Intact Pigs Research Articles

The effect of peroral and intracaecal 3-methylindole administration on the quantitative absorption to the portal vein in growing intact male pigs

This study intends to extend knowledge on the fate of intestinal 3-methylindole (3MI) in vivo as the substance is a key causative agent in the expression of boar taint in pig carcasses. Eleven multi-catheterized and caecum-fistulated intact male pigs were used to examine the effects of peroral and intracaecal challenges of 1, 5 and 10 mg 3-methylindole per kilogram body weight (BW) on the quantitative net absorption from specific sites of the alimentary canal (AC), measured as 3MI portal net appearance (PNA). Faeces were collected once a day while portal, hepatic and jugular vein as well as arterial blood were collected during the experiments lasting 300 min. Portal blood flow was recorded by ultrasonic blood flow probes. The BW of the pigs averaged 73 to 89 kg at the beginning and end of the experiments. All pigs on the untreated control treatment absorbed 3MI from the AC. Faecal 3MI concentrations did not differ between control and 3MI-treated pigs. On the other hand, an evident difference was observed in the PNA between the controls with an average of 11.2 mg 3MI (300 min)−1 and 3MI-treated animals varying from 23.9 to 308 mg 3MI (300 min)−1 After application of 3MI, the net absorption from the AC to the portal blood plasma increased up to 147 times. Depending on the site of administration and the dosage application, plasma peak values of 3MI occurred within the first 30 min after the challenge. Within the doses of 1 to 10 mg 3MI (kg BW)−1, no absorption plateau was to be reached. The observed rapid absorption of 3MI leads to the assumption that the mechanism is mainly by passive diffusion. Intravenous 3MI injections indicated diffusion from the blood circulation to the intestinal lumen. The site of administering exogenous 3MI was of less importance for the PNA than the dosage applied. This implies that the permeability for 3MI along the AC is identical, no matter where it is introduced. Results indicate a proportional relation between the 3MI dosage administered and the PNA. Finally, it was observed that a) pigs with high (pre-experimental) initial PNAs subsequently also absorbed more 3MI after challenges of additional 3MI, expressed as PNAs; and b) pigs with increasing BW exhibited higher PNAs, indicating a rise of 3MI absorption with advancing age. Key words: Boar taint, 3-methylindole, quantitative absorption, pig, portal vein, skatole

Relationship between oxidation and conjugation metabolism of skatole in pig liver and concentrations of skatole in fat.

High concentrations of skatole in fat of some intact male pigs are a major cause of boar taint. In this study, we investigated the effect of oxidative and conjugative metabolism of skatole in liver on the concentrations of skatole in the fat of intact male pigs. In Trial 1, 18 Yorkshire intact males were equally divided into two treatments with high (mean, .42; SD, .26 ppm) and low (mean, .06; SD, .02 ppm) fat skatole levels. There was an increased rate of skatole metabolism, an increased glucuronidation activity, and a decreased sulfation activity toward 2-naphthol in liver from pigs with high skatole levels (P < .05). In Trial 2, Swedish Yorkshire x F4 European Wild Pig intact males were used. Among skatole metabolites that were produced in incubations with liver microsomes, pro-MII was conjugated with glucuronic acid and sulfate, and metabolite F-1 was conjugated with glucuronic acid. The rates of formation of various skatole metabolites and conjugation of pro-MII were evaluated for 22 pigs with different levels of cytochrome P4502E1 in the liver. The formation of F-1 and sulfation of pro-MII were negatively correlated with fat skatole levels (r = -.59, and r = -.56, respectively) and were decreased in pigs with high fat skatole levels and low P4502E1 levels (P < .01). The results indicate that oxidation and conjugation reactions of skatole in pig liver have a dramatic effect on skatole levels in the fat. In particular, the formation of F-1 and formation and subsequent sulfation of pro-MII are related to low levels of skatole in the fat, presumably due to rapid metabolic clearance of skatole.

Hepatic metabolism of skatole in pigs by cytochrome P4502E1.

