scholarly journals A conjugate of pyridine-4-aldoxime and atropine as a potential antidote against organophosphorus compounds poisoning.

2011 ◽  
Vol 58 (2) ◽  
Author(s):  
Jasna Lovrić ◽  
Suzana Berend ◽  
Ana Lucić Vrdoljak ◽  
Božica Radić ◽  
Maja Katalinić ◽  
...  
Keyword(s):  
Therapeutic Effect ◽  
Organophosphorus Compounds ◽  
Human Lymphocytes ◽  
Human Erythrocytes ◽  
Antidotal Activity

A conjugate of pyridine-4-aldoxime and atropine (ATR-4-OX) was synthesized and its antidotal efficiency was tested in vitro on tabun- or paraoxon-inhibited acetylcholinesterase (AChE) of human erythrocytes as well as in vivo using soman-, tabun- or paraoxon-poisoned mice. Its genotoxic profile was assessed on human lymphocytes in vitro and was found acceptable for further research. ATR-4-OX showed very weak antidotal activity, inadequate for soman or tabun poisoning. Conversely, it was effective against paraoxon poisoning both in vitro and in vivo. All animals treated with 5 % or 25 % LD(50) doses of the new oxime survived after administration of 10.0 or 16.0 LD(50) doses of paraoxon, respectively. Based on the persistence of toxicity symptoms in mice, the atropine moiety had questionable effects in attenuating such symptoms. It appears that ATR-4-OX has a therapeutic effect related to the reactivation of phosphylated AChE, but not to receptor antagonization.

A Sensitive Method for Assay of Mixed-Function Oxygenase (p-450 complex) in Cell Culture

1988 ◽  
Vol 15 (3) ◽  
pp. 219-223
Author(s):  
Jørgen Clausen ◽  
Søren Achim Nielsen
Keyword(s):  
Human Lymphocytes ◽  
Cellular Systems ◽  
Metabolic Effects ◽  
Assay Method ◽  
Related Family ◽  
Oxygenase Activity ◽  
Metabolic Transformation ◽  
Mixed Function Oxygenase

The mixed-function oxygenase system involved in the metabolism of drugs and xenobiotics has been extensively studied in various animal species and in various organs (1). It is now apparent that in humans the p-450 complex is one representative of a related family, expressed by 13 c-DNA genes showing approximately 36% similarity between the different subfamilies (2). In order to compare the in vivo and in vitro metabolic effects of drugs and xenobiotics, the induction capabilities of the mixed-function oxygenase must be known. The most sensitive non-isotopic assay system for determination of mixed-function oxygenase activity is the method of Nebert & Gelboin (3,4), which is based on the metabolic transformation of benzo-(a)-pyrene to its fluorescent hydroxyl derivatives (5). However, the levels of the mixed-function oxygenase enzymes in different cellular systems show great variations, with the highest activities in liver cells. Therefore, in order to use human lymphocytes and other cellular systems with low mixed-function oxygenase activities, the assay method for determining oxygenase activity must have the highest possible sensitivity. The present communication is devoted to a study aimed at increasing the sensitivity of Nebert & Gelboin's methods for assay of mixed-function oxygenase subfamilies using benzo-(a)-pyrene as a substrate.

scholarly journals Pharmacological comparison of four biopolymeric natural gums as hemostatic agents for management of bleeding wounds: preliminary in vitro and in vivo results

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Himanshu Kushwah ◽  
Nidhi Sandal ◽  
Meenakshi Chauhan ◽  
Gaurav Mittal
Keyword(s):  
Xanthan Gum ◽  
Guar Gum ◽  
Human Lymphocytes ◽  
Sprague Dawley ◽  
Gum Tragacanth ◽  
Civilian Trauma ◽  
Sprague Dawley Rats ◽  
Cytotoxicity Studies

