A remarkable level of cross-reactivity was observed when adult F. hepatica extract was used. However, a low degree of cross-reactivity was found with ES antigen. The ELISA for circulating antigens was performed at weekly intervals for 8 wk. Antigens were detected as early as the first week of infection, although differences were statistically significant from week 5 onward. The highest values were observed at 7 week PI.

Animals↗

PubMed1999

[Preliminary results of horizontal gastroplasty with Roux in Y anastomosis in patients with severe and morbid obesity].

BACKGROUND: Morbidly obese subjects have a high incidence of complications. The poor results of dietary treatments, has prompted the search of new therapies for obesity and among these, surgical procedures. AIM: To report the long term results of horizontal gastroplasty with Roux en Y anastomosis in morbidly obese subjects. PATIENTS AND METHODS: Fifty patients with an initial body mass index of 41.3 +/- 6 kg/m2 have been subjected to a horizontal gastroplasty with Roux en Y anastomosis. During the study period, surgical techniques were modified, reducing the gastric pouch size, adding a truncal vagotomy, cholecystectomy, and increasing the length of the Roux en Y loop from 70 to 100 cm. Twenty five patients have been followed for two years. RESULTS: There was no operative mortality and one patient had an anastomotic leak that required 35 days of hospitalization. During follow up, in one patient, the stapled suture line loosened. After two years of follow up, weight decreased from 112 +/- 19 to 77.2 +/- 14 kg. CONCLUSIONS: Horizontal gastroplasty with Roux en Y anastomosis achieved an adequate weight loss with a low rate of complications in this group of morbidly obese subjects.

Adolescent↗

PubMed1999

[Clinical and endoscopic findings and magnitude of gastric and duodenal reflux in patients with cardial intestinal metaplasia, short Barrett esophagus, compared with controls].

BACKGROUND: The diagnosis of patients with short segments of intestinal metaplasia in the distal esophagus, has increased in recent years. AIM: To assess the clinical, pathological and functional features of patients with esophageal intestinal metaplasia. PATIENTS AND METHODS: A prospective study was performed in 95 control subjects, 115 patients with cardial intestinal metaplasia and 89 patients with short Barret esophagus with intestinal metaplasia. All had clinical and endoscopic assessments, esophageal manometry and determination of 24 h esophageal exposure to acid and duodenal content. RESULTS: Control patients were younger and, in this group, the pathological findings in the mucosa distal to the squamous-columnar change, showed a preponderance of fundic over cardial mucosa. In patients with intestinal metaplasia and short Barret esophagus, there was only cardial mucosa, that is the place where intestinal metaplasia implants. Low grade dysplasia was only seen in the presence of intestinal metaplasia. Gastroesophageal sphincter pressure decreased and gastric and duodenal reflux increased along with increases in the extension of intestinal metaplasia. CONCLUSIONS: These findings confirm the need to obtain multiple biopsies from the squamous-columnar mucosal junction in all patients with gastroesophageal reflux symptoms, for the detection of early pathological changes of Barret esophagus and eventual dysplasia.

Barrett Esophagus↗

PubMed1999

[Prevalence of cardial or fundic mucosa and Helicobacter pylori in the squamous-columnar mucosa in patients with chronic patological gastroesophageal reflux without intestinal metaplasia comparated with controls].

BACKGROUND: The mucosa distal to the endoscopic mucosal change zone can have easily diagnosed early alterations, in patients with chronic gastroesophageal reflux. AIM: To determine the type of mucosa existent in the zone distal to the squamous-columnar junction in patients with chronic gastroesophageal reflux without intestinal metaplasia. PATIENTS AND METHODS: One hundred thirty four controls and 208 patients with chronic gastroesophageal reflux lasting two years were studied. Forty three of these patients had a normal endoscopy, 54 had an erosive esophagitis and 111 had a short columnar epithelium covering the distal esophagus, without intestinal metaplasia. In all subjects, four biopsies were obtained from a zone distal to the squamous-columnar junction and two from the distal gastric antrum. RESULTS: In 59% of control subjects, fundic mucosa was present in the zone distal to the squamous-columnar junction. Cardial mucosa was present in the rest. In patient with chronic gastroesophageal reflux, cardial mucosa was predominant. Helicobacter pylorii infection decreased along with increasing extension of cardial mucosa covering the distal esophagus. CONCLUSIONS: In patients with chronic gastroesophageal reflux there is a metaplasia of fundic mucosa towards cardial mucosa. On the other hand, Helicobacter pylorii infection decreases gradually.

