bluuebunny/crossref_metadata_2025 huggingface dataset:
Cystic fibrosis affects chloride and sodium channels in human airway epithelia
Authors: Duszyk Marek , French Andrew S. , Man S. F. Paul
Published: April 2011

Abnormalities of epithelial function in cystic fibrosis (CF) have been linked to defects in cell membrane permeability to chloride or sodium ions. Recently, a class of chloride channels in airway epithelial cells have been reported to lack their usual sensitivity to phosphorylation via cAMP-dependent protein kinase, suggesting that CF could be due to a single genetic defect in these channels. We have examined single chloride and sodium channels in control and CF human nasal epithelia using the patch-clamp technique. The most common chloride channel was not the one previously associated with CF, but it was also abnormal in CF cells. In addition, the number of sodium channels was unusually high in CF. These findings suggest a wider disturbance of ion channel properties in CF than would be produced by a defect in a single type of channel.Key words: ion channels, cystic fibrosis, airway, epithelium.
Evidence from immunoblotting studies on uncoupling protein that brown adipose tissue is not present in the domestic pig
Authors: Trayhurn Paul , Temple Norman J. , Aerde Johny Van
Published: April 2011

Adipose tissues and other tissues of the pig have been examined for the presence of the mitochondrial "uncoupling protein," characteristic of brown adipose tissue, in order to assess whether brown fat is present in this species. Mitochondria were prepared from various tissues and the proteins separated on the basis of molecular weight by sodium dodecyl sulphate – polyacrylamide gel electrophoresis. Immunoblotting procedures were then used to probe for uncoupling protein, employing a rabbit anti-(rat uncoupling protein) serum. Pigs were examined at 4 days, 4 weeks, and 8 weeks of age. No evidence for the presence of uncoupling protein was found at any of these ages. The protein was, however, readily detected in brown adipose tissue from rats, mice, golden hamsters, guinea pigs, Richardson's ground squirrel, and lambs. An additional group of pigs was acclimated to the cold (10 °C) for a period of 10 days prior to the examination of tissues, but again uncoupling protein was not detected in any tissue. These results indicate that uncoupling protein is either absent from adipose tissues of the pig or is present at such a low concentration that it is unlikely to support thermogenesis. It is concluded that the pig does not contain adipose tissue that is functionally "brown;" adipose tissues in this species appear to be exclusively "white."Key words: brown adipose tissue, white adipose tissue, uncoupling protein, thermogenesis, immunoblotting.
Effect of dietary sodium intake on the pressor reactivity to angiotensin II in rats with experimental cirrhosis of the liver
Authors: Villamediana L. M. , García-Villalón Angel L. , Caramelo Carlos , López-Novoa José M.
Published: April 2011

The present experiments were designed to evaluate vascular reactivity to angiotensin II in rats with experimental cirrhosis of the liver (induced with CCl4 and phenobarbital) before ascites appearance. The systemic pressor response to angiotensin II in conscious animals and the contractile effect of angiotensin II in isolated femoral arteries were studied. In addition, the effect of high sodium intake on these parameters was also analyzed. Both renin and aldosterone plasma concentrations were similar in control and cirrhotic rats on the normal or on the high sodium diet. Basal mean arterial pressure was higher in control rats than in cirrhotic rats on the normal sodium (116 ± 4 vs. 101 ± 4 mmHg (1 mmHg = 133.3 Pa),p < 0.05) or on the high sodium diet (118 ± 7 vs. 98 ± 6 mmHg). No differences in plasma renin activity or plasma aldosterone were found between control and cirrhotic rats. Upon injection of angiotensin II, control rats show a dose-dependent increase in mean arterial pressure which is higher in high sodium than in normal sodium rats. Cirrhotic rats showed a lower hypertensive response to angiotensin II than their corresponding control rats. In addition, no difference between pressor responses to angiotensin II was observed when normal sodium and high sodium cirrhotic rats were compared. On application of angiotensin II, femoral arteries of control and cirrhotic rats exhibited a dose-dependent contraction. However, maximal contraction was higher in high sodium control rats (145 ± 12 mg) than in normal sodium control rats (99 ± 6 mg, p < 0.05). No significant differences between control and cirrhotic rats on either sodium diet were observed. In conclusion, cirrhotic, nonascitic rats showed an impaired pressor response to angiotensin II that is more marked after a high sodium diet. These differences are not due to changes in the contractility of peripheral arteries to angiotensin II.Key words: angiotensin II, liver cirrhosis, sodium intake, mean arterial pressure, vascular reactivity.
The effect of sialoadenectomy on gastric mucosal integrity in the rat: roles of epidermal growth factor and prostaglandin E2
Authors: Tepperman B. L. , Kiernan J. A. , Soper B. D.
Published: April 2011