Abstract Background Uncontrolled bleeding is one of the primary reasons for preventable death in both civilian trauma and military battle field. This study evaluates in vitro and in vivo hemostatic potential of four biopolymeric natural gums, namely, gum tragacanth, guar gum, xanthan gum, and gum acacia. In vitro evaluation of whole blood clotting time and erythrocyte agglutination assay were carried out. In vitro cytotoxicity studies with respect to each gum were done in human lymphocytes to ascertain percent cell viability. In vivo hemostatic potential of each gum (as sponge dressing and powder form) was evaluated in Sprague Dawley rats using tail bleeding assay and compared with commercially available hemostatic sponge. Other important parameters like (a) time taken for complete hemostasis, (b) amount of blood absorbed, (c) adherence strength of developed hemostatic dressing(s), (d) incidence of re-bleeding, and (e) survival of animals were also studied. Results Of the four test gums studied, xanthan gum (@3mg/ml of blood) and gum tragacanth (@35mg/ml of blood) were able to clot blood in least time (58.75±6.408 s and 59.00±2.082 s, respectively) and exhibited very good hemostatic potential in vitro. Except for xanthan gum, all other test gums did not exhibit any significant cytotoxicity at different time points till 24 h. In rat tail bleeding experiments, gum tragacanth sponge dressing and powder achieved hemostasis in least time (156.2±12.86 s and 76±12.55 s, respectively) and much earlier than commercially available product (333.3±38.84 s; p˂0.01). Conclusion Results indicate potential of gum tragacanth to be developed into a suitable hemostatic product.

scholarly journals Surface-Engineered Dendrimeric Nanoconjugates for Macrophage-Targeted Delivery of Amphotericin B: Formulation Development andIn VitroandIn VivoEvaluation

2015 ◽  
Vol 59 (5) ◽  
pp. 2479-2487 ◽  
Author(s):  
Keerti Jain ◽  
Ashwni Kumar Verma ◽  
Prabhat Ranjan Mishra ◽  
Narendra Kumar Jain
Keyword(s):  
Drug Release ◽  
Amphotericin B ◽  
Human Erythrocytes ◽  
Antileishmanial Activity ◽  
Cell Uptake ◽  
Antiparasitic Activity ◽  
Content Type ◽  
Drug Localization

ABSTRACTThe present study aimed to develop an optimized dendrimeric delivery system for amphotericin B (AmB). Fifth-generation (5.0G) poly(propylene imine) (PPI) dendrimers were synthesized, conjugated with mannose, and characterized by use of various analytical techniques, including Fourier transform infrared spectroscopy (FTIR),1H nuclear magnetic resonance (1H-NMR) spectroscopic analysis, and atomic force microscopy (AFM). Mannose-conjugated 5.0G PPI (MPPI) dendrimers were loaded with AmB and evaluated for drug loading efficiency,in vitrodrug release profile, stability, hemolytic toxicity to human erythrocytes, cytotoxicity to and cell uptake by J774A.1 macrophage cells, antiparasitic activity against intracellularLeishmania donovaniamastigotes,in vivopharmacokinetic and biodistribution profiles, drug localization index, toxicity, and antileishmanial activity. AFM showed the nanometric size of the MPPI dendrimers, with a nearly globular architecture. The conjugate showed a good entrapment efficiency for AmB, along with pH-sensitive drug release. Highly significant reductions in toxicity toward human erythrocytes and macrophage cells, without compromising the antiparasitic activity of AmB, were observed. The dendrimeric formulation of AmB showed a significant enhancement of the parasiticidal activity of AmB toward intramacrophagicL. donovaniamastigotes. In thein vitrocell uptake studies, the formulation showed selectivity toward macrophages, with significant intracellular uptake. Further pharmacokinetic and organ distribution studies elucidated the controlled delivery behavior of the formulation. The drug localization index was found to increase significantly in macrophage-rich organs.In vivostudies showed a biocompatible behavior of MPPIA, with negligible toxicity even at higher doses, and promising antileishmanial activity. From the results, we concluded that surface-engineered dendrimers may serve as optimized delivery vehicles for AmB with enhanced activity and low or negligible toxicity.

