Sinus Of Animals Research Articles

Биохимические показатели крови и их диагностическая эффективность у экспериментальных животных с моделью хронического синусита верхнечелюстной пазухи

Биохимические показатели крови и их диагностическая эффективность у экспериментальных животных с моделью хронического синусита верхнечелюстной пазухи

Direct evidence of a role for Nox2 in superoxide production, reduced nitric oxide bioavailability, and early atherosclerotic plaque formation in ApoE−/−mice

The Nox family NADPH oxidases are reactive oxygen species (ROS)-generating enzymes that are strongly implicated in atherogenesis. However, no studies have examined which Nox isoform(s) are involved. Here we investigated the role of the Nox2-containing NADPH oxidase in atherogenesis in apolipoprotein E-null (ApoE(-/-)) mice. Wild-type (C57Bl6/J), ApoE(-/-), and Nox2(-/y)/ApoE(-/-) mice were maintained on a high-fat (21%) diet from 5 wk of age until they were 12 or 19 wk old. Mice were euthanized and their aortas removed for measurement of Nox2 expression (Western blot analysis and immunohistochemistry), ROS production (L012-enhanced chemiluminescence), nitric oxide (NO) bioavailability (contractions to N(omega)-nitro-L-arginine), and atherosclerotic plaque development along the aorta and in the aortic sinus. Nox2 expression was upregulated in the aortic endothelium of ApoE(-/-) mice before the appearance of lesions, and this was associated with elevated ROS levels. Within developing plaques, macrophages were also a prominent source of Nox2. The absence of Nox2 in Nox2(-/y)/ApoE(-/-) double-knockout mice had minimal effects on plasma lipids or lesion development in the aortic sinus in animals up to 19 wk of age. However, an en face examination of the aorta from the arch to the iliac bifurcation revealed a 50% reduction in lesion area in Nox2(-/y)/ApoE(-/-) versus ApoE(-/-) mice, and this was associated with a marked decrease in aortic ROS production and an increased NO bioavailability. In conclusion, this is the first demonstration of a role for Nox2-NADPH oxidase in vascular ROS production, reduced NO bioavailability, and early lesion development in ApoE(-/-) mice, highlighting this Nox isoform as a potential target for future therapies for atherosclerosis.

Delivery of Doxorubicin to Solid Tumors using Thermosensitive Liposomes

ABSTRACTLiposomes are lipid vesicles with an aqueous interior size between 50 nm and 200 nm in diameter. Liposomal drugs currently in clinical use are characterized primarily by their decreased side effects rather than improved therapeutic potency. Significant improvements in the efficacy of liposomal drug therapy may be obtained using thermosensitive liposomes (TSL) in combination with local hyperthermia (HT). TSL release their content at a specific formulation-dependent gel to liquid-crystalline phase transition temperature. At this temperature the membrane's permeability increases by several orders of magnitude. The purpose of present work was preparation of TSL loaded with doxorubicin (Dox) and investigation of their effect on B-16 mouse melanoma and Ehrlich (line ELD) carcinoma in combination with HT. TSL were prepared using 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, 1,2-distearoyl-sn-glycero-3-phosphocholine, PEGylated 1,2-distearoyl-sn-glycero-3-phosphoethanolamine, cholesterol and α-tocopherol acetate in molar ratios of 9:1:0.02:0.2:0.2 (composition 1); 9:1:0.1:0.5 (composition 2); 9:1:0.2:0.75 (composition 3); 9:1:0.3:1 (composition 4); 9:1:0.4:1.2 (composition 5). The extrusion was performed through 200 nm polycarbonate membranes at 50 °C. Dox was loaded into TSL by ammonium ion gradient. Drug-to-lipid ratio was 0.13:1 (w/w). Dox-TSL were lyophilized for better stabilization with 4 % sucrose added as a cryoprotectant. Vesicle size was measured using Nicomp-380 Submicron Particle Sizer. Dox-TSL were separated from untrapped Dox by gel filtration. In biological experiments tumors were transplanted in the shank muscle of mice. Dox-TSL or free Dox were injected in retroorbital sinus of animals at doses of 9 and 4.5 mg Dox per kg body weight. HT treatment of shank with transplanted tumor was performed at 43 °C for 30 min using water bath. Efficacy of Dox encapsulation in TSL of compositions 4 and 5 was 60 % (diameter of vesicles was 175 ± 10 nm). TSL of compositions 2 and 3 encapsulated 88 % and 86 % of Dox, respectively (diameter of vesicles was 160 ± 10 nm). TSL of composition 1 trapped 88-94 % of Dox (diameter of vesicles was 175 ± 15 nm). The composition 1 has been chosen for preparation of lyophilized drug, which has been assessed in biological experiments. The doubling time of B-16 melanoma was 9 days after heating on a background of Dox injection at dose of 9 mg/kg, while heating of tumors after injection of Dox-TSL at doses of 4.5 and 9 mg/kg increased tumor doubling time up to 12 and 16 days, respectively. The doubling time of Ehrlich carcinoma increased from 3 days in the control group up to 14 days for the group of mice administered 9 mg/kg of Dox-TSL followed by HT in 15-20 min. Encapsulation of Dox in TSL has resulted in decrease of its toxicity as judged by animal survival. Thus, Dox-TSL in combination with HT has shown more efficiency than free Dox in suppression of tumor growth.

