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Biomedical subjects

A J Lewis

Publications and source records attributed to A J Lewis.

At least 127 records · Page 7Linked to original sources

Threonine requirement of pigs weighing 5 to 15 kg.

Weanling crossbred pigs (avg initial wt 6.4 kg) were fed diets containing six levels of threonine to determine the threonine requirement of young pigs fed diets somewhat similar to those used in commercial swine production. The diets (16% crude protein) were composed primarily of grain sorghum, oat groats and soybean meal supplemented with minerals, vitamins, lysine, tryptophan, methionine and isoleucine, and were calculated to be adequate in all nutrients except threonine and crude protein. Threonine levels were .53, .57, .62, .68, .75 and .83% of the diet. There were two trials, each with 96 pigs. The pigs were fed the experimental diets for 28 d. The addition of threonine increased weight gain (P less than .02) and feed efficiency (P less than .001), with most of the response occurring between .53 and .68% threonine. There was little further response when threonine was increased above .68%. Plasma threonine concentrations increased as dietary threonine increased, with a sharp rise when dietary threonine exceeded .68%. Concentrations of most other essential amino acids in the plasma declined in response to increasing dietary threonine, and reached minimum values at either .68 or .75% threonine. Plasma urea concentrations decreased as threonine was increased in the diet, reaching a plateau at .68% dietary threonine. The data indicate the young pigs weaned at 3 to 4 wk of age require approximately .70% threonine.

Animals↗

Zinc-amino acid complexes for swine.

Two experiments were conducted to determine the effect of sources of dietary zinc on gain, feed conversion and blood and bone traits of swine. In the first experiment 96 pigs were used in a 28-d study. The pigs were fed diets with no supplemental Zn or with either 9 or 12 ppm supplemental Zn from zinc sulfate (ZnSO4), zinc methionine (ZnMet) or zinc methionine with picolinic acid (ZnMet w/PA), each with or without 5% added corn oil. There were differences (P less than .05) in average daily gain (ADG) and average daily feed intake (ADFI) between the pigs fed the two organic Zn sources, with those fed ZnMet w/PA showing the better gains and feed conversion. However, neither organic Zn source resulted in pig performance that was different from either the diet with no supplemental Zn or the diets supplemented with Zn from ZnSO4. In the second experiment the same dietary Zn sources and treatments were fed as in Exp. 1 except that corn oil was deleted as a variable. No differences in ADG, ADFI, feed/gain (F/G) or in changes in serum Zn or Cu were observed among treatments during either the 21-d nursery or the 56-d growing periods. During the subsequent 56-d finishing period ADG and ADFI were greater (P less than .01) for pigs fed the Zn-supplemented diets than for those fed the diets without supplemental Zn. There were no differences among treatments in F/G during the finishing period. Zn content of bone ash was lower (P less than .01) in the non-Zn-supplemented pigs. These data suggest that the Zn sources used are of similar biological value and do not support the theory that picolinic acid aids Zn absorption.

Amino Acids↗

Effect of dry, high-moisture and reconstituted normal and high-lysine corn diets and particle size on energy and nitrogen metabolism in growing swine.

Two metabolism studies were conducted with 24 (Exp. 1) and 36 (Exp. 2) crossbred barrows (initial weight 35 kg) to determine the effect of corn type--normal corn (NC) and high-lysine corn (HLC)--and storage method--dry (D), high-moisture (HM) and reconstituted (RC)--on energy and N digestibility. Diets fed in Exp. 1 were: 1, NC-soybean meal formulated at .78% lysine (dry matter basis); 2, HLC-soybean meal containing the same amount of corn as diet 1 (.87% lysine); 3, HLC-soybean meal with the same lysine level as diet 1. In Exp. 1, dry matter, energy and N digestibilities were not different between corn types or lysine levels (P greater than .16). These results indicate that energy and N digestibility of HLC in typical diets for growing swine are similar to those for NC diets when both are balanced on a lysine basis. Also, replacing NC with HLC on an equal-weight basis did not affect energy and N digestibility. In Exp. 2 six diets balanced on an isonitrogenous and dry-matter basis were tested. Normal corn and HLC diets, which had been stored by three different methods (D, HM and RC) were arranged in a 2 X 3 factorial plan. There were no differences between corn types in dry matter, energy and N digestibilities. The HM and RC treatments had larger particle sizes than the dry corn diets. For diets balanced on an isonitrogenous basis, dry corn storage improved energy digestibility (P less than .10). Reconstitution appeared to improve energy balance and N digestibility of HLC, while HM storage improved energy balance and N digestibility of NC.