Tat-BMPs-PAMAM Conjugates Enhance Therapeutic Effect of Small Interference RNA on U251 Glioma Cells In Vitro and In Vivo

2010 ◽  
Vol 21 (4) ◽  
pp. 417-426 ◽  
Author(s):  
Lei Han ◽  
Anling Zhang ◽  
Hanjie Wang ◽  
Peiyu Pu ◽  
Xinguo Jiang ◽  
...  
Keyword(s):  
Therapeutic Effect ◽  
Glioma Cells ◽  
Small Interference Rna ◽  
Interference Rna

scholarly journals Antigenicity of the infected-erythrocyte and merozoite surfaces in Falciparum malaria.

1979 ◽  
Vol 150 (5) ◽  
pp. 1241-1254 ◽  
Author(s):  
S G Langreth ◽  
R T Reese
Keyword(s):  
Plasmodium Falciparum ◽  
Falciparum Malaria ◽  
Infected Erythrocyte ◽  
Falciparum Infection ◽  
Human Erythrocytes ◽  
Cross Linking ◽  
Common Antigens

The antigenicity of altered structures induced by Plasmodium falciparum in the membranes of infected Aotus monkey and human erythrocytes was examined. Antisera were obtained from monkeys made immune to malaria. Bound antibodies were shown to be localized on the knob protrusions of infected erythrocytes of both human and monkey origin and from both in vitro and in vivo infections. Therefore, P. falciparum infection has produced similar antigenic changes in the erythrocyte surfaces of both man and monkey. Uninfected erythrocytes and all knobless-infected erythrocytes bound no antibody from immune sera. Strains of P. falciparum from widely different geographic areas that were cultured in vitro in human erythrocytes induced structures (knobs) which have common antigenicity. Merozoites were agglutinated by cross-linking of their cell coats when incubated with immune sera. The binding of ferritin-labeled antibody was heavy on the coats of both homologous and heterologous strains of the parasite, indicating that the merozoite surfaces of these strains share common antigens.

In vitro and in vivo acetylcholinesterase-inhibiting effect of new classes of organophosphorus compounds

1999 ◽  
Vol 18 (2) ◽  
pp. 241-246 ◽  
Author(s):  
Murat Ozmen ◽  
Sadiye Sener ◽  
Ahmet Mete ◽  
Hasan Kucukbay
Keyword(s):  
Organophosphorus Compounds ◽  
Inhibiting Effect

Age-dependent changes in volume and haemoglobin content of erythrocytes in the carp (Cyprinus carpio L.)

1989 ◽  
Vol 141 (1) ◽  
pp. 133-149 ◽  
Author(s):  
W. Speckner ◽  
J. F. Schindler ◽  
C. Albers
Keyword(s):  
Gel Filtration ◽  
Linear Increase ◽  
Human Erythrocytes ◽  
Main Peak ◽  
Red Cell ◽  
Human Haemoglobin ◽  
Cell Fractions ◽  
Haemoglobin Content

Carp erythrocytes were fractionated by angle-head centrifugation which yielded fractions with a linear increase in density. Haematological examinations revealed that the heavier red blood cells of carp had greater volumes (MCV), more haemoglobin (MCH) and higher haemoglobin concentrations (MCHC) than light ones. The same experiments with human red cell fractions yielded a decrease in MCV, constant MCH and an increase in MCHC. Haemoglobin content in individual erythrocytes was also determined by scanning stage absorbance cytophotometry to establish the frequency distribution of the cellular haemoglobin contents. In carp, the distribution was symmetrical with the means increasing with density. No such change with cell density was found in human erythrocytes. Both carp and human erythrocytes incorporated [2-14C]glycine in vitro. After gel filtration, radioactivity was detected in carp, but not in human, haemoglobin fractions. 14C was found in all three haemoglobin fractions, obtained by isoelectric focusing, and was present in the haem and in the globin. [2-14C]glycine-labelled erythrocytes were reinjected into chronically cannulated carp and followed in vivo for several months. With time, the main peak of scintillation counts shifted from red cell fractions of low to high density. This is considered as evidence that density and age of red cells in carp are positively correlated and that erythrocytes can synthesize haemoglobin while circulating in the peripheral blood.

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