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Biomedical subjects

A J Lewis

Publications and source records attributed to A J Lewis.

At least 91 records · Page 5Linked to original sources

Efficacy of the urea dilution technique in estimating empty body composition of pigs weighing 50 kilograms.

The efficacy of the urea dilution technique in estimating the empty body composition of pigs weighing 50 kg was evaluated in three trials using 17 contemporary (Large White X Landrace X Hampshire X Duroc) and 8 Nebraska Gene Pool X contemporary pigs. Blood samples were collected via ear catheter before infusion (-60, -30 and 0 min) and at various times (3 to 90 min) after urea infusion (2.16 mmol/kg live BW), and analyzed for plasma urea. Backfat thickness of live pigs from the contemporary line was measured ultrasonically. Pigs then were killed by euthanasic injection, and total bodies (with gastrointestinal contents removed) were analyzed for water, protein and fat. In Trials 1 and 2, there were linear relationships (P less than .001) between chemically determined body water and fat and between body water and protein. Urea space was related (P less than .05) to empty body components with few exceptions, but regression coefficients for urea space in Trial 3 were different from those of Trials 1 and 2. Inclusion of additional independent variables with urea space improved estimation of empty body components. Although backfat alone did not estimate empty body components (except fat) as well as urea space alone, the addition of other common independent variables resulted in better estimates using backfat than urea space. The results of this experiment indicate that the urea dilution technique can be used to estimate the body composition of growing pigs. However, the accuracy obtained depended on the population of pigs being investigated and was no greater than the accuracy with appropriate equations based on backfat.

Animal Feed↗

Neuropharmacology of pineal secretions.

A connection between pineal function and several psychiatric diseases has been shown recently. The diurnal and seasonal rhythmicity of melatonin production is associated with affective disorders and several types of endogenous depression. The cortisolmelatonin ratio was significantly higher in depressed individuals than in healthy controls. Alterations in melatonin secretion may also occur in non-affective psychiatric disorders, such as chronic schizophrenia. Antidepressants and other psychotropic drugs modify melatonin synthesis. In rodents, monoamine oxidase (MAO) inhibitors (e.g. pheniprazine, harmine or nialamide) increase pineal concentrations of the melatonin precursors, serotonin (5HT) and N-acetyl serotonin (NAS), by enhancing N-acetyl transferase activity. These drugs also increase melatonin, 5HT and NAS in the cerebrospinal fluid. Chronically administered tricyclic antidepressants reduce pineal and serum melatonin content in rodents. In humans, both the MAO-A selective inhibitor clorgyline and the non-selective inhibitor tranylcypromine increase serum melatonin levels. In contrast, serum melatonin remains unaltered by the MAO-B selective inhibitor L-deprenyl. The actions of other drugs on melatonin production, including lithium, propranolol, amphetamine and several monoamine precursors, are in accordance with their psychotropic effects and with their effect on monoamine functions.

Animals↗

Protein digestion in weanling pigs: effect of feeding regimen and endogenous protein secretion.

Protein digestion and absorption were measured in weanling pigs (5 wk of age) using a total digesta collection procedure. In the first experiment, the objective was to measure the fate of nitrogenous digesta as it passed from the stomach to the terminal ileum when pigs were either allowed ad libitum access to feed or were fed four equal meals per day. Pigs were fed a standard corn-soybean meal diet in this experiment. There were no differences in flow rate or retention time of dry matter or nitrogen, and no differences in apparent nitrogen digestibility between the two feeding regimens. More than 80% of the soluble protein in the stomach and 65% in the small intestine was between 2,000 and 15,000 molecular weight. The molecular weight profiles of the soluble proteins were relatively constant throughout the small intestine, indicating that the products of protein hydrolysis were absorbed rapidly. The objective of the second experiment was to compare protein digestion and absorption in pigs fed a corn-soybean meal diet with those fed a protein-free diet. The molecular weight profiles of soluble protein were similar for the two groups of pigs. The data indicate that most of the endogenous enzymes were hydrolyzed rapidly, since little soluble protein corresponding to the molecular weight of pancreatic enzymes was detected.

Absorption↗

Protein digestion in weanling pigs: effect of dietary protein source.