Removal of the salivary glands (SALX) in rats has been shown to increase the susceptibility of gastric mucosa to ulcerogens. In the present study, we have investigated the role of specific salivary glands in this response. In addition, we have examined whether a functional link exists between the salivary glands, epidermal growth factor (EGF), and prostaglandin E2 (PGE2) by determining whether SALX decreases the responsiveness of the mucosa to the protective actions of either of both of these agents. Removal of the parotid salivary glands did not significantly increase ulceration in response to intragastric administration of 100% w/v ethanol. Animals were examined 60 min after ethanol administration. Removal of the submandibular–sublingual gland complexes was associated with a significant increase in the area of mucosal damage and a decrease in gastric pit depth in ethanol-treated animals when compared with sham-operated control rats. Furthermore, in both SALX and control animals, exogenous PGE2 and EGF resulted in a dose-dependent reduction in both groups of animals, although the protective effects of PGE2 and EGF were attenuated in SALX rats. PGE2 and EGF administered in combination resulted in the same degree of protection in both SALX and control rats. Sialoadenectomy resulted in a reduction in mucosal PGE2 synthesis. EGF administration did not consistently increase mucosal PGE2 synthesis. Conversely, sialoadenectomy did not reduce mucosal levels of EGF nor did exogenous PGE2 consistently increase salivary or mucosal content of EGF. If animals were examined 5 min after ethanol instillation, there were no differences in the degree of damage between SALX and control animals whether determined by measuring surface areas of lesions or changes in histology. These data suggest that SALX is associated with a reduction in the responsiveness of rat gastric mucosa to PGE2 and EGF. The data is not totally consistent with reductions in endogenous levels or synthesis of these agents.Key words: salivary glands, mucosal integrity, EGF immunoassay, PGE2 synthesis.
Plasma gonadotropin patterns characterizing the development of polycystic ovaries in the estradiol valerate treated rat
Authors: McCarthy Gerald F. , Farookhi Riaz , Brawer James R.
Published: April 2011

Polycystic ovaries (PCO) develop in female rats within 4 weeks of an injection of estradiol valerate (EV). The final morphological transition from a noncystic to a cystic state occurs in the presence of estrous (control) mean serum gonadotropin concentrations, suggesting that gonadotropin patterns rather than mean concentrations are causal to PCO. We have examined plasma luteinizing hormone (LH) and follicle-stimulating hormone (FSH) patterns in female rats at estrus and on days 5, 11, 16, and 21 following EV treatment. Estrous animals displayed large amplitude LH pulses of short duration, interspersed among frequent, low amplitude pulses of similar duration, and infrequent, broad-based LH episodes. Following EV treatment, there was a progressive decline in the frequency and magnitude of the large amplitude LH pulses, such that by day 16, they ceased altogether. Conversely, the frequency of the low amplitude pulses increased such that the total pulse frequency remained constant. The onset of this pattern coincides with the wave of atresia that precedes the emergence of cystic follicles. The pulsatile plasma pattern of FSH seen at estrus remained unaltered at all time intervals examined after EV treatment. We conclude that there is a specific LH pattern responsible for the generation and maintenance of the PCO condition.Key words: polycystic ovaries, gonadotropins, ovary, cysts.
Uptake and methylation of histamine by dispersed gastric mucosal cells and its possible influence on acid secretion
Authors: Wollin A.
Published: April 2011

Inactivation of histamine by gastric mucosal tissue was examined in dispersed rabbit gastric mucosal cells. Mucosal cells were incubated with [14C]histamine. The formed radioactive metabolites were separated and identified by thin layer co-chromatography and quantitated, in both the cellular and extracellular mediums. Gastric mucosal cells internalized histamine, most of which was immediately methylated primarily to Nτ-methylhistamine and released. Cellular histamine product accumulation reached a plateau. The rate of histamine methylation increased with increasing extracellular histamine concentration, moving towards a plateau above 5 μM. Histamine methylation was greatly decreased but not abolished at 4 °C, in the absence of Na+ and by phlorizin (0.5 mM), an inhibitor of Na+-dependent co-transport. Inhibition of histamine N-methyltransferase decreased intracellular methylhistamine content dose dependently without increasing intracellular histamine. The secretagogues pentagastrin and carbachol did not influence histamine metabolism but ethanol inhibited methylation. The data suggest that gastric mucosal cells take up histamine by a Na+-dependent and Na+-independent process. The histamine uptake capacity appears to be linked to the methylation activity within the cell. The decrease in histamine uptake and metabolism caused by ethanol could potentially increase histamine concentrations near the target cells and be the reason for the stimulatory effect of ethanol on acid secretion.Key words: rabbit mucosa, histamine uptake, histamine N-methyltransferase, Nτ-methylhistamine, ethanol.
Response to pinealectomy and blinding in vitellogenic female frogs (Rana perezi) subjected to high temperature in autumn
Authors: Alonso-Gómez A. L. , Tejera M. , Alonso-Bedate M. , Delgado M. J.
Published: April 2011

The present experiments were carried out to investigate the effects of pinealectomy and bilateral enucleation on the ovarian activity in Rana perezi frogs maintained in 12-h light – 12-h dark photoperiod and 20 ± 1 °C during the vitellogenetic growth in late autumn. These environmental conditions, mainly temperature, induce a gonadal and metabolic response similar to that observed in the natural habitat in summer: a marked ovarian follicular regression, a depletion of the energetic resources from fat bodies and liver, and a minimum in oestradiol circulating levels. This response is partially blocked by pinealectomy and blinding. Protein phosphorus, as an index of vitellogenic proteins, and total ovary lipid content were significantly higher in pinealectomized and blinded frogs with respect to sham-operated animals. Likewise, oestradiol concentrations showed a significant increase during the dark phase of the daily photocycle in pinealectomized and blinded animals. From our results, we can suggest that the arrest of vitellogenesis, the depletion of energetic resources, and the regulation of oestradiol levels induced by the high temperature in Rana perezi frogs can be influenced, at least in part, by the pineal complex and lateral eyes.Key words: pinealectomy, blinding, vitellogenesis, frog, temperature.
Relation between the O2 supply:demand ratio, , and adenosine formation in hearts stimulated with inotropic agents
Authors: Headrick John P. , Willis Roger J.
Published: April 2011

