Dispersion tailoring in wedge microcavities for Kerr comb generation.

The shaping of group velocity dispersion in microresonators is an important component in the generation of wideband optical frequency combs. Small resonators-with tight bending radii-offer the large free-spectral range desirable for wide comb formation. However, the tighter bending usually limits comb formation as it enhances normal group velocity dispersion. We experimentally demonstrate that engineering the sidewall angle of a small-radius (∼100µm), 3-µm-thick silica wedge microdisk enables dispersion tuning in both normal and anomalous regimes, without significantly affecting the free spectral range. A microdisk with a wedge angle of 55° (anomalous dispersion) is used to demonstrate a 300 nm bandwidth Kerr optical frequency comb.

Pharmacokinetics and physiological effects of repeated oral administrations of tramadol in horses.

This study evaluated the pharmacokinetics and physiological effects of tramadol during repeated oral administrations in horses. Nine adult healthy horses were administered tramadol at 5 and 10 mg/kg orally every 12 h for 5 days in a randomized, crossover design with a 3-week washout between treatments. Plasma concentrations of tramadol, O- and N-desmethyltramadol (M1 and M2) were measured using Liquid-Chromatography-Mass Spectrometry at predetermined time points following each tramadol administration. Cardiovascular, respiratory and gastrointestinal physiological variables were monitored and adverse events were recorded. Data were analysed with two-way repeated measures anova or Kruskal-Wallis one-way anova on ranks with P < 0.05 considered statistically significant. There were no significant effects of tramadol on the physiological variables. One horse receiving 10 mg/kg tramadol developed mild colic. Following tramadol at 5 and 10 mg/kg, respectively, maximum plasma concentrations (Cmax ) of tramadol ranged from 82-587 and 127-1280 ng/mL, nonconjugated M1 ranged from 2.51-26.7 and 4.88-34.3 ng/mL, and nonconjugated M2 from 12.5-356 and 35.4-486 ng/mL. Corresponding minimum plasma concentrations (Cmin ) of tramadol at 12 h following each dose ranged from 0.8-24 and 3-117 ng/mL. Tramadol accumulated considerably over time, more markedly when given at 10 mg/kg than at 5 mg/kg (accumulation indexes of 3.51 and 1.73 respectively). There was no accumulation of M1 but substantial accumulation of M2. In conclusion, there was accumulation and increase in exposure to tramadol and M2, but not M1, during repeated oral administrations in horses.

Role of purines on hepatic ischemia-reperfusion lesions in rabbit.

In this work, we evaluate the effects of adenosine 5' triphosphate (ATP) on hepatic lesions caused by ischemia/reperfusion (I/R) in liver rabbit. Rabbits were pretreated with ATP (15 mg/kg IV) or saline solution 0.9% (SS), before the hepatic I/R procedure. We evaluated the effects of ATP on hepatic injury before and after I/R. The warm hepatic I/R procedure caused profound acute liver injury, as indicated by elevated serum aspartate aminotransferase, alanine aminotransferase, and lactic dehydrogenase levels, as well as a high apoptotic cell count. All these changes were attenuate by ATP treatment before the hepatic I/R procedure. These results suggested that ATP exerted protective effects on hepatic I/R lesions in the rabbit. This ATP effect may be related to improved energy metabolism during reperfusion in ischemic livers protecting against functional damage of cellular and subcellular membranes during lipid peroxidation.

Evidence of increased cholecalciferol requirement in chicks with tibial dyschondroplasia.