High concentrations of skatole in fat are a major cause of boar taint in intact male pigs. Skatole is metabolized in the liver, and this metabolism could affect concentrations of skatole in fat. In this study, we evaluated the involvement of cytochrome P450, in particular cytochrome P4502E1, in skatole metabolism in pig liver. Liver microsomes from F4 European Wild Pig x Swedish Yorkshire intact male pigs were incubated in a buffer containing NADPH, NADH, and skatole. Several skatole metabolites were detected by HPLC, including 6-hydroxyskatole (pro-MII), 3-hydroxy-3-methyloxyindole (MIII), and five others not identified in this study. Inhibitors of P450 were added to microsomal incubations, and their effect on the formation of skatole metabolites and skatole disappearance was evaluated. The general cytochrome P450 inhibitors SKF 525A, at a concentration of .2 mM and metyrapone, at a concentration of .1 mM decreased the formation of pro-MII (P = .001) to 38.2 and 11.6%, respectively, of that of controls. The SKF 525A also reduced the synthesis of MIII and three other metabolites, whereas metyrapone only reduced the disappearance of skatole and synthesis of pro-MII. Inhibitors specific for cytochrome P4502E1 were more effective in reducing the formation of skatole metabolites than SKF 525A and metyrapone. Chlorzoxazone and diallyl sulfide reduced (P = .001) the synthesis of pro-MII to 9.7 and 30.9% of the control rate. The formation of most of the other skatole metabolites and disappearance of skatole were also reduced with these inhibitors. These results indicate that skatole is metabolized in pig liver to pro-MII and other metabolites by cytochrome P4502E1.

Effects of diet manipulation on growth performance, carcass characteristics, and meat quality of intact male pigs (1998)

Effects of diet manipulation on growth performance, carcass characteristics, and meat quality of intact male pigs (1998)

Effect of dietary crude protein and energy content on nitrogen utilisation, water intake and urinary output in growing pigs

A digestibility and balance trial was carried out with four intact castrated male pigs (live weight 33-82 kg) to study the effects of dietary crude protein and energy content on nutrient digestibility, nitrogen metabolism, water intake and urinary output. In a 4 x 4 Latin square design, four barley-oats-soya bean meal based diets were arranged 2x2 factorially. The corresponding factors were dietary crude protein (CP) content: high (180 g/kg CP) or low protein diet (140 g/kg CP) supplemented with free lysine, methionine and threonine; and dietary net energy content; high (1.05 feed units (FU)/kg) (feed unit=9.3 MJ net energy) or low net energy content (0.95 FU/kg). Lowering dietary CP content (mean values of 189 to 152 g/kg dry matter, respectively) by supplementation of free amino acids decreased urinary nitrogen (N) excretion by 6.9 g/day (32%) (P

Nutritive value of oats of different composition evaluated by intact and fistulated pigs

Heal and total tract digestibilities of dietary components and energy in eight oat diets varying in chemical composition were studied with growing pigs in two 4×4 Latin square experiments. The diet with partially dehulled oats had the significantly (P < 0.05) highest ileal and total tract digestibility of organic matter, crude protein, total fibre and energy. The metabolizable energy value of the oat batches tested varied between 15.4 and 10.9 MJ kg‐1 dry matter. Significant correlations (P < 0.05) were found between both total tract and ileal digestibilities of organic matter and energy, respectively, and the content of fibre components, starch, crude fat and nitrogen‐free extractives. Differences in the correlations as predictors between the content of crude fibre, total fibre, neutral detergent fibre or acid detergent fibre and the ileal and total tract digestibility of organic matter and energy, respectively, were limited.

Gender and transcriptional regulation of NO synthase and ET-1 in porcine aortic endothelial cells.

Experiments were designed to determine whether normal fluctuations in sex steroid hormones alter gene transcription for endothelial nitric oxide synthase (NOS) and preproendothelin-1 (prepro-ET-1). Aortic endothelial cells were removed from adult, gonadally intact male and female or ovariectomized Yorkshire pigs. Endothelial cells were prepared for Northern blot analysis, Western blot analysis or enzyme activity. Nitric oxide products (NOx) and endothelin-1 (ET-1) in plasma were measured by chemiluminescence and radioimmunoassay, respectively. Northern blot analysis identified single bands corresponding to endothelial NOS and prepro-ET-1. Quantification of the blots showed an increase in expression of mRNA for both endothelial NOS and prepro-ET-1 in ovariectomized pigs compared with gonadally intact male and female pigs. There were no differences in amount of endothelial NOS protein identified by Western blot analysis among groups. On the contrary, plasma concentrations of NOx were significantly decreased in ovariectomized pigs, and there were no differences either in the concentrations of ET-1 in the plasma or extracts from the coronary arteries. These results suggest that expression of endothelial NOS and prepro-ET-1 may be regulated at transcriptional level by ovarian hormones. In addition, the ovarian hormones may regulate production of these endothelium-derived factors at the posttranscriptional level.