Mooted controllers of adenosine formation in heart are the oxygen supply:demand ratio, myocardial oxygen consumption [Formula: see text], the cytosolic phosphorylation potential (log[ATP]/[ADP][Pi]). The relationship between these parameters and purine release (adenosine + inosine) into the venous effluent was examined in isovolumic rat hearts perfused at 20 and 12 mL∙min−1∙g−1 with a glucose containing crystalloid buffer and stimulated with inotropic agents (isoproterenol, norepinephrine, 3-isobutyl-1-methylxanthine, and ouabain). The oxygen supply:demand ratio and [Formula: see text] were continuously determined using an oxygen electrode to monitor oxygen supply and consumption. The phosphorylation potential was calculated from phosphorus metabolite levels determined by 31P-NMR spectroscopy and HPLC analysis. Left ventricular function was assessed as the rate-pressure product. All inotropic agents increased the rate-pressure product, with increases in function being greater in the hearts perfused at 20 mL∙min−1∙g−1. [Formula: see text] was linearly related to the rate-pressure product at each flow rate; however, the hearts perfused at 20 mL∙min−1∙g−1 exhibited approximately twofold greater [Formula: see text] values for similar rate-pressure product values. All inotropic agents increased adenosine release into the venous effluent. While there was a significant linear relation between adenosine formation and [Formula: see text] in hearts perfused at both flow rates and stimulated with drugs, the relations differed with adenosine release being approximately fourfold greater in hearts perfused at 12 mL∙min−1∙g−1 under similar conditions of [Formula: see text]. Adenosine formation correlated exponentially with the ratio of oxygen supply:demand under all conditions (r = 0.97) and the relation did not differ significantly between hearts perfused at different rates. The phosphorylation potential was decreased from control values by all drugs at both flow rates and plotted linearly with [Formula: see text], although the relations differed between hearts perfused at different rates. Alternatively, the phosphorylation potential plotted linearly with oxygen supply:demand under all conditions (r = 0.98) and did not differ at different flow rates. These results support the idea that adenosine formation depends on the oxygen supply:demand ratio and indicate that [Formula: see text] is not a consistent index of adenosine formation in the glucose-perfused isolated rat heart. The oxygen supply:demand ratio is reflected in the cytosol by changes in the cytosolic phosphorylation potential.Key words: O2 supply:demand ratio, adenosine, crystalloid-perfused rat heart, inotropic agents, myocardial oxygen consumption.
Digestive tract motor correlates of vomiting and nausea
Authors: Lang Ivan M.
Published: April 2011

The digestive tract from the upper esophageal sphincter to the ileum participates in the vomiting process, but the role of the digestive tract in nausea is unclear. In preparation for vomiting, the proximal stomach relaxes and the small intestine is evacuated orad in a single mass movement by a retrograde giant contraction and caudad in a stripping fashion by a series of phasic contractions. Orad evacuation of the small intestine may not only remove offending substances but may also dilute or buffer gastric contents with intestinal and pancreaticobiliary secretions. In association with retching and vomiting, the striated muscle of the esophagus contracts longitudinally, pulling the relaxed proximal stomach into the thoracic cavity forming a funnel from stomach to esophagus. However, gastric evacuation does not occur until the hiatal fibers of the diaphragm relax during vomitus expulsion. Nausea is a subjective feeling in humans that is difficult to identify in animals. Various changes in digestive tract activity have been associated with nausea, but no evidence suggests that these events cause nausea. The prodromal signs of vomiting (e.g., increased heart rate and respiration) that occur concomitantly with the gastrointestinal motor correlates of vomiting have been considered autonomic indices of nausea in animals, but this has not been proven. Regardless, the gastrointestinal motor correlates of vomiting do not cause the prodromata. The emetic central pattern generator may be organized in parallel with respect to its individual autonomic correlates, but as groups of responses, the autonomic and somatomotor correlates may be organized in series.Key words: vomiting, nausea, gastrointestinal motility.
Dibutyryl cAMP-induced Increases in triacylglycerol lipase activity in developing L8 myotube cultures
Authors: Palmer Warren K. , Oscai Lawrence B. , Bechtel Peter J. , Fisher Glenn A.
Published: April 2011

Triacylglycerol (TG) lipase activity, with an alkaline pH optimum, has been identified in the cellular fraction of L8 myotube cultures. This TG lipase activity was stimulated by serum and inhibited by NaCl and protamine sulfate. These characteristics have been classically described for lipoprotein lipase. It was possible to increase the activity of this TG lipase three- to fivefold by incubating the cells with dibutyryl cAMP Maximal enzyme activity was observed 16 h following the addition of 10–100 μM dibutyryl cAMP to the cultured cells. Enzyme activity returned to control levels 24 h after removal of the nucleotide from the culture medium. Serum-sensitive alkaline TG lipase activity was also identified in five other myotube preparations of cultured muscle cells. The highest levels of activity were found in rat skeletal muscle primary, H9, and L6 cell types. The finding that dibutyryl cAMP is an effective inducer of alkaline TG lipase activity provides us with a valuable model to investigate mechanisms regulating synthesis, compartmentalization, and transport of lipoprotein lipase in muscle.Key words: lipoprotein lipase, cultured muscle cells, enzyme induction.
Canine jejunal submucosa cultures: characterization and release of neural somatostatin
Authors: Buchan A. M. J. , Doyle A. D. , Accili E.
Published: April 2011

