Can renalase be a novel candidate biomarker for distinguishing renal tumors?

Renalase (RNLS) is synthesized mainly in renal tissues. The function of RNLS in cancerous renal tissues has not been investigated. We investigated the synthesis of RNLS in chromophobe renal cell carcinoma, papillary renal cell carcinoma and clear cell renal cell carcinoma with Fuhrman grades (FG): FG1, nucleoli are absent or inconspicuous and basophilic; FG2, nucleoli are conspicuous and eosinophilic and visible but not prominent; FG3, nucleoli are conspicuous and eosinophilic; FG4, extreme nuclear pleomorphism, multinucleate giant cells, and/or rhabdoid and/or sarcomatoid differentiation. We used 90 tissue samples including 15 healthy controls, 15 chromophobe renal cell carcinoma tissues and 10 papillary renal cell carcinoma renal tissues: 12 FG1, 14 FG 2, 14 FG 3 and 10 FG4. RNLS in the tissue samples was measured using enzyme linked immunosorbent assay and immunostaining of RNLS in these tissues. RNLS was significantly greater in the chromophobe renal cell carcinoma and papillary renal cell carcinoma tissues than the control. The least amount of RNLS was found in the renal tissues of clear cell renal cell carcinoma FG1; the amount of RNLS increased as the FG grades increased. Because RNLS increased significantly in renal tissues due to cancer, except for clear cell renal cell carcinoma FG1, RNLS may be useful biomarker for distinguishing grades of renal cancer. Because RNLS increases cell survival, anti-RNLS preparations may be useful for treating cancer in the future.

The effects of vitamin C and E supplementation on heat shock protein 70 response of ovary and brain in heat-stressed quail.

1. The effects of vitamin C (L-ascorbic acid) and vitamin E (alpha-tocopherol acetate) supplementation on egg production and heat shock protein 70 (Hsp70) response of ovary and brain in the Japanese quail (Coturnix coturnix japonica) exposed to high ambient temperature were evaluated. 2. The birds (n = 540; 55 d old) were randomly assigned to 18 groups consisting of 3 replicates of 10 birds each in a 2 x 3 x 3 factorial arrangement of treatments. Birds were kept in wire cages in a temperature-controlled room at either 22 degrees C (thermo-neutral, TN) or 34 degrees C (heat stress, HS) for 8 h/d (09:00 to 17:00 h; until the end of the study) and fed on a basal diet or the basal diet supplemented with either three levels of vitamin C (0, 250 and 500 mg of L-ascorbic acid/kg of diet) or three levels of vitamin E (0, 250 and 500 mg of dl-alpha-tocopheryl acetate/kg of diet). 3. Feed intake and egg production were not affected by vitamin C and E supplementation under thermo-neutral conditions. However, feed intake and egg production were increased with the vitamin C or E supplementation either singly or in combination in heat-stressed quail. When vitamin was added, feed intake and egg production of quails under TN were different from those raised under HS. However, in the absence of supplemental vitamins, feed intake and egg production at TN and HS were no different. 4. Heat exposure increased serum corticosterone levels and Hsp70 expression. Serum corticosterone level was significantly decreased by vitamin C or E supplementation in HS groups for quail. Ovary and brain Hsp70 expression linearly decreased as dietary vitamin C or vitamin E supplementation increased in heat-stressed groups. However, Hsp70 expression of ovary and brain was not affected by vitamin C or E supplementation under thermo-neutral conditions. 5. The present study showed that a combination of dietary vitamin C (500 mg) and E supplementation (500 mg) may alleviate some heat stress effects of heat shock proteins of ovary and brain and egg production of Japanese quail.

Equine goiter associated with excess dietary iodine.

Naturally occurring goiter cases are described in 2 newborn Arabian foals whose mares were supplemented with excess iodine during the final 24 w of the pregnancy. Six nursing foals and 2 mares were also affected clinically with thyroid hypertrophy. At least 12 times the maximum tolerable level of iodine supplementation was given, as the daily iodine intake for each mare was 299 mg. The prevalence of goiter cases was 2 and 9% in the mares and foals, respectively.

Toxicity of dietary Heliotropium circinatum to rats.

Pyrrolizidine alkaloid intoxication was produced in adult, male rats by feeding different levels (0, 1, 3, 5 or 10%) of Heliotropium circinatum for 20 w. Combined GC-MS revealed 0.15% total alkaloid content in the plant material of which 12% and 88% were basic and N-oxide forms, respectively. The specific alkaloids identified were europine (67.33%), heliotrine (16.34%), lasiocarpine (8.12%), heleurine (4.18%), echinatine (1.56%), 7-angeylheliotrine (1.19%), and an unknown alkaloid (1.28%). Neither mortality nor significant clinical changes occurred in test groups. Mild to moderate, dose-related hepatic megalocytosis was the most prominent histopathological finding. In addition to chronic hepatotoxicity, notable medial thickening occurred in the pulmonary arterioles and arteries of the high-dosed groups. This study indicated that H. circinatum plant has limited toxic potential in rats with mild to moderate histological changes and no mortality at the dosing levels, total doses, or time of exposure employed.