Topical Delivery of l-Ofloxacin: Characterization of Relevant Physicochemical Properties and Evaluation of a Polymeric Delivery System

The distribution coefficient of ofloxacin was determined between octanol and universal buffer in the pH range 3 to 10 at a constant ionic strength of 0.30. The in vitro skin permeability was studied in buffer systems ranging from pH 3 to 10 using side-by-side diffusion cells. A series of 0.05% w/w ofloxacin gels were formulated between pH 3 and 8 in a polymeric base, and their swelling and release kinetics were studied using synthetic membranes. The antimicrobial activity of ofloxacin gel formulated at pH 4 was measured in second-degree burn wounds on intact pigs. The octanol/buffer distribution coefficient was directly related to the percentage of zwitterion in the solution with a peak value at about the isoelectric point (6.70). Permeability coefficient increased with pH, with a steep rise above pH 8.00. The amount of drug in the skin also increased with pH. In the gel delivery system, the release rate of ofloxacin from various pH formulations was ranked as pH 4 > pH 3 > pH 5 > pH 6 > pH 7 > pH 8. In pig experiments, 0.05% ofloxacin was found to be most effective against Pseudomonas aeruginosa and other bacteria in second-degree burn wounds when compared with hexylene glycol, silver nitrate, and silver sulfadiazine. The study findings suggest that ofloxacin is a good candidate for topical therapy of skin and wound infections. The pH-sensitive polymeric base described suits well for the delivery of ofloxacin and the treatment of burn wounds.

Comparison of the accuracies of chemical and sensory tests for detecting taint in pork

Abstract Chemical and sensory tests are widely used to detect boar taint in meat from entire male pigs. Chemical tests typically assess tissue levels of the compounds associated with taint, including 16-androstenes, like 5α-androstenone, and skatole. Sensory tests classify boar carcasses into either tainted or untainted categories according to test criteria assessed by human evaluators. The threshold levels of taint compounds are typically determined according to the results of chemical tests. This experiment was designed to compare chemical analyses and sensory tests by a trained panel for the determination of taint and to study their accuracies. Fat samples were taken in a slaughterhouse from 220 intact male pigs killed at 100.4 ± 0.4 kg body weight. Fat samples, frozen after collection at slaughter, were subsequently analyzed for levels of androstenone and skatole using a colorimetric method. Samples also were evaluated by a trained sensory panel for the presence of boar taint. Forty-nine percent of males had fat androstenone levels above 1.0 ppm, the cutoff level used to discriminate tainted from untainted pork. Only 2% of pigs had fat skatole levels above 0.25 ppm of cutoff level. Fifteen percent of boars were judged as tainted by the sensory panel. Based on the cutoff levels of 1.0 ppm of fat androstenone and 0.25 ppm of fat skatole, the sensitivities and specificities of the chemical analysis were, respectively, 100% and 54.1% for androstenone, and 8.0% and 99.0% for skatole. The sensitivity and specificity of pooled data (combined androstenone and skatole) were 84.8% and 57.2%, respectively; positive and negative predictive values were 25.9% and 95.5%, respectively. These results suggest that fat androstenone is more reliable than skatole for identifying taint. Furthermore, chemical analysis of tissue levels of androstenone and skatole does not identify all tainted carcasses, suggesting that other compounds may also contribute to taint.