A primary culture of the canine jejunal submucosa has been established and used to investigate neuronal somatostatin release. Immunocytochemical characterization of the cultures demonstrated the presence of the following peptidergic neurons: neurotensin (30%), somatostatin (27%), vasoactive intestinal polypeptide (14%), neuropeptide Y (10%), and substance P (5%). No immunoreactive neurons were observed with the available antisera to galanin, gastrin-releasing peptide, and motilin. The concentration of somatostatin-like immunoreactivity, as determined by radioimmunoassay of cell extracts, was 358 ± 105 pmol/well. Basal release of somatostatin was 4.4 ± 0.9% total cell content and was significantly inhibited by the addition of substance P at 1 and 100 nM. The addition of the calcium ionophore, A23187, with phorbol 12-myristate 13-acetate stimulated somatostatin release in a concentration-dependent manner. These data indicate that short-term cultures of the jejunal submucosal plexus will be an excellent model for determination of the factors influencing the release of neural somatostatin.Key words: immunocytochemistry, neuronal cultures, neurofilament, substance P.
Demonstration of prostaglandin activity in longs of the rainbow lizard (Agama agama) by bioassay
Authors: Ajayi Funmilayo O. , Okpako David T.
Published: April 2011

Extracts and perfusate effluents of lungs of the rainbow lizard (Agama agama) were assayed for prostaglandin-like activity. Results of differential bioassay and thin-layer chromatography suggested that the prostanoid was predominantly PGE2-like. The mean PGE2-like content of 10 lizard lung extracts was 2.9 μg g−1 wet weight compared with 146 ng g−1 in rat lungs. Mechanical pressure applied to the lung during perfusion through the pulmonary vasculature provoked the release of large quantities of PGE2-like material. This release was blocked by fatty acid cyclooxygenase inhibitors. Compared with guinea-pig and rat lungs, lizard lungs exhibited a markedly low capacity for inactivating PGE2. In view of an apparently high prostaglandin-forming and a low inactivating capacity, we speculate that under certain circumstances, lizard lungs may release vasoactive substances into the circulation.Key words: rainbow lizard, cyclooxygenase, PGE2 lung inactivation.
Nω-Nitro-L-arginine: a potent inhibitor of the L-arginine-dependent soluble guanylate cyclase activation pathway in LLC-PK1 cells
Authors: Ishii Kunio , Kerwin Jr. James F. , Murad Ferid
Published: April 2011

Oxytocin increased cyclic GMP levels in LLC-PK1 porcine kidney epithelial cells through activation of soluble guanylate cyclase. NG-Monomethyl-L-arginine and Nω-nitro-L-arginine inhibited oxytocin (10 μM) induced cyclic GMP accumulation with IC50 values of 2.3 μM and 140 nM, respectively, and the inhibition was prevented with L-arginine. Both inhibitors at 100 μM lowered the basal levels of cyclic GMP, but did not affect those induced by 1 μM sodium nitroprusside and 100 nM atrial natriuretic factor. These data support our hypothesis that an endothelium-derived relaxing factor-like substance is formed as the endogenous activator of soluble guanylate cyclase in an L-arginine-dependent fashion in various cell types. Nω-Nitro-L-arginine is 16 times more potent than NG-monomethyl-L-arginine as a specific inhibitor of this pathway in LLC-PK1 cells.Key words: porcine kidney epithelial (LLC-PK1) cells, cyclic GMP, Nω-nitro-L-arginine, NG-monomethyl-L-arginine, endothelium-derived relaxing factor.
Characterization and regulation of sex-specific mouse steroid hydroxylase genes
Authors: Yoshioka Hidefumi , Lindberg Raija , Wong Garry , Ichikawa Takeshi , Itakura Takao , Burkhart Barbara , Negishi Masahiko
Published: April 2011

We characterized the genes of the male-specific mouse steroid 16α-hydroxylase (C-P-45016α) and the female-specific mouse steroid 15α-hydroxylase (P-45015α) within two distinct gene families. In spite of the high structural identities within each family, the expression of the hydroxylase genes is uniquely regulated. Moreover, the other family members encode the P-450s which are structurally very similar to the hydroxylases but are not able to catalyze steroid hydroxylase activities. For example, only a single amino acid substitution creates steroid 15α-hydroxylase activity in another family-member P-450coh, which catalyzes coumarin 7-hydroxylase but little steroid hydroxylase activity. It appears, therefore, that the mouse P-450 gene families evolved through gene duplication and selective mutation to create new P-450s structurally as well as to establish novel regulatory elements for the gene expressions.Key words: cytochrome P-450, steroid hydroxylase, site-directed mutagenesis, evolution, gene regulation.
Expression and catalysis of sex-specific cytochrome P450 isozymes in rat liver
Authors: Bandiera S.
Published: April 2011