A series of experiments was conducted to test the hypothesis that vitamin D utilization may not be as efficient in chicks with tibial dyschondroplasia (TD). The basal diet contained 1.0% Ca and 0.45% available P with no supplemental cholecalciferol (D3). Chicks from low TD (LTD) and high TD (HTD) selected lines were fed diets supplemented with various levels of vitamin D compounds and examined for rickets and TD. When chicks were fed a D3-deficient diet containing only 1.25 micrograms/kg added D3, HTD chicks had a greater incidence of severe rickets than LTD chicks (P < 0.05). The LTD chicks did not exhibit TD when fed a diet containing adequate (20 micrograms/kg) D3. The LTD chicks fed a diet supplemented with 5 micrograms/kg D3, however, had 22% incidence of TD. When HTD chicks were fed diets supplemented with 5 micrograms/kg D3 [control diet that meets NRC (1994) requirement for D3], 20 micrograms/kg D3, 5 micrograms/kg 1,25-dihydroxycholecalciferol [1,25-(OH)2D3] or the combination of both D3 (20 micrograms/kg) and 1,25-(OH)2D3 (5 micrograms/ kg), TD incidence was highest in HTD chicks fed the control diet. When HTD chicks were fed diets with an increased dietary level of 1,25-(OH)2D3 (10 micrograms/kg) further reduction of TD incidence (P < 0.05) occurred. A potentially toxic level (Soares et al., 1983) of 1,25-(OH)2D3 (15 micrograms/kg) fed to HTD chicks resulted in still greater suppression of incidence of TD even though growth and feed intake in HTD chicks was greater than those of LTD chicks. It is concluded that the development of TD in HTD chicks is associated with subnormal ability to metabolize vitamin D.

25-hydroxycholecalciferol in poultry nutrition.

Vitamin D is a complex of secosteroids that must undergo metabolic alterations to reach optimal biological activity. The parent compounds 1) ergocalciferol (D2) and 2) cholecalciferol (D3) can be synthesized in the leaves of many plants or in the skin of most animals, respectively. Transport of vitamin D steroids after absorption is associated with vitamin D binding proteins (DBP). In general, the relative binding affinities of the vitamin D steroids are: 25-hydroxy vitamin D3 [25-(OH)D3] = 24,25-dihydroxy vitamin D3 [24,25-(OH)2D3] = 25,26-dihydroxy vitamin D3 [25,26-(OH)2D3] > 25-hydroxy vitamin D2 (25-(OH)D2) > 1,25-dihydroxy vitamin D3 [1,25-(OH)2D3] > vitamin D3. The DBP in poultry does not bind D2 forms effectively, and therefore poultry can not use this form of vitamin D adequately. The concentration of 25-(OH)D3 in blood seems to be well correlated with dietary vitamin D intake or exposure to ultraviolet light. The 1 alpha hydroxylase enzyme in the kidney is subject to negative feedback regulation and is critical for formation of the active metabolite 1,25-(OH)2D3. The intracellular vitamin D receptor (VDR) specifically binds 1,25-(OH)2D3 and is necessary for cellular action. Increased levels of two to three orders of magnitude are required for 25-(OH)D3 to compete with 1,25-(OH)2D3 for binding on VDR. Feeding studies with 25-(OH)D3 suggest it has nearly twice the activity of vitamin D3. Hatchability studies have shown that 25-(OH)D3 supports good fertility and hatchability, whereas hens fed only 1,25-(OH)2D3 did not have normal hatchability. Likewise, 1,25-(OH)2D3 seems to reach toxic levels at dietary concentrations only two to three times optimal dietary levels whereas feeding 25-(OH)D3 for extended periods at levels 8 to 10 times requirement seems to have no adverse effects. It seems that 25-(OH)D3 is the most active metabolite of vitamin D3, ultimately capable of supporting both cellular functions and embryonic development in chickens and turkeys when fed as the sole source of vitamin D3.

Calcium homeostasis in in ovo and ex ovo turkey embryos.

Calcium homeostasis of in ovo (normal) and ex ovo (shell-less) turkey embryos was investigated at 15, 18, and 21 days of incubation. Hypocalcemia and an elevation in circulating 1,25(OH)2D3 in ex ovo embryos were observed by 15 days. Calcium and phosphorus concentrations in femora and tibiae in ex ovo embryos were significantly lower compared to their normal counterparts. These results suggest that shell calcium mobilization is required prior to 15 days of incubation for maintaining serum calcium and supporting bone mineralization. Furthermore, the elevation of 1,25(OH)2D3 is indicative of a functional calcium homeostatic mechanism responding to the absence of the primary calcium source (eggshell) during the second half of turkey embryonic development.

Effect of 1 alpha,25-dihydroxycholecalciferol on egg shell quality and egg production.