Quantitative assessment of aortic atherosclerosis in APOE*3 Leiden transgenic mice and its relationship to serum cholesterol exposure.

Transgenic mice overexpressing the human dysfunctional apolipoprotein E variant, APOE*3 Leiden, develop hyperlipidemia and are highly susceptible to diet-induced atherosclerosis. In the present study, we investigated the effects of diet composition and feeding period on serum cholesterol exposure and the amount of atherosclerosis in the aortic sinus in these mice, using quantitative image analysis. On each of the three diets tested--a low-fat diet, a high-saturated-fat/cholesterol diet, and a high saturated-fat/high-cholesterol/0.5%-cholate diet--transgenic animals showed a marked hyperlipidemia compared with nontransgenic littermates. Measurement of the atherosclerotic lesion areas in cross sections of the aortic sinus in animals exposed to these three diets for up to 6 months showed a 5 to 10 times greater lesion area in transgenic mice compared with nontransgenic controls. Highly significant positive correlations were found between the log-transformed data on lesion area and serum cholesterol exposure (r = .82 to .85 for the 1-, 2-, and 3-month treatment groups), indicating that the hyperlipidemia is likely to be a major determinant in lesion formation. On the basis of these findings, we suggest that the APOE*3 Leiden mouse represents a promising model for intervention studies with hypolipidemic and antiatherosclerotic drugs.

POSTOPERATIVE REPAIR OF THE PARANASAL SINUSES: EXPERIMENTAL STUDIES AND THEIR PRACTICAL APPLICATION

The purpose of this paper is to present experimental data on the reparative processes which follow the radical removal of the mucoperiosteal lining from the paranasal sinuses and their practical application. In the experiments and the radical surgical operations performed on the sinuses of animals and human beings moderate dissolution was produced in the compact and spongy bone preliminary to the complete removal of the mucoperiosteal lining. From the specific facts known 1 about the healing of bone and mucous membrane, it is reasonable to postulate that in the healing of the operative area granulation tissue will spring up to repair the bony defects and the sinuses. The intact periosteum of the anterior wall, the endosteum and the cellular elements of the bared bone will form the so-called callus of the long bones. This type of callus differs from the callus of the long bones in that there is a loss

RELATION OF THE CAROTID SINUS TO THE AUTONOMIC NERVOUS SYSTEM AND THE NEUROSES

Since the pioneer work of Hering 1 in 1926 a mass of experimental data has accumulated concerning the function of the carotid sinus in animals. The significance of the carotid sinus mechanism in man, particularly as regards certain abnormal bodily states, has, however, not been duly appreciated in the United States until recently. One of us (S. W.) and Baker 2 reported the cases of a series of fifteen patients, all of whom complained of attacks of unconsciousness, with or without convulsions, which were caused by a hypersensitive carotid sinus reflex. In a recent publication we 3 reported studies of thirty-two additional patients suffering from syncopal attacks of carotid sinus origin. This syndrome is reflex in nature, and the reflex pathways are parts of the autonomic nervous system. In other reports 4 we presented evidence of the nature of other types of reflex syncope, such as vasovagal, vagovagal and oculocardiac