Research interest in the study of cytochromes P450 has recently been shifting to the characterization of "constitutively" expressed isozymes from that of the inducible forms. Several "constitutive" cytochrome P450 isozymes have been purified from rat liver including five immunochemically related proteins designated cytochromes P450f, P450g, P450h, P450i, and P450k. These hemoproteins have been identified as distinct isozymes on the basis of spectral, electrophoretic, and catalytic properties and NH2-terminal sequence analysis. Purification and immunoquantitation studies have indicated that these isozymes are expressed in a developmental as well as sex-related manner, and are relatively refractory to induction by xenobiotics. Cytochromes P450h and P450g are male-specific proteins, cytochrome P450i is a female-specific isozyme, while cytochromes P450f and P450k are present in both male and female adult rats. In addition, the expression of cytochrome P450g was shown to segregate into two phenotypes in outbred rats. Genetic studies utilizing inbred strains have indicated that the gene responsible for inheritance of high levels of cytochrome P450g is autosomal. Although considerable progress has been made in understanding the role of gonadal hormones and growth hormone in the hepatic regulation of cytochromes P450g, P450h, and P450i in particular, the physiological significance of the "constitutive" isozymes in the liver remains largely unresolved.Key words: cytochrome P450, regulation, constitutive, liver, sex differences.
Tissue-specific regulation of cytochrome P-450 dependent testosterone 15α-hydroxylase
Authors: Squires E. James , Negishi Masahiko
Published: April 2011

Testosterone 15α-hydroxylase activity in kidney microsomes is higher in male mice than in female mice, while in the liver the activity is higher in females than in males. Cytochrome P-45Q15α, a specific form of cytochrome P-450 having testosterone 15α-hydroxylase activity, accounts for virtually all of the testosterone 15α-hydroxylase activity in female kidney microsomes, while other isozymes of testosterone 15α-hydroxylase are present in male kidney microsomes. In female kidney, P-45015α expression is regulated by a single sex-dependent locus, called Rsh for "regulation of steroid hydroxylase." The higher level of P-45015α expression in male kidneys is dependent on androgens. Of all mice strains, 129/J seems to be the least dependent on androgens to maintain a high expression of P-45015α in male kidneys. Castration of male mice lowers kidney levels of P-45015α but in the liver, P-45015α, levels rise after castration. This reciprocal regulation of P-45015α genes in liver and kidney was investigated by isolating cDNA clones encoding P-45015α from liver and kidney cDNA libraries. Two highly homologous cDNA clones encoding P-45015α designated type I and type II were identified, and levels of type I and type ÏI mRNA in liver and kidney were determined by differential restriction mapping of double-stranded cDNA prepared from mRNA from these tissues. Only type I mRNA is present in male kidney and only type II mRNA is present in female kidney, while both type I and type II mRNA are present in liver. Castration results in decreased levels of type I mRNA in male kidney but increased levels of type I mRNA in male liver. The levels of type II mRNA are not affected by androgens. We conclude that type I gene is induced in male kidneys and repressed in male liver by androgens, while type II gene expression is not affected by androgens.Key words: cytochrome P-450, 15α-hydroxylase, androgen-dependent expression, tissue-specific expression.
Effects of timolol, indomethacin, and MK-571 on bronchoconstriction to infused leukotriene D4 in guinea pigs
Authors: Masson P. , Jones T. R.
Published: April 2011

Continuous intravenous infusions of leukotriene D4 produced a prolonged but variable bronchoconstriction (approximately a 200% increase in lung resistance (RL) and a 50% decrease in dynamic compliance (Cdyn)) in anesthetized and paralysed guinea pigs that peaked within 1–1.5 min and was followed by a somewhat smaller secondary plateau response. The overall response was delayed (time to peaks) but not significantly reduced by pretreatment with the cyclooxygenase inhibitor indomethacin (1 mg/kg), was markedly potentiated by the β-adrenoceptor antagonist timolol (5 μg/kg), and was partially and completely blocked by pretreatment with 0.1 and 1.0 mg/kg, respectively, of the leukotriene D4 receptor antagonist MK-571. MK-571 prevented the response in indomethacin-treated guinea pigs but was considerably more active at preventing and reversing the potentiated responses (lower dose of leukotriene D4) in animals treated with indomethacin and timolol. Additional studies in indomethacin- and timolol-treated animals demonstrated that MK-571 was active with good duration of action by the aerosol route of administration (30 min and 4 h pretreatment). The technique of infusing leukotrienes into untreated, indomethacin-treated, and indomethacin- and timolol-treated guinea pigs is a useful method to study the action and interaction of leukotriene receptor antagonists.Key words: leukotriene receptor antagonists, cyclooxygenase inhibitor, β-adrenoceptor blockade in guinea pigs, MK-571, L-648,051.
Cerebral arteries can generate 5- and 15-hydroxyeicosatetraenoic acid from arachidonic acid
Authors: Schulz Richard , Jancar Sonia , Cook David A.
Published: April 2011

Products of the lipoxygenase pathway have been implicated in the development of the cerebrovascular spasm that arises after subarachnoid hemorrhage. In particular the hydroperoxyeicosatetranenoic acids (HPETEs), which are unstable and break down rapidly to the corresponding 5-hydroxy acids (HETEs), are vasoconstrictor agents that mimic some aspects of cerebrovascular spasm. It is not, however, well established whether segments of cerebral artery can manufacture these products. We have studied the lipoxygenase product profile of cerebral arteries stimulated with arachidonic acid. Rings of bovine cerebral arteries were incubated in Krebs solution containing arachidonic acid. The lipoxygenase products were studied using high performance liquid chromatography. The largest peaks had the retention times of 5- and 15-HETEs, and the identity of these peaks was confirmed using specific radioimmunoassays. Stimulation with arachidonic acid resulted in a time- and dose-dependent increase in the formation of both HETEs, with 15-HETE being most abundant. The release of both HETEs was markedly reduced in the presence of AA-861, an inhibitor of lipoxygenase, but not with the cyclooxygenase inhibitor indomethacin. These data are thus consistent with our previous suggestion that the contractile activity of arachidonic acid in cerebral arteries arises, at least in part, from HPETE formation and with a possible role for these compounds in cerebral vasospasm.Key words: arachidonic acid, cerebral artery, hydroxyeicosatetraenoic acid, lipoxygenase.
Pancreatic glucagon secretion during a short period of hemorrhage in anesthetized dogs
Authors: Briand Richard , Gagné Jacques , Yamaguchi Nobuharu
Published: April 2011