1. The effect of replacing dietary cholecalciferol (D3) by 1 alpha,25-dihydroxycholecalciferol (1,25-(OH)2D3) on egg shell quality and egg production was tested on 32-week-old White Leghorn laying hens over 9 weeks. 2. Hens fed on a diet supplemented with 5 micrograms 1,25-(OH)2D3/kg diet, tended to lay more eggs, and the eggs had significantly higher specific gravity and percentage shell than eggs from control hens fed on a diet supplemented with 27.5 micrograms D3/kg diet. 3. The effect became apparent after about 4 weeks of treatment and persisted until the end of the test. 4. Hens fed on a diet without D3 supplement started to lay very thin or soft shelled eggs within 4 weeks, suggesting that the birds' reserves of D3 or its metabolites were depleted within this period. 5. The results suggest that 1,25-(OH)2D3 can be substituted for D3 in layer diets to improve egg shell quality.

Ovariectomy, dietary zinc, and bone metabolism in retired breeder rats.

Bone mineral turnover was studied in sham and ovariectomized (ovax) retired breeder rats after 16 wk of dietary treatment. Rats were fed either a commercial rat diet (CRD) containing high calcium and cholecalciferol or egg-white diets (EWD) containing 2 g Ca/kg, 1,25-(OH)2cholecalciferol (5 micrograms/kg), and either 10 or 200 mg zinc/kg. In rats fed EWD, high Zn enhanced femoral Zn deposition and concentration but did not affect serum Ca levels, bone mineral content (BMC), or turnover. Serum Ca levels and BMC were greater in sham rats and there was a gain in femoral Ca and phosphorus compared with the loss of these minerals in ovax rats. In CRD-fed ovax rats, values for these variables were similar to those of CRD-fed shams and there was no bone mineral loss. These data suggest that ovarian function may be a prerequisite for the beneficial effects of diets containing 1,25-(OH)2cholecalciferol and low Ca on bone metabolism.

Exercise training and dietary chromium effects on glycogen, glycogen synthase, phosphorylase and total protein in rats.

The effects of exercise training and dietary chromium intake on rat liver and muscle glycogen metabolism, tissue and body weight and feed consumption were examined. After 16 wk of training, liver, gastrocnemius and biceps femoris glycogen concentrations were higher in the trained compared to sedentary groups, independent of dietary chromium. There was a chromium x training interaction on glycogen synthase activities in the liver and gastrocnemius muscle. Liver glycogen phosphorylase activities (expressed per g liver) were lower in the chromium-supplemented rats as compared to the non-supplemented rats after 5 wk of dietary treatment, but were similar after 8 wk and higher after 18 wk. Gastrocnemius phosphorylase activity (expressed per mg protein) was lower in the trained rats as compared to the sedentary rats after 16 wk, independent of dietary chromium. Biceps femoris phosphorylase activities were not altered due to training or dietary chromium. Total protein concentration increased in the liver but decreased in the gastrocnemius due to dietary chromium. In summary, liver glycogen synthase and phosphorylase activities were dependent upon dietary chromium. Dietary chromium altered gastrocnemius synthase, but not phosphorylase activities. Changes in enzyme activities may be related to the chromium-dependent effects on liver protein and the chromium and training-dependent effects on gastrocnemius total protein.

The effect of dietary calcium on bone metabolism in young and aged female rats using a short-term in vivo model.

The use of high dietary calcium supplementation in the treatment of patients with osteoporosis is controversial. The present study examined the mechanisms underlying the effects of calcium supplementation by investigating the influence of dietary calcium on bone dynamics in young and aged rats. A 2 x 2 x 2 factorial design was utilized with 0.2% (low) or 1.0% (high) calcium, 2- or 24-m-old female Long-Evans rats that were implanted subcutaneously with demineralized (DB) and mineralized (MB) bone powder. The four groups of rats were fed each of the respective diets for 11 wk and then implanted with one #5 gelatin capsule containing 30 mg of DB and another containing 100 mg of MB powder. The animals were injected intraperitoneally with 0.1 microCi/g body weight with 45Ca 14 h before the end of experiment. The ectopic bone as well as the right femurs were harvested 14 d after the rats were implanted. Marker enzyme activities (alkaline-formation and acid-resorption phosphatase), 45Ca uptake and calcium content were measured in the implants and the distal epiphyses of the right femurs. Bone turnover was higher in the young rats than in the old animals, and high dietary calcium in the young animals increased bone formation, as indicated by alkaline phosphatase activity. Dietary calcium level did not affect ectopic bone formation or resorption in the aged rats. The results indicate that high dietary intake of calcium does not affect bone dynamics in aged female rats but does increase bone formation in young rats.

