Studies on the course and therapy of the immunological and the nonspecific iridocyclitis in rabbits

The immune and carrageenin-induced models of iridocyclitis were elaborated. Characteristics of the dynamics and kinetics of the studied inflammatory processes were conducted on the basis of biochemical indices and of biomicroscopic observations of the anterior chamber of the eye. Evaluation of usefulness of the elaborated models of the uveitis for characterization of the therapeutic effectiveness of the drugs was based on the known antiinflammatory drugs.     

Role of endothelin-1 in carrageenin-induced inflammation.

Many vasal factors are produced during an experimental model of inflammation such as rat-paw oedema induced by carrageenin. We investigated whether among the other well-known mediators of inflammation, i.e. serotonin, PAF, eicosanoids and kinins, the peptide endothelin-1 is produced by this kind of inflammatory process caused by carrageenin. Our results indicated that plasma endothelin, and the tissue concentration of endothelin in the oedematous paw, is increased as compared to the control. Consequently, endothelin should also be considered as an important factor in inflammatory processes.     

The course of airborne infection in rabbits infected with the Venezuelan encephalomyelitis virus]

The experimental data on aerosol challenge of rabbits with Venezuelan equine encephalomyelitis (VEE) virus are presented. Lethal infection of rabbits was followed by a rise in body temperature (greater than 0.5 degrees C) within 1-2 days after challenge. Two waves of lethality in aerosol infection experiments were recorded. Three variants of the infection outcome were observed after VEE virus aerosol challenge of rabbits. The causes of death of the infected rabbits are discussed.     

The effect of plantain (Plantago major) on the course of experimental atherosclerosis in rabbits

Summary Experiments were performed on 50 rabbits. A possibility was established of preventing the experimental hypercholesteremia by the introduction of Plantago major leaves into the diet of experimental animals. Control group of rabbits received cholesterol alone. The content of blood cholesterol ranged in them from 350 to 785 mg percent. Lipoidosis of aorta was marked in the majority of the cases. In the experimental groups rabbits were given leaves of extract of Plantago major in addition to cholesterol. An inhibition in the development of hypercholesteremia and atherosclerosis was noted (see Table 1). By the third month of experiment blood cholesterol content in the majority of the experimental animals dropped to the initial level.(Presented by Active Member AMN SSSR V. V. Parin) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 53, No. 4, pp. 50–53, April, 1962     

Nitric oxide inhibits leucocyte migration in carrageenin-induced rat pleurisy

OBJECTIVE AND DESIGN: The role of nitric oxide (NO) on leucocyte migration has been investigated in rat carrageenin-induced pleurisy. MATERIAL: Male Wistar rats. TREATMENT: L-arginine, NOC-18 and aminoguanidine were administered subcutaneously 1 h prior to carrageenin injection. METHODS: Leucocyte accumulation into the pleural cavity was measured 4 h after carrageenin challenge. Statistical significance was calculated by Bonferroni test. RESULTS: L-arginine (10 mg/kg) or the NO donor NOC-18 (10 mg/kg), significantly inhibited leucocyte infiltration by 31% and 20% respectively (P<0.01). On the contrary, when these compounds were given at high doses (L-arginine 300 mg/kg; NOC-18 30 mg/kg), leucocyte accumulation was increased by 22% and 33% respectively (P<0.01). Aminoguanidine, a relatively selective inhibitor of the inducible NO synthase, depending on the dose, showed a biphasic effect on cell migration. Thus, at low doses (30 and 100 mg/kg), aminoguanidine increased (by 40% and 74% respectively, P< 0.01) leucocyte infiltration which was inhibited by 41% (P < 0.01) when the drug was given at high dose (300 mg/kg). CONCLUSIONS: These results suggest that in rat carrageenin-induced pleurisy NO primarily inhibits leucocyte migration.     

Effect of immunosuppressive agents on the course of experimental syphilis in rabbits.

Rabbits infected intradermally with T. pallidum at four sites on the clipped back were treated with cyclophosphamide, 1 mg/kg body weight, twice before and every two days after inoculation for five months, or 5-fluorouracil 2.5 mg/kg body weight, according to the same regimen. Humoral response, as measured repeatedly by VDRL, FTA, and hemagglutination tests, was not affected by the application of the immunosuppressors. In contrast, the cell-mediated response, as determined by the Macrophage Migration Inhibition test was completely abolished in the treated rabbits. In the group of rabbits which were given immunosuppressors, syphilitic lesions appeared not only at the challenge sites, as usual, but also multiple multiform lesions developed over the entire dorsum after healing of the primary lesions. Taking into account the fact that abolishment of the cell-mediated response led to an aggravated course of the syphilitic infection, the results of these experiments were interpreted as indicating the protective role of the cell mediated response in syphilis.     