Glucagon has been implicated in the hormonal metabolic response to hemorrhage. However, evidence for this has been obtained largely from observations of circulating plasma glucagon concentration. A clear increase in the pancreatic glucagon secretion remains to be demonstrated. Plasma concentrations of pancreatic immunoreactive glucagon (IRG) and insulin (IRI) were determined in portal venous and aortic blood, and plasma glucose in aortic blood. Dogs were bled (approximately 15 mL/kg) until aortic systolic blood pressure dropped to approximately 50% (70.5 ± 8.1 mmHg, n = 7) (1 mmHg = 133.32 Pa) of its control value (135 ± 7.1 mmHg, n = 7), and the hemorrhagic hypotension was maintained for 10 min. The net portal venous IRG delivery rate rose significantly and continued to increase during the hemorrhagic hypotension despite a significant fall in the portal venous blood flow. Aortic IRG increased significantly along with the increase in portal venous IRG delivery rate (r = 0.838, n = 42, p < 0.01). The portal venous delivery rate of IRI decreased significantly in response to hemorrhage. The aortic IRG/IRI concentration ratio increased significantly during the hemorrhage-induced hypotension. Aortic glucose concentration increased significantly 5 min after hemorrhage and continued to rise until the end of the hemorrhagic hypotension. The present study demonstrates that the secretion of pancreatic glucagon actually increases during the early phase of hemorrhage. The results also indicate that the increase in aortic IRG during the hemorrhagic hypotension is due to the increased pancreatic glucagon secretion. It is suggested that the pancreatic glucagon may be involved in the early hyperglycemic response to hemorrhage.Key words: glucagon, glucose, hemorrhage, hyperglycemia, hypotension, insulin, pancreas.
Effects of alkalosis on muscle ions at rest and with intense exercise
Authors: Lindinger Michael I. , Heigenhauser George J. F. , Spriet Lawrence L.
Published: April 2011

The effects of metabolic and respiratory alkalosis (MALK and RALK) on intracellular strong ion concentrations ([ion]i) and muscle to blood ion fluxes were examined at rest and during 5 min of intense, intermittent tetanic stimulation in the isolated, perfused rat hindlimb. Compared with the control (C), perfusion of resting skeletal muscle during MALK and RALK significantly increased [Cl−]i and [Na+]i, and RALK significantly lowered [K+]i; these changes, however, did not affect initial hindlimb force production. In both resting and stimulated muscle, the intracellular ion changes corresponded to appropriate perfusate to muscle ion fluxes. At rest, changes in slow-twitch soleus were greater than in fast-twitch white gastrocnemius (WG), but stimulation-induced changes in [Lac]i and [K+]i were greater in WG. At the end of stimulation [K+]i and [Mg2+]i had decreased less in MALK than in C and RALK, particularly in plantaris and WG muscles. Compared with C, the muscle to perfusate flux of Lac− increased by 37% in MALK and 27% in RALK. This was associated with significantly less Lac− accumulation in all muscles in MALK than in RALK, which, in turn, had significantly less lactate than C. Lactate efflux from contracting skeletal muscle was significantly correlated with an uptake of Cl− by muscle. It is concluded that extracellular alkalosis alters skeletal muscle intracellular ionic composition and increases Lac− efflux from skeletal muscle. In agreement with other studies, lactate release appears to occur by both ionic and molecular transport processes. Alkalosis had no apparent effect on muscle performance with this preparation.Key words: acid–base, skeletal muscle, potassium, lactate, ion transport.
Effect of acidosis on skeletal muscle metabolism with and without propranolol
Authors: Barclay J. K. , Graham T. E. , Wolfe B. R. , Duk J. Van , Wilson B. A.
Published: April 2011

Does the stimulatory effect of circulating catecholamines counteract the inhibitory effect of acidosis on skeletal muscle metabolism? To investigate this possibility, we studied gastrocnemii in dogs breathing either air (n = 10) or 4% carbon dioxide in air (n = 10) at rest and during contractions. In five dogs from each group, we infused propranolol into the arterial supply of the right and left muscles for 40 min. After 30 min of infusion, the left muscle was stimulated at 3 Hz for 10 min. During the 10th min of contractions, we removed and froze both muscles in liquid nitrogen. Oxygen uptake and blood flow to the left muscle prior to or during stimulation was not affected by acidosis either with or without propranolol. Glycogen concentration in resting muscle was unaffected by acidosis with or without propranolol. There was an acidosis related decrease of approximately 50% in the glycolytic intermediates (glucose 6-phosphate, fructose 1,6-diphosphate, α-glycerol phosphate, and dihydroxyacetone phosphate) in unstimulated muscles without β-blockade. At rest, acidosis decreased muscle lactate by 50% with and 64% without propranolol, but lactate release was decreased only with acidosis without propranolol (1.4–0.1 μmol/kg∙s). Acidosis without propranolol had no effect on the changes in glycogen concentration or the change in the concentration of glycolytic intermediates resulting from contractions. In β-blocked muscle, the difference between stimulated and unstimulated concentrations of glycogen and glycolytic intermediates including lactate was 20–50% smaller with acidosis. Thus, with β-blockade, the acidotic effects at rest disappeared and an inhibition of the metabolic adjustment to contractions appeared, indicating that circulating catecholamines do modify some metabolic effects of acidosis.Key words: oxidative muscle, glycogen, lactate efflux, glycolytic intermediates, β-blockade.
Increase in number of myocardial [3H]BAY K 8644 binding sites during adult maturation of rat
Authors: Navaratnam Srisala , Khatter Jagdish C.
Published: April 2011

