Tolerance of volunteers to cyclosporine A-dilauroylphosphatidylcholine liposome aerosol

Cyclosporine A (CsA) in liposomes of dilauroylphosphatidylcholine (DLPC), containing 118 micrograms of CsA/L of aerosol with a particle size of 1.6 to 1.7 micron diameter, was inhaled by 10 nonsmoking, normal volunteers each for 45 min. Aerosol was administered through an Aerotech II nebulizer (CIS-US, Inc., Bedford, MA) mouthpiece. Eight of the 10 volunteers had tracheal irritation and intermittent coughing following exposure. FEV1 and FVC values were mildly reduced, but returned to normal in 1 h. Blood chemical and hematologic values were unchanged at any time point after as opposed to before inhalation. Nine of the 10 volunteers later inhaled DLPC only, administered through the nebulizer mouthpiece. There was no change in FEV1 or FVC values, and there was no coughing or tracheal irritation. Subsequently, five of the volunteers who had previously had respiratory reactions inhaled CsA-DLPC liposome aerosol for 45-min, but through a mouth-only face mask. There was no tracheal irritation, coughing, or changes in spirometric measures. Blood concentrations of CsA at 15 min after the 45-min inhalation with a face mask averaged 83 +/- 42 ng/ml (mean +/- SD). At 24 h after treatment, CsA was undetectable in blood of the initial 10 volunteers. These studies indicate that CsA-DLPC liposome aerosol can be safely explored as a treatment for patients with moderately severe asthma.     

Formation of droplets on Si surfaces bombarded by In from a capillary type liquid metal ion source

Droplet formation on Si surfaces bombarded by 10 keV beams from a liquid metal indium ion source has been observed. It has been verified that excess indium is transported in the ion beam, probably in the form of charged droplets. SIMS, SEM and RBS techniques have been used to study the distribution of droplets at the surface. At the specified ion source operating conditions, equilibrium droplet coverage is of the order of 25%. Individual droplets have an average diameter of 0.35 ωm and an average height of 2.2 nm. At a bombardment current density of 0.1 mA cm^?2, equilibrium coverage is reached in about 1 s.     

The neurotrophic analogue of ACTH(4-9) reduces the perineuronal microglial reaction after rat facial nerve crush

Rats bled to a severe condition of volume-controlled hemorrhagic shock were randomly assigned to one of the following treatments: (1) saline, 1 ml/kg i.v.; (2) saline, 0.2 ml/kg per min i.v. for 10 min; (3) ACTH-(1-24), 160 micrograms/kg i.v.; 4) methylprednisolone, 40 mg/kg i.v.; (5) methylprednisolone, 80 mg/kg i.v.; (6) aprotinin, 10,000 KIU/kg i.v.; (7) norepinephrine, 5 micrograms/kg per min i.v. for 10 min; (8) norepinephrine, 10 micrograms/kg per min i.v. for 10 min. All rats treated with saline or with either of the two doses of methylprednisolone, and half of the rats treated with aprotinin, died within the subsequent 2 h. On the other hand, rats treated with norepinephrine, at either dose, or with ACTH-(1-24) were all still alive 2 h later, a similar improvement in cardiovascular and respiratory parameters being obtained with the two treatments. The effect of ACTH on mean arterial pressure was however more sustained throughout the observation period. These results further support the potential usefulness of ACTH-(1-24) as first-aid treatment in cases of severe blood losses.     

Results of bypasses to the anterior tibial artery through the interosseous membrane