Animal Feed↗

The effects of sorbic acid in high moisture sorghum grain diets on performance of weanling swine.

Three experiments were conducted with 288 weanling pigs to determine the effects of sorbic acid (SA) added to dry (DSG), high moisture (HMSG) or reconstituted (RSG) sorghum grain diets on gains and feed conversion. Dietary treatments for Exp. 1 were: DSG with and without .1% SA; HMSG with .1% SA and RSG with .1% SA. The DSG diets were fed ad libitum. The HMSG and RSG diets were mixed fresh from oxygen-limiting storage every 3 and 7 d and were also fed ad libitum. Pigs fed RSG diets consumed more feed than those fed HMSG diets (P less than .08). Performance was similar between pigs fed DSG diets without or with SA. Dietary treatments for Exp. 2 and 3 consisted of sorghum grains reconstituted to two moisture contents (MC), with additions of either 0, .05 or .1% SA. The diets were mixed fresh from oxygen-limiting storage every 7 d and fed ad libitum. In Exp. 2 and 3, pigs fed the higher MC diets were more efficient in feed conversion (P less than .03) than those fed the lower MC diets. In Exp. 3, a quadratic response (P less than .04) for average daily gain and average daily feed intake was observed for the main effect of SA. Feed efficiency improved (P less than .05) in a linear fashion as SA levels were increased in the diets. The results of these experiments indicate that weanling pigs may be fed HMSG or RSG without adverse effects on pig performance. Inconsistencies in pig response to SA were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Feed↗

Effect of dietary fluorine on growth, blood and bone characteristics of growing-finishing pigs.

Three hundred eighty-four growing-finishing pigs were used in two experiments to determine the effect of dietary fluorine (F) on growth, blood and bone physical characteristics. Fourteen dietary treatments were formulated by supplementing F (as NaF) to a milo-soybean meal basal diet (7 ppm F) to provide levels of 7, 132, 257, 382, 507 and 632 ppm F for Exp. 1, and 7, 25, 43, 61, 79, 97, 115 and 133 ppm F for Exp. 2. Average daily gain (ADG) and average daily feed intake (ADFI) were not affected (P greater than .09) when F was fed at levels between 7 and approximately 132 ppm. Average daily gain and ADFI were reduced (P less than .0001) for pigs consuming diets with F concentrations greater than 132 ppm (Exp. 1). Feed conversion was not affected (P greater than .17) by any level of F fed. Serum F and alkaline phosphatase concentrations increased (P less than .01) with increasing dietary F levels. Serum and bone Ca and P concentrations were not affected (P greater than .13) by dietary F levels (Exp. 1). In Exp. 1 and 2, bone F increased (P less than .0001) and metatarsal stress and modulus of elasticity decreased (P less than .0001) as level of F increased in the diet. Bone thickness decreased quadratically (P less than .02) in Exp. 1 and linearly (P less than .0007) in Exp. 2 with increased dietary F levels. Scanning electron microscopy showed an increase in porosity of bones from pigs fed the higher levels of F. Growing-finishing pigs were able to tolerate approximately 132 ppm F for growth, but all of the F levels (greater than or equal to 7 ppm) fed in these two experiments affected bone integrity.

Alkaline Phosphatase↗

Immunomodulating activity of Wy-41,770 (5H-dibenzo[A,D]cyclohepten-5-ylidene) acetic acid.