In the present study we investigated the binding properties of [3H]BAY K 8644 to the purified sarcolemmal membrane, isolated from 2- and 12-month old Sprague–Dawley rats. Specific binding of [3H]BAY K 8644 was saturable and the Scatchard plot analysis revealed a single class of binding sites in purified sarcolemmal membrane. The estimated maximum number of binding sites in the membrane of 12-month-old rat was 2.4 ± 0.1 pmol/mg protein, which was significantly greater than the maximum number of binding sites in 2-month-old rats (1.7 ± 0.2 pmol/mg protein). The affinity to bind [3H]BAY K 8644 was, however, reduced in older rats (KD, 14.5 ± 0.8 vs. 4.8 ± 0.3 nM). Measurement of activities of sarcolemmal and subcellular marker enzymes showed that the purification of membrane was virtually identical in two age groups. This would suggest that membrane purity was not a contributing factor to the observed increase in [3H]BAY K 8644 receptor density. Since dihydropyridine receptor sites are very likely to represent voltage-gated calcium channels of sarcolemma, it is concluded that the density of myocardial voltage-gated calcium channels increases during adult maturation.Key words: BAY K 8644, Ca2+ channel, maturation, age.
Differences in vascular responses to vasoactive agents of basilar artery and aorta from rabbits with alloxan-induced diabetes
Authors: Abiru Toichi , Kamata Katsuo , Miyata Noriyuki , Kasuya Yutaka
Published: April 2011

Responses of the basilar artery and aorta to vasoactive agents in alloxan-induced diabetic and age-matched control rabbits were examined. There were no significant differences in the reactivity of the basilar artery to norepinephrine (NE), 5-hydroxytryptamine (5-HT), and K+ between age-matched control and diabetic rabbits. The maximal contraction of the aorta with endothelium in response to NE was significantly enhanced in the case of the aorta from diabetic rabbits. Pretreatment with 10−6 M methylene blue or removal of the endothelium enhanced the contractile response of aorta to NE from control rabbits and, after such treatment, the concentration–response curve to NE was almost identical to that of aorta from diabetic rabbits. Basal levels of cyclic GMP but not cyclic AMP in the diabetic aorta with endothelium were significantly lower than those in the control aorta with endothelium. These results demonstrate that the cerebral artery is resistant to diabetes mellitus within 10 weeks as compared with the peripheral artery. The enhancement in the contractile response of aorta to NE in diabetic rabbits is due to the attenuation of the spontaneous release of endothelium-derived relaxing factor, through an impairment of the function of endothelial cells.Key words: alloxan, diabetes mellitus, basilar artery, aorta, endothelium, cyclic GMP, contraction, relaxation.
A model for nonexercising hindlimb muscles in exercising animals
Authors: Bonen Arend , Blewett Cameron , McDermott John C. , Elder Geoffrey C. B.
Published: April 2011

Nonexercising muscles appear to be metabolically active during exercise. Animal models for this purpose have not been established. However, we have been able to teach animals to run on their forelimbs while their hindlimbs are suspended above the treadmill with no visible limb movement. To document that indeed this mode of exercise does not provoke additional muscle activity, we have compared the levels of neural activation of the soleus and plantaris muscles using a computer analysis of the electromyographic interference pattern, recorded from bipolar fine wire electrodes implanted across each muscle. Via computer analyses of the electromygraphic interference patterns the frequencies and amplitudes of motor unit action potentials were obtained. The data were sampled during 20 s of every minute of observation. Comparisons were made in four conditions: (i) resting on the treadmill while bearing weight on the hindlimbs (normal rest), (ii) running on the treadmill (15 m/min, 8% grade) on all four limbs (normal exercise), (iii) resting while the hindlimbs were suspended in a harness above the treadmill (suspended rest), and (iv) exercising with the forelimbs (15 m/min, 8% grade) while the hindlimbs were suspended above the treadmill (suspended exercise). All four experimental conditions were carried out for 90 min each and were performed by each animal. The results clearly show that muscle activities (frequencies and amplitudes), when the hindlimbs are suspended above the treadmill, at rest or during exercise, are lower than the activities in these same muscles when the animals are at rest, supporting only their body weight. Activities in the same muscles during exercise were from 300 to 2000% greater than during hindlimb suspension. Despite these large differences in muscle activities, comparable quantities of glycogen are lost from these hindlimb suspended (nonexercising) muscles during exercise and when these same muscles are performing the exercise. The physiologic data indicate that suspending the hindlimbs of a rat during forelimb exercise provides a convenient animal model for the study of nonexercising muscle during exercise. In fact the soleus and plantaris activities during suspended exercise are less than during normal rest.Key words: soleus, plantaris, nonexercising muscle, electromyography.
Stable isotopes in the management and diagnosis of inborn errors of metabolism
Authors: Parsons Howard G.
Published: April 2011