Calcium and vitamin D in bone metabolism: analyses of their effects with a short-term in vivo bone model in rats.

A short-term in vivo system was developed to examine simultaneously bone formation and resorption, and the effects of dietary calcium and vitamin D on these processes. In experiment 1, 25 male Long-Evans rats were each implanted with two gelatin capsules containing mineralized bone (MB) powder subcutaneously in the thorax region. At 4, 6, 8, 10 and 12 d after implantation the acid phosphatase activity (resorption) increased significantly (P less than 0.01), whereas alkaline phosphatase activity (formation) did not change. In experiment 2, both MB and demineralized bone (DB) powder were implanted on contralateral dorsal sites of the thorax in 40 male Long-Evans rats and harvested after 7, 9, 11 and 13 d. Enzyme, mineral and histological assessment indicated bone formation in DB implants with bone resorption in MB implants. In experiment 3, the effects of dietary calcium (0.2 or 1.0%) and vitamin D (cholecalciferol at 300 ng/d or 1,25-dihydroxycholecalciferol [1,25(OH)2D3] at 75 ng/d) were examined using 40 male Long-Evans rats. These rats were implanted with both DB and MB powders and the implants were harvested on d 12. Both low (0.2%) dietary calcium and 1,25(OH)2D3 stimulated resorption of MB implants. Therefore, the physiological processes of bone formation and resorption were mimicked in this system of bone powder implants. Further, dietary calcium and 1,25(OH)2D3 were shown to modulate these processes.

Effect of vitamin E and synthetic antioxidants on the survival rate of mercury-poisoned Japanese quail.

The effect of vitamin E and the synthetic antioxidants, 6-ethyoxy,1,2-dihydro 2,2,4-trimethylquinoline (ethoxyquin), 2,6 bis(1,1 dimethyethyl)-4-methylphenol (BHT), N,N-diphenyl-p-phenylene diamine (DPPD), bis-(diethyl thiocarbamoyl) disulfide (Antabuse), and 2 tertiary-butyl-4-methoxyphenol (BHA) on organic mercury-induced mortality was investigated in Japanese quail. When the synthetic antioxidants, ethoxyquin, BHT, and Antabuse were fed at 1% of the diet, they induced mortality. Ethoxyquin was less toxic in combination with mercury (Hg) than when it or mercury was given alone. Of the antioxidants tested at .5% of the diet, only Antabuse was toxic as shown by increased mortality. At .5% of the diet, both ethoxyquin and DPPD reduced mortality associated with organic Hg poisoning. Neither BHA nor BHT had any effect in reducing Hg toxicity. In fact, mortality from organic Hg was greater when organic Hg was given in combination with .5% BHT than when given alone. Vitamin E was equal or superior to all synthetic antioxidants tested in alleviating the toxicity of organic Hg poisoning. The cause of observed antioxidant protection during organic Hg stress is not known but the protection may result from the ability to scavenge free radicals generated by induction of in vivo peroxidation by the Hg compound.

Scanning electron microscopy of thin and soft shells induced by feeding calcium-deficient or vitamin D-deficient diets to laying hens.

A scanning electron microscopic study was conducted on shells from eggs laid by four groups of hens maintained on different types of diets: a) control, b) vitamin D3-deficient, c) Ca-deficient, and d) vitamin D3-deficient supplemented with 1,25-(OH)2D3. After 1 week for Ca-deficient hens and after 4 weeks for vitamin D3-deficient hens, the thickness of the shell decreased abruptly and numerous thin-shelled and soft-shelled eggs were laid. The study showed that with both Ca-deficient and vitamin D3-deficient diets, the outer layers of the shell (cuticle and spongy) were reduced or absent but the mammillary layer was present even in the thinnest soft-shelled egg. The order in which layers disappeared as treatment progressed was exactly the reverse of the order in which these layers are formed in normal eggs. No eggs were found without mammillary knobs, which suggests that the hens stop laying before Ca concentrations in blood become too low for the formation of the mammillary knobs. Uncalcified portions of the shell organic matrix were never found, suggesting that Ca deposition and matrix formation were inhibited simultaneously. The relationship between fibers of the shell membrane and mammillary knobs was preserved in all cases. The eggshells from hens on 1,25-(OH)2D3-supplemented diets were ultrastructurally indistinguishable from those of hens on diets adequate in vitamin D3.

