Tubulointerstitial nephritis induced by Tamm-Horsfall protein sensitization in guinea pigs

Experimental tubulointerstitial nephritis (TIN) was induced in guinea pigs by immunization with homologous Tamm-Horsfall protein (THP). This disease was characterized by focal interstitial mononuclear cell infiltration around the distal nephron segments with degeneration of renal tubular cells. Although concomitant granular immunoglobulin deposition on the tubular basement membrane and a rise of serum anti-THP antibodies were recognized, they were related to the severity of the lesion. Lymphocytes from lymph nodes of animals with TIN showed blast transformation in the presence of THP in vitro. Following the transfer of lymphocytes and spleen cells from guinea pigs with THP-induced TIN to nonimmunized animals, the recipient animals developed TIN 7 days later. These observations suggest that TIN induced in guinea pigs by challenge with homologous THP may, at least in part, be related to a cell-mediated immune response.     

A gamma Bence-Jones protein in guinea pigs.

1. The L2C lymphocytic leukaemia in strain-2 guinea pigs is accompanied by a protein in the urine resembling a homogenous immunoglobulin light chain. 2. The amino acid sequence over the first 20 residues demonstrates a close analogy with a human gamma chain of V region subgroup IV. 3. The protein is apparently synthesized by the leukaemic cells and thus represents a monoclonal light chain, i.e. a Bence-Jones protein.     

Elevating dietary salt exacerbates hyperpnea-induced airway obstruction in guinea pigs.

Previous studies have indicated that increased dietary salt consumption worsens postexercise pulmonary function in humans with exercise-induced asthma (EIA). It has been suggested that EIA and hyperpnea-induced airway obstruction (HIAO) in guinea pigs (an animal model of EIA) are mediated by similar mechanisms. Therefore, the purpose of this study was to determine whether altering dietary salt consumption also exacerbated HIAO in guinea pigs. Furthermore, the potential pathway of action of dietary salt was investigated by blocking leukotriene (LT) production during HIAO in guinea pigs. Thirty-two male Hartley strain guinea pigs were split into two groups. One group (n = 16) of animals ingested a normal-salt diet (NSD) for 2 wk; the other group (n = 16) ingested a high-salt diet (HSD) for 2 wk. Thereafter, animals were anesthetized, cannulated, tracheotomized, and mechanically ventilated during a baseline period and during two dry gas hyperpnea challenges. After the first challenge, the animals were administered either saline or nordihydroguaiaretic acid, a LT inhibitor. Bladder urine was analyzed for electrolyte concentrations and urinary LTE(4). The HSD elicited higher airway inspiratory pressures (Ptr) than the NSD (P < 0.001) postchallenge. However, after infusion of the LT inhibitor and a second hyperpnea challenge, HIAO was blocked in both diet groups (P < 0.001). Nonetheless, the HSD group continued to demonstrate slightly higher Ptr than the NSD group (P < 0.05). Urinary LTE(4) excretion significantly increased in the HSD group compared with the NSD group within treatment groups. This study has demonstrated that dietary salt loading exacerbated the development of HIAO in guinea pigs and that LT release was involved in HIAO and may be moderated by changes in dietary salt loading.     

Inhibition of inducible nitric oxide synthase lowers the cochlear damage by lipopolysaccharide in guinea pigs

Endotoxin-treated cochleas of the guinea pig were examined electrophysiologically and immunohistochemically concerning the expression of inducible nitric oxide synthase (iNOS/NOS II). One mg of bacterial lipopolysaccharide (LPS, 5 mg/ml) or mixed solution of 1 mg of LPS plus 1 mg of N^G-nitro-L-arginine methyl ester (L-NAME, 5 mg/ml) (L-NAME/LPS) was injected into the middle ear of guinea pigs transtympanically. The electrocochleograms were measured prior to, immediately and 48 h after the injection. Immunohistological studies for iNOS followed after fixation, embedding and sectioning of the temporal bones.

The threshold and amplitude of the compound action potential (CAP) became significantly worse in the LPS treated group. In contrast, the changes of the threshold and amplitude of CAP were decreased in the L-NAME/LPS group. iNOS was expressed in the stria vascularis, the spiral ligament, the organ of Corti and the spiral ganglion in the LPS group. These immunore-activities in the L-NAME/LPS group were less intense than that in the LPS group. These results indicate that LPS has an ototoxic effect on the cochlea and that this effect could be mediated by iNOS produced high nitric oxide under inflammatory conditions.     

