Subchronic oral hepatotoxicity of turmeric in mice--histopathological and ultrastructural studies

OBJECTIVE: To analyze the effects of flutamide in patients with physical and/or mental disorders consulting for urinary symptoms secondary to benign prostatic hyperplasia (BPH). METHODS: 50 patients with BPH in whom surgical treatment was contraindicated due to their physical and/or mental condition were treated with flutamide 250 mg/day. Four patients presented with urinary retention and 46 patients had prostatic symptomatology. Patients were evaluated using the symptoms score (I-PSS) and quality of life (QL). Prostate volume was measured by transabdominal US; the maximum flow rate at spontaneous micturition and residual urine were determined. RESULTS: At 12 months, the I-PSS and QL scores decreased by a mean of 7 and 3 points, respectively. The US demonstrated that treatment had reduced prostatic volume by a mean of 10 gms. The maximum flow rate at spontaneous micturition increased 3 ml/sec and residual urine decreased by 15 ml. CONCLUSION: Flutamide is another alternative to surgery in specific patients with BPH.     

Double minutes in the papillary thyroid cancer cell line PTC-1113A

A light microscopy system has been designed for freezing and lyophilization studies of protein pharmaceuticals. The system consists of a cascade of four Peltier thermoelectric modules in the lyophilization cell to freeze samples to -60 degrees C, controllers to regulate temperature and pressure conditions, and a video camera to record the events under study. Specific demonstration of the system was conducted using recombinant CD4-IgG and human growth hormone (hGH) as model proteins. Observations of recrystallization during warming of frozen CD4-IgG solution and lyophilization of hGH solution are discussed. These examples demonstrate that the system is a useful tool for the fundamental understanding of freezing and lyophilization of protein pharmaceuticals.     

Suprasellar osteolipoma: case report

BACKGROUND: Osteolipomas are distinguished from other intracranial lipomas by their arrangement of central adipose and peripheral osseous tissues and by characteristically arising in the suprasellar/interpeduncular region. METHODS: We report computed tomography (CT), magnetic resonance imaging (MRI), and pathology findings from this 34-year-old man who underwent surgical removal of this benign lesion. RESULTS: This case displays the distinctive histopathology that has been reported in 13 of 31 (42%) lipomas in this region. In contrast, ossification of lipomas at other intracranial sites is relatively rare. CONCLUSIONS: Ossification should be expected in many suprasellar/interpeduncular lipomas, and osteolipoma should be included in the radiologic differential diagnosis of fat-intensity masses with calcification in this region.     

Effects of interleukin-2 on bone resorption and natural immunity in osteopetrotic (ia) rats

Cells of the immune system and the cytokines they produce have been shown to function in the regulation of bone turnover. Incisors absent (ia) osteopetrotic rats demonstrate defects in natural immunity and bone resorption, even though they have excess numbers of both natural killer (NK) cells and osteoclasts. In an attempt to correct these defects, mutant (ia) and normal rats were infused with 3 x 10(4)U recombinant interleukin-2 (rIL-2)/day for 14 days using osmotic minipumps. The effects of IL-2 on natural immune function and bone resorption were evaluated after the infusion period. The percentage of NK cells in the spleen after treatment was quantitated by phenotypic analysis using monoclonal antibodies and flow cytometry. The elevated levels of NK cells normally seen in ia mutants were reduced to normal in the IL-2-infused rats. NK cell activity was evaluated by the 51Cr release assay and found to be enhanced to normal killing levels in the IL-2-treated mutants. The defects in NK function are corrected by IL-2 therapy. Likewise, the bone resorption defect appears to be corrected by the IL-2 infusions. The bone marrow cavity size was significantly increased in the IL-2-treated mutants compared with control mutants. Additionally, the percentage of osteoclasts exhibiting normal morphology was significantly increased in the IL-2-treated mutants. The bone density of the caudal vertebrae, evaluated by gray-scale analysis of x-rays, was found to be reduced in the IL-2-treated mutants. Interleukin-2 corrects both the bone resorption and natural immune defects in the ia mutation.     