Cholesterol fatty kidney: Morphological changes in the course of its development in rabbits

Kidneys from 90 rabbits were examined by light microscopy after an experiment designed to assess the possible relation between the cholesterol content of various tissues and two other factors: the serum cholesterol level and duration of hypercholesteremia. An additional eight rabbits were fed a 2% cholesterol diet for various periods up to 90 days. These kidney tissues were examined under electron microscope after aldehyde fixation with 0.2% digitonin. Digitonin-induced laminar and microtubular structures appeared in the capillary lumen and endothelia 5 hr after cholesterol feeding. Subsequently, similar structures appeared in the glomerular visceral epithelia and tubular epithelia. Fat vacuoles were usually not observed by light microscopy because of their small size and number. The interstitial cells in the medulla were sensitive to hypercholesteremia and were transformed into foam cells. As these grew in number, fatty streaks appeared and extended from the subcortical zone toward pyramidal papilla. The glomerular mesangial cells also took up cholesterol, but only after prolonged exposure to extreme hyperlipidemia, they formed glomerular micro-xanthomas.     

Effect of intraarticular injections of emoxypine on the course of immunogenic arthritis in rabbits

Institute of Rheumatology, Russian Academy of Medical Sciences, Moscow. (Presented by Academician of the Russian Academy of Medical Sciences V. A. Nasonova.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 114, No. 10, pp. 393–395, October, 1992.     

Acid-stable protease inhibitor in chronic phase of carrageenin-induced inflammation in rats

The activity and kinetics of acid-stable protease inhibitor (ASPI) were investigated in the chroric phase of carrageenin-induced inflammation in rats. The ASPI activity was 19.6+3.1 units/ml in the plasma and 15.4+2.1 units/ml in the inflammatory exudate. The plasma value was significantly higher than that of the control (11.6+1.3 units/ml). A kinetics study was performed using purified and radiolabeled rat plasma ASPI, whose NH₂-terminal amino acid sequence was Ala-Val-Leu-Pro-Gln-Glu-Asn-Glu-Gly-X-Gly-Ser-Glu-Pro-Leu-Ile-Thr-Gly-Thr-Leu-Lys-Lys-Glu-Asp-Ser-Asn-Gln-Leu-Lys-Tyr-Ser-Glu-Gly-Pro. The half-life of the distributive phase was 4.3+0.4 min and that of the postdistributive phase (biological half-life) was 42.2+9.2 min in inflammation. There was no significant difference compared with the values in the control (3.9+0.4 min and 40.7+6.5 min, respectively). It appeared that the increase in ASPI in inflammation was not due to prolonged excretion of the inhibitor but to an increased production of it, and ASPI was rapidly distributed to the fluids and tissues.     

Production of pyrogen by polymorphonuclear leukocytes during the course of casein-induced peritonitis in rabbits

Rabbits with casein-induced peritonitis were febrile only during the early stage (1.5 to 12 hours) of inflammation. At that stage, peritoneal exudate cells (PEC) had preformed endogenous pyrogen (EP), while blood leukocytes and leukocytes obtained at the later stage of the inflammatory process did not. Early PEC consisted of 99% polymorphonuclear leukocytes (PMN). As early PEC and highly purified PMN (almost 100% pure) released almost identical amounts of EP, we concluded that PMN were the EP-producing cells in the early PEC. EP from PMN of rabbits was composed of three factors with similar molecular weight (8,000 to 18,000) but different pI values (pI 7.2, 5.4, and 4.5). EP in the three fractions could not be separated from thymocyte comitogenic factor (TMF) in terms of m.w. and pI values. About 60% of EP activity and 92% of TMF activity in the culture supernatant were present in the pI 7.2 fraction. The pI 7.2 factor was weaker in EP activity and stronger in TMF activity than the other acidic fractions (pI 5.4 and 4.5). After high purification, 42 ng of the pI 7.2 factor had one unit of EP activity: one unit of TMF activity was present in 126 pg of highly purified pI 7.2 factor.     

Studies on the experimental therapy of iridocyclitis.

Effectiveness of selected anti-inflammatory drugs on the experimental model of uveitis was evaluated. Studies on the biochemical parameters of inflammation in the aqueous humor and biomicroscopic evaluation of the clinical condition of the anterior chamber of the eye, carried out in the therapy course, allowed to establish the following order of the studied drugs, according to their therapeutical effectiveness (from the most effective): indomethacin greater than ibuprofen greater than hydrocortizone greater than 6-mercaptopurine.     

Cholesterol fatty liver. Morphological changes in the course of its development in rabbits.

Livers from 90 rabbits used in a factorial experiment relating cholesterol contents of various tissues to their serum cholesterol levels and duration of exposure were observed under light microscope. Livers from eight additional rabbits fed a 2% cholesterol diet for various periods up to 90 days were fixed in an aldehyde fixative containing 0.2% digitonin and observed under electron microscope. Digitonin-induced laminar and microtubular structures appeared five hours after cholesterol feeding. Fat vacuoles in both hepatocytes and Kupffer cells were first noted on the third day and increased in number and size to the 60th day but decreased on the 90th day. Adaptation of the liver to such excessive fat accumulation was evidenced by the gradual decrease of fat vacuoles and increase of binucleated cells.