The digestion and absorption of dietary protein was measured in weanling pigs (5 wk of age). Diets containing corn and either dried skim milk (DSM), soybean meal (SBM) or corn gluten meal (CGM) were fed for 7 d, and the contents of the stomach and six segments of the small intestine were collected. Nitrogen digestibility increased linearly from the proximal duodenum to the distal ileum, and was highest for DSM, intermediate for SBM and lowest for CGM diets at the distal ileum. The content of free amino acids in digesta increased 8-fold (SBM and CGM) to 12-fold (DSM) between the stomach and the proximal duodenum and reached a maximum concentration in the distal jejunum. Digestion of DSM was more proximal than was that of SBM. Although there was some accumulation of small peptides in the duodenum with a subsequent decrease in the jejunum, the molecular weight profiles of the soluble proteins were relatively constant throughout the small intestine. Protein solubility and the rate of proteolysis in the stomach and upper small intestine were the primary factors that limited the digestion of SBM and CGM.

Absorption↗

Effect of exogenous thyroxine on the interval from weaning to estrus of the primiparous sow.

A total of 159 primiparous sows were fed 0 (C) or 675 mg/d of thyroprotein (TP) from d -2 until d 14 postweaning. Sows received 8 (LE) or 14 (HE) Mcal of ME/d during a 28-d lactation period. Plasma levels of 3,5,3'-triiodothyronine (T3) and 3,5,3',5'-tetraidothyronine (T4) were determined for d -4, -2, 0, 1, 2, 3, 5 and 7 postweaning. Sows consuming LE lost more weight and backfat during lactation (P less than .01) than HE sows. Litters of sows consuming LE gained less weight than litters of sows consuming HE (P less than .01). Thyroprotein increased plasma levels of both T3 and T4 (P less than .01), whereas energy intake had no effect (P greater than .10) on either of the two hormones. The response to thyroid hormone was not consistent across days postweaning (TP x day, P less than .01). Feeding TP increased T4 (P less than .01) on all days, and T3 was increased (P less than .05) on d 0, 2 and 3 postweaning. Thyroid hormones rose markedly following weaning regardless of TP level. Percentage of sows in estrus by d 7 postweaning for LE-C, LE-TP, HE-C and HE-TP were 80, 78, 92 and 90, respectively. Energy restriction during lactation resulted in fewer sows returning to estrus by d 7 (P less than .03) than those fed HE. However, feeding TP postweaning had no effect on return to estrus, suggesting that the effect of dietary energy restriction during lactation on the interval from weaning to first estrus is not mediated through postweaning thyroid hormone concentrations.

Animals↗

Anticholesteremic property of Lactobacillus acidophilus yogurt fed to mature boars.

Three strains of Lactobacilus acidophilus (LA) were isolated from the feces of mature boars that were not being fed antibiotics from the Nebraska Gene Pool (NGP). All three LA isolates were screened in vitro for anticholesteremic and antimicrobial activities. One strain, LA16, caused the greatest reduction in cholesterol and inhibited both Bacillus subtilis and Escherichia coli the most. LA16 was used to produce 16, 18.9-liter quantities of acidophilus yogurt (AY), over a period of 8 wk, for use as a feed ingredient in diets for the NGP boars. Colony forming units (cfu), pH, protein, energy, Ca and P were consistent across all 16 batches of yogurt. All of the 18 boars were fed a high-cholesterol diet for a period of 56 d at a rate of 2.268 kg/(hd.d) to furnish 6.661 g/(hd.d) of cholesterol. Nine of the boars then were fed 1.81 kg/(hd.d) of a second diet that was supplemented with .454 kg/(hd.d) of AY. The other nine boars were fed the original diet. Cholesterol intake was the same for the two dietary treatments. Blood samples were collected weekly from the brachial-jugular region and the sera were analyzed for lipids. Acidophilus yogurt reduced serum cholesterol (P less than .01) and low density lipoproteins (P less than .08), but it had no effect on serum triglycerides (P greater than .23) or on high density lipoproteins (P greater than .11).

Animal Feed↗

Influence of energy and protein intake during lactation on body composition of primiparous sows.