Inhibition of inducible nitric oxide synthase lowers the cochlear damage by lipopolysaccharide in guinea pigs

Endotoxin-treated cochleas of the guinea pig were examined electrophysiologically and immunohistochemically concerning the expression of inducible nitric oxide synthase (iNOS/NOS II). One mg of bacterial lipopolysaccharide (LPS, 5 mg/ml) or mixed solution of 1 mg of LPS plus 1 mg of N^G-nitro-L-arginine methyl ester (L-NAME, 5 mg/ml) (L-NAME/LPS) was injected into the middle ear of guinea pigs transtympanically. The electrocochleograms were measured prior to, immediately and 48 h after the injection. Immunohistological studies for iNOS followed after fixation, embedding and sectioning of the temporal bones.

The threshold and amplitude of the compound action potential (CAP) became significantly worse in the LPS treated group. In contrast, the changes of the threshold and amplitude of CAP were decreased in the L-NAME/LPS group. iNOS was expressed in the stria vascularis, the spiral ligament, the organ of Corti and the spiral ganglion in the LPS group. These immunore-activities in the L-NAME/LPS group were less intense than that in the LPS group. These results indicate that LPS has an ototoxic effect on the cochlea and that this effect could be mediated by iNOS produced high nitric oxide under inflammatory conditions.     

Lipid peroxidation associated protein damage in rat brain crude synaptosomal fraction mediated by iron and ascorbate

In crude synaptosomal fractions from rat brain exposed to iron and ascorbate, enhanced lipid peroxidation (more than 3-fold compared to control), loss of protein thiols up to the extent of 40% compared to control, increased incorporation of carbonyl groups into proteins (more than 4.5-fold compared to control) and non-disulphide covalent cross-linking of membrane proteins have been observed. The phenomena are not inhibited by catalase or hydroxyl radical scavengers like mannitol or dimethyl sulphoxide. However, chain breaking antioxidants like alpha-tocopherol and butylated hydroxytoluene prevent both lipid peroxidation and accompanying protein oxidation. It is suggested that in this system lipid peroxidation propagated by the decomposition of preformed lipid hydroperoxides by iron and ascorbate is the primary event and products of the peroxidation process cause secondary protein damage. In view of high ascorbate content of brain and availability of several transition metals, such ascorbate mediated oxidative damage may be relevant in the aetiopathogenesis of several neurodegenerative disorders as well as ageing of brain.     

短波长单色光对豚鼠眼屈光发育的影响

目的研究短波长单色光对豚鼠的屈光发育和眼生物学参数的影响。方法 20只出生约2周的健康雄性豚鼠,随机分成两组（n=10）,分别在蓝光（430 nm）和白光（色温5000 K）下进行饲养。蓝光组为实验组,白光组为对照组,实验周期为12周。两种光照的光量子数均为每秒3×10-4μmol/cm2,测量光强度蓝光为0.527mW/cm2,白光为0.247 mW/cm2。实验前后均进行屈光度、角膜曲率、眼轴各部分长度的测量。结果实验前两组测量参数差异无显著性（P〉0.05）。光照12周后,蓝光组屈光度增加（1.20±0.66）D,白光组减少（1.18±0.85）D,蓝光组与白光组相比平均形成约2.40 D远视,统计学差异显著（P〈0.0001）;蓝光组眼轴和玻璃体腔分别增长（0.77±0.12）mm与（0.05±0.10）mm,白光组分别增长（0.95±0.18）mm与（0.21±0.13）mm。蓝光组的眼轴和玻璃体腔长度增长较白光组慢（P〈0.05）。但实验后两组角膜曲率半径、前房深度和晶状体厚度的变化差异无显著性（P〉0.05）。结论 430 nm短波长单色光诱导豚鼠眼轴和玻璃体腔长度延长较慢,产生远视。     

Changes in the plasma lipoprotein-apoproteins of guinea pigs in response to dietary cholesterol.