The immunomodulatory effects of Wy-41,770 (5H-dibenzo[a,d]cyclohepten-5-ylidene) acetic acid, were compared to levamisole and indomethacin in several in vivo models. In the Jerne plaque assay, Wy-41,770 (1 and 100 mg/kg, p.o.) administered on day 1 after sensitization suppressed IgM plaque forming cells (PFC) while levamisole was active when given on days 1 and 2 after sensitization. In contrast, indomethacin administered on days 2 and 3 after sensitization increased PFC. In the rat experimental allergic encephalomyelitis (EAE) model, Wy-41,770 reduced limb paralysis at 10 and 100 mg/kg, p.o. when dosed before sensitization. Indomethacin was active too when predosed in the rat EAE model. In the methylated bovine serum albumin model (MBSA) delayed hypersensitivity (DH) model in mouse, Wy-41,770 (10 mg/kg, p.o.) given on day 1 prior to sensitization and day 2 after sensitization in subliminally sensitized animals augmented the DH response while inhibiting the subliminal DH response when administered at 6 hr after challenge. Levamisole showed similar activity in this subliminal model while indomethacin given 6 hr post challenge was inhibitory. All three drugs were inactive in mice normally sensitized to MBSA at the same drug regimens. In guinea pigs, subliminally sensitized to tuberculin, Wy-41,770 (10 and 100 mg/kg, p.o.) and levamisole augmented the DH response. No changes in DH response were observed for both drugs in normally sensitized guinea pigs. In the rat adjuvant arthritic model, Wy-41,770 (5 and 15 mg/kg, p.o.) inhibited day 16 uninjected paw edema and restored significantly the depressed proliferative responses to mitogen by spleen cells taken from the same arthritic rats at day 16. The moderate immunomodulatory activity of Wy-41,770 may contribute along with its antiinflammatory activity, towards the treatment of arthritic diseases.

Acetates↗

Epidermoid tumor: an unusual cause of ossification within the spinal canal.

Epidermoid tumors of the spinal canal are rare. We report two patients with intraspinal lesions and radiographically evident calcification. One proved to have an epidermoid tumor. Although the tissue diagnosis in the second was not definitive, it suggested an epidermoid tumor as well. Radiographically visible ossification or calcification has not been reported before in intraspinal epidermoids.

Calcinosis↗

Inhibition of platelet and neutrophil phospholipase A2 by hydroxyeicosatetraenoic acids (HETES). A novel pharmacological mechanism for regulating free fatty acid release.

The present study demonstrated that acid-extracted platelet phospholipase A2 (PLA2) exhibited marked hydrolytic activity against both [1-14C]oleic acid- and [1-14C]arachidonic acid-labeled Escherichia coli. The rate of hydrolysis was linear up to 30 min and was directly proportional to the amount of enzyme added to the reaction mixture. The data further indicated that 5-hydroxy-6,8,11,15-eicosatetraenoic acid (5-HETE) inhibited platelet PLA2 in a dose-dependent manner (IC50 = 42 microM), whereas 5-lactone HETE had no inhibitory effect up to 100 microM. The degree of inhibition of PLA2 activity was unaffected by Ca2+ concentrations but was reduced in the presence of increasing amounts of E. coli substrate. Both 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE) and 15-hydroxy-5,8,11,13-eicosatetraenoic acid (15-HETE) also inhibited platelet PLA2 activity (IC50 = 26 and 72 microM respectively). Furthermore, the inhibitory effects of these monoHETEs were confirmed with a PLA2 preparation derived from rat neutrophils. Thus, these data suggest a novel pharmacological action of HETEs on PLA2 which may have potential ramifications in the regulation of arachidonic acid metabolism.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

Modulation by hydroxyeicosatetraenoic acids (HETEs) of arachidonic acid metabolism in mouse resident peritoneal macrophages.

The effects of 5-, 5-lactone, 12- and 15-hydroxyeicosatetraenoic acids (HETEs) on the synthesis of leukotriene C4 (LTC4), thromboxane B2 (TXB2) and prostaglandin E2 (PGE2) by mouse resident peritoneal macrophages incubated with zymosan particles (100 micrograms/ml) were investigated. Zymosan phagocytosis stimulated a 110-, 16-, and 16-fold increase in LTC4, TXB2 and PGE2 synthesis, respectively. 15-HETE inhibited zymosan-induced LTC4 (IC50 = 1.1 microM) and TXB2 (IC50 = 38.9 microM) synthesis; in contrast, 15-HETE induced a consistent but variable enhancement of PGE2 synthesis. 5-HETE (IC50 = 15 microM), 5-lactone HETE (IC50 = 10.4 microM) and 12-HETE (IC50 = 13 microM) also inhibited LTC4 synthesis but they were approximately an order of magnitude less potent than 15-HETE. Furthermore, 5-HETE, 5-lactone HETE and 12-HETE inhibited TXB2 (IC50 = 20.4, 16.9 and 11.8 microM, respectively) and PGE2 (IC50 = 38.6, 2.3 and 11.6 microM, respectively) synthesis. Thus, monoHETEs exert modulatory actions on arachidonic acid metabolism and the different isomers of HETE differ quantitatively and qualitatively in their actions.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

Differential effects of monoHETEs (monohydroxyeicosatetraenoic acids) on arachidonic acid metabolism in glycogen-elicited rat polymorphonuclear leukocytes.