The effects of energy and protein intakes by 32 primiparous sows during a 28-d lactation on sow and litter performance and sow body composition and bone properties were examined. Dietary treatments were energy intakes of 8 (LE) and 16 (HE) Mcal of ME/d and protein intakes of 380 (LP) and 760 (HP) g of CP/d in a 2 x 2 factorial arrangement. Sows fed diets that were inadequate in either energy or protein lost more weight than did sows fed the HE-HP diet, but backfat losses were greater when energy intake was deficient than when protein was deficient. Carcass measurements were influenced in a similar manner, with energy intake affecting (P less than .001) backfat thickness and protein intake affecting (P less than .05) longissimus muscle area. Heart, kidneys and liver of sows fed LP diets weighed less (P less than .01) and contained less water and protein (P less than .05) than those of sows fed HP. Sows fed LE had heart, liver and viscera that weighed less (P less than .05) than those of sows fed HE. There was less fat (P less than .05) in the heart, lung, liver and viscera of sows fed LE than in those of sows fed HE. Carcass components of the supraspinatus muscle and standardized sections through the longissimus muscle and right shoulder weighed less (P less than .05) from sows fed LP rather than HP, and these components contained less water and protein. Sows fed the LE diets had less fat in the loin soft tissue section, right shoulder section and supraspinatus muscle than sows fed HE. Bone composition and strength were not influenced by dietary treatment. The composition of weight lost during lactation was diet-dependent. Sows fed diets that were deficient in protein but adequate in energy lost large amounts of protein from muscles and internal organs. Energy deficiency resulted primarily in fat loss.

Adipose Tissue↗

Quantitative evaluation of myocardial injury induced by acute cerebral ischaemia and its prevention by beta 1-adrenergic blockade. An ultrastructural morphometry study.

The protective effects of beta 1-adrenergic blockade with metoprolol (Betaloc Astra) were demonstrated in the gerbil model of myocardial injury provoked by acute ischaemic brain lesions. The myocardial injury was reversible and lipid droplet accumulation was its most striking morphological feature. These droplets were easy to measure in EM photographs and their size was expressed as percentage of sarcoplasmic volume. The EM data of fat accumulation were compared in hearts of carotid-ligated animals with and without metoprolol pretreatment, and in animals with the carotid isolated only, at standard intervals 3-48 h after operation. While in carotid-ligated-only animals the average myocardial fat contents rose to a peak of 1.9% at 10 h, in metoprolol pretreated animals the amount of fat was always significantly lower and started to return earlier to basal values (peak at 6 h, 1.1%). In carotid-isolated-only animals, fat accumulation peaked at 6-10 h (1.1%) and returned quickly to normal levels (0.34 +/- 0.18%). This effective pharmacological blockade with metoprolol strongly supports the concept of catecholamine mediation between acute intracranial lesions and myocardial injury. The background and significance of myocardial fat accumulation is discussed. The EM morphometry of fat droplets appears to be a suitable tool for quantification of reversible myocardial damage most useful for experimental evaluation of cardioprotective measures. As changes in succinic dehydrogenase histochemistry (from 'myofibrillar' to 'granular' pattern) correlated with EM measured fat accumulation, the simplicity and speed of the SDH method recommends itself for fast orientation about presence of myocardial damage.

Acute Disease↗

Sarcoma metastatic to the brain.

Five patients with nonlymphomatous sarcoma metastatic to the brain are presented and the literature reviewed. In 50 patients, brain metastasis was verified pathologically and some case data were available, including the five reported here. In five patients, there was pathologic verification but no case data. Thirty-nine other patients were found without such verification. Reportedly, most types of sarcomas are able to metastasize to the brain, and are represented in these 94 patients. Fibrosarcoma and alveolar soft-part sarcoma tumors metastasize to the brain without regard to treatment technique. There may be a group of tumors, including malignant fibrous histiocytoma, rhabdomyosarcoma, and perhaps leiomyosarcoma and osteosarcoma, in which the incidence of brain metastases has increased with improved sarcoma chemotherapy (CT). In this group particularly, but also in alveolar soft-part sarcoma and others, the presence of lung metastases may increase the probability of brain metastasis occurring subsequently.

Adolescent↗

Do anti-allergic drugs or anticholinergic drugs have a role in the treatment of asthma?