Neutrophil adhesion to histamine stimulated cultured endothelial cells is primarily mediated via activation of phospholipase C and nitric oxide synthase isozymes

OBJECTIVE AND DESIGN: In order to understand the underlying mechanism of histamine stimulated inflammatory responses, histamine receptor subtypes and signal transduction pathways by which histamine mediates the stimulation of neutrophil adhesion to endothelial cells has been studied in vitro. MATERIAL: Human neutrophils and human umbilical vein endothelial cells. TREATMENT: Confluent human endothelial cell layer were incubated with histamine (1 mM), H1, H2 or H3 receptor agonists: fluorophenylhistamine (10 microM), amthamine (10 microm), methylhistamine (10 microM), respectively. Ten minutes prior to histamine (1 mM) stimulation H1, H2 or H3 receptor antagonists (dimethindene, 100 microM; famotidine, 1OO microM, thioperamid 100 microM, respectively) were added. Histamine stimulated signal transduction pathways were inhibited by adding phospholipase C inhibitor 2-nitro-4-carboxyphenyl N,N-diphenylcarbamat (200 microM), adenylate cyclase inhibitor 9-(2 tetrahydrofuryl)adenine (80 microM), nitric oxide synthase isozymes inhibitor S-ethylisothiourea (1 microM) or guanylate cyclase inhibitor (LY 83583; 10 microM). Neutrophil adhesion was monitored at 30, 60, 90, 120, 150, 180 and 210 min. METHODS: Neutrophil adhesion to endothelial cells was quantified by analysing alkaline phosphatase activity. RESULTS: Histamine stimulation of endothelial cells resulted in a biphasic time and concentration dependent pattern of neutrophil adhesion. This pattern of neutrophil adhesion was mimicked by stimulation of endothelial cells with H1 or H2 agonists. Stimulation of endothelial cells with an H3 agonist had no effect on neutrophil binding. Inhibition of phospholipase C (PLC), nitric oxide synthase isozymes (NOS) or guanylate cyclase (GC) resulted in a significant decrease of neutrophil binding to histamine or agonist stimulated endothelial cells. An increase of neutrophil binding to unstimulated or to agonist stimulated endothelial cells was observed during inhibition of adenylate cyclase. CONCLUSIONS: Our results suggest that histamine stimulated neutrophil adhesion is due to H1 and H2 receptor mediated activation of PLC, NOS and GC. Increase of cAMP concentration seems to mediate an inhibitory effect on PMN adhesion to endothelial cells.     

Effect of nitrogen dioxide and other combustion products on asthmatic subjects in a home-like environment

Nitrogen dioxide (NO2) is one of a number of nitrogen compounds that are by-products of combustion and occur in domestic environments following the use of gas or other fuels for heating and cooking. In this study, we examined the effect of two levels of NO2 on symptoms, lung function and airway hyperresponsiveness (AHR) in asthmatic adults and children. In addition, in the same subjects, we examined the effects of the same levels of NO2 mixed with combustion by-products from a gas space heater. The subjects were nine adults, aged 19-65 yrs, and 11 children, aged 7-15 yrs, with diagnosed asthma which was severe enough to require daily medication. All subjects had demonstrable AHR to histamine. Exposures were for 1 h on five separate occasions, 1 week apart, to: 1) ambient air, drawn from outside the building; 2) 0.3 parts per million (ppm) NO2 in ambient air; 3) 0.6 ppm NO2 in ambient air; 4) ambient air+combustion by-products+NO2 to give a total of 0.3 ppm; and 5) ambient air+combustion by-products+NO2 to give a total of 0.6 ppm. Effects were measured as changes in lung function and symptoms during and 1 h after exposure, in AHR 1 h and 1 week after exposure, and in lung function and symptoms during the week following exposure. Exposure to NO2 either in ambient air or mixed with combustion by-products from a gas heater, had no significant effect on symptoms or lung function in adults or in children. There was a small, but statistically significant, increase in AHR after exposure to 0.6 ppm NO2 in ambient air. However, there was no effect of 0.6 ppm NO2 on AHR when the combustion by-products were included in the test atmosphere nor of 0.3 ppm NO2 under either exposure condition. We conclude that a 1 h exposure to 0.3 or 0.6 ppm NO2 has no clinically important effect on the airways of asthmatic adults or children, but that 0.6 ppm may cause a slight increase in airway hyperresponsiveness.