We investigated the effects of monohydroxyeicosatetraenoic acids (monoHETEs) on lipoxygenase- and cyclooxygenase-catalyzed reactions in glycogen-elicited rat PMNs challenged with A23187 and exogenous [14C]arachidonic acid. A23187 (10 microM) stimulated a 10-, 4-, 1.7- and 1.8-fold increase in the synthesis of radiolabeled 5-HETE, LTB4, TxB2, and PGE2 by rat PMNs. Addition of 5-HETE, 5 lactone-HETE, 12-HETE, and 15-HETE led to a dose-related reduction in [14C]5-HETE and [14C]LTB4 synthesis by these cells. These monoHETEs also inhibited [14C]TxB2 synthesis, but only 5-HETE and 5 lactone-HETE inhibited the synthesis of [14C]PGE2. Both 12-HETE and 15-HETE failed to reduce the formation of [14C]PGE2. These results suggest that monoHETEs differ significantly in their effects on arachidonic acid metabolism in rat PMNs and may play a role in modulating the synthesis of both lipoxygenase and cyclooxygenase products.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

Modulation of mouse ear edema by cyclooxygenase and lipoxygenase inhibitors and other pharmacologic agents.

Inhibitors of arachidonic acid (AA) metabolism and other pharmacologic agents were evaluated against ear edema produced in mice by tetradecanoylphorbol acetate (TPA) or AA. Drugs were administered orally and topically either 30 min prior to AA or 30 min after TPA, except for steroids which were administered 2.5-3 hr prior to AA. Several cyclooxygenase (CO) inhibitors including indomethacin, aspirin, piroxicam and timegadine were without effect when administered orally against either irritant; the same drugs inhibited TPA edema when they were administered topically. Mixed CO/lipoxygenase (LO) inhibitors, phenidone and BW755C, were active orally against AA edema (ED50S of 84 and 65 mg/kg, respectively) and against TPA edema (ED50S of 235 and 88 mg/kg, respectively). Phenidone was more active topically against AA edema (ED50, 0.1 mg/ear) than BW755C (ED50, 2.8 mg/ear); however, BW755C was more active topically against TPA edema (ED50, 0.2 mg/ear) than phenidone (ED50, 0.6 mg/ear). Methylprednisolone was very effective in the AA (oral ED50, 17 mg/kg; topical ED50, greater than 1 mg/ear) and TPA models (oral ED50, 4.3 mg/kg; topical ED50, 0.03 mg/ear. MK-447 was topically and orally effective only in the TPA model. Not surprisingly, drugs were more effective topically than orally in both mouse ear edema assays. The models were somewhat selective for CO and CO/LO inhibitors; however, dapsone was orally effective in the ear models, and a number of mediator antagonists and CNS drugs, especially anti-psychotics, were topically active primarily against TPA edema. These models may be useful for the detection of in vivo activity of CO/LO or 5-LO inhibitors.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗

The antiinflammatory activity of the immunomodulator Wy-18,251 (3-(p-chlorophenyl)thiazolo[3,2-a]benzimidazole-2-acetic acid).

The antiinflammatory activity of the immunomodulatory agent Wy-18,251 (3-(p-chlorophenyl)thiazolo-[3,2-a]benzimidazole-2-acetic acid) was examined using a variety of antiinflammatory, analgesic and antipyretic animal models in comparison to aspirin, levamisole and indomethacin. The acute antiinflammatory and analgesic activity of Wy-18,251 (ED50 = 100-200 mg/kg, p.o.) was similar to aspirin, but in contrast to aspirin Wy-18,251 failed to demonstrate antipyretic activity. Wy-18,251 (10-100 mg/kg, p.o.) also inhibited chronic inflammatory responses in the adjuvant- and collagen-induced arthritis models. Wy-18,251 was a modest inhibitor of prostaglandin biosynthesis but did not inhibit either 5- or 15-lipoxygenase enzymes. Wy-18,251 (up to 480 mg/kg, p.o.) produced little gastrointestinal pathology in 16 h fasted rats. The combined immunomodulatory and antiinflammatory activity of Wy-18,251 suggests that this agent may have therapeutic promise in certain immunoinflammatory diseases including rheumatoid arthritis.