After the successful introduction of sodium cromoglycate (SCG) for the treatment of asthma, emphasis was placed on its apparent novel mechanism of action, the inhibition of inflammatory mediator release from mast cells. This opened the flood gates for numerous SCG-derivatives, many with oral efficacy and improved potency. The majority of these compounds were ineffective clinically, casting doubts on SCG's mechanism of action and questioning the importance of mast cells in asthma. However, information on the heterogeneity of mast cells has directed recent drug screening to new, more relevant models of asthma involving other inflammatory cells. Consequently, nedocromil sodium has emerged to perhaps lead a new generation of antiallergic drugs. Bronchodilator anticholinergic drugs have met with a resurgence of interest of late with the development of a number of quaternary ammonium homologues of atropine. While not as effective as beta-adrenoceptor agonists in asthma they are particularly effective in chronic obstructive pulmonary disease. Drugs with anticholinergic properties and associated beneficial effects are also under investigation.

Animals↗

The NINCDS-ADRDA Work Group criteria for the clinical diagnosis of probable Alzheimer's disease: a clinicopathologic study of 57 cases.

Neuropathologic confirmation is required to validate the NINCDS-ADRDA Work Group criteria for the clinical diagnosis of Alzheimer's disease (AD). Neuropathologic inclusion and exclusion criteria for AD, however, are not uniform. The purpose of this investigation was to examine the confirmation rate for the Work Group criteria against differing neuropathologic criteria for AD. The sample consisted of 57 cases, 22 of which had received a clinical diagnosis of AD. Nine neuropathologic criteria for AD were applied in a blind fashion to each of the 57 cases. Our results indicated that, depending on the neuropathologic criteria applied, the clinicopathologic agreement ranged from 64% to 86%. These findings demonstrate the need for universally accepted neuropathologic and clinical criteria for AD.

Aged↗

Reversible myocardial damage in gerbil brain ischaemia and its prevention by beta-adrenergic blockade.

Acute cerebral infarction in gerbils, produced by unilateral carotid ligation, was used as a model to investigate secondary myocardial changes. The extent of the myocardial damage revealed by succinic dehydrogenase (SDH) histochemistry and by release of myocardial creatine phosphokinase (MB-CK) was measured in gerbils sacrificed from 3 to 48 h after either carotid ligation, carotid isolation only or skin incision only. For technical reasons dead animals were excluded from analysis. Of surviving ligated animals 74% developed neurological deficits related to brain ischaemia. A significant weight increase in the ipsilateral hemisphere was found at 6-10 h, and maximal histological damage at 16 h, both partially reversible thereafter. Non-ligated animals did not develop neurological changes, and showed neither brain swelling nor cerebral histopathology. Extensive cardiac damage was shown by the SDH method from 3 h postoperatively, and confirmed by the elevated serum levels of MB-CK in the carotid-ligated group. The SDH changes were identical with those described in the hearts of patients with acute intracranial lesions, and appeared to be reversible. The effect of beta-adrenergic blockade was assessed in this model. Metoprolol tartrate injected intraperitoneally 3 h before and 1 h after carotid ligation (10 mg/kg each dose) significantly decreased the extent of myocardial damage as estimated both with SDH histochemistry and MB-CK serum levels. It had no effect on the ischaemic brain changes. These results strongly support the concept of catecholamine mediation of myocardial injury resulting from acute brain lesions.

Animals↗

Effects of thiazinamium chloride and other antihistamines on phosphatidylcholine secretion in rat type II pneumocyte cultures.

Thiazinamium chloride (TCl) stimulated phosphatidylcholine secretion in cultures of adult rat type II pneumocytes in a concentration-dependent manner in the range 10(-9)-10(-6) M. At the optimal concentration, secretion was stimulated by 46% which is approximately half the stimulatory effect of the beta-agonists terbutaline and isoproterenol. TCl did not increase the rate of choline incorporation into cellular phosphatidylcholine or of lactate dehydrogenase release so its effect on secretion was not secondary to phosphatidylcholine synthesis or cell injury. Since TCl has antihistaminic properties, we examined the effects of other antihistamines. The H-1 antagonists promethazine, which is structurally similar to thiazinamium, and pyrilamine, which has a different structure, also stimulated secretion but the H-2 antagonist, cimetidine, did not. The effects of TCl and pyrilamine were additive to those of terbutaline, suggesting that the mechanisms of action of the antihistamines and the beta-agonist were different. Although we were unable to demonstrate an inhibitory effect of histamine itself on either basal or terbutaline-stimulated phosphatidylcholine secretion, it is possible that histamine plays a regulatory role in lung surfactant secretion.

