chiniofon and Body-Weight

Angiogenesis and antiangiogenesis, as applied to oncology, are phenomena in which (1) tumors acquire a new blood vascular system from the host that is needed for their growth progression and metastasis; and (2) factors are produced that interfere with neovascularization, thereby inhibiting growth and metastasis of the tumor. Linomide, a chemical antiangiogenesis agent, inhibited the growth of transplanted tumors in mice and rats and inhibited the early development of metastasizing tumors induced in the prostate-seminal vesicle (P-SV) complex of genetically susceptible Lobund-Wistar (L-W) rats.. L-W rats with small induced P-SV tumors were treated with a recommended dosage of linomide (100 mg/kg BW/day) by the intraperitoneal and oral routes. The rats were monitored for the next 1-2 months, and the primary and metastatic tumors were compared with related data in drug-free tumor-bearing control rats.. P-SV tumors in linomide-treated and untreated control rats continued to grow, except that in the former (1) the tumors were marginally smaller, (2) the centers of the primary P-SV tumors had failed to grow, (3) the peripheral areas of the tumors contained actively proliferating tumor cells, and (4) metastatic P-SV tumors in the lungs were disrupted with focal areas of necrosis, but areas of intact tumor cells survived. Spread of tumor cells into the peritoneal cavity was not inhibited. Rats on orally administered linomide lived significantly longer than rats inoculated by the intraperitoneal route and untreated control rats. The dosage of linomide used showed evidence of toxicity.. Although primary and metastatic P-SV tumors were damaged in L-W rats treated with linomide, this antiangiogenic drug was of minimal therapeutic benefit to rats in which a palpable P-SV tumor had developed before onset of treatments.

Topics: Animals; Antineoplastic Agents; Body Weight; Genital Neoplasms, Male; Hydroxyquinolines; Male; Neoplasm Metastasis; Neovascularization, Pathologic; Prostatic Neoplasms; Rats; Rats, Wistar; Seminal Vesicles

Linomide (quinoline-3-carboxamide) is a synthetic immunomodulator that suppresses several experimental autoimmune diseases. Here we report the effects of Linomide on chronic progressive and/or relapsing experimental autoimmune encephalomyelitis (PR-EAE), a CD4+ T cell mediated animal model of multiple sclerosis (MS). PR-EAE induced in DA rats by inoculation with homogenized guinea pig spinal cord and Freund's complete adjuvant, was strongly suppressed by Linomide administered daily subcutaneously from the day of inoculation. Linomide dose-dependently delayed the interval between immunization and onset of clinical PR-EAE, reduced severity and relapse of clinical PR-EAE, and shortened clinical PR-EAE. These clinical effects were associated with the down-modulation of CNS antigen-induced T cell responses and production of proinflammatory cytokines (IFN-gamma and TNF-alpha) as well as with upregulation of IL-4 (except in spleen MNC), IL-10 and TGF-beta in both spleen MNC and the spinal cord. These effects indicate that Linomide can suppress PR-EAE and may mediate its suppressive effects by regulation of cytokines.

Topics: Adjuvants, Immunologic; Animals; Body Weight; Cell Division; Cells, Cultured; Cytokines; Dose-Response Relationship, Drug; Encephalomyelitis, Autoimmune, Experimental; Guinea Pigs; Hydroxyquinolines; Leukocytes, Mononuclear; Male; Rats; Rats, Inbred Strains; RNA, Messenger; Spinal Cord; Spleen; T-Lymphocytes; Time Factors

The changes in lipid peroxide concentrations in plasma and tissues after subcutaneous administration of clioquinol to clioquinol-sensitive (S-rats) and -resistant neonatal rats (R-rats) were investigated. When a fixed dose of 150 mg/kg/d of clioquinol was given to R-rats for 14 d after birth, no significant difference in lipid peroxide concentrations in plasma, liver, kidney, brain and spinal cord at 5, 10 and 15 d was observed between clioquinol-treated and untreated rats. However, with increasing doses of clioquinol to R-rats every 5 d (150----300----600 mg/kg/d), the lipid peroxide concentrations at 15 d were higher in plasma, brain and spinal cord of clioquinol-treated rats than in those of untreated rats. These results suggested that repeated administrations of large doses of clioquinol to rats increased the lipid peroxides in nerve tissues. With S-rats at 5 d after birth, the lipid peroxide concentrations in liver were approximately twice those in R-rats regardless of the clioquinol administration.

Topics: Animals; Animals, Newborn; Ataxia; Body Weight; Central Nervous System; Clioquinol; Drug Resistance; Female; Hydroxyquinolines; Kidney; Lipid Peroxides; Liver; Male; Rats; Rats, Inbred Strains

Three experiments utilizing three Holstein steers (235 and 299 kg avg body weight for Exp. 1 and 2, respectively) were conducted to evaluate the effects of decoquinate, a synthetic coccidiostat, on ruminal fermentation, diet digestibility and performance of steers fed a finishing diet containing monensin and tylosin. Experiment 1 utilized a 70% forage diet, whereas Exp. 2 utilized a 20% forage diet. Each experiment was a 3 X 3 Latin-square design with treatments being 0, .5 and 5 mg decoquinate/kg body weight. Ruminal fermentation characteristics, water kinetics and blood constituents were measured on d 11 of each period, and zero-time volatile fatty acid (VFA) production was measured at 3 and 6 h post-feeding on d 12 to 14. No changes were seen in plasma glucose or L-lactate, ruminal pH, NH3-N or ruminal L-lactate for either experiment. Dry matter digestibility was depressed (P less than .05) at the .5- and 5-mg levels of decoquinate in Exp. 1, but dry matter digestibility was not affected in Exp. 2. No changes were seen in ruminal volume, outflow or total VFA concentration for either experiment. Molar proportions of VFA were not affected in Exp. 1, but the proportions of isobutyrate and butyrate decreased (P less than .05) at the 5-mg level of decoquinate in Exp. 2. Volatile fatty acid production was not changed in Exp. 1, but butyrate production was decreased (P less than .05) at the 5-mg level in Exp. 2. Experiment 3 involved 135 crossbred steers (259 kg avg initial wt), which were stratified by weight into 12 pens.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Body Weight; Cattle; Decoquinate; Digestion; Fermentation; Hydroxyquinolines; Male; Rumen