Stable isotope techniques offer advantages over older methods in safety, sensitivity, specificity, and reduction in number of subjects required for analytic determinations in some types of studies in "inborn errors of metabolism." In addition to their use as internal standards for gas chromatography – mass spectrometry, quantitation of plasma substrates, and their urinary metabolites, stable isotopes have been successfully employed in studies of metabolite identification, enzyme activity, nutrient turnover and requirements, and diagnosis of inborn errors of metabolism.Key words: metabolism, inborn errors, stable isotopes.
Isotope fractionation by plants and animals: implications for nutrition research
Authors: Kennedy Brenda V. , Krouse H. Roy
Published: April 2011

The isotopic compositions of animal tissues, minerals, and fluids reflect those of ingested food and water and inhaled gases. This relationship is illustrated by a review of data pertaining to five light elements of biological interest (carbon, nitrogen, hydrogen, oxygen, and sulphur). Processes affecting the isotopic composition of inorganic compounds in reservoirs are summarized, and isotope fractionation during transfer of elements from these inorganic reservoirs through progressive trophic levels of food webs is discussed. Variability of δ values within and among individuals, populations, and species of plants and animals is attributed to at least six factors: locality, dietary selectivity, biochemical composition of food, isotope effects in metabolic processes, turnover rates, and stress. Features of a variety of terrestrial and aquatic ecosystems are used to illustrate basic concepts. Future research should seek to clarify specific mechanisms affecting δ values during the transfer of elements through food webs.Key words: food webs, stable isotopes, isotope fractionation, ecosystems.
Mycotoxicoses of domestic animals and their diagnosis
Authors: Schiefer H. B.
Published: April 2011

Mycotoxins have been named "agents in search of a disease," and the considerable progress in analytical methodology over the last 10 years has not changed this very much. The following are factors that contribute to the difficulty of making a diagnosis: (1) nonspecificity of lesions; (2) masking of mycotoxic effects by secondary effects, e.g., through immunosuppression; (3) late appearance of a lesion, e.g., bone marrow damage or neoplasia; (4) interaction of several mycotoxins or presence of other toxicants or deficiency states; (5) species variation in the response to the mycotoxin(s); (6) difficulty of linking a late appearing effect with a demonstrable cause; (7) low doses of mycotoxins may cause stimulating effects; and (8) not being aware of the potential of a mycotoxin as a causative factor in disease. The mycotoxins of major importance in Canada are trichothecenes, ochratoxin, zearalenone, and ergot. It is concluded that the significance of mycotoxins for animals in Canada is likely generally underestimated.Key words: mycotoxins, domestic animals, diagnosis of mycotoxicoses.
Ochratoxin A: an important western Canadian storage mycotoxin
Authors: Marquardt Ronald R. , Frohlich Andrzej , Abramson David
Published: April 2011

Ochratoxin A (OA) is a mycotoxin produced by certain species of storage fungi of the Penicillium and Aspergillus genera. Toxin production by these fungi is influenced by species and even strain of fungi, time and temperature of incubation, moisture content of substrate, and type of substrate. OA has been shown to occur in various grains, cereals and other plant products, animal feeds, meats, and human tissues in countries throughout the world. Of interest is the discovery of OA in a high percentage of blood from humans in Germany. OA is acutely toxic to many different animals and in addition to being a nephrotoxin, it is a hepatotoxin, a teratogen, a very potent carcinogen, possibly a mutagen, and an immunosuppressive agent. OA is rapidly absorbed throughout the entire gastrointestinal tract and distributes itself in the body as a two-compartment open model and has a particular high affinity for serum albumin. OA is hydrolyzed by the intestinal microflora into nontoxic compounds (7-carboxy-5-chloro-8-hydroxy-3,4-dihydro-3R-methylisocoumarin (Oα) and phenylalanine). It is excreted as either OA, hydroxylated OA, or Oα in both the urine and feces. OA appears to exert its toxic effect by promoting an increased level of lipid peroxidation, by inhibition of an amino acylation reaction, and possibly by conversion into metabolites that are capable of binding DNA. These in turn cause other secondary effects associated with OA. It would appear that this compound presents a true potential hazard for humans as its occurrence is wide spread and it is highly carcinogenic.Key words: ochratoxins, ochratoxin A, metabolic effects.
The use of trichothecene-contaminated grains in feeds
Authors: Smith T. K.
Published: April 2011

A review is presented describing the relative efficiencies of the various technologies that have been proposed to permit incorporation of mycotoxin-contaminated grains into animal diets without adversely influencing growth rate or resulting in hazardous residues in edible animal tissues. When the degree of contamination is modest, it may be possible to dilute the contaminated materials with uncontaminated grain to lower the concentration of trichothecenes below the threshold of significant biological activity. A less useful alternative to dilution is the other mechanical approach of milling to remove the most heavily contaminated fractions of the grain. Chemical destruction of trichothecenes is also a possibility. An example is the use of sodium bisulfite treatment to destroy deoxynivalenol in contaminated corn. Such treatments may, however, reduce palatability and nutritional value. When the biochemical mechanism of trichothecene toxicity is known, in vivo therapeutic treatments may be possible. It has been shown, for example, that T-2 toxin-induced changes in brain prostaglandin production can be overcome by treatment with dexamethasone resulting in increased survival. A similar effect was seen using the selective platelet activating factor antagonist BN 52021. Another approach is the use of dietary treatments to either promote in vivo detoxification of mycotoxins or to reduce absorption from the digestive tract with the aid of nonnutritive binding agents.Key words: trichothecene, Fusarium, mycotoxin, utilization, feed.