Animals↗

Chronic regenerative changes in the spinal cord after cord compression injury in rats.

Long-term regenerative changes and pathological effects after acute compression injury of the spinal cord were studied in rats. Twenty adult female Wistar rats underwent cord injury by the extradural clip compression technique at T6-7. Following injury, extradural electrodes attached to receiver-stimulators that were implanted subcutaneously were placed proximal and distal to the injury site. The animals were maintained in cages with electromagnetic fields created by encircling antennae. The control animals were in a field adjusted to a frequency below the sensitive frequency range of the receiver-stimulators so that they received no spinal cord stimulation. After 15-20 weeks of continuous spinal cord stimulation, histological sections of the cords were assessed and scored blindly for pathological changes including magnitude and extent of cord injury, and cystic cavitation, and for regenerative changes including proliferation of axons, Schwann cells and ependymal cells, and formation of myelin. In all 20 animals, there was a complete absence of normal cord tissue at the injury site, and cystic cavitation was frequently present at the injury site and beyond. Extensive regenerative changes were seen in all animals including regeneration of axons, Schwann cells and ependymal cells, and formation of myelin. Statistical analysis did not show a significant difference between treatment and control groups.

Animals↗

Inhibition of leukotriene-induced contraction of guinea pig trachea by 5-lipoxygenase inhibitors.

The effects of the 5-lipoxygenase inhibitors nordihydroguiaretic acid (NDGA), 5, 8, 11, 14-eicosatetraynoic acid (ETYA), 1-phenyl-3-pyrazolidone (phenidone) and BW-755c, on the contractile response to LTC4 or LTD4 were examined on the isolated guinea pig trachea. Responses to either LTC4 or LTD4 were obtained on indomethacin treated tissues, in the presence of either L-serine-borate complex or L-cysteine, respectively, to inhibit metabolic conversion of the leukotrienes. NDGA (30 microM) and ETYA (100 microM) produced a selective competitive antagonism of LTD4-induced contractions, while phenidone antagonized both LTC4- and LTD4-induced responses in a non-competitive manner. In contrast, BW-755c (30 microM) did not significantly antagonize LTC4 or LTD4 concentration-response curves. The results suggest that leukotriene antagonism may be produced by large concentrations of some 5-lipoxygenase inhibitors.

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

Immunological abnormalities in rats with adjuvant-induced arthritis--II. Effect of antiarthritic therapy on immune function in relation to disease development.

The effects of the experimental immunomodulatory agent tilomisole (Wy-18,251; (3-(p-chlorophenyl) thiazolo [3,2-a]benzimidazole-2-acetic acid) on disease development and immune function in rats with adjuvant-induced arthritis was assessed in comparison with indomethacin and levamisole. Daily p.o. administration of tilomisole (100-200 mg/kg/day) to M. butyricum-injected rats significantly reduced both edema and bone erosion in the uninjected paw. Moreover, tilomisole treatment restored to normal the diminished Con A-induced proliferative response and IL 2 synthesis observed in spleen cells from arthritic rats, but had no effect on macrophage IL 1 production. In contrast, levamisole treatment (25 mg/kg/day) of arthritic rats improved splenic immune function but did not influence paw edema or bone erosion. Conversely, indomethacin (1 mg/kg/day) significantly reduced paw edema and bone erosion but did not improve the deficient proliferative response or IL 2 synthesis by "arthritic" spleen cells. These results indicate that tilomisole possesses combined antiinflammatory and immunomodulatory activity in adjuvant-arthritic rats which is distinctly different from the effects of either indomethacin or levamisole. Moreover, these data suggest that tilomisole has potential disease-modifying activity in arthritis, which is currently being more closely examined in clinical trials.

Animals↗