scholarly journals Action of Deferoxamine againstPneumocystis carinii

2001 ◽  
Vol 45 (12) ◽  
pp. 3560-3565 ◽  
Author(s):  
Allen B. Clarkson ◽  
David Turkel-Parrella ◽  
Jonathan H. Williams ◽  
Lung Chi Chen ◽  
Terry Gordon ◽  
...  
Keyword(s):  
High Pressure ◽  
Animal Model ◽  
Rat Model ◽  
Mode Of Action ◽  
Pneumocystis Carinii ◽  
Irreversible Damage ◽  
Cell Numbers ◽  
Chromatography Analysis ◽  
Calcein Am

ABSTRACT We found earlier that deferoxamine (DFO), a drug used for treatment of iron overload, is active against a rat model of Pneumocystis carinii pneumonia (PCP). We had assumed a mode of action by deprivation of nutritional iron; however, data here show that DFO penetrates P. carinii, causing irreversible damage, thus indicating a different mode of action. Penetration was demonstrated by showing DFO uptake by high-pressure liquid chromatography analysis. By using calcein-AM as an indicator, exposure to DFO was shown to cause a reduction inP. carinii cytoplasmic free iron. Exposure to ≥100 μM DFO for ≥8 h in vitro caused growth to cease and cell numbers to decline over several days. This direct and irreversible damage to P. carinii led to the prediction that infrequent delivery of DFO to the lungs via an aerosol would be an effective treatment in the animal model of PCP. This prediction was confirmed by demonstrating that a once-a-week aerosol treatment of rats was 100% effective both as a prophylactic and as a curative treatment in a rat model of PCP.

scholarly journals Continuous infusion of DL-alpha-difluoromethylornithine and improved efficacy against a rat model of Pneumocystis carinii pneumonia.

1996 ◽  
Vol 40 (10) ◽  
pp. 2318-2320 ◽  
Author(s):  
K Chin ◽  
S Merali ◽  
M Sarić ◽  
A B Clarkson
Keyword(s):  
Drinking Water ◽  
Continuous Infusion ◽  
Rat Model ◽  
Pneumocystis Carinii ◽  
Bolus Administration ◽  
Drug Concentrations ◽  
Water Administration ◽  
Standard Animal

The rapid depletion of Pneumocystis carinii polyamines caused by in vitro exposure to DL-alpha-difluoromethylornithine (DFMO; also called eflornithine or Ornidyl) and the rapid repletion following removal of this drug suggested that the in vivo efficacy of DFMO against P. carinii pneumonia (PCP) may be limited by troughs in drug concentration resulting from the schedule of administration. This led to the prediction that, compared with the response to the standard animal protocol of administering DFMO in drinking water, the response of a rat model of PCP to DFMO would be lessened by bolus administration and improved by continuous infusion. These predictions were confirmed. Intraperitoneal bolus administration of up to 3 g of DFMO kg of body weight-1 was completely ineffective, although this dose has been shown to be effective when given in the drinking water. Conversely, continuous infusion improved the response against PCP seven- to ninefold over the response to drinking water administration. These findings suggest that, compared with the standard clinical investigational protocol for treatment of PCP with DFMO given in four divided daily doses, continuous infusion combined with monitoring of drug concentrations in plasma may improve efficacy and/or reduce the already low rate of adverse effects.

Neurofilaments and Paired Helical Filaments

1985 ◽  
Vol 43 ◽  
pp. 740-743
Author(s):  
J. Metuzals
Keyword(s):  
Animal Model ◽  
Posttranslational Modifications ◽  
Posttranslational Modification ◽  
Giant Axon ◽  
Paired Helical Filaments ◽  
Squid Giant Axon ◽  
In Vitro Experiments ◽  
Thin Sections ◽  
Structural Relationships

It has been demonstrated that the neurofibrillary tangles in biopsies of Alzheimer patients, composed of typical paired helical filaments (PHF), consist also of typical neurofilaments (NF) and 15nm wide filaments. Close structural relationships, and even continuity between NF and PHF, have been observed. In this paper, such relationships are investigated from the standpoint that the PHF are formed through posttranslational modifications of NF. To investigate the validity of the posttranslational modification hypothesis of PHF formation, we have identified in thin sections from frontal lobe biopsies of Alzheimer patients all existing conformations of NF and PHF and ordered these conformations in a hypothetical sequence. However, only experiments with animal model preparations will prove or disprove the validity of the interpretations of static structural observations made on patients. For this purpose, the results of in vitro experiments with the squid giant axon preparations are compared with those obtained from human patients. This approach is essential in discovering etiological factors of Alzheimer's disease and its early diagnosis.

“In vitro” and in Animal Model Studies on a Double Virus- Inactivated Factor VIII Concentrate

1995 ◽  
Vol 74 (03) ◽  
pp. 868-873 ◽  
Author(s):  
Silvana Arrighi ◽  
Roberta Rossi ◽  
Maria Giuseppina Borri ◽  
Vladimir Lesnikov ◽  
Marina Lesnikov ◽  
...  
Keyword(s):  
Heat Treatment ◽  
Animal Model ◽  
Factor Viii ◽  
Hepatitis A ◽  
Hepatitis A Virus ◽  
Virus Inactivation ◽  
Enveloped Viruses ◽  
Model Studies ◽  
Heat Treated

SummaryTo improve the safety of plasma derived factor VIII (FVIII) concentrate, we introduced a final super heat treatment (100° C for 30 min) as additional virus inactivation step applied to a lyophilized, highly purified FVIII concentrate (100 IU/mg of proteins) already virus inactivated using the solvent/detergent (SID) method during the manufacturing process.The efficiency of the super heat treatment was demonstrated in inactivating two non-lipid enveloped viruses (Hepatitis A virus and Poliovirus 1). The loss of FVIII procoagulant activity during the super heat treatment was of about 15%, estimated both by clotting and chromogenic assays. No substantial changes were observed in physical, biochemical and immunological characteristics of the heat treated FVIII concentrate in comparison with those of the FVIII before heat treatment.

High-Pressure Homogenization Alters Physicochemical Properties and In Vitro Digestibility of Chinese Yam (Dioscorea Opposita Thunb.) Starch

2018 ◽  
Vol 18 (1) ◽  
pp. 10-15
Author(s):  
Wang Yi-Wei ◽  
He Yong-Zhao ◽  
An Feng-Ping ◽  
Huang Qun ◽  
Zeng Feng ◽  
...  
Keyword(s):  
High Pressure ◽  
Physicochemical Properties ◽  
Starch Content ◽  
In Vitro Digestibility ◽  
High Pressure Homogenization ◽  
Starch Granules ◽  
Cross Polarization ◽  
Chinese Yam ◽  
Crystal Type

In this study, Chinese yam starch-water suspension (8%) were subjected to high-pressure homogenization (HPH) at 100 MPa for increasing cycle numbers, and its effect of on the physicochemical properties of the starch was investigated. Results of the polarizing microscope observations showed that the starch granules were disrupted (i.e. greater breakdown value) after HPH treatment, followed by a decrease in cross polarization. After three HPH cycles, the crystallinity of starch decreased, while the crystal type remained unaltered. Meanwhile, the contents of rapidly digestible starch and slowly digestible starch were increased. On the contrary, resistant starch content was decreased. Our results indicate that HPH treatment resulted in reduction of starch crystallinity and increase of starch digestibility.

Sign in / Sign up

Export Citation Format

Share Document