Adolescent↗

PubMed1998

Photodegradation and phototoxicity studies of furosemide. Involvement of singlet oxygen in the photoinduced hemolysis and lipid peroxidation.

The phototoxic diuretic drug furosemide (1), a 5-(aminosulfonyl)-4-chloro-2-[(2-furanylmethyl)-amino] benzoic acid is photolabile under aerobic and anaerobic conditions. Irradiation of a methanol solution of 1 under oxygen produces photoproducts 2, 3, 4 and singlet oxygen, while under argon the photoproducts 2 and 4 were isolated. A peroxidic unstable photoproduct was detected during the photolysis under oxygen atmosphere. The formation of singlet oxygen by photolysis of 1 was evidenced by trapping with 2,5-dimethylfuran (GC-mass), furfuryl alcohol and 1,3-cyclohexadiene-1,4-diethanoate (HPLC) as 1O2 scavengers and by the histidine test. Furosemide was screened in vitro at different concentrations for UV-Vis-induced phototoxic effects in a photohemolysis test, in the presence and absence of different radical scavengers, singlet oxygen and hydroxyl radical quenchers. However, furosemide photosensitized the peroxidation of linoleic acid, as monitored by the UV-detection of dienic hydroperoxides and it also photosensitized the oxidation of histidine. The photodegradation was catalyzed in the presence of human serum albumin. Studies on peripheral blood mononuclear and polymorphonuclear cells (lymphocytes and neutrophils) demonstrated no phototoxicity on these cell lines.

Dermatitis, Phototoxic↗

PubMed1998

'Carditis': an objective histological marker for pathologic gastroesophageal reflux disease.

In a prospective endoscopic and bioptic study, 141 control subjects and 359 patients with symptoms of gastroesophageal reflux (GER) were included to determine the prevalence of cardial epithelium inflammation or 'carditis' and to determine the prevalence of Helicobacter pylori in this area. Two biopsies at the antrum, four distal to the squamous-columnar junction and two proximal in the esophageal mucosa, were taken. Patients with gastroesophageal reflux were divided into four groups, according to the severity of endoscopic findings: patients without esophagitis, patients with erosive esophagitis, patients with short-segment and long-segment Barrett's esophagus (BE). Control subjects had normal histological findings at the cardia in 90% of cases, fundic mucosa being present twice as cardial epithelium. Carditis was present in 8% of cases and intestinal metaplasia (IM) in 2%. On the contrary, patients with GER had carditis in nearly 50% of cases. Intestinal metaplasia was present in 12% of cases with GER without esophagitis or erosive esophagitis, in 35% of cases with short-segment BE and in 65% of the cases with long-segment BE. IM at the antrum was present in only 5% of cases. Helicobacter pylori at the squamous-columnar junction was present in 13% of control subjects and in 30% of the patients with GER. It is concluded that carditis is an easy and objective marker for the presence of chronic gastroesophageal reflux and the presence of Helicobacter pylori at this region must be carefully evaluated in order to determine some pathogenic role for the development of Barrett's esophagus.

Adolescent↗

PubMed1998

[Effects of dehydroepiandrosterone on blood cells of the rat].

The effects of dehydroepiandrosterone (DHEA) on haemoglobin, hematocrit and white cell counts values were studied in male and female rats, castrated rats and pregnant rats. After 5 continuous days of DHEA administrated subcutaneously (80 mg/kg/d; body w.) haemoglobin and hematocrit values were similar those values obtained before the treatment. White cell counts were reduced (40%) in female no castrated rats due to a significantly lymphopenia. The white cell counts were increased in castrated rats and with DHEA administration there were reduced to the initial values. Estradiol treatment had the same effect as DHEA on castrated rats. These data suggest that DHEA administrated to castrated or sexually active male and female rats affects the white cells without important effects on red blood cells.

Adjuvants, Immunologic↗

PubMed1998

[Intestinal trichobezoar: report of a case].

Trichobezoars are rare medical entities that must be considered in the differential diagnosis of patients with abdominal mass. We describe a case of an unsuspected intestinal trichobezoar in a nine years old girl. The patient presented an acute lower abdominal pain. We found an echogenic abdominal mass in the pelvic sonography. A double contrast barium enema was scheduled and a rapid relief of symptoms during the preparation of it was accomplished with the expulsion of a mass of hair.

Bezoars↗