Serum biochemical changes associated with cystic ovarian degeneration in pigs after atrazine treatment

Biochemical and histopathological parameters of the ovarian function were observed to assess the toxic effect of low dose of atrazine, an s-triazine herbicide, in female pigs (gilts) undergoing intensive breeding. Female pigs (cross-bred between Swedish and German landrace) received 2 mg atrazine kg −1 body wt. in feed daily during 19 days of the oestrous cycle. The last treatment day corresponded to day -3 of the onset of the next expected oestrus. Blood samples were collected 3 times daily at 3-h intervals on the first 5 post-treatment days. Serum 17β-oestradiol (17β-E) and progesterone (P) concentrations were determined. A significantly higher ( P < 0.05 and P < 0.001, respectively) serum P concentration and significantly lower ( P < 0.01 and 0.001, respectively) serum 17β-E concentration was recorded 48 and 24 h before the onset of the next expected oestrus in atrazine-treated pigs, as compared to intact pigs. The onset of the next expected oestrus failed to occur, but no other adverse clinical reactions associated with the treatment were recorded. Histopathological examination of the ovaries of treated pigs indicated multiple ovarian follicular cysts and persistence of corpus luteum. Biochemical and histopathological findings showed that subacute exposure of female pigs to low dose of atrazine prolonged their oestrous cycle.

Chronic inhibition of endothelium-derived nitric oxide synthesis causes coronary microvascular structural changes and hyperreactivity to serotonin in pigs.

Endothelium-derived nitric oxide (NO) is believed to regulate myocardial perfusion and structural changes in the vascular wall. Our objective was to determine whether chronic inhibition of NO synthesis causes structural and functional changes in coronary arteries. Coronary vasomotor response was studied in pigs before and after chronic oral administration of the NO synthesis antagonist N omega-nitro-L-arginine methyl ester (L-NAME) 30 mg.kg-1.d-1 for 2 weeks. Chronic L-NAME treatment increased (P < .01) arterial pressure but did not alter baseline coronary blood flow (CBF), epicardial coronary diameter, or heart rate. Chronic L-NAME treatment augmented (P < .01) the decrease in CBF in response to intracoronary serotonin (30 micrograms/kg) from 5 +/- 14% to 40 +/- 5% but did not alter the CBF response to prostaglandin F2 alpha. The serotonin-induced decrease in CBF after acute L-NAME administration was still less before (1.3 +/- 0.4%) than after chronic L-NAME treatment (51 +/- 6%). Chronic L-NAME treatment attenuated the increase in CBF with bradykinin (100 ng/kg) but did not alter the CBF response to nitroglycerin (10 micrograms/kg). Compared with intact pigs without L-NAME treatment, L-NAME-treated pigs had significant thickening of the media in the microvessels (diameter, < 300 microns) but not in the large epicardial vessels. Chronic intracoronary infusion of L-NAME at 3 mg.kg-1.d-1 for 2 weeks, which did not produce arterial hypertension, caused similar microvascular medial thickening. These results indicate that chronic administration of L-NAME caused coronary microvascular structural changes and hyperreactivity to serotonin in pigs in vivo, suggesting an important role of defective NO synthesis in coronary microvascular disorders.

Computed tomography evaluation of regional increases in microvascular permeability after reperfusion of locally ischemic myocardium in intact pigs

I evaluated how well fast computed tomography (CT) scanning could quantify altered myocardial microvascular function resulting from transient ischemia and subsequent reperfusion. A major epicardial coronary artery of anesthetized pigs was occluded for either 0, 15, 30, 60, or 120 min. Fast X-ray CT scan sequences were performed before and during occlusion and 30, 60, and 90 min after onset of subsequent reperfusion. Regional myocardial perfusion, intramyocardial blood volume, and myocardial microcirculatory permeability-surface area product were estimated from the CT scan sequences. With the increasing duration of ischemia, the permeability-surface area product remained unchanged during reperfusion (p > .05), but an index of myocardial microvascular permeability increased with the progressive duration of ischemia and of reperfusion (p < .05). These CT-based findings are consistent with published, more invasive demonstrations that capillary permeability is increased during postischemic reperfusion in proportion to the duration of the preceding ischemia.