Oral and intramuscular toxicity of inorganic and organic mercury chloride to growing quail.

The lethal toxicity of inorganic (HgCl2) and organic (CH3HgCl) mercury chloride was compared for Coturnix (Japanese quail, Coturnix japonica) of different ages from hatch through adulthood by single-dose acute oral and intramuscular injections and by a 5-d dietary trial. Sublethal mercury toxicity was studied by evaluation of plasma and brain cholinesterase activity. CH3HgCl was more toxic than HgCl2 in all tests at each age tested. LD50s consistently increased over the first 4 wk for both acute methods and both mercurials and then stabilized. The striking difference between single-dose acute and 5-d dietary tests was that CH3HgCl averaged about twice as toxic as HgCl2 by both acute methods, compared to 100 times as toxic by the dietary method. For example, at 2 wk of age, the oral LD50s for CH3HgCl and HgCl2 were 18 and 42 mg/kg and the dietary LC50s were 47 and 5086 ppm. When birds were fed HgCl2 and developed clinical signs of intoxication, they could recover once treatment was withdrawn; however, on CH3HgCl, clinical signs often commenced after treatment was withdrawn, and then actually intensified for several days and culminated in death.

The effects of vitamin D3 on leg abnormalities in broilers.

Variable quantities of vitamin D3 (D3) ranging from 0 to 20,000 IU D3/kg of diet were incorporated in a corn-soybean meal basal diet and fed to male broiler chicks from day-old until 56 days of age. Four experiments were conducted to determine: 1) the requirement of D3 for growth and bone calcification of normal chicks, 2) the requirement of D3 for deficient chicks, and 3) if feeding up to 20,000 IU D3/kg of diet affects bone metabolism or increases the incidence of leg abnormalities. The parameters measured included: body weight, feed consumption, feed conversion, mortality rate, ionic and total serum calcium, kidney calcium, total blood phosphorus, tibial ash, tibial breaking strength, and tibial length. In addition, the type and the incidence of occurrence of skeletal abnormalities were recorded. The data indicate that feeding less than 200 IU D3/kg of diet produced significantly lower body weights, feed consumption and conversion values, serum ionic calcium, total serum calcium, tibial breaking strength, and percentage tibial ash values (P less than .05). For example, rachitic chicks fed 200 IU D3/kg of diet had significantly lower (P less than .05) levels of ionic calcium at 21 days than rachitic chicks fed 300, 400, or 1,500 IU D3/kg of diet. The optimal level of D3 for 0 to 56-day-old male broiler chicks, based on body weight and percentage tibial ash, is 400 IU D3/kg of diet. The vitamin D3 requirement for deficient chicks repleted with D3 appears to be between 300 to 400 IU D3/kg of diet. Feeding 1,500 to 20,000 IU D3/kg of diet does not appear to alter bone metabolism or increase the incidence of leg abnormalities.

Effect of dietary calcium stress on plasma vitamin D3 metabolites in the egg-laying Japanese quail.

Experiments were performed to ascertain whether circulating levels of 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 varied in a cyclic manner during the 24-hr ovulatory period in Japanese quail hens and to assess the effects of dietary calcium restriction upon levels of the plasma vitamin D3 metabolites during that period. Birds fed a marginally-deficient calcium diet (1.7%) had significantly elevated plasma 1,25-dihydroxyvitamin D3 (.71 +/- .11 ng/ml, mean +/- SEM) compared with those fed high (3.5%) calcium (.35 +/- .04; P less than .01), although these values did not reveal any significant cyclic variation or correlation with known diurnal pulses in circulating 17 beta-estradiol. The magnitude of the plasma 1,25-dihydroxyvitamin D3 response to dietary calcium stress in some individuals was as great as 2.2 ng/ml, which are certainly among the highest values reported in any avian or mammalian species to date. These observations suggest that the total circulating level of plasma 1,25-dihydroxyvitamin D3 is not important in the direct cyclic regulation of laying hen calcium metabolism. The levels of free plasma hormone, target cell membrane permeability of the hormone, or regulation of cytosolic/nuclear 1,25-dihydroxyvitamin D3 receptor activity are potential aternate levels of the control of vitamin D3 mediated calcium metabolism in the quail hen.