Two month-old Wistar male albino rats were exposed during a 30-day period to a daily oral intake ad libitum of either 200 microg/mL Cd (as CdCl2), 0.1 microg/mL Se (as Na-selenite), or the same dosages of Cd + Se in drinking water. The daily intake from the water was calculated to be 15 mg Cd/kg and 7 microg Se/kg. Cadmium (Cd) accumulates in the heart (p < 0.005) and, in rats, decreases both body mass growth (p < 0.005) and heart mass (p < 0.02). Selenium (Se) significantly decreases the negative effect of Cd on body mass growth. In the hearts of Cd-treated rats, cadmium caused the decrease (p < 0.05) of selenium-dependent glutathione peroxidase (GSH-Px, EC 1.11.1.9) activity. At the same time, the activities of total superoxide dismutase (total SOD, EC 1.15.1.1), manganese-containing superoxide dismutase (Mn SOD), and copper-zinc-containing superoxide dismutase (CuZn SOD) were increased (p < 0.005). The activities of total SOD, CuZn SOD (p < 0.005), GSH-Px (p < 0.02), and glutathione-S-transferase (GST, p < 0.005) were increased in the hearts of Se-treated rats. However, by concomitant administration of Cd and Se, these changes were diminished (total SOD, GST) or were completely eliminated (Mn SOD, GSH-Px). These results indicate that Se only partly diminishes the effects of Cd cardiotoxicity.     

Survival of patients with carcinoma of the esophagus treated with combined-modality therapy

Since 1985, 229 cases of carcinoma of the esophagus have been considered for entry into a protocol with the use of preoperative chemotherapy and radiation therapy followed by surgical intervention as the primary element of treatment. One hundred sixty-five patients (93 with adenocarcinoma and 72 with squamous cell carcinoma) had esophagogastrectomy. The 5-year survival of the protocol patients who underwent resection was 25% for both groups--squamous cell carcinoma and adenocarcinoma. Of the protocol patients with squamous cell carcinoma who underwent resection, 40% had a sterilized specimen, whereas of those with adenocarcinoma, 20% had a sterilized specimen. If the patient had a sterilized specimen, the 5-year survival was approximately 60% for adenocarcinoma and 40% for squamous cell carcinoma. Those patients with adenocarcinoma and Barrett's esophagus had a 5-year survival of 55%. Of the patients who underwent only esophagectomy and esophagogastrectomy and had not been entered into the protocol, none lived beyond 3 years. The operative mortality rate for those who had esophagogastrectomy was 5%. Sixty-four patients completed the radiation therapy and chemotherapy but did not undergo surgical procedures because of progressive disease or refusal. Of those patients who completed chemotherapy and radiation therapy without surgical intervention, 5-year survival was 18% in patients with squamous cell carcinoma, whereas no patients with adenocarcinoma survived beyond 3 years. The finding of a sterilized specimen after esophagectomy is a favorable prognostic factor in patients with adenocarcinoma or squamous cell carcinoma. The finding that patients with Barrett's esophagus and adenocarcinoma have an improved chance for survival is perhaps related to an earlier diagnosis. It is clear that some patients with squamous cell carcinoma who did not undergo surgical procedures did have a sterilized specimen, because the survival in this group approached 20% at 5 years.     

Establishment of human parotid pleomorphic adenoma cells in culture: morphological and biochemical characterization

This study reports the establishment of alpha-amylase-producing human parotid pleomorphic adenoma cell lines (2HP and 2HP1) which have been maintained in culture for over 1 yr. The procedures required preparation of cellular clumps from tumor tissue and plating them on plasma clot or precoated dishes. During the initial phase of growth they required modified MCDB-153 medium without serum. When cells showed signs of degeneration they were changed to MCDB-153 medium containing first 2% and then 10% heat inactivated fetal bovine serum. Although cells grew well in MCDB-153 containing 10% serum, the epithelial cell morphology was not distinct. Therefore, the growth and morphology of cells grown in MCDB-10% serum were compared with those in RPMI growth medium containing 10% fetal bovine serum and F12 containing 10% agammaglobulin newborn bovine serum. Although the growth of cells was a little slower in F12 medium than those in MCDB and RPMI, the epithelial cell morphology was maintained better than in other growth media. The cells of 2HP and 2HP1 produce low levels of alpha-amylase and relatively high levels of alpha-amylase mRNAs of 1176 and 702 bp and contain neurofilament-160, a neuronal-specific marker. The cells of 2HP1 are tumorigenic when tested in athymic mice, but the cells of 2HP are not. The establishment of amylase-producing human parotid adenoma cell lines of different characteristics in culture provides a new opportunity to study the mechanisms of differentiation and transformation, and regulation of alpha-amylase in these cells.