Decoquinate was evaluated as a coccidiostat in domestic goats. Fifty goats less than 4 months of age were assigned to 5 groups (pens) of 10 goats each and were treated for 87 days with 0 (control), 0.3, 0.5, 1.0, or 4.0 mg of decoquinate in feed/kg of body weight. Goats were inoculated orally weight. Goats were inoculated orally with 30,000 oocysts, mainly Eimeria christenseni (74%) and E ninakohlyakimovae (20%) on day 19. Nontreated goats developed profuse watery diarrhea and tenesmus and gained weight poorly; 2 died. Treated goats did not develop clinical coccidiosis and gained significantly more weight (P less than 0.05), regardless of the dose used. Treated goats also had significantly fewer (P less than 0.05) oocysts in feces than did nontreated controls. Oocyst numbers were inversely related to dose; a more rapid decrease in oocyst numbers occurred as the dose was increased. At the doses used, decoquinate was safe in goats and was an effective drug for the prevention of clinical coccidiosis.

Topics: Animal Diseases; Animals; Body Weight; Coccidia; Coccidiosis; Decoquinate; Dose-Response Relationship, Drug; Female; Goats; Hydroxyquinolines; Male; Time Factors

The percutaneous absorption and disposition of iodochlorhydroxyquin (5-chloro-7-iodo-8-quinolinol; I) from a 3% cream were studied in five dogs over a 28-d topical treatment period. Plasma levels, determined by HPLC, were 0.275-0.525 microgram/mL. The steady-state elimination rate of total I in urine was 2.4-3.0 mg/d. The apparent elimination rate constant and half-life were 0.25 +/- 0.05 d-1 and 3.1 +/- 0.5 d, respectively. Greater than 50% of topically applied I was absorbed over 16 h. Occlusion of the skin without the drug indicated that the skin acted as a reservoir for the drug. Feces analysis for iodochlorhydroxyquin from one dog showed that 27.1 +/- 8.5 mg/d was eliminated via this route. Tissue levels of I 15 d after the 28-d topical treatment were 0.7 microgram/g of liver, 0.2 microgram/g of kidney, and 0.8 microgram/g of mesenteric fat. The apparent rate constants of plasma level decline after a 100-mg iv bolus dose of I were alpha = 3.9 h-1 and beta = 0.6 h-1. The urinary elimination after intravenous administration was biphasic. The rate constant for the slow elimination phase was 0.4 +/- 0.1 d-1, and the half-life was 2.0 +/- 0.5 d. The primary neurological symptoms observed during topical treatment were ataxia and hind limb paralysis. Microscopic examination revealed liver necrosis. A weight loss of 15.3 +/- 2.7% was also observed over the 28-d topical treatment period. The results indicate that significant percutaneous absorption of I occurs, and that chronic high-dose topical treatment may lead to toxicity.

Topics: Adipose Tissue; Animals; Body Weight; Clioquinol; Dogs; Half-Life; Hydroxyquinolines; Kidney; Kinetics; Liver; Male; Skin Absorption; Time Factors; Tissue Distribution

12 groups of 8 young male Sprague-Dawley rats received a semisynthetic casein-diet, whose zinc concentration (1.3 ppm) was adjusted to 5, 10 and 15 ppm by supplementation of various Zn complexes or salts like Zn citrate, Zn picolinate, Zn 8-hydroxyquinolate and Zn sulfate. After 24 days all animals were killed and examined on parameters of zinc supply status. The weight gain of the animals with 5 ppm dietary zinc was strongly reduced compared to groups with the higher dietary zinc content. The type of the supplemented Zn compound showed in no way an influence on the live-weight of the animals. The zinc concentration of the tissues, too, was only dependent on the level of the dietary zinc concentration and not on the type of supplemented zinc compound. The activity of the alkaline phosphatase in serum, a zinc metalloenzyme, was altogether reduced in the zinc-deficient animals with 5 ppm dietary zinc content, but showed a significant higher activity in the citrate and 8-hydroxyquinolate group than in the sulfate and picolinate group. Also the percent zinc-binding capacity of serum, a good indicator for estimating the zinc supply status of rats, showed a better zinc supply of the citrate group with 5 as well as 10 ppm dietary zinc, compared with the other groups on the same dietary zinc content. The serum zinc concentration of rats with 5 ppm as Zn citrate was more than twice higher than in animals given zinc as picolinate, 8-hydroxyquinolate or sulfate. The results indicate a better utilization of zinc chelated by citric acid than by picolinic acid, 8-hydroxyquinoline or as salt like sulfate. But the higher bioavailability of zinc in human milk should not only be attributed to the presence of citrate.

Topics: Alkaline Phosphatase; Animals; Body Weight; Citrates; Citric Acid; Diet; Hydroxyquinolines; Male; Oxyquinoline; Picolinic Acids; Rats; Rats, Inbred Strains; Sulfates; Tissue Distribution; Zinc; Zinc Sulfate