The pattern of the circadian rhythm of pancreatic secretion in fed pigs

The pattern of the circadian rhythm of pancreatic secretion was studied in four 6- to 7-wk-old intact male pigs that were kept in metabolic cages under 12 h light:12 h dark cycles and fed three times a day at 0800, 1500, and 2200. Three 24-h collections of pancreatic juice and blood were begun at 0800 every 2nd day during 5 d. A biphasic pattern of the exocrine pancreas was detected. Secretions during the first phase (postprandial peak) contained large amounts of protein and enzymes, and secretions appeared immediately after feed ingestion. Secretions during the second phase (between meals) had lesser amounts (P < .001) of protein and enzymes, but were of longer duration (P < .001). The output of protein and trypsin activity were generally correlated (P < .001) with each other, but the correlation of either with the volume outflow were small. However, these variables were correlated (P < .01) with the volume outflow at night during the second phase. Plasma concentrations of insulin and glucose increased after each meal, but the increase was significant (P < .05) only for insulin. Insulin and glucose concentrations were correlated (P < .01) with each other after the meals at 0800 and 1500. The results indicated a biphasic pattern of the exocrine pancreas and a monophasic pattern of the endocrine pancreas in pigs. The regulation of these patterns seems to vary during the 24-h period. Furthermore, feed enhanced secretion, but it did not seem to be the only factor controlling the circadian pattern.

Supercritical Carbon Dioxide Extraction of Androstenone and Skatole from Pork Fat

ABSTRACTBoar taint, an unpleasant odor observed in pork from some mature intact male pigs, is attributed primarily to the presence of two compounds in boar fat, androstenone (Sα‐androst‐16‐ene‐3‐one) and skatole (3‐methyl indole). A rapid extraction method for the preparation of fat samples for androstenone/skatole screening assays would lead to more efficient use of boar carcasses for pork production. Supercritical carbon dioxide removed 97 ± 2% of the androstenone (extraction at 40°C; 5 min) and 65 ± 3% of the skatole (extraction at 40°C; 20 min) from 0.5 g of boar backfat. Supercritical CO2 provides the basis for a fairly rapid extraction method to remove compounds associated with boar taint.

Myocardial Protection by Na + -H + Exchange Inhibition in Ischemic, Reperfused Porcine Hearts

Studies in isolated myocytes and isolated heart preparations have suggested that Na(+)-H+ exchange is an important mechanism for myocardial ischemia-reperfusion injury. This study was undertaken to determine whether inhibition of Na(+)-H+ exchange limits infarct size and improves regional systolic shortening in regional ischemia and reperfusion in intact pigs. The left anterior descending coronary artery was occluded in 18 anesthetized and thoracotomized pigs for 45 minutes and then reperfused for 24 hours. As main end points of this study, regional systolic shortening (sonomicrometry) and infarct size (percentage of infarcted to ischemic myocardium) were determined at the end of the experiments. Infarcted myocardium was assessed by histochemistry (tetrazolium stain) and by quantitative histology of one heart slice. The Na(+)-H+ exchange inhibitor Hoe 694 was administered intravenously at a dose of 3 mg/kg in 6 pigs each either 10 minutes before ischemia (group A) or 10 minutes before the onset of reperfusion (group B). Six pigs served as controls (group C). Treatment with Hoe 694 before ischemia decreased histochemical infarct size from 65 +/- 18% (control group) to 13 +/- 8% (P < .01) and histological infarct size from 49 +/- 20% (control group) to 14 +/- 4% (P < .01). Histochemical (55 +/- 19%) and histological (42 +/- 15%) infarct sizes of group B were insignificantly reduced by 15%. Myocardial protection in group A was associated with an attenuated contracture after 10 minutes of reperfusion and an improved regional systolic shortening after 24 hours of reperfusion (group A, 25 +/- 12%; control group, 6 +/- 5%; P = .01). These parameters remained unaffected in group B. This study clearly demonstrates that Na(+)-H+ exchange is an important mechanism for cell death in myocardial ischemia and reperfusion in intact pigs; thus, inhibition of this exchange system may prove a promising new strategy in the clinical treatment of myocardial ischemia and reperfusion.

F182. Treatment of polycythemia vera with hydroxyurea: Effects on red blood cell filterability and geometry