The major apoproteins from four plasma lipoproteins were isolated from control and cholesterol-fed guinea pigs. Apoproteins were studied by column chromatography, polyacrylamide gel electrophoresis, and amino acid analysis. Dietary cholesterol altered the plasma apolipoproteins mainly by an enrichment in the content of arginine-rich polypeptide (ARP) in all density fractions. This protein had a similar molecular weight (34 000), electrophoretic mobility, amino acid composition, and microheterogeneity as ARP reported in other mammalian species. The estimation of plasma concentration of ARP indicates a higher correlation coefficient with plasma unesterified cholesterol (r = 0.98) compared with cholesterol esters (r = 0.62).     

Study of anaphylectic hypersensitivity manifestations to blood protein in guinea pigs with using the neutrophil damage test in vitro]

The paper is devoted to the study of hypersensitivity of anaphylactic type to horse serum in guinea pigs by means of neutrophil injury index in vitro. Simultaneously, for control, the same method was applied to the study of delayed hypersensitivity manifestations; for this purpose allergy to hemolytic staphylococcus was reproduced in these animals. The state of hypersensitivity of "anaphylactic type" against the foreign serum in guinea pigs was not accompanied by any enhanced blood neutrophil reactions, whereas high values of the test under study were characteristic of the process of guinea pigs sensitization with staphylococcus culture.     

Effect of dietary alpha- and gamma-linolenic acid on tissue fatty acids in guinea pigs

Guinea pigs were fed regular chow diets supplemented with 5% (by weight) safflower oil, evening primrose oil, or linseed oil for 6 weeks. The unsaturated fatty acid content of these oils was 78.9% of 18:2n6, 74.1% of 18:2n6, and 9.2% of 18:3n6, or 21.5% of 18:2n6 and 46.9% of 18:3n3, respectively. In comparison with 18:2n6, dietary supplementation with 18:3n6 significantly increased the tissue levels of 18:3n6 and 20:3n6, whereas dietary 18:3n3 significantly elevated the levels of 18:3n3 in plasma and liver lipids. Dietary 18:3n3 also significantly increased 22:5n3 and 22:6n3 in total phospholipids. The tissue levels of 20:4n6, on the other hand, were not affected by either treatment. These data suggest that both delta 6- and delta 5 desaturation of n-6 fatty acids in guinea pigs are low, and that the metabolism of n-3 and n-6 fatty acids may be regulated by two different enzyme systems.     

Efficient repair of protein radicals by ascorbate

Protein radicals were selectively generated by reaction with azide radicals on Trp and Tyr residues in insulin, β-lactoglobulin, pepsin, chymotrypsin, and bovine serum albumin at rate constants in the range (2.9–19) × 10⁸ M^? 1 s^? 1. Monohydrogen ascorbate reduced tryptophanyl radicals in chymotrypsin and pepsin with rate constants in the narrow range of (1.6–1.8) × 10⁸ M^? 1 s^? 1, whereas β-lactoglobulin tryptophanyl radicals reacted almost 10 times slower. The corresponding values for the protein tyrosyl radicals were about an order of magnitude smaller. Comparison of the rate constants of reactions of free and protein-bound tryptophanyl and tyrosyl radicals showed that, in most cases, the location of the radicals in the protein chain did not constitute a major barrier to the reaction with monohydrogen ascorbate. The results suggest that, under physiological concentrations of dioxygen, monohydrogen ascorbate is likely to be a significant target of protein radicals. It seems likely, therefore, that reaction with protein radicals may be responsible for much of the well-documented loss of ascorbate in living organisms subjected to oxidative stress.     

Comparative study of Helicobacter pylori infection in guinea pigs and mice - elevation of acute-phase protein C3 in infected guinea pigs

Eighteen Dunkin-Hartley guinea pigs and 50 NMRI mice were inoculated with Helicobacter pylori and the infection followed by culture, histopathology, antibody response, and plasma levels of the acute-phase proteins albumin, C3, and transferrin for up to 7 weeks. The immune response to H. pylori surface proteins was studied by an enzyme immunoassay (EIA) and Western immunoblot and the plasma levels of albumin, C3, and transferrin were analyzed by single radial immunodiffusion. Guinea pigs had a more severe gastritis and a higher EIA immune response than NMRI mice. Serum C3 levels were elevated in infected guinea pigs after 3 and 7 weeks indicating a systemic inflammatory response and a possible link between H. pylori infection and extragastric manifestations such as vasculitis associated with atherosclerosis. Serum cholesterol levels were analyzed in guinea pigs at 7 weeks and indicated a higher level in H. pylori-infected than in control animals, but this difference was not statistically significant.