Calcium metabolism and its control--a review.

It is now established that avians can only utilize the cholecalciferol form of vitamin D, which must be converted to the hormone 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] to perform normal calcium metabolism. Although 1,25(OH)2D3 is the final active form of vitamin D, hens fed only this form of vitamin D do not have normal hatchability of eggs. The problem appears to be caused by abnormal calcification and development of the embryonic beak. This appears to be caused by inadequate transport of 1,25(OH)2D3 into the egg. Although 1,25(OH)2D3 is not incorporated into the egg adequately, its precursor, 25-hydroxyvitamin D3 (25-OH-D3), is. The developing embryo however, can utilize 1,25(OH)2D and does so at least as early as Day 10 of incubation. During periods of maximal shell calcification and high circulating estradiol levels, the hen produces high levels of 1,25(OH)2D3. The kidney hydroxylase responsible for the final hydroxylation of the vitamin D hormone can be further stimulated by in vivo or in vitro administration of estradiol and, to a lesser extent, prolactin and parathyroid hormone. When eggs are not produced, as in the senescent or prepubertal stages of life, plasma 1,25(OH)2D3 concentrations are less than half that occurring during periods of active lay. Hens selected for their ability to produce thin or thick shells have 1,25(OH)2D3 concentrations in plasma that are positively correlated to their ability to produce egg shell.

Isolation of a 110 000 molecular weight protein in the purification of the nuclear chick intestinal 1,25-dihydroxyvitamin D-3 receptor.

A single protein band of molecular weight 110 000 has been obtained after sodium dodecyl sulfate polyacrylamide gel electrophoresis of purified 1,25-dihydroxyvitamin D-3 (1,25-(OH)2D-3) receptor from crude nuclear extracts of chick intestinal mucosa, prepared in the presence of the protease inhibitors phenylmethylsulfonyl fluoride and epsilon-aminocaproic acid. The nuclear extract was subjected to a six-step purification scheme, involving polymin P and ammonium sulfate fractionation, DNA-cellulose affinity chromatography, Sephacryl S-200 gel filtration, blue dextran-Sepharose and a final DNA-cellulose chromatographic step. The receptor was obtained in about 1% yield and was purified approx. 3700-fold from the nuclear extract, as assessed by specific activity. Single peaks were observed with 3H-1,25-(OH)2D-3-labeled crude nuclear extracts on Sephacryl S-200 gel filtration (Stokes' radius = 35.5 A) and sucrose density gradient centrifugation (3.5 S). Although the identity of the Mr 110 000 protein will remain inconclusive until methods for further characterization are available, it may represent evidence for a higher molecular weight form of the 1,25-(OH)2D-3 receptor than that observed previously.

Escleroterapia endoscopica de varizes de esofago. / Endoscopic sclerosis therapy of varices of the esophagus

Os autores estabelecem consideracoes sobre uma tecnica endoscopica, a escleroterapia de varizes de esofago. Discorrem sobre a importancia clinica-cirurgica da ruptura de varizes esofago-gastricas, o historico e a tecnica endoscopica empregada. Enfatizam, no que diz respeito a indicacao cirurgica, os precarios resultados obtidos com as cirurgias de desvio do sangue portal, onde se verifica elevado indice de encefalopatia porto-sistemica complicacao nao observada em niveis tao acentuados quando se emprega a anastomose esplenorenal distal. Descrevem ainda o emprego dos endoscopios rigidos, dos flexiveis e suas modificacoes, tambem os diferentes agentes esclerosantes empregados, as complicacoes, indicacoes e efetividade do metodo