Acute renal and hepatic toxicity of 2-haloanilines in Fischer 344 rats.

Aniline and its halogenated derivatives are widely used as chemical intermediates. The purpose of this study was to determine the hepatotoxic and nephrotoxic potential of the 2-haloanilines. Male Fischer 344 rats (n > or = 4) were injected (i.p.) with 1.0 or 1.25 mmol/kg of: aniline (A), 2-fluoroaniline (2-FA), 2-chloroaniline (2-ClA), 2-bromoaniline (2-BrA), 2-iodoaniline (2-IA) or vehicle (0.9% saline, 2.5 ml/kg). All compounds were injected as hydrochloride salts. Renal and hepatic function was monitored 24 h after treatment. All of the 2-haloanilines induced oliguria, diminished kidney weight, tubular casts and decreased renal cortical slice accumulation of organic anions. Blood urea nitrogen (BUN) levels were increased (P < 0.05) by treatment with 1.0 or 1.25 mmol/kg of 2-FA, 2-ClA or 2-BrA. Hepatic alterations were also observed and characterized by elevated plasma ALT/GPT activity and altered morphology in the centrilobular region. The nephrotoxic and hepatotoxic potentials were similar among the 2-haloanilines but aniline was less toxic than its 2-halo derivatives. These results demonstrated that halogen substitution at the 2-position of aniline increased hepatic and renal toxicity. However, the severity of toxicity was not influenced by the nature of the halogen substituent.     

Cephaloridine nephrotoxicity in streptozotocin induced diabetic Fischer 344 (F344) rats

The purpose of this study was to determine if cephaloridine nephrotoxicity is attenuated in streptozotocin (STZ)-induced diabetic rats. Fischer 344 (F344) rats (205-250 g) were given a single injection (i.p.) of STZ (27-35 mg/kg) or citrate buffer. The nephrotoxicity of (750 mg/kg) cephaloridine (i.p.) was then compared with normoglycemic and 14-day diabetic rats. Increased blood urea nitrogen (BUN) levels as well as diminished renal cortical slice accumulation of tetraethylammonium (TEA) and lactate-stimulated p-aminohippurate (PAH) were measured (P less than 0.05) in normoglycemic rats 48 h after cephaloridine administration. Cephaloridine failed to alter BUN levels and organic ion accumulation in diabetic rats. Diabetes did not totally protect against cephaloridine toxicity since kidney weights were elevated in normoglycemic and diabetic rats 48 h after administration of 750 mg/kg cephaloridine. A series of experiments also measured BUN levels, kidney weight and renal cortical slice uptake of PAH and TEA 24, 48 and 72 h after (1500 mg/kg) cephaloridine administration. Cephaloridine increased (P less than 0.05) kidney wt and decreased PAH and TEA uptake (P less than 0.05) in the normoglycemic group at 24-72 h. No change in kidney wt, PAH or TEA uptake was observed in the diabetic rats. These data indicate diabetes reduces cephaloridine nephrotoxicity.     

Levels, Complement Activity and Polymorphisms of Mannan-Binding Lectin in Patients of Bronchial Asthma with Allergic Rhinitis

Activation of complement pathways, leading to production of C3a and C5a anaphylatoxins, has been postulated in the pathogenesis of asthma and allergic airway inflammation. The present study was undertaken to investigate the role of mannan-binding lectin (MBL), an initiator of the lectin pathway of complement, in asthma and allergic rhinitis. MBL levels and MBL-induced complement activity were determined in 19 patients of bronchial asthma with allergic rhinitis and 20 unrelated, age-matched controls of Indian origin. MBL levels and activity were correlated with percent eosinophilia and percent predicted FEV1 values of the patients. Association of single nucleotide polymorphisms (SNPs) in exon 1 and intron 1 of the MBL with the disease, clinical markers, MBL levels and MBL-induced complement activity was analysed using standard statistical tools. Significantly higher MBL levels and activity were observed in patients of bronchial asthma with allergic rhinitis as compared to the controls. We identified five SNPs, of which two, A816G in exon 1 and G1011A in intron 1 of the MBL, were novel. SNP G1011A was significantly associated with the disease ( P =  0.0024, OR = 5.8696, 95% CI: 1.7316 < OR < 19.8963). Individuals with 'A' allele at position 1011 showed increased MBL levels, activity and disease severity. Our results suggest that 'A' allele at position 1011 leading to high MBL levels and complement activity may be contributing to the severity of bronchial asthma and allergic airway inflammation.     

Identification of Brucella by Ribosomal-Spacer-Region PCR and Differentiation of Brucella canis from Other Brucella spp. Pathogenic for Humans by Carbohydrate Profiles

Molecular and chemical characteristics often provide complementary information in the differentiation of closely related organisms. The genus Brucella consists of a highly conserved group of organisms. Identification of the four species pathogenic in humans (Brucella melitensis, Brucella abortus, Brucella suis, and Brucella canis) is problematic for many clinical laboratories that depend primarily on serology and phenotypic characteristics to differentiate species. PCR amplification of the 16S-23S ribosomal DNA interspace region was evaluated for species-specific polymorphism. B. abortus, B. melitensis, B. suis, and B. canis produced identical PCR interspace profiles. However, these PCR products were unique to brucellae, allowing them to be readily distinguished from other gram-negative bacteria (including Bartonella spp. and Agrobacterium spp.). Carbohydrate profiles differentiated B. canis from the other three Brucella species due to the absence of the rare amino sugar quinovosamine in the three other species. PCR of the rRNA interspace region is useful in identification of the genus Brucella, while carbohydrate profiling is capable of differentiating B. canis from the other Brucella species.