Adjuvants, Immunologic↗

Comparison of inflammatory changes in established type II collagen- and adjuvant-induced arthritis using outbred Wistar rats.

Type II collagen- and adjuvant-induced arthritis in outbred Wistar rats were compared using parameters that measured the inflammatory response, cellular and humoral immunity, blood protein changes, drug metabolism and histopathological and bony changes of the inflamed paws. There was a lesser incidence (40-70%) and severity of collagen disease than the adjuvant model (incidence approximately 100%). The use of MDP increased the incidence and severity of collagen arthritis. The acute phase protein response (plasma fibrinogen) was similar in both models during the peak of inflammatory response. Drug metabolism was inhibited in both type II collagen boosted with MDP or M. butyricum sensitized rats with arthritis; however, arthritic rats sensitized with collagen alone produced no inhibition. Only collagen arthritic rats produced type II collagen antibody and exhibited delayed hypersensitivity to type II collagen. Bony changes as assessed by radiographic evaluation were more severe in adjuvant arthritic rats than in the collagen arthritic model; histopathological findings from these animals confirmed this observation. The primary lesions in both models were periosteal reaction of the bone and ankylosis. Several classes of antiarthritic drugs were compared in both models using paw edema measurements and bony changes by radiographic evaluation. Drugs with inhibitory activity in both models were indomethacin, methylprednisolone, D-penicillamine and gold sodium thiomalate. Levamisole, chloroquine and auranofin were inactive in both models.

Animals↗

Adenoid cystic carcinoma: an unusual neurosurgical entity.

Adenoid cystic carcinoma, or cylindroma, usually presents in the salivary glands or in the upper respiratory passages. We report an unusual case of adenoid cystic carcinoma in a 45-year-old woman who presented with a three-year history of progressive right trigeminal sensory palsy, most pronounced in the second division. There was, in addition, a right trigeminal motor palsy and a partial right 6th nerve palsy. CT scanning showed only a small soft tissue mass spanning an enlarged right foramen ovale. Solid adenoid cystic carcinoma was resected from Meckel's cave via a middle cranial fossa approach. A subsequent biopsy of the right maxillary antral mucosa found tumor tissue. We concluded that the tumor originated in the maxillary antrum and spread posteriorly along the infraorbital nerve to enlarge in the foramen ovale. Radiation to a total of 5,000 cGy was given. At 22 months there was neither radiographic nor clinical evidence of recurrence. At 30 months, the development of unsteady gait signalled the presence of recurrent tumor extending backwards from Meckel's cave into the right cerebello-pontine angle.

Carcinoma, Adenoid Cystic↗

IgDK multiple myeloma presenting as unilateral proptosis.

A 72-year-old woman presented with painful proptosis of the right eye and a large destructive tumour of the middle cranial fossa. A diagnosis of IgDK multiple myeloma was made, based on histopathologic and immunologic studies of the biopsy. Biochemistry and bone marrow examination further confirmed the myeloma as IgDK type. The clinical, radiological, and pathological findings are presented. The patient was treated with radiotherapy with satisfactory results.

Aged↗

The topical effects of Wy-41,195 [2-cyano-3-(methylamino)phenylamino] oxoacetic acid, sodium salt and disodium cromoglycate in the rat passive eyelid anaphylaxis.

Wy-41,195 demonstrated significant inhibitory effects (54-60%) when administered topically at 0.25-2% concentrations in a rat passive eyelid anaphylaxis assay. In contrast, topically applied disodium cromoglycate (DSCG) showed non significant inhibition at these concentrations. The potency of Wy-41,195 was more than 8 times greater than DSCG, and this compound may be an effective topical agent in man in preventing allergic and associated conditions.

Administration, Topical↗