Toxicity of Senecio vernalis to laying hens and evaluation of residues in eggs.

Diets with 0.0, 0.5,2.0, or 4.0% ground-aerIal parts of Senecio vernalis were fed to groups of 10 laying hens for 210 d. Plant alkaloid content was 0.14% with 8.57% in the basic form and 91.43% in the N-oxide form. Specific alkaloids were senecionin (66.65%), senecivernin (10.37%), seneciphylline (8.51%), integerrimine (8.44%), retrorsine (3.03%), senkirkine (2.35%) and hydroxysenkirkine (0.65%). At the end of the feeding period, no mortality or clinical signs occurred in any test group. However, decreases in egg production, feed efficiency, feed intake and body weight occurred on diets containing 2 or 4% of the plant. Serum gamma-GT was significantly elevated and serum albumin and protein were significantly decreased in hens fed the 2 and 4% diets. Total bilirubin was significantly higher in the 4% group. No free pyrrolizidine alkaloids were detected in eggs indicating that at these rates of dietary exposure, they did not produce residues at the level of detection or that they were bound irreversibly to egg proteins. Hens fed 2 or 4% plant diets had mild to moderate chronic liver changes of periportal or septal fibrosis, megalocytosis, bile duct hyperplasia and early regenerative nodule formation.

Toxicity of dietary Heliotropium dolosum seed to Japanese quail.

Five groups of 30 male Japanese quail, each 7-w-old, were fed diets containing 0, 1, 3, 5, or 10% (w/w) of dehulled H dolosum seed. Half of the birds from the each group were killed at 6 and 24 w after beginning of the trial. At the end of 6th w, neither mortality nor clinical sign occurred in test groups. In the 5 and 10% inclusion levels, mild to moderate hepatic injury was detected as evidenced by mild karyomegaly, moderate fatty change, focal or portal fibrosis, bile duct hyperplasie, and ovalocyte proliferation along with lower serum protein and albumin levels. By the termination of the experiment (24 w), 5 birds died in the 10% dosed group. Hepatic cirrhosis was the most prominent finding in the 5 and 10% group; at these levels, serum protein and albumin values decreased significanty while billuribin and ALP levels increased. Based on relative weights and histological evaluations, testicularatrophywasdosedependent. These results partly affirm earlier studies that the quail is highly resistant to the toxic effects of H dolosumseed. However, the resistance to H dolosum is less than Senecio Jacobae and Crotalaria spectabilis when considering tissue injury.

Toxicity of dietary Heliotropium dolosum seed to mice.

Experimental pyrrolizidine alkaloid intoxication was produced in inbred Swiss mice. Animals were fed diets containing 0, 1, 3, 5, or 10% Heliotropium dolosum seed for 24 w. The seeds contained 0.13% total alkaloid concentration composed of 4 specific components: lasiocarpine (78.79%), heliosupine (11.96%), echimidine (5.43%), and heliotrine (3.82%). Deaths occurred in all dosed groups and increased with dietary seed concentration. Massive to submassive liver necrosis together with sinusoidal congestion, and hemorrhage or multifocal hepatocytic necrosis was limited to animals which survived < 5 w and were fed on 10% seed. Moderate to severe hepatomegalocytosis, scattered single cell necrosis, and mild subcapsuler fibrosis were seen in all test group animals that survived > 5 w. Intranuclear eosinophilic inclusions in hepatocytes and bile duct and ductular cell hyperplasia were the most noticeable lesions in the 1, 3, and 5% groups. There was mild to moderate renal tubular megalocytosis in the 3, 5, and 10% groups. It seems likely that H dolosum seed, at least to a limited extent, constitutes a health hazard for certain animal species.

Toxicity of dietary Heliotropium dolosum seed to broiler chickens.

Five groups of 20 female broiler chicks were fed different levels of dehulled Heliotropium dolosum seed (w/w%; 0.0, 1.0, 3.0, 5.0 or 10.0%) from 10 to 52 d of age. In all doses the seed caused decreases in daily feed intake, weight gain, and feed efficiency, and biochemical findings, severity of pathologic changes, and mortality rate increased in a dose-dependent manner. Acute toxicity was observed in livers of chicks fed 10% seed. Other test groups had chronic changes. Livers had massive to submassive necrosis, hepatic megalocytosis, bile duct proliferation, fatty change, and periportal fibrosis. Biochemical evaluations revealed hypoalbuminemia, hypoprotienemia and increased ALP activity and billuribin. The seed of Heliotropium dolosum produced biochemical and specific pathologic changes in broiler chicks, as well as decreased food intake and feed efficiency. Higher seed levels induced more pronounced changes.