To determine if the vasodilatory response to the intracoronary injection of ionic and nonionic contrast media in intact pigs is dependent on nitric oxide (NO). The mechanisms responsible for inducing the increase in coronary blood flow in response to the intracoronary injection of contrast media during angiography are still not entirely understood. There is evidence to suggest that the response could be partially mediated by NO.We studied 14 anesthetized, open-chested pigs receiving ventilation.Changes in coronary blood flow and coronary vascular resistance were measured in response to the coronary artery injection of saline solution (0.5 mol/L, isosmolar with plasma) and three different contrast agents: meglumine sodium ioxaglate (Hexabrix; Mallinckrodt Medical; Point-Claire, Quebec, Canada), a low osmolar ionic contrast agent; iohexol (Omnipaque 300; Sanofi Winthrop; Markham, Ontario, Canada), a nonionic contrast agent; and diatrizoate meglumine 66%, diatrizoate sodium 10% (MD-76; Mallinckrodt Medical), an ionic contrast agent. Measurements were made during three experimental conditions: the coronary artery infusion of (1) saline solution, control; (2) L-nitro-arginine (LNNA; 10−3 mol/L and 10−2 mol/L), a competitive inhibitor of NO synthase; and (3)L-arginine 10−1 mol/L, a substrate for NO synthase. The infusion of LNNA produced an increase in baseline coronary vascular resistance (p < 0.001), but it did not attenuate the vasodilatory response to the infusion of the contrast agents. Both the high and low osmolar ionic and nonionic contrast media caused a decrease in baseline coronary vascular resistance. For all three conditions, MD-76, which has the highest osmolality, produced the greatest decrease in coronary vascular resistance.The vasodilatory response of the coronary vasculature to contrast agents is directly related to osmolality and is not mediated by NO.

F183. 5-Fluorouracil and blood viscosity

To determine if the vasodilatory response to the intracoronary injection of ionic and nonionic contrast media in intact pigs is dependent on nitric oxide (NO). The mechanisms responsible for inducing the increase in coronary blood flow in response to the intracoronary injection of contrast media during angiography are still not entirely understood. There is evidence to suggest that the response could be partially mediated by NO.We studied 14 anesthetized, open-chested pigs receiving ventilation.Changes in coronary blood flow and coronary vascular resistance were measured in response to the coronary artery injection of saline solution (0.5 mol/L, isosmolar with plasma) and three different contrast agents: meglumine sodium ioxaglate (Hexabrix; Mallinckrodt Medical; Point-Claire, Quebec, Canada), a low osmolar ionic contrast agent; iohexol (Omnipaque 300; Sanofi Winthrop; Markham, Ontario, Canada), a nonionic contrast agent; and diatrizoate meglumine 66%, diatrizoate sodium 10% (MD-76; Mallinckrodt Medical), an ionic contrast agent. Measurements were made during three experimental conditions: the coronary artery infusion of (1) saline solution, control; (2) L-nitro-arginine (LNNA; 10−3 mol/L and 10−2 mol/L), a competitive inhibitor of NO synthase; and (3)L-arginine 10−1 mol/L, a substrate for NO synthase. The infusion of LNNA produced an increase in baseline coronary vascular resistance (p < 0.001), but it did not attenuate the vasodilatory response to the infusion of the contrast agents. Both the high and low osmolar ionic and nonionic contrast media caused a decrease in baseline coronary vascular resistance. For all three conditions, MD-76, which has the highest osmolality, produced the greatest decrease in coronary vascular resistance.The vasodilatory response of the coronary vasculature to contrast agents is directly related to osmolality and is not mediated by NO.

901–40 Gender-related Differences in Smooth Muscle Cell Proliferation in Response to Estradiol and Dihydrotestosterone

The cardioprotective effect of estradiol (E 2 ) is strongly supported by the reduced incidence of coronary artery disease (CAD) observed in premenopausal females versus age-matched males and in postmenopausal females on estrogen therapy. The favorable effect of estrogen on lipid profiles does not fully account for the observed cardiac benefits in females versus males. We have previously demonstrated that physiologic concentrations of E 2 inhibit female pig coronary vascular smooth muscle cells (VSMC) in vitro; this may partially account for estrogen's favorable cardiac effects. We determined the effect of sex steroids Idihydrotestosterone (DHT) and E 2 ) and tamoxifen Ian anti-estrogen) on proliferation of coronary VSMC obtained from male pigs. VSMC were cultured in phenol red-free Media 199 with 10% fetal calf serum. Cells obtained from mature adult male pigs were growth arrested in serum-free media for 24 hours, and treated with effectors in 2% charcoalstripped serum at concentrations ranging from 10 -11 to 10 -7 M for 24 hours. Cell proliferation was assessed by tritiated thymidine incorporation corrected for protein content. No significant effect on proliferation was observed in E 2 or tamoxifen-treated cells versus vehicle controls. Proliferation was significantly increased in cells treated with DHT at 10 -11 M. In conclusion, E 2 did not inhibit proliferation of coronary VSMC obtained from intact male animals, in contrast to the inhibition observed previously in VSMC obtained from intact female pigs. This gender-related differential response in vitro to E 2 may partially explain the reduction in CAD in estrogen-replete women compared to men. Tamoxifen had no effect on VSMC proliferation. The increased proliferation of VSMC in response to dihydrotestosterone may playa role in the pathogenesis of CAD in males.

