Application of high performance capillary electrophoresis on toxic alkaloids analysis.

We employed CE to identify mixtures of the toxic alkaloids lappaconitine, bullatine A, atropine sulfate, atropine methobromide, scopolamine hydrobromide, anisodamine hydrobromide, brucine, strychnine, quinine sulfate, and chloroquine in human blood and urine, using procaine hydrochloride as an internal standard. The separation employed a fused-silica capillary of 75 microm id x 60 cm length (effective length: 50.2 cm) and a buffer containing 100 mM phosphate and 5% ACN (pH 4.0). The sample was injected in a pressure mode and the separation was performed at a voltage of 16 kV and a temperature of 25 degrees C. The compounds were detected by UV absorbance at wavelengths of 195 and 235 nm. All the ten alkaloids were separated within 16 min. The method was validated with regard to precision (RSD), accuracy, sensitivity, linear range, LOD, and LOQ. In blood and urine samples, the detection limits were 5-40 ng/mL and linear calibration curves were obtained over the range of 0.02-10 microg/mL. The precision of intra- and interday measurements was less than 15%. Electrophoretic peaks could be identified either by the relative migration time or by their UV spectrum.

[The possible role of presynaptic effects in realizing the protective action of M-cholinolytics in dimethyl dichlorovinyl phosphate poisoning]. / Vozmozhnaia rol' presinapticheskikh éffektov v osushchestvlenii zashchitnogo deistviia M-kholinolitikov pri otravlenii dimetildikhlorvinilfosfatom.

Under the conditions of the constancy of the postsynaptic effect of two M-cholinolytics atropine and amizil the relationship between the presynaptic and protective effects of the drugs in DDVF intoxication was studied. The indication of the level of the postsynaptic activity was the suppression by the cholinolytics of tremor reaction in rats induced by the action of arecoline. The presynaptic effect of the drugs was judged by the charge of the "bound" acetylcholine content in the brains of the animals. It was found that when administered in the equieffective by the choline-blocking activity doses, atropine to a greater extent reduced the content of the "bound" acetylcholine which was increased due to the action of DDVF and at the same time it possessed the less pronounced protective activity in intoxication with DDVF than amizil. It is supposed that the removal of the presynaptic suppression of acetylcholine release due to the anticholinesterase substance action deteriorates the prognosis of the course of DDVF intoxication.

The effect of nebulized bronchodilator therapy on intraocular pressures in patients with glaucoma.

A controlled double-blind crossover study of ocular complications associated with nebulized ipratropium bromide and salbutamol therapy for respiratory distress was undertaken in 46 chronic bronchitis patients. There was no significant rise in intraocular pressure or change in anterior chamber angle in patients with open-angle glaucoma, narrow-angle glaucoma or control subjects following treatment with either drug. However, when the two drugs were used in combination, intraocular pressure rose in patients with narrow-angle glaucoma but not in patients with open-angle glaucoma or in control subjects. Transient angle closure was seen in five of these patients. Intraocular pressures did not rise when swimming goggles were used to protect the eyes or when antiglaucoma treatment was continued. Nebulized bronchodilator therapy is safe in nonglaucomatous patients and those with open-angle glaucoma. Ocular complications can follow combined ipratropium bromide and salbutamol nebulization in patients with narrow-angle glaucoma, but can be prevented by using the drugs separately, protecting the eyes and ensuring continued antiglaucoma measures.

Changes in blood-brain barrier permeability to drugs in decompressed rats.

A study has been made of changes in permeability of the blood-brain barrier (BBB) to drugs following exposure to compression-decompression. Fifty-five rats were exposed to 6.1 b (abs) air for 90 min and subsequently linearly decompressed to the ambient pressure during a period of 3 min. Thirty-five rats serving as controls were kept at the ambient pressure. Catalepsy, which is mediated through the striatal dopamine receptors, was used as a behavioral indicator for the penetration of drugs into the brain. A comparison was made between drugs that normally pass the BBB (atropine, 10 mg/kg; haloperidol, 2 mg/kg) and drugs that do not readily pass the BBB as a rule (methylatropine, 10 mg/kg; domperidone, 10-20 mg/kg). Evans blue, injected intravenously, was used for the visualization of possible changes in the BBB permeability. It was found that methylatropine significantly prevented haloperidol-induced catalepsy in decompressed rats, in comparison with control rats. However, this prevention was not so intense as that found after injection of a similar dose of atropine. Domperidone induced a weak catalepsy in decompressed rats, but failed to induce any catalepsy in control rats. Gross and fluorescence-microscopic examination revealed an increased penetration of Evans blue into the brains of the decompressed rats. It is concluded that compression-decompression exposure can induce a limited but significant breakage of the BBB, leading to an increase in the central effects of the drugs that normally display poor penetration of the BBB. The measurement of behavioral changes provided a new and relevant technique for studying the changes of BBB permeability to drugs.