Delivery of therapeutic doses of doxorubicin to the mouse lung using lung-accumulating liposomes proves unsuccessful

Cancer Chemotherapy and Pharmacology - Addition of solid doxorubicin or solutions to pre-formed liposomes proved to be the optimal method for incorporating the drug into liposomes whilst...     

Effects of partial hepatectomy on organ-specific toxic response to 1,2-dibromo-3-chloropropane (DBCP)

The organ-specific toxic potency of subcutaneously administered 1,2-dibromo-3-chloropropane (DBCP) was compared in partially hepatectomized and sham-operated rats over a dose range of 20--80 mg kg-1 to assess the roles of hepatic and extrahepatic metabolism in protection against acute renal and gonadal injury. Relative kidney weight and the severity of DBCP-induced renal proximal tubular cell necrosis were increased in rats subjected to a partial (70%) surgical hepatectomy 48 h prior to treatment with DBCP at 80 mg kg-1. Relative liver weight was reduced by DBCP in the hepatectomized, but not in the sham-operated rats. The severity of DBCP-induced (80 mg kg-1) hepatocellular centrilobular necrosis was greater in hepatectomized than in sham rats. DBCP reduced the relative weights of the testis and epididymis in a progressive manner and produced dose-dependent seminiferous tubular atrophy within 12 days of treatment. The morphologically apparent lesions of the testis and epididymis were enhanced by hepatectomy. The concentration of non-protein sulfhydryl groups (NPS) in rat liver was increased by partial hepatectomy. Because of the resulting decrease in liver size, however, the total amount of hepatic NPS per kg body weight 48 h post-surgery was lower than in sham rats. The surgery had no effect on renal, testicular or epididymal NPS concentrations of organ weights. Partial hepatectomy greatly increased pentobarbital and ethanol sleeping times, while sleep induction time for pentobarbital was decreased.(ABSTRACT TRUNCATED AT 250 WORDS)     

Current trend in the treatment of Hodgkin's disease

The analysis of three subsequent randomized trials carried out within the frame of the European Organization for Research on Cancer (E.O.R.T.C.) enables to define a strategy for the staging and the treatment of early stages of Hodgkin's disease. Several prognostic factors were identified by multivariate analyses: 1) erythrocyte sedimentation rate, which has a greater impact on relapse-free survival than systemic symptoms but which can be combined with them; the combination of the two is a more powerful prognostic indicator than ESR alone; 2) the number of involved lymphatic areas: patients with one or two lymphatic areas involved (CS I and II2) have a better outcome than stage II patients with 3 or more areas involved (CS II3). Patients with favorable prognostic indicators are submitted to staging laparotomy because for them spleen involvement has a pejorative impact. For patients with unfavorable indicators, the spleen involvement has little prognostic significance and therefore those patients who need, anyway, an aggressive treatment do not undergo staging laparotomy. Patients with favorable prognostic indicators and negative staging laparotomy can be treated by radiotherapy alone, patients with positive laparotomy or patients with unfavorable prognostic indicators are treated by combination of multiple chemotherapy and radiotherapy.     

Sphincter injury after anal dilatation demonstrated by anal endosonography.

Anal dilatation is still used in the treatment of anal fissure and haemorrhoids. Using anorectal physiology and anal endosonography we have studied 12 men presenting with faecal incontinence following anal dilatation. Resting anal pressures were low, pudendal nerve latencies were normal; 11 men had a disrupted internal anal sphincter and in ten this was extensively fragmented. Three also had defects of the external anal sphincter. These findings demonstrate for the first time the nature of the structural injury which may be caused by anal dilatation.     

Protein-calorie malnutrition impairs host defense against Candida albicans.

Protein-calorie malnutrition (PCM) impairs immune responsiveness predisposing to Candida albicans sepsis, but mechanisms are unclear. This study examined the effect of PCM on enteric-derived C. albicans intestinal translocation and the ability of in vivo interferon-gamma (IFN-gamma) to upregulate macrophage (MO) candidacidal mechanisms in PCM mice. Control (24% casein) and low protein (2.5%) diets were given for 4 weeks. Mice (n = 160) were fed C. albicans in their drinking water for 3 days and C. albicans translocation (mean colony-forming units (CFU)/g tissue +/- SEM) to the GI tract, liver, spleen, and kidney was assessed at 1 and 5 days following endotoxin challenge of 1, 5, and 10 mg/kg body wt. In a separate study (n = 100 mice), IFN-gamma (1000-10,000 U/day ip) vs saline was given for 3 days prior to harvesting peritoneal macrophages for assay of superoxide anion (O2-), percentage macrophage phagocytosis of C. albicans, and percentage killing of C. albicans. On Day 1, fungal translocation to the intestinal wall and systemic organs in the PCM group was significantly higher. On Day 5, mean CFU were significantly higher in the PCM group, indicating impaired organ clearance. Mean O2-, phagocytosis, and killing were significantly impaired in the PCM group (P less than 0.05), but IFN-gamma improved all functions. PCM significantly depressed host responses to C. albicans. IFN-gamma treatment enhanced candidacidal mechanisms, suggesting a therapeutic role in the malnourished host predisposed to C. albicans sepsis.     

The effect of sodium fluoride on trabecular architecture.

The effect of sodium fluoride therapy on iliac trabecular bone has been studied in 15 patients with primary osteoporosis by comparing bone biopsies taken before and after two years of treatment. A marked increase in bone volume (43%) was observed, which was attributable to an increase in trabecular thickness (46%) rather than their number. Because the trabecular bone surface, the trabecular number, the bone volume/trabecular width ratio, and the trabecular terminus number do not change significantly after fluoride treatment, we conclude that fluoride does not induce the de novo generation of trabeculae, nor does it restore trabecular connectivity despite the restoration of bone mass. These data suggest that the restoration of skeletal mass with fluoride may not lead to a comparable decrease in the risk of future fracture.     

Studies of pickled vegetables and cause of esophageal cancer in Linxian. II. Determination of nitrosamines and their precursors]

Pickled vegetables are daily food consumed in the high-risk areas for esophageal cancer in China. We analyzed the nitrosamine content of Linxian pickles by GC/TEA and found that trace amounts of six nitrosamines (NDMA, NDEA, NMBA, NMAMBA, NDPA, NPYR) were present, with the highest concentrations being NDMA and NDEA (1.7 and 1.9 micrograms/kg wet weight respectively). The average level of nitrosamine precursors, such as nitrate (111.22 mg/L), nitrite (0.152 mg/L) and secondary amines (4.223 mg/L), in pickled vegetables were determined, and their pH values ranged from 3 to 5.