35] Ebselen

This chapter focuses on Ebselen. Ebselen, 2-phenyl-1, 2-benzisoselenazol-3(2H)-one, has attracted interest since it was found that it exhibits activity as an enzyme mimic. The reaction catalyzed is that of a glutathione (GSH) peroxidase—namely, the reduction of a hydroperoxide at the expense of thiol. In 1984, the glutathione peroxidase-like activity of ebselen (then called PZ 51) was described. Since then, extended research on this interesting molecule has covered areas from pulse radiolytic studies on radical reactivity through its biological properties in cells and organs, all the way to clinical settings. Basically, this compound is considered capable of contributing to the antioxidant defense in tissues, so that a potential pharmacological application becomes of interest. Clinical studies are underway. Ebselen metabolism has been studied in isolated perfused liver and intact rats, pigs, and human volunteers. The detected metabolites share the characteristics that the isoselenazole ring is opened by cleavage of the Se-N bond. It is important to note that no unchanged ebselen was detectable in urine, plasma, or bile. The physiological transport of ebselen across cell membranes and into the cytosol and further subcellular compartments is likely to involve ebselen in its protein-bound form.

Sex differences in the distribution of estrogen receptors in the septal area and hypothalamus of the domestic pig (Sus scrofa).

Recently in the pig hypothalamus a vasopressin- and oxytocin-containing nucleus was identified which, like the supraoptic nucleus, becomes sexually dimorphic after puberty. Following the increase in circulating steroids at puberty, the vasopressin- and oxytocin-containing nucleus becomes twice as large in both males and females. In adulthood, the vasopressin- and oxytocin-containing nucleus of females is approximately twice as large as that in males. Because these alterations are possibly due to an influence of gonadal steroids, i.e. estrogens, the vasopressin- and oxytocin-containing nucleus cells were tested for the presence of estrogen receptors. In addition to the area of the vasopressin- and oxytocin-containing nucleus, the present study documented the distribution of estrogen receptors in the septal area and other parts of the hypothalamus of intact post-pubertal male and female pigs, by utilizing immunocytochemical methodology. Intense nuclear estrogen receptor staining was found in a number of areas, i.e. the medial preoptic area, the oxytocin-containing dorsomedial extension of the supraoptic nucleus, a possible homologue of the sexually dimorphic nucleus of the preoptic area, the median preoptic nucleus, the medial and lateral part of the bed nucleus of the stria terminalis, the ventromedial hypothalamus and the arcuate nucleus. In the ventral part of the lateral septum, the septohypothalamic nucleus, the nucleus subfornicalis and the stigmoid nucleus estrogen receptor immunoreactivity was less intense. Dorsolaterally of the vasopressin- and oxytocin-containing nucleus, estrogen receptor positive cells were observed, but the vasopressin- and oxytocin-containing nucleus itself lacked such receptors. In the magnocellular supraoptic nucleus and paraventricular nucleus no nuclear estrogen receptor staining was found. However, a weak cytoplasmic staining was present in all cells. There was a clear sex difference in the estrogen receptor-immunoreactive cell number in a possible homologue of the sexually dimorphic nucleus of the preoptic area. Compared to male pigs, in female pigs the number of cells showing estrogen receptor immunoreactivity in this area, which is known to be sexually dimorphic in various species, was twice as high. In other areas, such as the medial part of the bed nucleus of the stria terminalis, the medial preoptic area, the arcuate and ventromedial hypothalamic nucleus, a similar sex difference was found. In addition estrogen receptor immunoreactivity was generally more intense in females. No sex differences were noted in the overall distribution of estrogen receptor cells in the areas studied.(ABSTRACT TRUNCATED AT 400 WORDS)